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What's Worse: Drinking or Smoking While Pregnant?

LilSugar — Tue, 13 May 2008 09:00:05 -0700

Tie one on or light 'em up? There are mamas-to-be that hang on to their habits despite being pregnant. And while heading to the bar for a cocktail or stepping outside for a cigarette may not have garnered a second glance a generation ago, times have changed.

According to the U.S. Department of Health and Human Services:

"We do not know what, if any, amount of alcohol is safe. But we do know that the risk of a baby being born with any of the fetal alcohol spectrum disorders increases with the amount of alcohol a pregnant woman drinks, as does the likely severity of the condition. And when a pregnant woman drinks alcohol, so does her baby.

And, in regards to smoking, HHS cautioned:

Smoking during pregnancy can lead to a low birthweight baby and can reduce your baby's lung function.

Which expectant woman bothers you more - those who booze or those blowing smoke?
Source

Smoking

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Smoking and Your Health

Smoking may worsen knee osteoarthritis in men. A study published in the Annals of Rheumatic Disease found that male smokers have more pain and cartilage loss than men who do not smoke. Previous studies have not found such a link.
Smoking greatly increases the risk of age-related macular degeneration. An Australian study reports that smokers are four times more likely to develop the eye condition than those who have never smoked. Smokers also developed the condition at an earlier age.
Analysis of several studies suggests that smoking cigarettes and, in some cases, cigars or pipes, may reduce the risk of Parkinson's disease. However, smoking causes many other serious health conditions and should not be considered a means for preventing Parkinson's.
A small study suggests that infants who are breastfed just after their mother smokes sleep less than those whose mothers did not smoke.

Smoking Cessation

Certain genes may make it easier for you to quit smoking. Researchers at Duke University have identified more than 200 genes that distinguish those who have successfully kicked the habit. It is the first time such genes have been identified. The findings could lead to new smoking cessation therapies that target a person's specific genetic makeup.

Smoke Free Zones

More and more households in the United States are banning smoking. The U.S. Centers for Disease Control and Prevention (CDC) reports that 75% of households now forbid smoking at any time or place in the home.

Smoking in the Movies

Teens who see actors smoke on screen are more likely to become established smokers, according to an updated study in the Archives of Pediatric Adolescent Medicine. Study authors say the likelihood of smoking increases with exposure to movies that depict such behavior.

Introduction

More than 20% of adults in the United States smoke, according to a 2006 report by the U.S. Centers for Disease Control and Prevention (CDC). More than 80% of them smoke every day. Although smoking had steadily declined among adults in recent years, the trend now appears to have stalled. Between 2004 and 2005, the CDC says there was no observable change in smoking rates among U.S. adults.

The addictive effects of tobacco have been well documented. Tobacco is considered to be a mood and behavior altering substance that is psychoactive and abusable. Tobacco is believed to be as potentially addictive as alcohol, cocaine, and morphine. Tobacco and its various components increase the risk of cancer (especially in the lung, mouth, larynx, esophagus, bladder, kidney, pancreas, and cervix), heart attacks, strokes, and chronic lung disease.

The younger children start smoking, the more likely they will smoke as an adult. Smoking is often immediately addictive. According to the American Cancer Society, the earlier you start smoking, the more likely you are to develop long-term nicotine addiction.

In the past, advertising was responsible for encouraging some teens to smoke. New regulations have made it much more difficult for advertisers to promote smoking to young people. However, scenes that show people smoking are still common in movies and television shows, often in a positive light. This may be a major influence on the attitude toward smoking in children and adolescents. An updated study in the Archives of Pediatric Adolescent Medicine found that adolescents that watch movies that portray smoking are more likely to become established smokers.

To prevent children from smoking, parents should not smoke, and they should tell their child that they disapprove of smoking. Schoolchildren who believed that both their parents strongly disapproved of smoking were less than half as likely to smoke as those kids whose parents did not show as much disapproval towards smoking. Other research has supported these findings.

Children whose parents closely monitor their television and music-listening habits are less likely to drink, use drugs, and smoke cigarettes.

Neglected children, or children with absentee parents, were four times as likely to abuse drugs, drink, and smoke as children living with parents who were regularly present and who offered a structured lifestyle.

In a 2002 study, children who regularly attended religious services were also less likely to smoke.

Doctors can have a major effect on young people. However, in one survey, less than half of teenagers had ever been asked by their doctors if they smoked or were counseled not to smoke, even though most teen smokers said they would admit to it if asked.

More American men smoke than women. The following chart details the rate of current smoking in the United States among adults aged 18 years and over, grouped by age and sex:

Age	Total	Men	Women
18 - 44 years	24.1%	27.1%	21.2%
45 - 64 years	21.9%	25.2%	18.8%
65 years and older	8.6%	8.9%	8.3%

Source: CDC/National Health Interview Survey 2005

While the number of adults over 65 who smoke is lower than those in other age groups, older adults usually have smoked for a long time (about 40 years) and tend to be heavier smokers, according to the American Lung Association. Because of this, older smokers are more likely to have smoking-related illnesses.

Caucasian students (under age 18) are more likely to smoke than Hispanics and African-Americans. In 2005, the rate of smoking was highest among American Indians and Alaskan natives. Hispanics and Asians had the lowest rates.

In general, the rate of smoking is highest in the Midwest and South and lowest in the Northeast and West. Utah has the lowest rate of smoking in the United States.

A major U.S. government study reported that people who have not graduated from high school or received their General Education Development (GED) certificate tend to have higher smoking rates than those who attended college.

Higher rates of cigarette smoking have been reported among adults who have earned a GED and those with a 9 – 11 grade education. The lowest rates are seen among those with advanced college degrees.

People with low self-esteem and adolescents with behavioral problems have a higher risk for smoking. Men and women with mental disorders are 50% more likely to smoke than those without such illness.

For example, depression and schizophrenia are known risk factors for smoking. Both may actually have biologic effects that are responsible for this higher risk.

Smoking is much more common among persons with disabilities than those without emotional, mental, or physical limitations. A 2007 Centers for Disease Control study found that the rate of smoking is nearly 50% higher among persons with disabilities. The CDC survey included those with mental illness and drug and alcohol addictions in the disabled group.

Evidence now strongly supports the idea that genes play a role in a person's dependence on nicotine. Researchers are now targeting specific genes that may be responsible for nicotine dependence. So far, research has been shown that there is a common genetic vulnerability to both nicotine and alcohol dependence.

Some studies suggest that the cheaper it is to buy cigarettes and smoke, the more widespread smoking will be. For example, states that have low taxes on cigarettes have a high proportion of smokers. Making it more expensive to smoke may reduce the number of smokers.

Nicotine Addiction

Nicotine is the chemical in cigarettes that makes them addictive. Higher levels of nicotine in a cigarette can make it harder to quit smoking. A report by the Massachusetts Department of Health found that the amount of nicotine in cigarettes has steadily increased over the last 6 years. Higher nicotine levels were found in all cigarette categories, including “light" brands. Massachusetts is one of several states that require tobacco manufacturers to submit yearly reports regarding cigarettes.

Some researchers feel nicotine is as addictive as heroin. In fact, nicotine has actions similar to heroin and cocaine, and the chemical affects the same area of the brain.

Depending on the amount taken in, nicotine can act as either a stimulant or a sedative. Cigarette smoking has definite immediate positive effects. For example, it can:

Boost mood and relieve minor depression
Suppress little fits of anger
Enhance concentration and short-term memory
Produce a modest sense of well-being

Most smokers have a special fondness for the first cigarette of the day because of the way brain cells respond to the day's first nicotine rush. Nicotine, particularly taken in the first few cigarettes of the day, increases the activity of dopamine, a chemical in the brain that elicits pleasurable sensations, a feeling similar to achieving a reward.

Over the course of a day, however, the nerve cells become desensitized to nicotine. Smoking becomes less pleasurable, and smokers may be likely to increase their intake to get their "reward." A smoker develops tolerance to these effects very quickly and requires increasingly higher levels of nicotine.

A smoker may "forget" their craving for nicotine if a part of the brain called the insula becomes damaged. A 2007 study published in the journal Science found that smokers with brain damage to this area were 136 times more likely to forget their addiction to nicotine. The findings may one day lead to new drugs that better help a person quit.

Smokeless tobacco, also called spit tobacco, includes chewing tobacco (dip and chew), tobacco powder (snuff), as well as flavored tobacco lozenges. These products also contain nicotine. There are two forms of spit tobacco.

These products allow tobacco to be absorbed by the digestive system or through mucous membranes. Smokeless tobacco contains at least 28 cancer-causing substances. Smokeless tobacco is not a safe substitute for smoking cigarettes or cigars. According to the National Institutes of Health, chewing on an average-size piece of chewing tobacco for 30 minutes can deliver as much nicotine as smoking three cigarettes.

Although research is inconsistent, some evidence suggests that smokeless tobacco produces a 50-fold increase in the risk of oral cancer, gingivitis, and tooth loss.

Health Risks

Smoking -- even just a few cigarettes a day -- has been linked to many serious health risks. Some are listed below.

According to the American Lung Association, smoking is directly responsible for about 90% of the deaths due to lung cancer. Smoking is also responsible for the majority of deaths due to chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis.

A study in the July 2006 American Journal of Respiratory and Critical Care Medicine showed that smokers with asthma who give up smoking can improve their lung function in as little as 1 week. The small study involved 21 smokers with asthma. Ten of them quit smoking for 10 weeks, while the others continued to smoke. After just a week, lung function test scores in those who stopped smoking improved considerably. In less than 2 months, lung function scores among those who stopped smoking improved by more than 15%.

Study authors say their findings show that there is a “reversible component to the harmful effects of smoking on the airways in asthma.”

All forms of tobacco raise heart attack risk. Smoking, chewing tobacco, and being exposed to secondhand smoke greatly increase the risk of a heart attack. In some cases, the risk of heart problems in people who smoke or are exposed to smoke may be three times greater, according to a study published in the journal Lancet. However, the study also found that the risk of a heart attack among those who stopped smoking slowly decreased over time.

Smoking has a negative affect on a man's sexuality and fertility. Heavy smoking is frequently cited as a contributory factor in impotence because it decreases the amount of blood flowing into the penis. One study noted that among men with high blood pressure, smoking caused a 26-fold increase in impotence.

Smoking impairs sperm motility, reduces sperm lifespan, and may cause genetic changes that can affect a man's offspring. One 2002 trial found that men or women who smoke have lower success rates with fertility treatments. An earlier study reported that men who smoke also have lower sex drives and less frequent sex.

Studies have linked cigarette smoking to many reproductive problems. Continuing to smoke during pregnancy may also cause health problems in the baby.

Negative effects of smoking on female fertility include:

Greater risk for infertility. Women at greatest risk for fertility problems are those who smoke one or more packs a day and who started smoking before age 18.
Earlier menopause. Women who smoke tend to start menopause at an earlier age than nonsmokers, perhaps because toxins in cigarette smoke damage eggs.
Pregnancy complications. Women who smoke have a greater risk for ectopic pregnancy and miscarriage.

Click the icon to see an image of an ectopic pregnancy.

Effects on Unborn Child. Smoking during pregnancy increases the risk for stillbirth, prematurity, and low birth weight in their babies. Women who smoke during pregnancy have lower levels of folate, a B vitamin that is important for preventing birth defects.

Children of mothers who smoke during pregnancy may also be at increased risk for obesity and diabetes.

Some women have particular genes that may make them especially likely to deliver low birth weight infants if they smoke, although newborns of all female smokers have a greater risk for low weight. The good news is that women who quit before becoming pregnant or even during the first trimester reduce the risk for a low birth weight baby to that of women who never smoked.

Women who want to become pregnant should make every attempt to quit and should use smoking cessation aids before they try to conceive. After birth, if new mothers cannot quit, they should at least be sure not to smoke in the same room as their infant.

Smoking and Breastfeeding. Smoking right before breastfeeding may interrupt the child's sleep patterns. A small study found that such infants sleep less than other infants, and that their sleep time dropped significantly as levels of nicotine in breast milk increased.

Smoking has many harmful effects on bones and joints:

Smoking can keep new bone from forming. Women who smoke are at high risk for loss of bone density and osteoporosis.

Click the icon to see an image of osteoporosis.

Postmenopausal women who smoke have a significantly greater risk for hip fracture than those who do not.
Men who smoke may have more severe symptoms of knee arthritis, according to a study published in the Annals of Rheumatic Disease.
Smokers are more apt to develop degenerative disorders and injuries in the spine.
Smokers have more trouble recovering from surgeries, including knee or hip replacements. A 2006 study published in the Journal of Bone & Joint Surgery suggests that smoking delays tendon-bone healing, which may lead to a slower recovery after rotator cuff repair surgery.
Smokers whose jobs involve lifting heavy objects are more likely to develop low back pain than nonsmokers.
Smoking may increase the risk of rheumatoid arthritis in some older women. A 2006 study in Annals of the Rheumatic Diseases showed that smoking nearly doubled the risk of rheumatoid arthritis in postmenopausal women who did not have the most established genetic risk factor for the disease, a genotype called HLA-DRB1 SE.

Click the icon to see an image of rheumatoid arthritis.

Smoking may increase the risk of developing diabetes. Researchers involved in the Insulin Resistance Atherosclerosis Study (IRAS) looked at the relationship between smoking and diabetes and found that 25% of smokers who started the trial with normal blood sugar had diabetes 5 years later compared to 14% of nonsmokers. The results were published in Diabetes Care.

A study released in 2006 supports earlier beliefs that smokers have a higher risk of developing glucose intolerance, a condition that precedes diabetes. The study, published in the British Medical Journal, involved 4,572 people. The findings suggest that chemicals in smoke could affect the pancreas. The pancreas is the organ that produces insulin, which helps control blood sugar (glucose) levels.

Smoking increases acid production in the stomach. It also reduces blood flow and production of compounds that protect the stomach lining.

Diverticulitis. One study suggested that smoking was a major risk factor in diverticulitis, a condition in which small bumps develop in the wall of the colon. In addition, smokers were at risk for complications from diverticulitis, including bleeding and abscess. Diverticulitis mostly affects people over age 50.

Inflammatory Bowel Disease. Smoking has mixed effects on inflammatory bowel disease. Inflammatory bowel disease is the collective term for ulcerative colitis and Crohn's disease. Smokers have been shown to have lower than average rates of ulcerative colitis, but higher than average rates of Crohn's disease. Smokers with Crohn's disease who quit are said to have less severe symptoms.

Click the icon to see an image of inflammatory bowel disease.

Peptic Ulcers. Results of studies on the effect of smoking on ulcers are mixed. Some evidence suggests that smoking delays the healing of gastric and duodenal ulcers. One study reported that after ulcers healed, about half of smokers relapsed after a year, and that all heavy smokers relapsed after 3 months. Other studies, however, have found no increased risk for ulcers in smokers. Smoking does not appear to increase susceptibility to Helicobacter pylori (H. pylori), the bacteria that causes many peptic ulcers.

Click the icon to see an image of peptic ulcers.

Hepatitis and Cirrhosis. Smoking is linked to increased liver scarring (cirrhosis) caused by either excessive drinking or chronic hepatitis B or C viruses.

Cyanide, a chemical found in tobacco smoke, interferes with thyroid hormone production. Smoking triples the risk for developing thyroid disease, particularly hyperthyroidism and hypothyroidism. Women smokers with subclinical hypothyroidism (a symptom-free condition in which the thyroid gland is mildly underactive) have a higher risk for developing full-blown hypothyroidism than their nonsmoking peers. Smoking has also been linked to goiter, a swelling of the thyroid that occurs in people who do not get enough iodine.

Click the icon to see an image of the thyroid.

Smokers are at increased risk for heart and circulatory problems and delayed wound healing after surgery. In one study, patients who were able to cut down or quit smoking 6 - 8 weeks prior to knee or hip replacement surgery were much less likely to suffer complications.

The following age-related conditions occur at higher rates in smokers than nonsmokers:

Cataracts. Quitting smoking reduces your chances of needing cataract surgery in the future, although not to the level seen with nonsmokers.

Click the icon to see an image of a cataract.

Age-related macular degeneration (AMD). AMD is a leading cause of blindness in older people. An Australian study, published in 2007 found that the condition is four times more likely in persons who smoke than those who have never done so. Symptoms of macular degeneration include a loss of central vision, which makes it difficult to read.
Gum disease and tooth loss. A government study found that more than half of the cases of severe gum disease in adults in the United States may be due to cigarette smoking.
Wrinkles. Studies confirm that smokers are nearly five times more likely to develop more and deeper wrinkles as they age compared to nonsmokers.
Baldness and premature gray hair. Certain chemicals in smoke break down in hair cells, which leads to hair damage.
Hearing loss, particularly high-frequency hearing loss. Some experts believe that losing the ability to hear high pitched sound in smokers may be due to a decrease in blood flow to the cochlea, the part of the ear that carries sound to the brain.
Incontinence. One study of 600 women indicated that smokers and former smokers are twice as likely to develop incontinence as women who never smoked.

Secondhand Smoke

Secondhand smoke is produced by a burning cigarette or other tobacco product. An estimated 4 million children a year get sick from being around secondhand smoke. Parental smoking has been shown to affect the lungs of infants as early as the first 2 - 10 weeks of life, and such abnormal lung function could persist throughout life.

Exposure to secondhand smoke in the home increases the risk for asthma and asthma-related emergency room visits in children who have existing asthma.

Parental smoking is believed to increase the risk for lower respiratory tract infections (such as bronchitis or pneumonia) by 50%. Environmental exposure to smoke is thought to be responsible for 150,000 - 300,000 such cases every year.

Smoking Bans

Smoking bans have spread across the country. By October 2007, at least 22 states and the District of Columbia have passed some type of law banning smoking in almost all public places and workplaces, including restaurants and bars. The date an individual state's ban takes effect varies greatly; some do not take effect until 2008 or 2009.

As of January 1, 2006, nine states were considered "smoke-free" -- California, Connecticut, Delaware, Massachusetts, Maine, New York, Rhode Island, Vermont, and Washington.

Quitting Smoking

It's never too late to quit smoking. According to the American Cancer Society, about half of all smokers who keep smoking will die from a smoking-related disease. Quitting has immediate health benefits.


Time after last cigarette	Physical Response
20 minutes	Blood pressure and pulse rates return to normal.
8 hours	Levels of carbon monoxide and oxygen in the blood return to normal.
24 hours	Chance of heart attack begins to decreases.
48 hours	Nerve endings start to regrow. Your ability to taste and smell increases.
72 hours	Bronchial tubes relax and the lungs can fill with more air.
2 weeks to 3 months	Improved circulation; lung function increases up to 30%.
1 to 9 months	Decreased rates of coughing, sinus infection, fatigue, and shortness of breath; regrowth of cilia in the airways, increasing the ability to clear mucus and clean the lungs and reducing the chance of infection; overall energy level increases.
Long-Term Effects	After a year, the risk of dying from heart attack and stroke is reduced by up to 50%.

According to the National Institutes of Health, about 40% of smokers who want to quit make a serious attempt to do so each year, but fewer than 5% actually succeed. A June 2006 report published by the NIH says that the available smoking cessation products and therapies are greatly underused. If more smokers asked for or were offered such help, the agency says quit rates could double or triple.

Some people have certain genes that make quitting easier. Researchers at Duke University have identified more than 200 genes that distinguish those who have successfully kicked the habit. It is the first time such genes have been identified. The findings could lead to new smoking cessation therapies that target a person's specific genetic makeup.

Methods of quitting smoking include counseling and support groups, nicotine patches, gums, lozenges, and sprays, smoking cessation pills, and slowly cutting back on the number of cigarettes smoked (incremental reduction).

About 4% of smokers who quit without any outside help succeed. Nevertheless, most people try to quit alone, and many have reported activities that can help the process of withdrawal. The primary obstacle in trying to quit alone is making the behavioral changes necessary to eliminate the habits associated with smoking. Excellent books, tapes, and manuals are available and are strongly recommended to help people who want to quit without other assistance.

Nicotine replacement therapy involves the use of products that provide low doses of nicotine that do not contain the contaminant found in smoke. The goal of therapy is to relieve cravings for nicotine and ease the symptoms of withdrawal.

In general, nicotine replacement therapy benefits moderate-to-heavy smokers the most. However, it does appear somewhat helpful for light smokers (people who smoke fewer than 15 cigarettes a day).

Nicotine Patches. Nicotine patches deliver nicotine through the skin. This is called transdermal nicotine delivery. It is effective in reducing symptoms during withdrawal. Nicotine patches are available over the counter.

Patches may work in different ways:

Step-Down Approach. Patches that use this method include NicoDerm CQ. The patches come in three strengths (21, 14, and 7 mg). You use the strongest dose first and reduce it gradually over a period of 8 - 10 weeks. A 21 mg patch is about equal to 15 cigarettes. A heavy smoker may need to wear two patches at first.
Single-Step Approach. The single-step patch (Nicotrol) can be taken off after 16 hours and replaced 8 hours later. It can be used for only 6 weeks.

Patches are applied and used in similar ways:

A single patch is worn each day and replaced after 24 hours.
To avoid skin irritation it is applied to different hairless locations above the waist and below the neck each day.
People can wear the patches for 24 hours, but some have reported odd dreams and have disliked the sensation of the patch during the night. People who wear the patch all the time, however, have fewer withdrawal symptoms and slightly better abstinence rates than those who take it off at night.
Patches should be stored and discarded safely, particularly in homes with small children. Small children have been poisoned and gotten sick from wearing, chewing, or sucking on nicotine patches. There have been no reports of death from children who have been poisoned.
The FDA recommends using the patches for 3 - 5 months, although some studies suggest that using them for 8 weeks achieves the maximum benefits.

Children should not come in contact with the patches, even while the smoker is wearing them. If the child has worn the patch, the affected skin should be washed right away. Urgent medical care may be required if the child has eaten nicotine or worn a patch for a prolonged time.

Nicotine Gum. Nicotine gum (Nicorette) is available over the counter and has helped many people quit. Some prefer it to the patch because they can control the nicotine dosage, and chewing satisfies the oral urge associated with smoking.

Tips for using the gum:

If you are just starting to quit, chew 1 - 2 pieces each hour. A smoker should not chew more than 20 pieces a day.
The goal is to stop using the gum by 6 months, but about 3% of people continue to use it long after they have quit smoking.
The gum must be chewed slowly until it develops a peppery taste. It is then tucked between the gum and cheek where it is stored so that the nicotine can be absorbed.
Coffee, tea, soft drinks, and acidic beverages may interfere with nicotine absorption, so people should wait at least 15 minutes after drinking before chewing a piece of gum.

Some people prefer other methods or cannot use the gum for the following reasons:

They find the gum unpleasant tasting.
Side effects specific to the gum may include upset stomach, mouth ulcers, hiccups, and throat irritation.
They are embarrassed by chewing gum.
They wear dentures.

Long-term dependence may be a problem with the gum. Although such dependence is probably safer than smoking, research is needed to confirm this, and experts recommend people chew gum for no more than 6 months.

The Nicotine Inhaler. The nicotine inhaler resembles a plastic cigarette holder. It comes with a number of nicotine cartridges, which are inserted into the inhaler and "puffed" for about 20 minutes, up to 16 times a day. The dose is gradually decreased. It requires a prescription in the United States. Several studies have reported that the inhaler triples abstinence rates (between 17 - 28%) compared with placebo (6 - 9%) after 6 months. It has some specific advantages over other nicotine replacement products:

The inhaler provides varying doses of nicotine on demand (as opposed to continuously with the patch or the gum) and is relatively fast-acting. Blood nicotine levels peak about 20 minutes after using the inhaler, comparable to the gum and faster than the 2 - 4 hours seen with the patch.
It satisfies oral urges.
Most of the nicotine vapor is delivered in the mouth, not into the lung airways (although some people experience mouth or throat irritation and cough).

Using a combination of the inhaler and the patch may be particularly effective. In one study, the combination led to an abstinence rate of over 60% after 6 weeks. While this percentage dropped off over time, it was still a large improvement over the use of the inhaler and a placebo patch.

The Nicotine Nasal Spray. The nasal spray satisfies immediate cravings by providing doses of nicotine rapidly and thus may play a useful role in conjunction with slower-acting nicotine replacement therapies. (Nicotine levels peak within 5 - 10 minutes after administering the spray). The spray can irritate the nose, eyes, and throat, so it may not be suitable for those with allergies or sinus infections. Most people, however, can tolerate the side effects, which usually go away within the first few days.

Nicotine Lozenge. A nicotine lozenge (Commit) is available over the counter. It is made from pressed tobacco and comes in two strengths for heavier or lighter smokers. In a large 2002 study, 15 - 18% of smokers who used it remained smoke free, compared to 6 - 10% who were given a dummy lozenge. Side effects included heartburn, hiccups, nausea, headaches, and cough. The Commit lozenge also contains phenylalanine, a chemical that certain people may need to avoid.

Facts about Nicotine Replacement Therapy:

Not cheating on the very first day of nicotine-replacement use increases the chance of quitting permanently by tenfold.
The more cigarettes a patient smokes, the higher the dose of nicotine replacement may be required at the start.
Adding a counseling program may boost the effect of any nicotine replacement program.
Do not smoke while using nicotine replacement. It can cause nicotine to build up to toxic levels.
Nicotine replacement helps prevent weight gain while it is being used, but people are still at higher risk for gaining weight when they stop all nicotine.

Side Effects. Side effects of any nicotine replacement product may include headaches, nausea, and other gastrointestinal problems. People often experience sleeplessness in the first few days, particularly with the patch, but the insomnia usually passes. Patients using very high doses are more likely to have symptoms. Reducing the dose can prevent them.

Special Concerns for Specific Individuals. There has been some concern that the patch might be harmful for people with heart or circulatory disease, but studies are finding that it poses no danger for these individuals. In fact, it may help reduce angina attacks brought on by exercise. However, unhealthy cholesterol levels (lower HDL levels) caused by smoking remain abnormal with use of the nicotine patch. HDL levels improve when all nicotine is stopped.

Nicotine replacement may not be completely safe in pregnant women, although it has been used successfully in this group without ill effect. There is an increase in heart rates in unborn children of women who use the patch as compared with those who smoke.

Keep all nicotine products away from children. Nicotine is a poison. All nicotine products should be kept safely away from small children. A parent should call a physician or a poison control center immediately if a child has been exposed to a nicotine replacement product, even for a short duration. Parents should also call the doctor if a small child has been exposed to a nicotine product and has any symptoms, including stomach upset, irritability, headaches, a rash, or fatigue.

Warnings Against Long-Term Use. No one should use nicotine replacement therapies as a long-term substitute for smoking. Any nicotine replacement therapy should be temporary. In one study, use of nicotine gum for more than a year was associated with insulin resistance, an abnormality that occurs in diabetes. Some studies have now suggested that nicotine itself may have properties that increase the risk for cancer, independent of carcinogenic chemicals in smoke. More studies are needed.

Bupropion (Zyban, Wellbutrin) is a type of antidepressant that is also an FDA-approved product for smoking cessation. It differs from most other antidepressants because it increases the effects of dopamine, the brain chemical that appears to play a strong role in nicotine addiction. Using Zyban along with nicotine replacement therapy may help you better control cigarette smoking cravings. Zyban does not contain nicotine. In most cases, Zyban is taken a week or two before quitting, and must be taken for 7 - 12 weeks. The usual maintenance dose is 150 mg tablet twice a day. No single dose should be higher than 150 mg.

Side effects of bupropion include gastrointestinal problems, headaches, insomnia, dry mouth, and irritation. In very rare cases, seizures have occurred, although usually in people who exceeded the recommended dose or who already had risk factors for seizures.

A newer drug called varenicline (Chantrix) may significantly reduce cigarette cravings and work better than Zyban. A study in the Archives of Internal Medicine found that almost 50% of those who took varenicline successfully quit. Varenicline mimics some effects of nicotine on the brain, but blocks others. Previous studies published in the Journal of the American Medical Association showed that Chantrix works twice as well as Zyban and quadruples one’s chances of successfully quitting. The FDA approved Chantrix as a smoking cessation aid in May 2006. It is for use in cigarette smokers age 18 and older. It should not be combined with nicotine replacement therapy.

The tricyclic antidepressant nortriptyline (Pamelor, Aventyl) may help reduce nicotine action. Quit rates with either of these medicines are as high as 30%. Long-term abstinent rates are more than twice those of placebo. Most other antidepressants, including fluoxetine (Prozac), have no additional benefits for smokers.

Nortriptyline has been specifically studied for helping smokers. It is best to start taking the medication 10 - 28 days before your intended quit date. Studies have reported quit rates of 14 - 24%. Side effects of nortriptyline include dry mouth and changes in taste. It should be noted that in rare cases, tricyclics can have serious side effects, and overdose can be deadly. Tricyclics may pose a danger for some patients with certain types of heart disease.

Smokers who use outside help have the best record for quitting, with success rates of 25 - 35%. Those who are counseled in addition to using nicotine replacement and Zyban have the best chance. Brochures, audio tapes, and other self-help materials are often ineffective when used alone, but may be helpful in conjunction with a counseling program.

Types of behavioral approaches:

Problem Solving or Coping Strategies. Smokers more likely to quit smoking when they learn thinking (cognitive) and behavioral techniques for breaking the link between certain cues and smoking, stress management techniques, and ways to handle the symptoms of withdrawal and the urge to relapse. The more intense the counseling program, the better. Smokers should look for programs that offer the following:

Session lengths of 20 - 30 minutes
Four to seven sessions
A 2-week program
Additional 2 weeks or more of follow-up contact

Scheduled Reduction. Scheduled reduction is a gradual way to stop smoking.

Divide the number of minutes per day that you are awake by the number of daily cigarettes you smoke. The number you get is how long you wait between smokes.
Week 1: Set up a schedule with time intervals based on this result and using a timer, smoke only at those intervals. If the "cigarette appointment" is missed by more than 5 minutes, you must skip that cigarette.
Week 2: Reduce the number of cigarettes you smoke by one-third and recalculate your time between smokes based on the lower number.
Week 3: Reduce the count again.
Week 4: Quit smoking

Those who are unable to smoke during working hours could try calculating the intervals based on the usual smoking times of the day.

The Staged Approach. The intent of the staged approach is to plan quitting interventions customized for each individual rather than imposing some general method for quitting. The approach takes the smoker through six stages with behavioral interventions at each point:

Pre-contemplation
Contemplation
Preparation
Action
Maintenance
Termination

Although some studies report this approach is significantly more effective than non-staged methods, an analysis of 23 trials did not find the staged approach to be any more effective than other methods. Most studies, however, were weak, and better research is needed on this approach.

People who follow this approach do not proceed from one stage to another in a simple, step-by-step fashion. They actually cycle or spiral back and forth, so that they may move from stage 1 to 2 to 3, and then back to 2 again. They may stay in maintenance mode for years and then fall back to stage 2. Remember that this is normal -- if you tried quitting in the past and didn't stick with it, don't consider yourself a failure. Just try again.

Stage 1: Pre-Contemplation.

People at this stage have no plans or desire to stop smoking. They aren't even considering quitting. People at this stage are generally unaware of the specific benefits that quitting can bring. Or, they may simply have "failed" in the past and have given up. There's no point in talking about how to start a cessation program at this stage. Instead, it is important to think about how quitting will help you feel better, have more confidence, or live longer. The benefits must be identified before a person will consider quitting. If you are at this stage, a good activity is to ask several friends or family members why they quit.

Stage 2: Contemplation.

A person at this stage is thinking, "I think I should probably quit, but I need help getting started." People at this stage know that quitting is good for them, but it seems like a daunting task or they don't think they can pull it off. Some may have tried and failed in the past. It's important for people at this stage to consider some of the truths and falsehoods of quitting. If you are at this stage, write down (brainstorm) all your potential roadblocks -- the things that you believe make quitting difficult -- and learn strategies for overcoming or side-stepping those hurdles. People at this stage might benefit from making a pledge, contract, or other commitment that they are going to get more active in the near future. The goal is to identify the roadblocks and ways to overcome these hurdles, and make a commitment to quitting.

Stage 3: Preparation.

Smokers at this stage are ready to quit. The goal of this stage is to create a specific action plan that takes all factors into account, so that quitting is successful. People at this stage need to know what methods work and what support exists to help them. If you are at this stage, you should consider some backup plans -- what to do when the urge to smoke hits you.

Stage 4: Action!

People at this stage have just quit. This stage is where the most behavioral change occurs. It requires significant commitment and energy. If you are at this stage, keep talking to friends and family for inspiration. Review your backup plans. Reward yourself for small achievements. Having a fellow smoker quit with you can be a huge support as you both get through this stage.

Stage 5: Maintenance.

People at this stage have been smoke-free at least 6 months. The goal now is to prevent relapse. If you are at this stage, continue to be wary of roadblocks and keep reminding yourself of the benefits you have gained. Think about what you have found most enjoyable about being smoke-free.

Hypnosis. Although rigorous studies are lacking, some people report successful cessation from smoking when hypnosis is given in individual sessions. The process is effective only if you trust the therapist and can feel completely at ease in the vulnerable and passive state necessary for hypnotic suggestion.

During a typical session, the hypnotherapist will use various techniques (such as imagery, silent counting) to put you in a relaxed state.

When you are very relaxed, but not asleep, the hypnotherapist quietly suggests motivations for not smoking. The hypnotherapist should also reinforce a positive self-image while you are in deep relaxation. This helps many people avoid the depression that accompanies withdrawal.

The sessions usually takes about 1 hour.

You should be taught methods of self-hypnosis to use at home, and follow-up once to reinforce what you've learned.

Acupuncture and Acupressure. The acupuncture technique for quitting smoking usually uses very tiny curved staples inserted into three different points around the edge of the ear. The procedure is painless. You will be told to press each staple in a certain order for a few seconds whenever the craving for a cigarette occurs. The acupuncturist may also use acupuncture points elsewhere on the body. There are no side effects except for some soreness if the acupuncture staple is pressed too hard.

A related technique called acupressure involves simply pressing select points on the body when a craving hits. Some studies have reported good quit rates with acupuncture, but few rigorous studies have been conducted using this approach.

Aim to Quit Completely

Everyone who quits should aim to quit completely. Most people who return to smoking "cheat" in the first few weeks. Quitting completely is essential to regain good health and reverse bad effects caused by smoking. Reducing smoking, even by half, does not eliminate the risk for cancer and other health problems. Although smokers take in less smoke and nicotine, the body is still unable to heal itself from the ongoing intake of toxins. It should also be noted that changing to low-tar cigarettes is not a solution. In fact, smokers of these cigarettes tend to inhale deeper, perhaps even increasing health risks.

Create a List

Write down 10 reasons to quit. In addition to health reasons, the list might include having better smelling hair, clothes, and breath; having fewer wrinkles; enjoying the taste of food; and saving money. Read the list often during the quitting process to help stay motivated.

Decide on a Specific Quit Date

Some people find it helpful to choose a particular date to quit when little or no stress is anticipated for at least the first 3 days. Women affected by PMS should avoid quitting right before their menstrual cycle. It may help to write out a quit contract, putting the date on paper, and getting a friend to sign it. Discard all smoking paraphernalia on the eve before the quit date, and make plans to stay busy on the day itself, and especially at night, when the urge to smoke will be high.

Make an Oath

Take an extreme oath. For example, "If I smoke one more cigarette my dog will die." Although this seems absurd, some people, even well-educated individuals, who have failed all other methods have reported that they quit completely and successfully after taking such an oath.

Let the Body and Mind Heal During Withdrawal

Retreat from the world when cravings become overwhelming. Take naps, warm baths or showers, meditate, or read novels.
Help your body get rid of nicotine. Drink plenty of water, eat fresh fruits, vegetables, whole grains, and fiber-rich foods. Carrots, apples, and celery are good munching foods.
When cravings occur, hold your breath as long as possible or take a few deep rhythmic breaths.
Use meditation or relaxation and deep breathing exercises. In fact, taking deep breaths when the urge to smoke occurs is a good stopgap measure.

Get Family and Friends Involved

Tell all your friends and family that you've already quit, so you'll be embarrassed if they catch you smoking.
Pay a family member or friend if they catch you smoking. The amount should be large enough ($5 - 20) to be a deterrent, but not so large as to be ridiculous.
If your partner or friend smokes, try persuading them to quit or, at the very least, not to smoke around you and others.

Exercise

Studies continue to show that smokers who exercise can greatly increase their ability to quit smoking while reducing their risk for weight gain. Move the muscles when cravings occur. Dance, run, walk, jump up and down, stretch, do push-ups. Yoga is an excellent exercise program for quitting. Older people and anyone with health problems should consult their health care provider before starting such a program.

Maintain a Healthy Diet

Eat plenty of fresh, crunchy fruits and vegetables. This is also a useful way of satisfying oral cravings without adding many calories.
Drink plenty of water and healthy beverages.
Moderate intake of coffee or tea may be helpful. A small study suggested that drinking caffeinated beverages (such as coffee or tea) while on nicotine replacement may enhance energy expenditure and may help prevent weight gain. Moderate coffee intake may also have antidepressant properties. Avoid caffeine in the evening, however, since sleep disturbances can be a problem during withdrawal.

Change Daily Habits

Change your daily schedule, particularly eating times, as much as possible. Eat at different times or eat many small meals instead of three large ones. Sit in a different chair or even a different room.
If you smoke after eating, find other ways to end a meal. Play a tape or CD, eat a piece of fruit, get up and make a phone call, or take a walk (a good distraction that burns calories as well). For example, if you normally have a cigarette with coffee, drink tea instead or use a different cup.
Substitute oral habits by eating celery, chewing sugarless gum, sucking on a cinnamon stick, or carrying worry beads.
Go to public places and restaurants where smoking is prohibited or restricted.
Set short-term quitting goals and reward yourself when they are met.
Every day put the money normally spent on cigarettes in a jar and buy something pleasurable at the end of a predetermined period of time.
Find activities that focus the hands and mind but are not taxing or fattening: Computer games, solitaire, knitting, sewing, whittling, and crossword puzzles.

Denormalization is the idea that smoking is no longer normal. This concept of denormalization is best instituted by laws and local regulations making smoking inaccessible in public places, raising prices, and putting stricter limitations on cigarette advertising.

Increasing taxes on cigarettes may be one of the most important methods for reducing smoking in the population, particularly in younger people.

Evidence is suggesting that banning smoking in work and public places may be leading to a higher quit rate than in places where smoking is permitted.

Denormalization can also work on a personal level. A British study showed that when one spouse makes healthy changes, including quitting smoking, the other one follows. In couples where smoking continues, it usually continues in both.

Symptoms of Withdrawal

After you quit smoking, you with have some withdrawal symptoms. Such symptoms generally peak in intensity 3 -5 days after you quit, and usually disappear after 2 weeks, although some may persist for several months.

The symptoms of withdrawal include both physical and mental difficulties.

Physical Symptoms.

Tingling in the hands and feet
Sweating
Intestinal disorders (cramps, nausea)
Headaches
Sore throat, coughing, and signs of a cold

Withdrawal symptoms should be treated accordingly, just as you would with physical symptoms due to an illness or disease.

Mental and Emotional Symptoms. Tension and craving build up during periods of withdrawal, sometimes to a nearly intolerable point. Nearly every moderate-to-heavy smoker experiences more than one of the following strong emotional and mental responses to withdrawal:

Temper tantrums, intense needs, feelings of dependency, and a state of near paralysis
Insomnia
Mental confusion, vagueness, or difficulty concentrating
Irritability, restlessness, impatience, or anger
Anxiety
Depression

The first signs of nicotine withdrawal seem to appear within 30 minutes of a smoker’s last cigarette. The findings, published in Psychopharmacology, are believed to be the first to show just how early nicotine withdrawal occurs. The study involved 50 people who smoked a pack of cigarettes daily. Half refrained from smoking for 4 hours, while the others smoked as usual. After 30 minutes, those who did not have a cigarette craved one and did more poorly on tasks requiring attention than those in the smoking group. Within 3 hours, the non-smoking group showed increases in anxiety, sadness, and difficulty concentrating.

Depression is common during withdrawal and over the long term. In the short term, it may mimic the feelings of grief felt when a loved one is lost. A smoker should plan on a period of actual mourning in order to get through the early withdrawal depression.

Smoking may be masking depression, which can become severe even after the early stages of withdrawal have passed.
For some smokers, the future physical damage incurred by smoking is an abstraction, which fails to motivate quitting when measured up against the very real emotional pain triggered by nicotine withdrawal.
Not only does the smoker suffer, but the negative emotions often harm relationships with friends and family, who might even urge the ex-smoker to take up cigarettes again.

People who suffer from depression while quitting might do better using a combination of emotionally supportive therapy (as opposed to behavioral therapy), nicotine replacements, and antidepressants, such as bupropion (Zyban). If severe depression lasts beyond the withdrawal period, professional help should be sought as soon as possible.

Quitting smoking does increase the risk for weight gain. But, kicking the habit of smoking may cause more weight gain than previously thought. A study in Health Services Research found that the average weight gain among former smokers was about 21 pounds, rather than the 5 - 15 pounds commonly cited. But, fear of weight gain shouldn’t stop a person from quitting smoking. Instead, the study authors encourage weight-control measures after quitting. To come up with a new average, the scientists re-analyzed data from the 1998 Lung Health Study of 5,887 American smokers. That study found that those who quit smoking gained about 12 pounds.

Smoking uses up calories -- about 200 a day according to one study. Burning calories helps you lose weight. After quitting, the body's metabolism slows down, and food is digested better. Insulin levels increase, enabling the body to process more sugar for energy. When you quit smoking, you may snack more frequently.

How to Keep the Weight Off After Smoking. Exercise is very helpful in controlling weight. To burn the same amount of calories as you did while smoking, you need only take an extra 15-minute daily walk and eliminate 100 calories a day from meals. Just a moderate increase in physical activity can help keep weight gain to a minimum.

Nicotine replacement therapy can help protect against weight gain. See the section on "Quitting Smoking" in this report.

Failure to Quit

Biologic, psychological, behavioral, and cultural factors all play a role in nicotine addiction, making smoking one of the hardest addictions to beat. About half of people who quit return to smoking. Even after years of not smoking, some ex-smokers still have occasional cravings for cigarettes.

Some experts suggest that, in addition to depression, there are three major areas responsible for the inability to quit:

Mental performance. Nicotine improves concentration and thinking. Quitting smoking temporarily impairs one's mental performance.
Stress. Although smoking many not reduce stress, stopping certainly increases it.
Weight gain. Quitting smoking can cause you to gain weight. Studies are mixed on whether weight gain is permanent in most smokers or not. Certainly, it is a major factor in relapse. [See "Weight Gain" section in this report.]

How well a person does in the first 2 weeks is critical to their success. Smokers should not be shy about seeking all the help they can during this period. Although withdrawal symptoms can be intense, treatments are available to reduce them.

Attempts to quit are never a waste of time, since the amount of smoking is reduced during these periods. People who keep trying still have a 50 - 50 chance of finally quitting.

Researchers have been trying to discover individual risk factors or sets of behaviors that can help predict why specific people fail to quit. Some factors include:

Being female
Being a heavy smoker
Inhaling deeply
Being a long-term smoker
Having severe withdrawal symptoms

Among many studies, however, only one found a single consistent factor for failure to quit:

Cheating during the first 2 weeks of withdrawal, even with the patch, nearly guarantees that a person will smoke again in 6 months.

Studies show that women have a harder time trying to quit smoking and have less success with abstinence programs than men. There are many proposed reasons for this:

Nicotine has different effects on mood in women compared to men. Women who quit may have greater anxiety and stress than men who quit.
Women are not as physically dependent on nicotine as men, but they are more addicted to the actual behavior of smoking, which is the more powerful deterrent to quitting. This may be the reason why nicotine replacement, which only reduces cravings, tends not to be as effective in women.
Women may fear weight gain after quitting more than men.
Certain phases in the menstrual cycle may reduce the response to drugs that are used to help women quit smoking.
Men may be less supportive than women in helping their partners to quit.
Women trying to quit may miss the feeling of control associated with smoking more than men.

On the positive side, evidence suggests that when women quit, their lung function seems to improve more rapidly than in men who quit.

Lifestyle Changes

Smokers and former smokers should immediately begin to implement a healthier lifestyle and change any other behaviors that might be damaging their health.

Everyone should also maintain a healthy diet, with foods rich in whole grains and fruits and vegetables (particularly dark colored ones). Avoid saturated fats and instead choose monounsaturated fats, which are found in olive oil or fats from oily fish. Two studies have indicated that eating fish more than twice a week might help limit the tobacco damage in people who do not smoke more than a pack and a half a day.

Even with a healthful diet, however, smoking reduces the levels of a number of vitamins, importantly vitamin C. Some research suggests that supplementation of folic acid, a B vitamin, and the antioxidants vitamins E and C and selenium may improve lung function or reduce the damage done by cigarette smoke. Studies have shown that daily vitamin E supplements are associated with reduced risk for prostate cancer among smokers and that higher levels of vitamin E are linked to a lower risk for lung cancer. The best way of achieving healthy levels of important nutrients is from healthy foods.

Click the icon to see an image of the benefits of vitamin E.

Click the icon to see an image of the sources of vitamin E.

Women who are pregnant and continue to smoke must be sure to take appropriate vitamins, particularly folic acid. In this way, they might reduce the increased risk of fetal injury and death, although they do not eliminate that risk.

Regular exercise reduces a smoker's risk of heart disease (although still not to the level of a nonsmoker). Exercise does not lower a smoker's risk for lung cancer or emphysema.

If you smoke, you should be screened for any smoking-related disorders. Have your cholesterol and blood pressure checked regularly. Women should have annual Pap smears to detect cervical cancer. All older adults should be screened for colon cancer. Computed tomography (CT) screening programs, which are becoming increasingly available, may detect lung cancer at an early stage. Ask your health care provider if you should have this test, and if your insurance will cover it.

Resources

www.cancer.org -- American Cancer Society
www.lungusa.org -- The American Lung Association

References

Alati R, Al Mamun A, O'Callaghan M, Najman JM, Williams GM. In utero and postnatal maternal smoking and asthma in adolescence. Epidemiology. 2006 Mar;17(2):138-44.

Amin S, Niu J, Guermazi A, et al. Cigarette smoking and the risk for cartilage loss and knee pain in men with knee osteoarthritis. Ann Rheum Dis. 2007 Jan;66(1):18-22. Epub 2006 Dec 7.

Breslau N., Novak SP, Kessler RC. Psychiatric disorders and stages of smoking. Biological Psychiatry. 55(1):69-76, 2004.

Centers for Disease Control and Prevention (CDC). Tobacco use among adults -- United States, 2005. MMWR. 2006 Oct 27;55(42):1145-8.

Centers for Disease Control and Prevention (CDC). Annual smoking-attributable mortality, years of potential life lost, and productivity losses -- United States, 1997-2001. MMWR. 2005;54:625-628.

Centers for Disease Control and Prevention (CDC). State-specific prevalence of smoke-free home rules -- United States, 1992-2003. MMWR. 2007 May 25;56(20):501-4.

Chaudhuri R, Livingston E, McMahon AD, et al. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am J Respir Crit Care Med. 2006 Jul 15;174(2):127-33.

Dobson R. Smoking may increase abdominal obesity. BMJ. 2005 Sep 17;331(7517):596.

Eisenberg D, Quinn BC. Estimating the effect of smoking cessation on weight gain: an instrumental variable approach. Health Services Research. 2006 July 6; (early online version).

Galatz LM, Silva MJ, Rothermich SY, Zaegel MA, Havlioglu N, Thomopoulos S. Nicotine delays tendon-to-bone healing in a rat shoulder model. J Bone Joint Surg Am. 2006 Sep;88(9):2027-34.

Health, United States, 2005, with Chartbook on Trends in the Health of Americans. Hyattsville, Md. National Center for Health Statistics; 2005.

Hendricks P, Ditre J, Drobes D, Brandon T. The early time course of smoking withdrawal effects. Psychopharmacology. 2006;187(3): 385-396.

Houston TK, Person SD, Pletcher MJ, Liu K, Iribarren C, Kiefe CI. Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study. BMJ. 2006 May 6;332(7549):1064-9.

Linn-Rasker SP, van der Helm-van Mil AHM, van Gaalen FA, et al. Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis. 2006;65:366-371.

Li YF, Langholz B, Salam MT, Gilliland FD. Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest. 2005 Apr;127(4):1232-41.

Mennella JA, Yourshaw LM, Morgan LK. Breastfeeding and smoking: short-term effects on infant feeding and sleep. Pediatrics. 2007 Sep;120(3):497-502.

Naqvi NH, Rudrauf D, Damasio H, Bechara A. Damage to the insula disrupts addiction to cigarette smoking. Science. 2007 Jan 26;315(5811):531-4.

Nides M, Oncken C, Gonzales D, et al. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med. 2006 Aug 14-28;166(15):1561-8.

Oncken C, Gonzales D, Nides M, Rennard S, Watsky E, Billing CB, Anziano R, Reeves K. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Arch Intern Med. 2006 Aug 14-28;166(15):1571-7.

Ritz B, Ascherio A, Checkoway H, et al. Pooled analysis of tobacco use and risk of Parkinson disease. Arch Neurol. 2007 Jul;64(7):990-7.

Sargent JD, Stoolmiller M, Worth KA, et al. Exposure to smoking depictions in movies: its association with established adolescent smoking. Arch Pediatr Adolesc Med. 2007 Sep;161(9):849-56.

Teo KK, Ounpuu S, Hawken S, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006 Aug 19;368(9536):647-58.

The Health Consequences Of Smoking: A Report Of The Surgeon General. Atlanta, GA: US Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, US Dept of Health and Human Services; 2004.

Tonnesen P, Mikkelsen K, Bremann L. Nurse-conducted smoking cessation in patients with COPD using nicotine sublingual tablets and behavioral support. Chest. 2006 Aug;130(2):334-42.

Uhl GR, Liu QR, Drgon T, Johnson C, Walther D, Rose JE. Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs. BMC Genet. 2007 Apr 3;8:10.

Wagena EJ, Knipschild P, Zeegers MP. Should nortriptyline be used as a first-line aid to help smokers quit? Results from a systematic review and meta-analysis. Addiction. 2005;100:317-326.

Review Date:
10/8/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

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Hump Day: Why Do I Get Dry Sometimes?

TresSugar — Wed, 30 Sep 2009 04:00:00 -0700

Welcome to Hump Day, TrèsSugar's sex advice column. Are you confused about sex? Do you have trouble having an orgasm? Is there something you'd like to try but you're worried it's too weird? Send your questions to TrèsSugar, and our friend Dr. Charlie Glickman from Good Vibrations will offer his sound advice!

Today's Question:

"I get really dry sometimes when my boyfriend and I are having sex. I know all about lubricants, but I'm having trouble guessing when I might need help." To read Dr. Glickman's response, read more

There are a lot of reasons why women experience fluctuations in how much they lubricate. For some, it’s just part of the menstrual cycle. Some women lubricate more at ovulation, while others say that’s when they’re driest. Lots of women also report that their vaginal lubrication changed when they got pregnant and again, some say that they became much wetter and others say that they got drier. So while we know that changes in hormones can influence it, there’s a lot of variation in how much and in what direction. It’s also worth mentioning that menopause generally reduces how much lubrication your body will produce.

Lots of medications and drugs also affect vaginal lubrication, even if it’s rarely listed on the bottle or box. For example, allergy medications are formulated to dry the mucous membranes in your sinuses, but they can do the same to the vagina. Anti-depressants, antihistamines, anxiety medications, smoking cigarettes or marijuana, and drinking alcohol can do the same. In general, if a medication or drug makes your mouth or sinuses dry, it could also reduce vaginal lubrication. Unfortunately, most doctors are unaware of these effects or they don’t feel comfortable talking to their patients about it.

I think it’s really unfortunate that we have this cultural myth that vaginal lubrication is proportional to arousal. Many women find that they can be totally turned on while being pretty dry and others might be quite wet while barely aroused. The best thing we can do is learn to separate the two things in our minds.

You say that you know about lubricants, but for the folks who don’t, here’s a little info.

There are pros and cons to the lubricants on the market, and it can take a little experimenting to find one that will work for you. You might also find that a lube that worked great for a long time isn’t working so well anymore. It’s kind of like shampoo or skin lotion - after a while, you might need to change brands as your individual chemistry changes.

Water-based lubricants can be thin and slippery, or they can be thicker gels. They rinse away really easily, making cleanup a snap, but they do dry out after a while. The glycerin-based lubes last a bit longer, but they tend to get sticky when they dry out. You can add a little water or saliva to freshen them up. While glycerin doesn’t cause yeast infections, it can make one worse if you get one for some other reason, so if you’re prone to yeast infections, avoid these lubes. The glycerin-free lubricants don’t get sticky, but they usually don’t quite last as long. They soak in like hand lotion, so adding water doesn’t work; you need to add some more.

Silicone lubricants don’t dry out (so if you spill some on the kitchen floor, be sure to wipe it up) and are hypoallergenic. They’re also waterproof, which is a plus if you want to have sex in the shower but it can make them a bit trickier to clean up and they sometimes stain sheets. They’re also hypoallergenic and have no taste or scent.

Some people like to use oils as sexual lubricants. If you want to give them a try, use something organic and vegetable-based, such as coconut or almond oils. Mineral oils like baby oil or Vaseline actually dry the skin since the body can’t absorb them or break them down. Coconut oil is solid at room temperature, so it doesn’t go rancid. Keep almond oil in the fridge. And never use oils with latex condoms, diaphragms or cervical caps. Oils will make them dissolve: a condom will break in about 30 seconds if it comes into contact with oil.

A few tips for using lubricants. First, keep the bottle near the bed. You’ll want to be able to grab it when you need it. Second, pump bottles make it a lot easier to add more without fumbling to get the bottle open. Third, if you accidentally get too much lube out of the bottle, don’t put the extra back in. You don’t want to contaminate the bottle with anything that might be on your hand. And lastly, many lube makers offer single-use packets or small bottles. While they cost more per ounce than larger bottles, you can stick them in a pocket or purse pretty easily, not to mention your carry-on bag.

So I think that the best thing for you to do is to keep lube handy and use it when you need it. It takes about 5 seconds to apply and it’ll make sex a lot more fun. And don’t stress about whether it means anything that you sometimes need a little extra slipperiness.

Don't forget to send your questions to TrèsSugar, and our friend Dr. Charlie Glickman will offer his sound advice!

When Pregnancy Doesn't Stop the Vices

babysugar — Thu, 24 Sep 2009 14:38:52 -0700

Someone might wanna tell Mrs. McSteamy that cream puffs are a much better (and dare I say tastier) alternative to smoke rings when it comes to breeding new life. Rebecca Gayheart's handsome hubby may play a doctor on television, but apparently any advice from her own doctor regarding the hazards of smoking while pregnant may have gone by the wayside. While it was acceptable in the past, we now know all the harm that can come with nicotine presence in the womb. In hopes of providing their child the best start in life, many expectant ladies take the nine months to rid themselves of the habit while others just keep on keepin' on like nothing has changed.

Did you give up your vices when you were expecting? Tell us more about it in the Pregnancy Posse in our LilSugar Community!

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Vitamins

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Carotenoids
Phytochemicals
Healthy Foods
Dietary Health Benefits
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer

Growing evidence suggests that vitamins and micronutrients, especially from foods, may play important roles in the prevention or treatment of certain cancers:

One study found that the risk of prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose.
A diet high in cruciferous vegetables has been found to reduce the risk of kidney cancer; low consumption of cruciferous vegetables increases the risk.

On the other hand, high amounts of folic acid (a B vitamin) may be associated with colorectal cancer, and beta-carotene supplements are associated with increased lung cancer risk in smokers and people exposed to asbestos.

Macular Degeneration

In 2007, the National Eye Institute recommended that people with intermediate or advanced macular degeneration in one eye take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc.

Osteoporosis

Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it also may be effective in treating rheumatoid arthritis.

Heart Disease

Although people with high levels of homocysteine are prone to developing blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with B vitamins and folic acid does not reduce the incidence of deep vein thrombosis (DVT). A 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with folic acid and other B vitamins had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke.

Introduction

Vitamins do not share a common chemistry, but they do share certain characteristics. They are all organic nutrients that are necessary in small amounts for normal metabolism and good health. Your diet or supplements provide most vitamins. The body can manufacture only three vitamins (D, K, and the B vitamin biotin) from nondietary sources. Unlike carbohydrates, fats, and proteins, vitamins are not sources of energy. Instead, vitamins are chemical partners for the enzymes involved in the body's metabolism, cell production, tissue repair, and other vital processes.

Vitamins are either fat soluble or water soluble. The fat-soluble vitamins, which include A, D, E, and K, are absorbed by the body using processes that closely parallel the absorption of fat. They are stored in the liver and used up by the body very slowly. The water-soluble vitamins include C and the B complex vitamins. The body uses these vitamins very quickly. Excess amounts are eliminated in urine.

The Recommended Daily Allowance (RDA) for vitamins, set by the Food and Nutrition Board of the National Academy of Sciences-National Research Council, has been used for years as a guide for determining the amount of vitamins needed for a healthy diet. The RDA refers to an estimate of the average daily requirement. It is not completely adequate, however, for informing people about the amounts of vitamins they may need.

The RDA is gradually being enhanced using a new standard called the Dietary Reference Intake (DRI). The DRI is based on the following ratings, which will eventually appear on labels:

The recommended daily allowance (RDA). This is the current rating on most vitamins.
The estimated average requirement (EAR). This is the amount adequate for 50% of all people, which will be put on labels when it can be calculated.
Adequate intake (AI). This is an amount that will be used if there is insufficient data to calculate the EAR.
Tolerable upper intake level (UL). This is the maximum dose likely to be safe in nearly all individuals. It will be included on labels if this amount is known.

Food and supplement labels now typically list the Daily Value (DV). This is the percentage of the amount of a nutrient that experts believe a person needs in their daily diet. On food labels it is usually based on one serving size for a person who takes in 2,000 calories a day.

Regulation of dietary supplements by the U.S. Food and Drug Administration (FDA) is a complex issue.

Labels on vitamins and other dietary supplements now include nutrient information and list all ingredients, including identifying parts of plants from which ingredients may be taken. Unlike the labels for drugs, however, labels for vitamins and supplements may not claim to prevent or treat any specific disease. Labels for vitamins and supplements include one of the following:

Health claim -- description of how the substance may reduce the risk of a health-related condition
Nutrient claim -- description of the amount of the nutrient in the product or
Structure or function claim -- description of how the product may affect organs or systems of the body, without claiming to prevent or treat specific disease

The quality of dietary supplements depends on the manufacturer and is not ensured by FDA. The U.S. government does not require that supplements be standardized, meaning that the amounts or quality of nutrients may vary depending on the batch. So, more expensive supplements are not necessarily better than the less expensive ones. Government regulations are in the process of catching up to the boom in the supplement industry. In the meantime, some companies voluntarily adhere to rigorous quality controls, while others do not.

The U.S. Pharmacopeia (USP), an independent organization that sets quality standards for drugs, has also implemented standards for vitamins. Consumers may look for the USP label on products of companies that adhere to these standards. USP verification means the following:

What is in the bottle matches what is listed on the label.
There are no harmful levels of contaminants.
The supplement will be absorbed properly into the body.
It has been produced according to good manufacturing standards.

Before selling any supplement introduced after 1994, manufacturers must submit information as to why the product is considered safe for people. The FDA may refuse to allow it on the market if it finds the evidence insufficient. The FDA does not require manufacturers to provide any scientific evidence that dietary supplements are safe and effective before a product is sold (unlike drugs, which must be proven both safe and effective through clinical trials). If a supplement causes side effects in people once it is for sale, the government may place restrictions on the supplement or withdraw it from the market. The FDA may also withdraw products from the market if their labels are misleading or false.

About 30% of Americans take at least one vitamin or mineral supplement daily. In a large study that examined the death rates of 11,000 people, however, there was no difference in mortality rate between those who took vitamin supplements and those who didn't. Most people who have a healthy diet do not need vitamins, but there are some exceptions.

Pregnant and Breast-Feeding Women. Women who are pregnant or who are breast-feeding generally need additional vitamins. Vitamins B6, B12, and folic acid are particularly important. Women who are vegetarians must be sure to avoid deficiencies, which can harm their offspring. Folic acid reduces the risk for neural tube defects and possibly facial abnormalities, such as cleft palate. Studies also show that low folate levels during pregnancy are associated with low birth weight, a risk factor for the development of cardiovascular disease in adulthood. Multivitamins that contain folic acid also appear to be somewhat protective. A woman's best approach is to take extra folic acid plus multivitamin supplements (which have additional benefits), starting them before becomming pregnant.

The human body stores several years' worth of vitamin B12, so nutritional deficiency of this vitamin is extremely rare. Although, people who follow a strict vegetarian diet and do not consume eggs or dairy products may require vitamin B12 supplements.

Pregnant women with healthy diets may have low folate levels and need to take supplements. Requirements are as follows:

The recommended daily allowance (RDA) for folic acid prior to conception and during pregnancy is 400 mcg.
During breast-feeding 260 - 280 mcg is recommended.

The following vitamins may have some value for pregnant women:

Choline, another vitamin B, is also essential for pregnant (450 mg) and nursing women (550 mg). Choline plays a key role in brain development. Not getting enough during pregnancy can lead to memory and cognitive defects in the baby. Choline supplements can also lessen the cognitive defects of prenatal alcohol exposure.
Vitamin B6 may help improve morning sickness.
Vitamin C may reduce the risk of urinary tract infections during pregnancy.
Vitamin D may help prevent preeclampsia.
One study also suggested that if pregnant women took vitamin K supplements, their infants might not need the required injection of this vitamin after birth, but supplements of vitamin K during pregnancy are not currently recommended.

Some women have low vitamin A reserves in their liver. It is important to note, however, that too much vitamin A significantly increases the risk for birth defects. Daily amounts of 10,000 IU (international units) of vitamin A in supplements and food (an amount not far above the RDA level) can pose a danger. Experts recommend that pregnant women take in no more than 8,000 IU per day and avoid eating liver.

Infants and Children. Infants who are breast-fed by healthy mothers receive enough vitamins except, in some cases, vitamins K and D. Human milk has low levels of K, and the newborn's immature intestinal tract may not produce enough of the baby's own supply. Most babies are given an injection of this vitamin at birth. Infants being breast-fed by malnourished women or those who lack sufficient exposure to sunlight may be deficient in vitamin D. In these cases, supplements of 200 - 300 IU are recommended. Formulas are required to contain sufficient vitamins and minerals. One study suggests that vitamin supplements for infants under 1 year of age may help protect them from developing type 1 diabetes later on. Beyond infancy, most American children receive all the vitamins they need from their diet unless they are living in severely deprived circumstances.

Smokers. Smoking interferes with absorption of several vitamins, importantly vitamins C and D. In one study nearly 25% of female smokers and 31% of male smokers were deficient in vitamin C. Smoking can interfere with the metabolims of vitamin D, resulting in poor muscle function. Taking high doses of antioxidant vitamins, however, may actually be harmful in smokers, especially beta carotene. Instead of taking supplements, most smokers should be sure their diets are rich in fresh fruits and vegetables and whole grains. Of course, smoking cessation is the most important intervention of all.

Click the icon to see an image of sources for vitamin C.

Alcoholics. Alcoholics often suffer from multiple vitamin deficiencies. The most dangerous deficiencies are from vitamins B1 (thiamin), folic acid, B6 (pyridoxine), B2 (riboflavin), and vitamin C. Low levels of B6 are associated with increased risk of colorectal cancer in men who drink large amounts of alcohol.

Overweight Adults. Overweight and obesity causes many problems that often result in metabolic syndrome or type 2 diabetes. Evidence suggests that isoflavones can help regulate cholesterol levels and reduce body weight and fat mass. Because some medications used to control blood sugar levels reduce folic acid and vitamin B12, some people may need vitamin supplements.

People Who Have Had Gastric Bypass Surgery. Vitamin deficiency is a recognized complication of gastric bypass surgery. Women, African-Americans of both sexes, and adults who have had laparoscopic Roux-en-Y bypass surgery are at highest risk. The deficiency is treated with water-soluble vitamin supplements.

Strict Vegetarians. Strict vegetarians need supplements of vitamin B12, unless they get enough of it from fortified cereals and other grain products.

Dieters and Vegetarians. People on weight-reduction diets with less than 1,000 calories a day should probably take a multivitamin and should also check regularly with a physician.

Vegetarians may need riboflavin, vitamin B12, and vitamin D supplements. Vegans, who do not eat dairy or eggs as well as meat, may be at further risk for vitamin A deficiencies if they do not also have plenty of dark colored fruits and vegetables. Those who eat eggs and dairy products need only watch their iron levels.

Deficiencies in vegetarian children may be particularly harmful. (One study, for example, reported that adolescents who had been on macrobiotic diets before age 6 and were deficient in vitamin B12 scored lower on psychological tests.) Pregnant and breast-feeding women who are vegetarians must be sure to have sufficient vitamins. Of special note, maternal deficiencies in vitamin B12 may cause delayed growth and neurologic problems in their newborns.

Click the icon to see an image of sources for vitamin D.

Older Adults. Deficiencies of vitamins and important minerals have been observed in almost a third of elderly people. Often their dietary habits slip and they fail to eat balanced meals regularly. Multiple drug regimens may prevent absorption of some vitamins. Elderly people, particularly if they are not exposed to sunlight, may be deficient in vitamin D. They also may have low levels of important B vitamins. (Older adults showing signs of dementia should be checked for B12 deficiencies as well as other disorders causing mental disturbances.) One study reported that the immune systems of elderly people may benefit from higher levels of vitamin E than the daily recommended dosage. It should be noted, however, that metabolism slows down as a person ages, and in elderly people it takes the liver longer to eliminate drugs and vitamins from the body. The effect of some vitamin supplements, therefore, may be intensified. Dosage levels of vitamin A, for instance, which might be harmless in a younger adult, could be toxic in an elderly patient. Nevertheless, experts are increasingly recommending extra vitamin and mineral supplements for older people.

People Who Need to Avoid Sunlight. People who need to avoid sunlight or are housebound, and whose diet is low in foods that contain vitamin D should take supplements. People with darker skin are at higher risk for deficiencies than those with whiter skin. (Note: vitamin D is toxic in high doses, and no one should exceed the recommended daily intake of vitamin D except under the direction of a physician.)


Benefits	Essential for growth, bone development, night vision, reproduction, and healthy skin.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	Vitamin A RDA and Upper Limit (when toxicity is risk) are the following: For children: 1,000 IU ages one to three (upper limit is 2,000 IU); 1,333 IU ages 4 - 8 (upper limit is 3,000 IU); and 2,000 IU for 9 - 13 (upper limit is 5,665 IU). For nonpregnant women: 2,330 IU ages 14 through adulthood. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For pregnant women: 2,500 IU for pregnant women under 18; 2,565 IU for pregnant women over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19. It should be noted that some experts recommend 8,000 IU as the upper limit during pregnancy.) Warning: Use of the topical acne medication tretinoin, a vitamin A derivative, during pregnancy can cause birth defects. For nursing women: 4,000 IU for nursing mothers under 18; 4,335 IU for nursing mothers over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For men: 3,000 IU ages 14 - 18; 3,000 IU for ages 19 and above. (Upper limit is 10,000 IU.) Note: In determining the daily vitamin A allowance, experts also take note of provitamins, such beta carotene, that convert to vitamin A. Some experts recommend 3 - 6 mg of beta-carotene. Vitamin A is also now being measured with a new unit called the Retinol Activity Equivalent (RAE or RE). One RE is equal to 1 mcg. Retinol is the most active form of vitamin A and it is also converted in the liver from carotenoids. One RE is equal to 12 mcg of beta-carotene or 24 mcg of alpha-carotene or beta-cryptoxanthin).
Foods containing the vitamin	Animal products, such as liver, dairy products, eggs, and fish liver oil. Provitamin A carotenoids are also found in dark red, green, and yellow vegetables and fruits. Requires some dietary fat to be absorbed.
Effects of deficiencies	Skin disorders, severe diarrhea, and eye damage. In less developed countries severe deficiencies cause blindness in 250,000 children each year. Diets low in vitamin A may also increase the risk of developing cancer. Low dietary intake of vitamin A has been associated with impaired lung function in children.
People at risk for deficiencies	Preschool children and any child with inadequate intake of protein, calories, and zinc. Iron deficiency may also impair metabolism of vitamin A. People with asthma. People with serious disorders in the intestine, liver or pancreas, such as cystic fibrosis, steatorrhea, biliary obstruction, inflammatory bowel disease, cirrhosis, and others. People who have undergone Roux-en-Y gastric bypass surgery. Vegans (vegetarians who do not eat eggs and dairy). Such individuals should be sure to have plenty of deep-colored fruits and vegetables. People who abuse alcohol. It should be noted, however, that people with alcoholism may be at risk for vitamin A deficiency, but a combination of high-dose vitamin A and alcohol may cause toxic effects in the liver. Healthy adults usually have a year's store of vitamin A in the liver, so temporary nutritional deficiencies or problems with fat absorption are unlikely to cause serious vitamin A deficiency problems.
Toxicities	Very toxic when taken in high-dose supplements for long periods of time. Symptoms of overdose include dizziness, nausea, vomiting, headache, skin damage, mental disturbances, and, in women, infrequent periods. Can affect almost every part of the body, including eyes, bones, blood, skin, central nervous system, liver, and genital and urinary tracts. Severe toxicity can cause blindness and may even be life threatening. In children, chronic overdose can cause fluid on the brain and as well as adult complications. High consumption of vitamin A may also increase the risk of gastric cancer and the risk of osteoporosis and fractures in both men and women. Pregnant women who take amounts not much higher than RDA levels increase the risk for birth defects in their children. Liver damage can occur in children who take RDA-approved adult levels over prolonged periods of time or in adults who take as little as five times the RDA-approved amount for 7 - 10 years.


	B Vitamins: General Information	Vitamin B1 (thiamin)
Benefits	The B vitamins have a wide and varied range of functions in the human body. Most B vitamins are involved in the process of converting blood sugar into energy.	Essential for converting blood sugar into energy and is involved in metabolic activities in nerves, heart, and muscles and in the production of red blood cells.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)		RDA is 1.2 mg per day for men and 1.1 mg for women.
Foods containing the vitamin		Best source is pork and good sources are dried fortified cereals, oatmeal, corn, nuts, cauliflower, and sunflower seeds. Supplements for people with normal diets and health are unnecessary.
Effects of deficiencies	Deficiencies are uncommon in the U.S., but when they occur, they usually involve several B vitamins, since many of them come from the same food groups.	Severe vitamin B1 deficiency is known as beriberi. It can cause visual disturbances, paralysis, staggering, loss of sensation in the legs and feet, psychosis, and congestive heart failure.
People at risk for deficiencies	Alcohol interferes with these vitamins, and some of the physical and mental problems that alcoholics experience may be attributed to a deficiency of B vitamins. Elderly people are also at risk for deficiencies because of inadequate diets and potential interference with B-vitamin absorption by medications. Deficiencies can occur in severely malnourished people or in those receiving long-term dialysis or intravenous feeding. Vegetarians may be at risk.	See general vitamin B description.
Toxicities	Because the B vitamins are water-soluble and eliminated in the urine, toxic reactions from oral administration of most of them are extremely rare. (Exceptions are niacin and B6.) It should be noted that substances known as B15 (pangamic acid) and B17 (laetrile) are neither vitamins nor nutrients; both chemicals are highly dangerous and have no proven nutritional or health value.	No toxic effects have been reported from thiamin.


	Vitamin B2 (riboflavin)	Vitamin B3 (niacin) also known as nicotinic acid	Vitamin B5 (Pantothenic Acid)
Benefits	Important in the production of energy.	Helps break down blood sugar for energy. Acts as a vasodilator, widening blood vessels and increasing blood flow. May be prescribed for improving cholesterol levels.	Important for metabolism of fats, carbohydrates, and proteins, as well as production of steroid hormones and other important chemicals.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 1.7 mg.	DRI is 20 mg.	Adequate intake (AI) is 4 - 7 mg.
Foods containing the vitamin	Liver, dried fortified cereals, dairy products, fish. Some dark green vegetables. Supplements for people with normal diets and health are unnecessary.	Mackerel, swordfish, chicken, veal, dried fortified cereals, pork, salmon, and beef liver. Supplements are unnecessary in people with normal health and diets.	Whole grains, beans, milk, eggs, and liver. Supplements are unnecessary in people with normal health and diets.
Effects of deficiencies	Deficiencies affect the skin and mucous membranes and can cause cracks on the lips or corners of the mouth, eczema of the face and genitals, a burning sensation on the tongue, eye irritation. May contribute to anemia when iron levels are low and contribute to elevated levels of homocysteine, a heart risk factor.	Deficiency causes pellagra; symptoms can include eczema, intestinal and stomach distress, depression, headache, thinning of the hair, and excess saliva production.	Deficiency is unlikely except in company with other B vitamin deficiencies. Symptoms include abdominal distress, burning sensation in the heels, and sleep problems.
People at risk for deficiencies	See general vitamin B description.	Alcoholics and any malnourished persons.	Alcoholics and any malnourished persons.
Toxicities	Until recently, no toxic effects had been reported even from large doses of riboflavin. However, one study indicated that high consumption of vitamin B2 might increase the risk of stomach cancer. More research is needed. (In the same study, vitamins B1, B3, and B6 were protective.)	Even mildly high doses of niacin can cause hot flushing of the face and shoulders, headache, itchiness, and stomach problems. Some report heart disturbances and temporarily lowered blood pressure. Large doses may produce ulcers, gout, diabetes, and liver damage, which are usually reversed when high doses are discontinued.	Although no toxicity has been reported in humans, high dosages have caused liver damage in rats.


	Vitamin B6 (pyridoxine)	Vitamin B12 (cobalamin)
Benefits	Has an effect on over 60 proteins in the body, importantly, those that play a role in the nervous system, in red and white blood cell production, and in heart disease.	Essential for the production of blood cells, manufacturing genetic material, and for healthy functioning of the nervous system. New evidence suggests that high levels of B12 may protect against colon and rectal cancer.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 1.3 mg in adults under 50 and 1.7 mg for older men and 1.5 for older women. (Some experts recommend 3 to 6 mg for people who need heart protection.) Upper limit is 100 mg for adults.	RDA is 2.4 mcg in men and nonpregnant women, 2.6 mcg in pregnant women, and 2.8 mcg in nursing mothers.
Foods containing the vitamin	Meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.	The only natural dietary sources are animal products, including meats, dairy products, eggs, and fish (clams and oily fish are very high in B12). Like other B vitamins, however, B12 is added to commercial dried cereals.
Effects of deficiencies	Increased levels of homocysteine, associated with heart disease and possibly Alzheimer's disease. Skin problems and nervous system disorders, including impaired memory and concentration. Increased risk for kidney stones. One study found a correlation between vitamin B6 deficiency and inability to conceive or carry a child to term. In unborn children, some evidence shows that lack of vitamin B6, in addition to vitamin B12 and folic acid, may be responsible for defects such as cleft lip and palate and spina bifida. Supplementation with these vitamins is advised during pregnancy. Note: People who have been taking more than 50 mg for some time and stop suddenly are at risk for a so-called rebound deficiency. When people stop, they should taper off slowly.	Deficiencies elevate homocysteine, a possible risk factor for heart disease and Alzheimer's disease. Increased risk of bone fractures. Abnormal gaits in the elderly. May cause severe depression, memory loss, instability, disorientation, and decreased reflexes, and possibly hearing loss. Children who are deficient may experience growth failure. Deficiencies in pregnant and breast-feeding women may cause neurologic harm in their offspring. A genetic defect that causes vitamin B12 deficiencies is responsible for pernicious anemia, a serious disorder that causes rapid heart rate, shortness of breath, dizziness, weakness, and fatigue. It must be treated with injections of vitamin B12 or else neurologic damage may occur.
People at risk for deficiencies	Alcoholics and any malnourished person. In rare cases, infants are born unable to metabolize pyridoxine; in such cases, seizures or convulsions can occur and vitamin B6 must be administered.	Alcoholics and any malnourished persons. Evidence suggests deficiencies may be caused by Helicobacter pylori (H. pylori) bacteria (a cause of ulcers). Nearly 30% of patients with inflammatory bowel disease have vitamin B6 deficiency, as well as low levels of iron and vitamin D. People who take the antibiotic isoniazid, high blood pressure medication hydralazine, and the drug penicillimine are at risk for vitamin B6 deficiency. The elderly and people with Crohn’s disease and those who have undergone ileal and ileocolonic resection may have trouble absorbing natural vitamin B12 and require supplements. Some evidence shows that patients with Parkinson’s disease treated with levodopa plus dopa decarboxylase inhibitor (DDC-i) and catechol-O-methyltransferase inhibitor (COMT-i) have low levels of both vitamin B12 and folate. As a result, they need to take supplements of these vitamins. Other studies have found that patients with diabetes treated with metformin, but not roziglitazone, are at risk for low levels of vitamin B12. Vitamin B12 deficiency is also common in patients with polyneuropathy. In up to one-third of patients, vitamin B12 deficiency is the sole or major contributing cause of their neuropathy. Treatment with vitamin B12 has a high success rate in improving the symptoms. Vegetarians are at higher risk for deficiencies.
Toxicities	Very high doses can cause nerve damage with symptoms of instability and numbness in the feet and hands, which may be permanent in some cases. Of specific concern are possible adverse effects on nerve development in the offspring of pregnant women who take large doses, such as for morning sickness.	There is no evidence of toxicity with this vitamin.


	Biotin (a B vitamin)	Choline (a B vitamin)	Folate, or Folic Acid, its synthetic form (a B vitamin)
Benefits	Involved in the production of amino acid proteins and fatty acids.	Essential for fetal brain development and for learning and memory.	Important for many metabolic processes in the body. It is used in the manufacturing of neurotransmitters (chemical messengers in the brain), in protecting the heart, and for synthesizing genetic materials (DNA) in the cells. It may improve blood flow.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	There is no DRI for biotin; some experts suggest 30-100 mcg.	RDA 425 mg for nonpregnant women, 450 mg for pregnant women, and 550 mg for nursing women.	Supplements may be folate (natural) or folic acid (synthetic). Folic acid is nearly twice as potent as folate. DRI is 400 mcg (.4 mg) of folate for the general population, 600 mcg during pregnancy and 500 mcg while nursing. Women who are planning to be pregnant should certainly take 400 mcg of folic acid before conception, during pregnancy, and while nursing.
Foods containing the vitamin	Dietary sources are eggs, milk, liver, mushrooms, bananas, tomatoes, whole grains, nuts, and brewer's yeast. Also produced by bacteria in the intestines.	Peanuts, eggs, cauliflower, and meats, especially liver.	Avocado, bananas, orange juice, cold cereal, asparagus, green leafy vegetables, dried beans and peas, and yeast. Folic acid supplements are now added to commercial breads and cereals.
Effects of deficiencies	Deficiencies are almost unheard of.	Low levels during pregnancy increase risk of birth defects in newborns.	As with vitamins B6 and B12, deficiencies of folate elevate levels of homocysteine, an amino acid in the body that may increase the risk for heart disease, and possibly Alzheimer's disease. Folic acid supplements lower homocysteine levels, but with little or no impact on risk of atherosclerotic disease in the heart or in the peripheral arteries and veins. This suggests that homocysteine may be a marker of cardiovascular disease, rather than a cause. This being said, one 2007 study found that folic acid supplementation in patients with low folic acids levels substantially reduced the risk of a first stroke. Low levels during pregnancy increase risk of birth defects in newborns, and folic acid supplementation plays a key role in preventing birth defects. Folic acid deficiencies Deficiencies can also cause depression and megaloblastic anemia and impair concentration, memory, and hearing.
People at risk for deficiencies			Alcoholics, malnourished persons, people with conditions that disturb the small intestine, people taking certain drugs, particularly methotrexate. Other risk factors for deficiency: high-dose aspirin, smoking, treatment for seizures, taking oral contraceptives.
Toxicities		Excessive doses can cause intestinal problems, and there is also some concern that high doses can be carcinogenic.	Possible connection between high consumption of folate/folic acid and colorectal cancer now under exploration. Some link between high doses and central nervous system disorders, zinc deficiency, and seizures in epileptics. This risk appears to be low, but results indicate that megadoses should be avoided. High amounts in the elderly may mask symptoms of vitamin B12 deficiencies.


Benefits	Vitamin C is a water-soluble vitamin. Acts as an antioxidant (reduces harm from damaging chemical processes in the body). Essential for the production of collagen, the basic protein in bones, cartilage, tendons, and ligaments. A 2007 study found that vitamin C supplements can help prevent the development of complex regional pain syndrome following wrist fracture. Another study found that prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose. It may also protect against brochoconstriction during exercise in people with asthma. May help boost the immune system.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 75 mg (women) and 90 mg (men). (Smokers need an additional 35 mg.)
Foods containing the vitamin	Citrus fruits and juices, papayas, hot chili peppers, bell peppers, broccoli, potatoes, dark leafy greens, kale, red cabbage, cauliflower, cantaloupe, sweet potatoes, and Brussels sprouts. Orange juice is the most important source of vitamin C in the U.S., with frozen juice being the best source of the vitamin.
Effects of deficiencies	Scurvy is the primary deficiency disease. Affects most body tissues, particularly bones, teeth, and blood vessels. Early symptoms include tiredness, weakness, irritability, weight loss, and vague muscle aches. Later symptoms are bleeding gums, wounds that won't heal, rough skin, and wasting away of the muscles. Deficiencies may contribute to periodontal disease and gallstones. Low dietary intake of vitamin C has been associated with impaired lung function in children. Low intake may also increase lead levels in the blood.
People at risk for deficiencies	Deficiency has been uncommon in the U.S., usually occurring in the elderly, alcoholics, cancer patients, and some people on severely limited diets low in fresh fruits and vegetables. Surprisingly, however, studies now suggest that as many as 16% of middle-aged Americans, with the highest risk in smokers and middle aged men, are deficient in vitamin C. High doses of aspirin taken over a long period of time can interfere with vitamin C.
Toxicities	Tolerable upper limit is 2000 mg/day. High doses may cause headaches and diarrhea. Long-term high doses may increase risk for kidney stones. Ascorbic acid increases iron absorption so people with blood disorders, such as hemochromatosis, thalassemia, or sideroblastic anemia, should avoid high doses. Large doses may also thin blood and interfere with anticoagulant medications, blood tests used in diabetes, and stool tests. Rebound scurvy can occur after abrupt withdrawal from long-term large doses. This may affect infants or pregnant women who withdraw suddenly from high doses.


Benefits	Vitamin D is actually a single term for several hormones that are stored mainly in the liver and also in fat and muscle tissue. It is essential for the absorption of calcium into the bone and for normal bone growth.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 200 IU (5 mcg) per day for children and most adults to age 50, 400 IU (10 mcg) for people between ages 50 and 60, and 600 IU over age 70. and 1000 IU (15 mcg) for those over 70. People who are housebound, do not have sufficient exposure to sunlight, or are dark-skinned individuals, as well as breast-fed infants, should take need vitamin D supplements. The maximum tolerated dose after the age of 12 months is 2,000 IU/day
How the body gets the vitamin	There are two forms of vitamin D. Vitamin D3 is made in the body from a chemical reaction to the ultraviolet radiation in sunlight. Vitamin D2 is found in a few food sources, including vitamin D fortified milk, fatty fish, egg yolk, and liver.
Effects of deficiencies	Softening of the bones caused by low levels of calcium and phosphorous (called rickets in children and osteomalacia in adults). Also increases the risk for bone-related knee problems, and hip fractures in postmenopausal women. Associated with a higher risk for prostate cancer and breast cancer risk. Evidence suggests that vitamin D deficiency may be responsible for poor muscle strength after bone fracture. The deficiency is associated with high blood pressure and diabetes, but it is unknown whether supplementation with vitamin D impacts these diseases. Studies now suggest vitamin D plays a role in age-related macular degeneration (AMD), and that drinking milk with added vitamin D can help protect against AMD.
People at risk for deficiencies	Older people, particularly if they live in the North, who are underexposed to sunlight. Obesity may also increase risk. There is some concern, in fact, that vitamin D deficiency may be a growing problem in the US among younger adults as sunscreen use becomes widespread. Individuals at highest risk for vitamin D deficiency are those who assiduously avoid the midday sun, wear protective clothing, regularly use sunscreen, and have dark skin. Exposure to sunlight for about 15 - 20 minutes at mid-morning or mid-afternoon three times a week is recommended for most people who live in temperate climates.
Toxicities	Vitamin D is very toxic in high doses. In infants, daily amounts higher than 1,000 IU can cause mental and growth retardation, kidney failure, and death. In children and adults, daily amounts over 50,000 IU can cause weakness, anorexia, vomiting, diarrhea, and mental changes. Prolonged use of megadoses can cause calcification of soft tissue and life-threatening kidney failure. Low-calcium diets and withdrawal from the vitamin can usually reverse the side effects except for kidney failure.


	Vitamin E (Tocopherol or Tocotrienol)	Vitamin K
Benefits	A fat-soluble antioxidant vitamin that helps prevent cell membrane damage and may inhibit oxidation of LDL cholesterol (a process that increases its harmful effects on arteries). Researchers once thought that vitamin E might protect against cardiovascular disease. This theory has been debunked. However, a 2007 study found that vitamin E supplementation reduced the risk of deep vein thrombosis (DVT) in women at risk for, or with a history of, DVT. Vitamin E supplements have also been shown to produce a statistically significant decrease in menopausal hot flashes. There is also early evidence that vitamin E may protect against ovarian cancer.	The most important function of vitamin K is its role in blood clotting and prevention of bleeding. As a result, the vitamin may be able to help treat hepatoma, leukemia, and hepatocellular carcinoma, a form of liver cancer. The vitamin also contributes to maintaining healthy bones and healing fractures. Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it may be effective in treating rheumatoid arthritis.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 15 mg (22 IU) for all adults, including pregnancy women. Nursing mothers need 19 mg (28 IU). (Supplements should be taken along with some oil or fat to be absorbed.) Vitamin E is composed of 8 compounds (four tocopherols and four tocotrienols). Vitamin E is most often available as supplements of dl alpha tocopherol (a synthetic form). Other vitamin E compounds may prove to be more active than the standard synthetic supplement. They include natural vitamin E, called d-alpha- or RRR-alpha-tocopherol succinate (VES). Other vitamin E compounds of interest are tocotrienol and beta and gamma tocopherol. Supplements that contain a combination of some of these forms may be most beneficial.	RDA is 60 - 65 micrograms (women) and 70 - 80 micrograms (men).
Foods containing the vitamin	Vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Tocotrienol (a possibly beneficial form) is found in natural tropical oils. Palm oil sold in the US is refined and does not contain tocotrienol.	Best dietary sources are canola oil, cruciferous vegetables, and soybean oil. Good sources are beef liver, bran, and olive oil. Also produced by bacteria in the intestines.
Effects of deficiencies	Deficiencies have not been established.	Easy bruising, bleeding. May increase the risk of hip fractures in women.
People at risk for deficiencies	Low-birth weight infants. People who eat a low-fat diet. People with medical problems that impair fat absorption, such as Crohn's disease, cystic fibrosis, steatorrhea, liver diseases (such as cirrhosis). People with abetalipoproteinemia, a rare genetic disorder that impairs fat metabolism.	Deficiency may occur in patients who have problems absorbing fats, such as those with cirrhosis, people who are on long-term antibiotic therapy, or who are taking other medications, including cholestyramine, Dilantin, and phenobarbital. Some evidence suggests that more young people may be deficient than previously believed.
Toxicities	Upper level recommended is 1,500 IU of alpha tocopherol. Large doses may cause bleeding problems, particularly in people taking anti-clotting medications. Some research now indicates that vitamin E, like other antioxidants, may have pro-oxidant and damaging effects. Although vitamin E is one of the best studied vitamins, research has yielded conflicting results, and definitive conclusions about the benefits and toxicity of vitamin E have not yet been determined. In a major 2005 study, there was no significant difference in cancer rates between people who took 400 IU of vitamin E daily and those who did not, although those who took the supplement had a higher risk of heart failure. Additional studies also link high levels of vitamin E with a slightly increased risk of heart failure and death. On the other hand, studies show that vitamin E may reduce heart problems in high-risk patients such as certain people with diabetes.	Allergic-type responses, including rash and itching, to high doses have been reported. Those who are taking Coumadin, an anticoagulant, should not take vitamin K without consulting a physician. Vitamin K deficiency can cause anorexia, lethargy, growth retardation, bone loss, soft tissue calcification, and death.

Carotenoids

Carotenoids are a group of more than 700 fat soluble nutrients that produce the colors in foods such as carrots, pumpkins, sweet potatoes, tomatoes, and other deep green, yellow, orange, and red fruits and vegetables. Many are proving to be very important for health. Beta carotene is the most widely studied carotenoid, but others are proving to be of great interest. As with some, but not all, carotenoids, beta carotene is known as a provitamin A because it converts to the vitamin in the body.

They are categorized as either xanthophylls or carotenes according to their chemical composition.

Carotenes are hydrocarbons and most are found in yellow, orange, and red vegetables. They include beta and alpha carotene and lycopene.

Beta Carotene and other Provitamin A Carotenoids. Beta carotene, alpha-carotene, and beta-cryptoxanthin are carotenes that are converted into vitamin A or retinol (the active form of vitamin A) in the body. They are found in many yellow fruits and vegetables. Beta carotene is the most widely studied carotenoid. Evidence now strongly suggests that when taken as a separate supplement it can have harmful effects.
Lycopene. Lycopene is responsible for the red color in fruits and vegetables, including tomatoes, red grapes, watermelon, and pink grapefruit. It is also found in papayas and apricots. It does not convert to vitamin A but may have important cancer fighting properties and other health benefits.
The beneficial actions of most carotenes such as those tomatoes, corn, and carrots, appear to be enhanced by cooking them, especially in oil (preferably olive, canola, or another monounsaturated oil). (Note: Cooking can also destroy certain nutrients, such as vitamin C, in these vegetables.)

Xanthophylls contain oxygen and most are found in green vegetables, such as broccoli, cabbage, and kale. They are also in yellow fruits and vegetables. Xanthophylls include lutein and zeaxanthin, which are both stored in the retina of the eye. Neither converts to vitamin A. Both are powerful antioxidants and may be very important for healthy eyes. Unlike carotenes, cooking may reduce the antioxidant activity of some xanthophylls in foods, although probably not to any significant degree.

Phytochemicals

The word phytochemicals means plant chemicals. Hundreds of phytochemicals are being studied. Many are believed to have a major positive impact on human health. Some contribute to the bright and vivid colors found in fruits and vegetables. The results of studies on specific phytochemicals are not necessarily applicable to the vegetables or fruits that harbor small concentrations of these chemicals.

Nevertheless, it is obvious that vegetables and fruits are healthful, which is probably due to some balance of phytochemicals, carotenoids, vitamins, fibers, and minerals rather than any single substance.

The benefits of individual phytochemical supplements are largely unproven. Furthermore, they are not regulated and high concentrations of some may behave like drugs and can be toxic and possibly even contribute to cancer cell growth.

Polyphenols are important phytochemicals, and flavonoids (or catechins) are members of the polyphenol family that may have significant health benefits. Laboratory studies have shown that specific flavonoids suppress tumor growth, interfere with sexual hormones, prevent blood clots, and have anti-inflammatory properties. In general, flavonoids are found in celery, cranberries, onions, kale, dark chocolate, broccoli, apples, cherries, berries, tea, red wine or purple grape juice, parsley, soybeans, tomatoes, eggplant, and thyme. Most common berries contain flavonoids and are particularly rich in potent antioxidants.

Among the important flavonoids are resveratrol, quercetin, and catechin. Evidence suggests that resveratrol (found in red wine, grapes, olive oil) may be extremely potent. In laboratory studies, it increases cell survival and has been shown to increase the life span of worms and fruit flies. Catechins are the primary flavonoids in tea and may be responsible for its possible beneficial effects. Flavonoids in dark chocolate may also be health protective.

Isoflavones, commonly known as phytoestrogens, have actions that are similar to the female hormone estrogen. A high consumption of soy, which is primarily composed of isoflavones, may reduce symptoms resulting from estrogen depletion during menopause. In a recent study, supplementation with isoflavones decreased hot flashes by 57% and night sweats by 43%, but other research is less favorable.

Lignan is another phytoestrogen and is found in the fiber layers of whole-grains, berries, some seeds, some vegetables, and a few fruits.

Isothiocyanates and related substances, indoles, are also known as mustard oils and are responsible for the sharp taste in cruciferous (also called brassica) vegetables. Such vegetables include broccoli, cabbage, Brussels sprouts, cauliflower, collards, kale, kohlrabi, mustard greens, rutabaga, turnips, and bok choy. Isothiocyanates also stimulate enzymes that convert estrogen to a more benign form and may block steroid hormones that promote breast and prostate cancers. (Cruciferous vegetables are also high in fiber, vitamin C, and selenium.)

Monoterpenes have two important phytochemicals, perillyl alcohol and limonene. They block proteins that stimulate cell growth and reproduction and are being tested for actions against cancer. Limonene is found in the peels of citrus fruits.

Organosulfurs are part of the allium family of phytochemicals. Compounds, such as allicin, may have benefits on the immune system, assist the liver in rendering carcinogens harmless, and reduce production of cholesterol in the liver. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots.

Capsaicin seems to reduce levels of substance P, a compound that contributes to inflammation and the delivery of pain impulses from the central nervous system. Research suggests that it may inhibit cancer-generating substances. It is found in hot red peppers.

Sterols, which include sitosterol, stigmasterol, campesterol, and squalene, are found in vegetable oils. Sitosterol is the most studied and appears to have cholesterol-lowering effects.

Beta-sitosterols may help improve urine flow and urinary symptoms in men with enlarged prostate glands (benign prostatic hyperplasia, or BPH). A recent review study of five randomized trials (519 men) found that urinary flow and other urinary symptoms improved in men who took the herbal remedy from 4 - 26 weeks. The study’s authors cautioned that while beta-sitosterols show effectiveness in the short term, their long-term effectiveness, ability to prevent complications from BPH, and safety are not known. More research is necessary. Beta-sitosterols come from South African star grass, Hypoxis rooperi, or species of Pinus and Picea.

Healthy Foods

Evidence increasingly suggests that a varied diet, not individual food chemicals, is essential for basic health and a longer life. Such diets are rich in fresh fruits and vegetables and whole grains, and low in saturated fats.


Foods	Phytochemicals and Carotenoids	Vitamins and other valuable food components	Benefits
Apples	Flavonoids		May have activity against certain cancers (lung). Also may help maintain healthy cholesterol. May protect against asthma.
Beans	Flavonoids	Folate, iron, potassium, and zinc	Some experts believe beans are the perfect food.
Berries, all kinds of dark colored	Ellegic Acid	Vitamin C, minerals	The anthocyanins in berries such as bilberries, blueberries, cranberries, elderberries, and others, have numerous healthful properties including anti-cancer and antioxidant effects. Bilberry (Vaccinium myrtillis) is widely used to prevent macular degeneration. Blueberries may protect the aging brain. (In one study blueberries were most effective.)
Broccoli (also kale, Brussels sprouts, cauliflower)	Flavonoids, isothiocyanates, lutein, beta and alpha carotene. Note: Young sprouts of broccoli and cauliflower contain much higher levels of isothiocyanates than their mature forms.	Vitamin C, folate, fiber, and selenium	Anticancer properties. Protective against heart disease and stroke.
Carrots and other bright yellow vegetables	Lutein, beta carotene and other provitamin A carotenoids	Vitamin A (converted from carotenoids), vitamin C	Protects eyes, lungs. (Cooking carrots may increase the potency of food nutrients.)
Chocolate, dark. Note: Milk chocolate does not have benefits.	Flavonoids		Heart protective (may improve lipids and help prevent blood clotting. May have protective properties against lung cancer (not other cancers).
Eggs	Lutein	Many B vitamins, vitamin A, vitamin D	Although egg yolks are high in cholesterol, very little of it has a negative effect on people with normal levels. And the health benefits of eggs are now known to be very high. (People with diabetes or those with high cholesterol should restrict eggs, however.)
Fish, oily (mackerel, salmon, sardines)		Vitamin B3, B12. Essential fatty acids, selenium	Heart and brain protective.
Garlic	Allium (organosulfurs)		Possibly protective against certain cancers, heart diseases, and infection. Heating garlic can reduce benefits. Allowing crushed fresh garlic to stand 10 minutes before heating, however, may preserve beneficial chemicals while cooking.
Ginger	Zingiberaceae		Cancer fighting properties.
Grains (whole)	Lignans (phytoestrogens)	Vitamin B, Selenium (important antioxidant mineral), fiber, folate	May help reduce the ability of cancer cells to invade health tissue.
Grapes, including purple grape juice, and red wine	Flavonoids, (resveratrol, quercetin and catechin)		Fight heart disease and cancer. May help lower the risk for asthma.
Nuts		Vitamin E, vitamin B1, essential fatty acids, folate	Protects the heart and may help prevent stroke.
Onions	Flavonoids, allium (organosulfurs)		May have activity against certain cancers (lung).
Oranges	Monoterpenes	Vitamin C, folate, potassium.	Many health benefits. Increases HDL levels.
Potatoes (Sweet)		Vitamin C, vitamin E, vitamin A	Many health benefits.
Soy. The best products are tofu, soy milk, or whole soy protein.	Isoflavones (phytoestrogens), flavonoids, phytosterol, phytate, saponins.		May have effects similar to estrogen, including maintaining bone and benefiting the heart in women. May also be protective against prostate cancer and possibly other cancers. More studies are needed. Effects on breast cancer are uncertain. (Note: Soy may have different effects in men than in women. Of some concern is one study reporting more mental decline in men who consume greater amounts of tofu.)
Spinach and other dark green leafy vegetables	Zeaxanthin, Beta carotene	Vitamin C, folate, vitamin A (converted from carotenoids)	Protects lungs and brain.
Tea (Both black and green tea are beneficial. Best results associated with green tea.)	Flavonoids (primarily catechins)		Cancer fighting properties, particularly in green tea, which may be especially beneficial for smokers. Both black and green tea may protect against heart disease and stroke, although studies are mixed. Tea drinking also may help with weight control and help prevent osteoporosis.
Tomatoes	Lycopene, Flavonoids	Vitamin C, biotin, minerals	Studies link to reductions in prostate and other cancers. Infection fighters.
Note on Organic versus Inorganic Products. There is some evidence that organic produce has higher levels of antioxidants and that some agricultural chemicals may destroy flavonoids. Nevertheless, organic produce is expensive, and fruits and vegetables, no matter how they are grown, are still filled with healthful nutrients.

Dietary Health Benefits

The benefits of any dietary factors are very difficult to prove, and, to date, there is little evidence that most dietary supplements protect against major diseases in otherwise healthy people with normal eating habits. An exception is lutein, which is known to reduce the risk of macular degeneration. However, a diet naturally high in vitamins and minerals can be the best defense against many diseases. Fresh fruits and vegetables and whole grains are the primary sources of vitamins, carotenoids, and vitamins, as well as of fiber and important minerals.

Description of Oxygen-Free Radicals (Oxidants). Currently, the most important benefit claimed for vitamins A, C, E, and many of the carotenoids and phytochemicals is their role as antioxidants, which are scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). These chemically active particles are by-products of many of the body's normal chemical processes. Their numbers are increased by environmental assaults, such as smoking, chemicals, toxins, and stress. In higher levels, oxidants can be very harmful in the following way:

They can damage cell membranes and interact with genetic material, possibly contributing to the development of a number of disorders including cancer, heart disease, cataracts, and even the aging process itself.
Oxygen-free radicals can also enhance the dangerous properties of low-density lipoprotein (LDL) cholesterol, a major player in the development of atherosclerosis.

Description of Antioxidants and Warnings on High-Dose Supplements. Antioxidant vitamins (A, C, and E), carotenoids, and many phytochemicals can neutralize free radicals. Unfortunately, although it is clear that vitamins are required to prevent deficiency diseases, high doses of vitamin C, vitamin E, and beta carotene supplements may also have pro-oxidant effects, which can be harmful in patients with cancer. In these people, high doses of antioxidant vitamins may actually protect cancer cells just as they do healthy cells.

The strongest evidence on negative effects to date comes from studies reporting an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. One study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E.

Some evidence also indicates that high doses of vitamin C may speed up atherosclerosis, or hardening of the arteries. In one study, women with heart disease who took antioxidant vitamins had a higher risk for heart attack or death than those who didn't take one.

Another study also reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. Some researchers speculate that certain immune factors generate oxidants to fight bacteria. This antioxidant vitamin, then, may block that action. Research published in 2005 suggests that those who take large amounts of vitamin E (1,500 IU/day) may slightly increase their risk for heart failure and death, but this evidence is not considered conclusive. Further study is necessary.

Vitamins and Heart Protection.

Antioxidant Vitamins A, C, and E. Deficiencies in vitamins A, C, E, and beta carotene have been linked to heart disease. All of these nutrients have antioxidant effects and other properties that should benefit the heart. A study in patients with heart failure has shown that vitamin C can work with dobutamine, a powerful intravenous medication, to strengthen the heart’s ability to contract following a heart attack. In fact, a 2005 study has found that taking high doses of vitamin E is associated with an increased risk of heart failure. In 2007, the Women’s Antioxidant Cardiovascular Study failed to find that vitamins C, E, and beta carotene could reduce the risk of heart attack, stroke, need for revascularization, or cardiovascular death in women. According to the U.S. Preventive Service Task Force, evidence is insufficient to confirm or refute the benefits of supplements of any of these vitamins in protecting against heart disease.
Folate and B12 Vitamins. Deficiencies in the B vitamins folate (known also as folic acid) and B12 have been associated with elevated blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. One study, reported lower failure rates after heart surgery in patients who took folic acid and vitamins B12 and B6. And a major 2002 study suggested that lowering homocysteine levels with folic acid would reduce the risk for heart disease by 16% and stroke by 24%. However, a 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with B vitamins and folic acid had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke. More evidence is needed to determine whether homocysteine plays a causal role in cardiovascular disease and whether the B vitamins are protective. Folate improves blood flow through the arteries, which may be important for the heart, regardless of its effect on homocysteine. Although people with high levels of homocysteine are prone to damaging blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with folic acid and other B vitamins does not reduce the incidence of blood clots in the peripheral veins (deep venous thrombosis).
Niacin. Niacin (vitamin B3) is used for lowering unhealthy cholesterol levels. Although vitamin B3 is available over the counter, it can have significant side effects. A physician should prescribe niacin in order to ensure its safety and effectiveness. [See In-Depth Report #23, Cholesterol.]

Carotenoids and Heart Protection. Studies have reported that a diet high in fruits and vegetables containing beta carotene, lycopene, and other carotenoids may reduce the risk of heart attack. A small Finish study found that a diet high in tomatoes reduced total cholesterol and LDL ("bad") cholesterol. Diets low in lycopene (particularly from tomatoes) were associated with a significantly higher risk of heart disease and stroke.

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Phytochemicals and Heart Protection. Several phytochemicals are associated with heart protection.

Flavonoids. Certain flavonoids, found in both black and green tea, dark chocolate, onions, red wine or red grape juice, and apples, appear to be strongly heart protective. In one study, people who consumed the most flavonoids in foods had a 20% lower risk for heart disease than those with low consumption. Flavonoids may protect against damage done by cholesterol and help prevent blood clots. A number of studies have now reported heart protection from the flavonoid catechin, which is found in both black and green tea. The flavonoid resveratrol, which is found in grape skin, appears to be responsible for the well-known heart protective effects in red wine and purple grape juice.
Organosulfurs. Organosulfurs found in onions and garlic have been under investigation for possible beneficial effects on cholesterol levels. One study reported an association between taking garlic capsules and significantly lower cholesterol-build up in the arteries of older women but not in older men. In the study, daily garlic supplements dramatically reduced the build-up of newly formed plaque in the arteries, while having much less effect on older, harder plaque deposits. Garlic supplements for cardiovascular disease may be most beneficial when used during earlier years among men and later years among women.
Isoflavones. Soy protein is the most studied source of isoflavones (known as phytoestrogens, or plant estrogens). Not all studies are consistent, but the majority has shown an improvement in at least one of the cholesterol components in people who consumed at least 25 grams of soy protein. A 2007 meta-analysis of all soy protein studies performed from 1990 - 2006 found that soy protein significantly decreased total cholesterol and LDL cholesterol, but had no effect on HDL or triglycerides. The effect was particularly evident in people with hypercholesterolemia. A 2007 study found that 12 weeks of soy supplement lowered total cholesterol and LDL levels in both Caucasian and African-American postmenopausal women. Soy may also reduce other heart risk factors, at least in certain populations. For example, in one 2002 study, soy was beneficial for controlling blood sugar and lowering LDL in postmenopausal women with type 2 diabetes. In a 2007 study of overweight men and postmenopausal women, soy protein reduced blood pressure and arterial stiffness. In another study, soy protein was associated with lower systolic blood pressure in men. The best sources are soy products (tofu, soy milk) or whole soy protein. Powdered soy protein that contains at least 60 mg of isoflavones may provide similar benefits.
Sterols. The plant sterols, including sitosterol, are also proving to be potent cholesterol fighters by blocking the absorption of cholesterol in the intestine. Sitostanol, a derivative of sitosterol, is being used in new margarine products to lower cholesterol levels. Sterols and stanols are now found in breads, cereals, yogurt, and fruit juices.

A healthy diet rich in fruits and vegetables and low in salt and saturated fats may significantly lower the risk for a first stroke, perhaps by helping to protect against high blood pressure -- a major risk factor for stroke.

Vitamins and Stroke Protection. The effects of antioxidant vitamins and carotenoids on stroke, dementia, or both are being studied. Studies are conflicting, however. A 2007 study of 8,171 women with cardiovascular disease reported that vitamins C, E, and beta carotene offered no protection against heart attack and stroke.

The B vitamin folate (usually in the form of folic acid) may protect against stroke. However, exactly which people benefit from this therapy has yet to be determined. Studies have suggested that people who have higher blood levels of folate have a lower than average risk for stroke. Its primary benefit in this case appears to be to reduce levels of homocysteine, an amino acid that has been strongly linked to an increased risk of coronary artery disease, stroke, and Alzheimer's disease. A 2007 meta-analysis of 8 trials found that folate supplements decreased homocysteine 20% and lowered stroke risk 18%. Interestingly, lowering homocysteine with folic acid and B vitamins had no effect on heart attack, strokes, amputations, need for dialysis, or death in patients with chronic or end-stage kidney disease.

Carotenoids and Stroke Protection. Some, but not all, studies have reported a lower risk of stroke from carotenoids, including beta carotene and lycopene.

Many fresh fruits and vegetables contain chemicals that may fight many cancers, including lung, breast, colon, and prostate cancers. Examples of important cancer fighting foods include the following:

Cruciferous vegetables (such as cabbage, Brussels sprouts, and broccoli)
Tomatoes (which contain lycopene)
Carrots (which contain alpha carotene)

Some evidence suggests that antioxidants may enhance the anticancer effects of chemotherapy. In multiple studies, patients who maintained their antioxidant levels were better able to withstand the high stress caused by chemotherapy or radiation therapy compared to those with low antioxidant levels. Antioxidant nutrients that may help reduce the side effects of chemotherapy include vitamins E and C, beta carotene, genistein and daidzein (isoflavones found in soy), and quercetin (found in red wine an purple grape juice).

Any protective effects of vitamins or specific phytochemical against cancer, however, appear to depend on the cooperative effort among them. Individual supplements of any vitamin or food chemical have not as yet shown any benefits.

Additionally, certain supplements may actually encourage tumor growth, particularly when taken in large amounts. Two 2007 studies found a connection between folate supplements and colorectal cancer. In one study, which was designed to evaluate the benefits of folic acid in patients who had previous colorectal adenomas (precancerous polyps), the researchers instead found that folic acid was associated with a higher risk of having 3 or more adenomas and noncolorectal cancers. In another study, it was noted that the downward trend in colorectal cancer diagnoses abruptly started to rise in 1996 when mandatory folate enrichment of grains within the U.S. and Canada began. Rates continue to exceed pre-1996 levels. Additionally, a large 2007 National Cancer Institute/AARP study found an increased risk of advanced and fatal prostate cancer in men who took more than 7 multivitamins a week, but no association between multivitamin use and localized prostate cancer.

High consumption of cruciferous vegetables (at least once per week) was associated with lower risk of kidney cancer, and low consumption (less than once per month) of cruciferous vegetables was associated with higher risk of kidney cancer in a multinational 2007 European study. Cruciferous vegetables also appear to offer protection against head and neck cancer resulting from chemical toxins found in cigarettes and alcohol, for example.

Vitamins and Cancer Protection. Because many cancers are thought to be initiated by the effects of oxygen-free radicals on DNA, the antioxidants A, C, and E and beta carotene have been intensively studied. A major study found that men who took selenium for 6 or 7 years reduced their risk of prostate cancer by 52%. Nevertheless, most individual supplements have not been proven to protect against cancer, and high doses may be dangerous.

A 2007 review of the diets of men exposed to asbestos found a decreased risk of prostate cancer associated with increasing intakes of vitamin C-rich vegetables, but not fruits and vegetables high in vitamin A. The chemopreventive role of silymarin (Silybum marianum), found in milk thistle extract, has been extensively studied and has shown anticancer efficacy against various cancers, especially prostate and skin, by inhibiting UVB radiation.

A review of 13 cancer registries found 416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first cancer. Rates from cancer registries in sunny countries (such as Australia and Spain) and less sunny countries (such as Canada and Iceland) were compared. The researchers concluded that vitamin D production in the skin decreases the risk of several solid cancers, especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder, and kidney cancers. The apparently protective effect of sun exposure against second primary cancer is more pronounced after non-melanoma skin cancers than melanoma.

Consumption of aflatoxins, a common fungus-related toxin infecting cereal grains, oil seeds, spices, tree nuts, and the milk of animals fed contaminated feed, is known to cause hepatocellular carcinoma, a deadly form of liver cancer. Rodent studies have shown that phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids may act as chemopreventive agents, dispersing aflatoxins and protecting against hepatocellular carcinoma. Human trials are planned. A similar study found that several isothiocyanates, diallyl sulfide, and polyphenolic compounds can prevent esophageal dysplasia from progressing to squamous cell carcinoma.

A review of all articles on vitamins and cancer published through February 2007 found that multivitamin/mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status. One trial on poorly nourished Chinese showed supplementation with combined Beta-carotene, vitamin E and selenium reduced gastric cancer incidence and mortality, and overall cancer mortality. In a French trial, combined vitamin C, vitamin E, beta-carotene, selenium, and zinc reduced cancer risk in men but not in women. With few exceptions, neither beta-carotene nor vitamin E had benefits for preventing cancer. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos.

A 2007 study of nearly 82,000 men and women in Sweden found that high intake of methionine was associated with reduced risk of pancreatic cancer. The same relationship was not seen with vitamin B6 or folate.

Vitamin A, C, and E. Although some studies have reported an association between low blood levels of these antioxidant vitamins and a higher risk for cancer, supplements of vitamins A, C, and E appear to have few advantages in most cases. And there are some studies finding higher cancer risks with high intakes of antioxidants. For example, a 2003 study reported a higher risk in melanoma in people with vitamin-C rich diets. Another study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. (Vitamin E may be protective against bladder cancer and ovarian cancer.)
Vitamin D. Some studies have suggested that certain vitamin D compounds may inhibit certain cancer cells, specifically prostate cancer, from proliferating. More research is needed. In 2007, the National Cancer Institute confirmed that ultraviolet (UV) radiation exposure may reduce the risk of developing non-Hodgkin lymphoma (NHL), but only in patients with certain variations in the D vitamin receptor gene. A second 2007 study found that variations in this gene increase the risk of diffuse large B-cell lymphoma. A 2007 prospective analysis of 31,500 women in the Women’s Health Study evaluated calcium and vitamin D intake. The researchers found a moderately lower risk of premenopausal, but not postmenopausal, breast cancer with higher intakes of total calcium and vitamin D. A 2007 review of breast cancer cases reported in Ontario, Canada, found reduced breast cancer risks were associated with increasing sun exposure in women ages 10 - 19, less evidence for associations in women ages 20 - 29, and no evidence for ages 45 - 54. Researchers concluded that sun exposure earlier in life, particularly during breast development, may be key in the connection between vitamin D exposure and breast cancer risk.
Folic acid and B12. These B vitamins convert the amino acid homocysteine to methionine, a substance that helps prevent cells from becoming malignant. Folic acid may provide some protection against cervical and colon cancer. One small study showed a reduction of lung cancer cells in smokers taking folic acid and vitamin B12, but the study was very small, of short duration, and other factors might have biased the results. Still another study reported that folic acid may reduce the risk for breast cancer among women who regularly drink alcohol. (In the study, folic acid had no other effect on breast cancer.)

In 2006, a study for the National Institutes of Health reviewed randomized trials evaluating the effectiveness and safety of multivitamin and mineral supplements in preventing cancer and chronic disease. The studies had mixed results, and some supplements reduced cancer rates in certain populations. However, the reviewers concluded that current evidence is not sufficient to determine whether multivitamin and mineral supplements may prevent cancer and chronic disease.

Carotenoids and Cancer Protection. A number of studies have reported that fruits and vegetables rich in carotenoids are associated with protection against many cancers. Lycopene, found in tomatoes, may have particular value in protection against prostate, colon, lung, and bladder cancer. A 2005 study found that in one out of four men with genetic variations that cause them to be more sensitive to oxidative stress, supplementation with selenium, vitamin E, and lycopene significantly reduces the risk of prostate cancer. Individual supplements, however, do not offer any advantage. In fact, evidence now strongly suggests that beta carotene supplements increase the risk for lung cancer in smokers and people exposed to asbestos

Phytochemicals and Cancer Protection. The following phytochemicals appear to have cancer-protecting properties.

Isothiocyanates. Isothiocyanates and sulforaphane, found in cruciferous vegetables, may block the effects of carcinogens and suppress tumor growth. In one study, for example, women with the highest consumption of cruciferous vegetables had a 24% lower risk of breast cancer than women with the lowest consumption.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Researchers are very interested, then, in their effects on hormone-related cancers, including breast and prostate cancers. Much research has focused on soy. In general, a number of Asian studies have reported an association between a higher intake of soy and a lower incidence of reproductive and breast cancers. The effects of phytoestrogens, however, in all women are far from settled. Some evidence suggests the genistein in soy may have properties that are protective against lung cancer. Nonfermented soy products (tofu, soy milk) also may protect against stomach cancer, while fermented soy products (miso, soy paste) appears to increase the risk.
Organosulfurs. The organosulfur compounds found in the onion and garlic family may have very potent properties in suppressing or blocking carcinogenic substances. A 2007 study found that synthetic organosulfur compounds act as selective inhibitors of growth in breast cancer cells. Studies indicate that people who regularly consume fresh or cooked garlic have about half the risk of developing stomach cancer and two thirds the risk of colorectal cancer as people who eat little or no garlic. One possible explanation for garlic's anti-cancer effect in the stomach is its antibacterial action against H. pylori, which can promote stomach cancer. Taking garlic supplements, however, did not offer these benefits.

It should be noted that studies on the health benefits of vitamins and minerals have some important limitations. Some are held to rigorous standards, while others are not. In most cases, the results of existing research are complex, as they can easily be complicated by factors such as diet, exercise, the presence of healthy or unhealthy lifestyle behaviors, environmental factors, and more.


Disease or Condition	Vitamins	Carotenoids, Phytochemicals, and Healthy Foods
Alzheimer's Disease	Vitamin E. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. (One study suggested that the vitamin protected only those who carried the apoE4 gene. No strong evidence to date has found any protection from antioxidant supplements.) Some studies performed since 2002 challenge this finding, while others agree with it. B Vitamins. Some studies suggest that deficiencies of the B vitamins B6, B12, and folate may be a risk factor for Alzheimer' diseases, possibly because deficiencies elevate homocysteine levels, which some research now associated with a higher risk for Alzheimer's disease. Of these, folates may offer the best protection. In 2007, researchers at Tufts-New England Medical Center reviewed all human studies on folate, vitamin B-6, vitamin B-12, and cognitive function in the elderly conducted between 1966 and November 2006. Six of 10 folate studies reported a significant association between low baseline blood folate concentrations and poor cognitive test performance; 4 of 9 folate studies found associations between low blood folate concentrations and increased prevalence of Alzheimer's disease. No association between vitamin B-6 and vitamin B-12 blood concentrations and cognitive-test performance or Alzheimer's disease was seen, and B-vitamin dietary intake was not associated with cognitive function. Although the majority of studies indicated that low blood folate concentrations predicted poorer cognitive function, data are not solid, due to variations in the way the studies were conducted and lack of agreement on what constitutes a low B-vitamin status.	According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. The estrogen-like properties in isoflavones are of interest in the study of Alzheimer's disease. Animal studies suggest that soy might be protective against AD, particularly in postmenopausal women. Of some concern, however, were one population and a few animal studies suggesting that soy intake may pose a risk for greater mental decline among older men. More research is needed to confirm the effects of soy on the aging brain and to determine if there are gender differences.
Infectious Disease	Studies are mixed whether vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place, even after exposure to a cold virus. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems. A review of all studies on vitamin C and pneumonia prevention found only 1 placebo-controlled, randomized trial conducted in an English boarding school during World War II. The trial found a statistically significant (80% or greater) reduction in pneumonia incidence among boys consuming vitamin C. Two less-well-constructed trials arrived at the same conclusion. Therapeutic trials were even scarcer. Only one randomized, double-blind, placebo-controlled study of vitamin C for treatment of pneumonia was found. In this trial, elderly patients given vitamin C had lower mortality and respiratory symptom scores. However, the benefits were restricted to the sickest patients. One other trial of adults in the former Soviet Union found a dose-dependent reduction in the time to recover with two vitamin C doses. One 2007 study on vitamin D found that a single dose by mouth of this vitamin might prevent healthy individuals from activating the bacterium that causes tuberculosis in patients who harbor the infection. Studies on vitamin E specifically have been mixed. A 2002 study, in fact, reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. However, a 2004 clinical trial conducted among elderly nursing home residents found that daily supplementation with 200 IU of vitamin E did provide protection from upper respiratory infections, especially the common cold. At present, there is not enough evidence to recommend vitamin E for infection prevention. Diarrhea is a worldwide problem, particularly in developing countries and those with poor sanitation. Taking supplements with B-complex vitamins, vitamin C, vitamin E, and selenium may reduce the risk of diarrhea, depending upon the organism that causes the disease. Meanwhile, iron supplements appear to increase the risk of infection from organisms that cause diarrhea. Vitamin A has not been shown to prevent diarrhea. Urinary tract infections (UTIs) may affect as many as 25% of pregnant women. A 2007 study found that women who took vitamin C (100 mg) for 3 months had significantly fewer UTIs than women who did not take vitamin C supplements. Rotavirus is a common cause of acute gastric pain in children under age 5. A 2007 study showed that the high amount of isoflavones found in soy-based infant formula can help prevent rotavirus infection.	Lycopene, found in tomatoes, appears to have properties that protect infection-fighting white blood cells. Saponins extracted from ginseng and allicin (found in garlic) have properties that boost the immune system. Both ginseng and garlic have long been traditionally used for their health benefits.
Asthma	Vitamin C from diet has been associated with lower risk for asthma. In one study, some people with exercise-induced asthma benefited from taking vitamin C one hour before strenuous physical activity. In a 2007 study, taking 1,500 mg supplements of vitamin C for 2 weeks helped prevent exercise-induced airway narrowing in patients with asthma.	Flavonoids found in apples and red wine may help lower the risk for asthma. Some evidence indicates that a low dietary intake of antioxidant nutrients could increase the risk for lung damage. Such nutrients should be obtained from fresh, deep green and yellow-orange fruits and vegetables. A 2007 study found low blood lycopene levels in people with asthma. Increasing lycopene- and vitamin A-rich foods may help raise lycopene levels.
Eye Disorder	Cataracts and Macular Degeneration. Oxygen-free radicals play a role in cataract formation and age related macular degeneration, the most common cause of irreversible blindness in the elderly. Bilberry (Vaccinium myrtillis), which contains powerful anthocyanins, is widely used to prevent macular degeneration. Low levels of vitamin C in the lens of the eye have been particularly strong predictors of cataracts. People with cataracts are frequently deficient in vitamin A, the carotenes, lutein, and zeaxanthin. Studies on protection against cataracts using antioxidant supplements have been mixed, including two identically conducted studies that reported opposite results. Vitamin C currently has the strongest evidence for protection, but even with this antioxidant studies are not consistent. A combination of zinc and antioxidants, including vitamin C and E, may slow the progression of macular degeneration. (Vitamin E alone does not appear to be protective.) Glaucoma. Although no evidence exists that antioxidants will prevent glaucoma, some studies reported an association between vitamin E and improved visual fields in patients with glaucoma.	Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein, lycopene, and zeaxanthin, are especially eye-protective and may help prevent cataracts and macular degeneration. The National Eye Institute in 2007 suggested that people with intermediate- or advanced macular degeneration in one eye may want to take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc. They also suggest that a diet high in lutein and zeaxanthin may help reduce the risk of advanced age-related macular degeneration. Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein lycopene, and zeaxanthin are especially eye-protective and may help prevent cataracts and macular degeneration.
Skin Disorders and Wrinkles	Topical vitamin A (retinol) has been shown to improve fine wrinkles due to aging, by increasing glycosaminoglycan, which retains water, and increasing collagen production. One small study found that taking a combination of vitamins oral C and E supplements may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins singly did not have any effect. In fact, a 2002 study reported that oral vitamin C had no effect on sunburn reaction. Of concern, in the same study some natural antioxidants in the body were reduced in people who took the vitamin. Also of concern are studies reporting no benefits and possibly harm from topical vitamin C in the form of ascorbyl palmitate, which is soluble in fat. One study reported that older adults had fewer wrinkles if they ate whole grains, fresh fruits and vegetables, and the use of healthy oils (such as olive oil). Diet played a role in improving skin regardless of whether the people in the study smoked or lived in sunny countries.	The following foods and phytochemicals may be especially skin protective: Both green tea and ginger appear to have properties that may provide some protection against skin cancer. Green tea skin care products are now available. The substance silymarin, found in the milk thistle family (which includes artichokes), may inhibit UVB-promoted cancers in animals. In one interesting study, eating garlic protected animals very effectively against UVB damage by interfering with urocanic acid in the skin. Whether these results may apply to humans (and what quantities of garlic might be beneficial) is still unknown.
Osteoporosis	Vitamin D. Vitamin D is the essential companion to calcium in maintaining strong bones. Supplements may be needed for people who have poor exposure to sunlight. It should be noted that diet supplies most people's need and high amounts of vitamin D can be toxic. Of interest: Taking vitamin D supplements does not prevent bone loss in post-menopausal African American women, according to research published in 2005. Further study will be needed to determine whether vitamin D prevents bone loss in women from other ethnic groups. Vitamin K. Studies suggest that vitamin K has properties that protect bone and prevent fracture. Vitamin K2 (menatetrenone), a form of vitamin K, is proving to prevent fractures in people with osteoporosis. Vitamin K affects blood clotting, and supplements are not recommended without specific physician instruction. Vitamin B12. One study reported that in people with osteoporosis and pernicious anemia, taking vitamin B12 (which is used to treat the anemia) also increased bone density. Vitamin C and E. There has been some indication of a positive association between vitamin C and E intake and bone density, although evidence proving actual benefits is weak. Note on Vitamin A. High amounts of dietary vitamin A reduces bone density and may even increase the risk for fracture in both postmenopausal women and men. (A form of vitamin A, retinoic acid, has been found to stimulate bone break down.) Beta carotene does not appear to increase risk. Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones.	Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones. Studies are suggesting that isoflavones-rich soy products may actually improve bone density in postmenopausal women. A 2007 study of postmenopausal women in Italy found that 24 months of treatment with genistein plus calcium and vitamin D increased bone density, while women who took calcium and D alone lost bone density. Flavonoids and other compounds in tea may protect the bones.
Menstrual Disorders	Vitamin B6. Limited clinical evidence suggests that vitamin B6 may be beneficial in reducing premenstrual symptoms, including depression. Typically, women take 100 mg per day, although one study suggested that a lower dose (50 mg) may have the same effect. Other preliminary research indicates that women who receive the equivalent of 1,200 mg of calcium and 400 IU of vitamin D per day (through food or supplements) have a significantly lower incidence of premenstrual symptoms than women who did not. Vitamin B1. One study reported relief from menstrual pain using vitamin B1 (thiamin). Vitamin E. Several randomized controlled trials have shown that vitamin E significantly improves both physical and emotional premenstrual symptoms. One study reported that high doses of vitamin E helped reduce menstrual cramps. The doses were much higher than those recommended and could possibly increase the risk for bleeding. Although anecdotal evidence reports that vitamin E helps reduce the frequency of hot flashes for menopausal women, there is no clinical evidence to support this claim.

Resources

http://fnic.nal.usda.gov -- The Food and Nutrition Information Center
http://dietary-supplements.info.nih.gov -- Office of Dietary Supplements, National Institutes of Health
www.ars.usda.gov/ba/bhnrc/ndl -- Nutrient Data Laboratory
www.fda.gov -- Food and Drug Administration
www.eatright.org -- The American Dietetic Association
www.acsh.org -- American Council on Science and Health
www.aicr.org -- American Institute for Cancer Research
www.nutritiondata.com -- Information on vitamins and nutrients in foods
www.consumerlab.com -- Independent testing of nutritional supplements' contents and quality
www.usp.org -- US Pharmacopeia
www.herbs.org -- Herb Research Foundation

References

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Bermudez Y, Ahmadi S, Lowell NE, Kruk PA. Vitamin E suppresses telomerase activity in ovarian cancer cells. Cancer Detect Prev. 2007;31(2):119-28. Epub 2007 Feb 28.

Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin d deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007 ;92(9):3517-22. Epub 2007 May 29.

Clements RH, Katasani VG, Palepu R, Leeth RR, Leath TD, Roy BP, Vickers SM. Incidence of vitamin deficiency after laparoscopic Roux-en-Y gastric bypass in a university hospital setting. Am Surg. 2006;72(12):1196-202.

Coull DB, Tait RC, Anderson JH, McKee RF, Finlay IG. Vitamin B12 deficiency following restorative proctocolectomy. Colorectal Dis. 2007;9(6):562-566.

Dietary Guidelines for Americans 2005. Dept of Health and Human Services, US Dept of Agriculture. Accessed 10/3/2007.

Fischer Walker CL, Black RE. Micronutrients and diarrheal disease. Clin Infect Dis. 2007;45 Suppl 1:S73-S77.

Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE. Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study. Circulation. 2007;116(13):1497-503.

Headstrom PD, Rulyak SJ, Lee SD. Prevalence of and risk factors for vitamin B(12) deficiency in patients with Crohn's disease. Inflamm Bowel Dis. 2007 Sep 20; [Epub ahead of print]

Inderjeeth CA, Glennon D, Petta A, Soderstrom J, Boyatzis I, Tapper J.Vitamin D and muscle strength in patients with previous fractures. N Z Med J. 2007;120(1262):U2730.

Ishihara J, Otani T, Inoue M, Iwasaki M, Sasazuki S, Tsugane S; Japan Public Health Center-based Prospective Study Group. Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men. J Nutr. 2007;137(7):1808-1814.

J.G. Ray, C. Kearon, Q. Yi, P. Sheridan, and E. Lonn, for the Heart Outcomes Prevention Evaluation 2 (HOPE-2) Investigators. Randomized Trial of Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism. Ann Intern Med. 2007;146(11):761-767.

Kitchin B, Morgan SL. Not just calcium and vitamin D: other nutritional considerations in osteoporosis. Curr Rheumatol Rep. 2007;9(1):85-92.

Kune G, Watson L. Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene. Nutr Cancer. 2006;56(1):11-21.

Lim MR, Huang RC, Wu A, Girardi FP, Cammisa FP Jr. Evaluation of the elderly patient with an abnormal gait. J Am Acad Orthop Surg. 2007;15(2):107-117.

Martin H, Lindblad B, Norman M. Endothelial function in newborn infants is related to folate levels and birth weight. Pediatrics. 2007;119(6):1152-1158.

Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, Rosenberg IH. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1325-1329.

Nardin RA, Amick AN, Raynor EM. Vitamin B(12) and methylmalonic acid levels in patients presenting with polyneuropathy. Muscle Nerve. 2007;36(4):532-535.

Ochoa-Brust GJ, Fernández AR, Villanueva-Ruiz GJ, Velasco R, Trujillo-Hernández B, Vásquez. Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy. Acta Obstet Gynecol Scand. 2007;86(7):783-787.

Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol. 2007;125(5):661-669.

Pham DQ, Plakogiannis R. Vitamin E supplementation in Alzheimer’s disease, Parkinson’s disease, tardive dyskinsia, and cataract: Part 2. Ann Pharmacother. 2005;39(12): 2065-2072.

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Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Psoriasis

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

Highlights
Introduction
Types of Psoriasis
Causes
Risk Factors
Diagnosis
Treatment
Topical Medications
Systemic Medications
Phototherapy
Managing Psoriasis
Outlook
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Treatment

Psoriasis that develops on the hands or feet is often very difficult to treat. However, an advanced clinical trial showed that a medication called efalizumab (Raptiva) effectively cleared or nearly cleared moderate-to-severe symptoms in adults after 12 weeks.

Several studies have shown that most people with severe psoriasis who are treated with infliximab (Remicade) have significant improvement in symptoms by week 10. The findings were presented at the 2007 annual meeting of the American Academy of Dermatology.

Continuing etanercept (Enbrel) after 12 weeks improves disease severity without an increase in infections or side effects, according to a study published in the Archives of Dermatology.

Disease classification

The National Psoriasis Foundation has proposed a new way to classify psoriasis. Instead of being grouped as mild, moderate, or severe, the group suggests a new two-tiered system that classifies patients as needing either local or body-wide (systemic) treatment.

Coexisting conditions

Studies from Newfoundland and Germany have revealed increased cases of diabetes, obesity, arthritis, and cancer in patients with psoriasis. Previous research has found an increased risk of heart disease in psoriasis patients. Research is underway to determine if there are genetic links between psoriasis and these conditions.

Severe psoriasis has been linked to a significant increase in a patient's risk of death. A study of more than 713,000 patients showed that severe psoriasis increased mortality by 50%. Such patients should receive comprehensive health examinations to reduce the risk, the authors recommended. Study participants were considered to have severe psoriasis if they required systemic treatment.

Smoking and psoriasis

Introduction

Psoriasis is a chronic skin disorder marked by periodic flare-ups of sharply defined red patches, covered by a silvery, flaky surface. The main disease activity leading to psoriasis occurs in the epidermis, the top five layers of the skin.

The process starts in the basal (bottom) layer of the epidermis, where keratinocytes are made. Keratinocytes are immature skin cells that produce keratin, a tough protein that helps form hair, nails, and skin. In normal cell growth, keratinocytes grow and move from the bottom layer to the skin's surface and shed unnoticed. This process takes about a month.

In persons with psoriasis, the keratinocytes multiply very rapidly and travel from the basal layer to the surface in about 4 days. The skin cannot shed these cells quickly enough, so they build up, leading to thick, dry patches, or plaques. Silvery, flaky areas of dead skin build up on the surface of the plaques before being shed. The underlying skin layer (dermis), which contains the nerves and blood and lymphatic vessels, becomes red and swollen.

Types of Psoriasis

Various forms of psoriasis exist. Some can occur alone or at the same time as other types, or one may follow another. The most common type is called plaque psoriasis, also known as psoriasis vulgaris.

Plaque psoriasis leads to skin patches that start off in small areas, about one-eighth of an inch wide. They usually appear in the same areas on opposite sides of the body.

The patches slowly grow larger and develop thick, dry plaque. If the plaque is scratched or scraped, bleeding spots the sizes of pinheads appear underneath. This is known as the Auspitz sign.

Some patches may become ring shaped (annular), with a clear center and scaly raised borders that may appear wavy and snake-like.

As the disease progresses, eventually separate patches may join together to form larger areas. In some cases, the patches can become very large and cover wide areas of the back or chest. This is known as geographic plaques because the skin lesions resemble maps.

Plaque psoriasis may persist for long periods. More often it flares up periodically, triggered by certain factors such as cold weather, infection, or stress.

Patches most often occur on the:

Elbows
Knees
Lower back

The may also be seen on the:

Upper pelvic bone area
Bottom of the feet
Calves and thighs
Genital areas
Palms of hands

Psoriasis of the scalp affects about 50% of patients. In some cases, the psoriasis may cover the scalp with thick plaques that extend down from the hairline to the forehead.

Psoriasis patches rarely affects the face in adulthood. In children, psoriasis is most likely to start in the scalp and spread to other parts of the body. Unlike in adults, it also may occur on the face and ears.

Psoriatic arthritis (PsA) is an inflammatory condition characterized by stiff, tender, and inflamed joints. Estimates on its prevalence among those with psoriasis range from 2 - 42%. AIDS patients and those with severe psoriasis are at higher risk for developing PsA.

About 80% of PsA patients have psoriasis in the nails. Arthritic and skin flare-ups tend to occur at the same time. It is not clear whether psoriatic arthritis is a unique disease or a genuine variation of psoriasis, although evidence suggests they are both caused by the same immune system problem.

Although patients with psoriatic arthritis tend to have mild skin symptoms, the disease affects the entire body. PsA, therefore, is more serious than the more common plaque psoriasis. Infrequently, the course of PsA has been associated with a syndrome known by the acronym SAPHO, which stands for:

Synovitis (inflammation in the joints)
Acne
Pustule eruptions
Hyperostosis (abnormal bony growths)
Osteolysis (bone destruction)

Some experts group PsA into five forms. The forms differ according to the location and severity of the affected joint:

Symmetric PsA: Symptoms occur in the same location on both sides of the body. It usually affects multiple joints. In about half of the cases, the condition will get worse. The condition is very similar to, but less disabling than, rheumatoid arthritis. The psoriasis itself is often severe.
Asymmetric PsA: This form involves periodic joint pain and redness, usually in only one to three joints, which can be the knee, hip, ankle, wrist, or one or more fingers. The pain does not occur in the same location on both sides of the body.
Distal interphalangeal predominant (DIP): DIP involves the joints of the fingers and toes closest to the nail. It occurs in about 5% of PsA cases.
PsA in the spine: Inflammation in the spinal column (spondylitis) is the primary symptom in about 5% of PsA cases. Such patients may have stiffness and burning sensations in the neck, lower back, sacroiliac, or spinal vertebrae. The spine can be involved in many patients with PsA, even though stiffness and burning sensations in these areas are not the primary symptoms. When it affects the spine, psoriatic arthritis most frequently targets the sacrum (the lowest part of the spine). Movement is difficult.
Arthritis mutilans: This is a severe, deforming, and progressive form of arthritis. It affects less than 5% of PsA cases. It mainly affects the small joints of the hands and feet, but it can also be found in the neck and lower back. Arthritic and skin flares and remissions tend to coincide.

People who start to smoke after developing psoriasis may delay the onset of psoriatic arthritis, according to research presented at the 2007 annual meeting of the Society for Investigational Dermatology. Researchers found that in nonsmokers, the time between psoriasis diagnosis and psoriatic arthritis development was 13 years, compared to 23 among those who started smoking after the onset of psoriasis. Study participants who smoked before developing psoriasis had psoriatic arthritis occur in about 8 years. However, smoking causes serious health problems and should not be considered as a way to delay this type of psoriasis.


Psoriasis Form	Description of Skin Patches	Comments
Guttate Psoriasis	The patches are teardrop-shaped and appear suddenly, usually over the trunk and often on the arms, legs, or scalp. They often disappear without treatment.	Guttate psoriasis can occur as the initial outbreak of psoriasis, often in children and young adults 1 - 3 weeks after a viral or bacterial (usually streptococcal) respiratory or throat infection. A family history of psoriasis and stressful life events are also highly linked with the start of guttate psoriasis. Guttate psoriasis can also develop in patients who have already had other forms of psoriasis, most often in people treated with widely-applied topical (rub-on) products containing corticosteroids.
Inverse Psoriasis	Patches usually appear as smooth inflamed patches without a scaly surface. They occur in the folds of the skin, such as under the armpits or breast, or in the groin.	Inverse psoriasis may be especially difficult to treat.
Seborrheic Psoriasis	Patches appear as red scaly areas on the scalp, behind the ears, above the shoulder blades, in the armpits or groin, or in the center of the face.	Seborrheic psoriasis may be especially difficult to treat.
Nail Psoriasis	Tiny white pits are scattered in groups across the nail. Toenails and sometimes fingernails may have yellowish spots. Long ridges may also develop across and down the nail. The nail bed often separates from the skin of the finger and collections of dead skin can build up underneath the nail.	Over half of patients with psoriasis have abnormal changes in their nails, which may appear before other skin symptoms. In some cases, nail psoriasis is the only symptom.
Generalized Erythrodermic Psoriasis (also called psoriatic exfoliative erythroderma)	This is a rare and severe form of psoriasis, in which the skin surface becomes scaly and red. The disease covers all or nearly all of the body.	About 20% of such cases evolve from psoriasis itself. The condition may also be triggered by certain psoriasis treatments, and other medications such as corticosteroids or synthetic antimalarial drugs.
Pustular Psoriasis	Patches become pus-filled and blister-like. The blisters eventually turn brown and form a scaly crust or peel off. Pustules usually appear on the hands and feet. When they form on the palms and soles, the condition is called palmar-plantar pustulosis.	Pustular psoriasis may erupt as the first occurrence of psoriasis, or it may evolve from plaque psoriasis. A number of conditions may trigger pustular psoriasis, including infection, pregnancy, certain drugs, and metal allergies. It can also accompany other forms of psoriasis and be very severe.

Causes

The precise causes of psoriasis are unknown. It is generally believed to be due to damage in factors in the immune system, enzymes, and other materials that control skin cell division. This prompts an abnormal immune response, which causes rapid production of immature skin cells and inflammation.

The Normal Immune System Response. The inflammatory process is the result of the body's immune response, which fights infection and heals wounds and injuries:

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign invaders, such as bacteria or viruses.
The masses of blood cells that gather at the injured or infected site produce factors to repair wounds, clot the blood, and fight infections.
In the process, the surrounding area becomes inflamed (red and swollen), and some healthy tissue is injured.

The Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign substances (antigens) and launch an offensive or defensive action against them:

B cells produce antibodies, which are designed to attack the antigens. Antibodies can either ride along with a B cell or travel on their own.
T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells (TH cells).

Killer T cells directly attack antigens found on bacteria or other cells.
Helper T stimulate B cells and other white cells to attack the antigen.

The actions of the helper T cells are of special interest. Researchers have found high numbers of helper T cells in psoriatic plaques. Helper T cells normally stimulate B cells to produce antibodies. In psoriasis, however, they appear to direct the B cells to produce autoantibodies ("self" antibodies), which attack skin cells. In psoriatic arthritis, cells in the joints also come under attack.

Helper T cells also release or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are very important for healing. If overproduced, however, they can cause serious damage, including inflammation and injury during the psoriasis disease process. In psoriasis, researchers are particularly interested in cytokines known as GRO-alpha, tumor necrosis factor, and certain interleukins.

Cytokines attract large numbers of other large white blood cells known as neutrophils. Neutrophils stimulate the production of arachidonic acid, producing two key players in the inflammatory process:

Leukotrienes: These chemicals attract even more white blood cells to the inflamed area.
Prostaglandins: These chemicals widen blood vessels and increase blood flow.

A combination of genes is involved with increasing a person's susceptibility to the conditions leading to psoriasis.

HLA Molecules. The processes leading to all autoimmune diseases involve the human leukocyte antigen (HLA) system. HLA molecules pick off parts of antigens and present them on the surface of a cell so that the various infection-fighting factors in the immune system can recognize and destroy them. Most immune disorders, including psoriatic arthritis, are due to problems with this system. For example, psoriasis patients with an HLA genetic factor called HLA-CW6 tend to develop psoriasis at an earlier than average age. However, only 10% of people who have this gene develop psoriasis. Other genetic and environmental factors are required to actually trigger the disease.

PSORs. Researchers have now identified four key genes (named PSOR 1 - 4) that are involved with psoriasis. Of particular interest are the genes located in regions on specific chromosomes that are linked to HLA and tumor necrosis factor, another immune factor strongly associated with psoriasis.

Weather, stress, injury, infection, and medications, while not direct causes, are often important in triggering the disease process leading to the start and worsening of psoriasis.

Weather. Cold, dry weather is a common trigger of psoriasis flare-ups. Hot, damp, sunny weather helps relieve the problem in most patients. However, some people have photosensitive psoriasis, which actually improves in winter and worsens in summer when skin is exposed to sunlight.

Stress and Strong Emotions. Stress, unexpressed anger, and emotional disorders, including depression and anxiety, are strongly associated with psoriasis flare-ups. In one study, nearly 40% of patients remembered a specific stressful event that occurred within a month of a psoriasis flare. Other research has suggested that stress can trigger specific immune factors associated with psoriasis flares.

Infection. Infections caused by viruses or bacteria can trigger some cases of psoriasis. For example:

Streptococcal infections in the upper respiratory tract, such as tonsillitis, sinusitis, and strep throat, are known to trigger guttate psoriasis in children and young adults. The infections may make ordinary plaque psoriasis worse.
Human immunodeficiency virus (HIV) is also associated with psoriasis.
An uncommon form of human papillomaviruses (HPV) called EV-HPV has been associated with psoriasis. Although EV-HPV is probably not a direct cause, it may play a role in the continuation of psoriasis. This HPV form is not the virus associated with cervical cancer and genital warts.

Skin Injuries and the Köbner Response. The Köbner response is a delayed response to skin injuries, in which psoriasis develops later on at the site of the injury. In some cases, even mild abrasions can cause an eruption, which may be a factor in the frequency of psoriasis on the elbows or knees. It should be noted that psoriasis can develop in areas with no history of skin injury.

Medications. Drugs that can trigger the onset of the disease, worsen symptoms, or cause a flare-up include:

Angiotensin-converting enzyme (ACE) inhibitors, drugs used to treat high blood pressure and heart problems
Beta-blockers, drugs used to treat high blood pressure and heart problems
Chloroquine, a medicine used to treat malaria
Lithium for bipolar disorder treatment
Indomethacin, a nonsteroidal anti-inflammatory drug (NSAIDs) -- Note: Other NSAIDs, such as meclofenamate, may actually improve the condition.
Progesterone, used in female hormone therapies

Flare-ups of severe psoriasis may occur in persons who stop taking steroids taken by mouth, or who discontinue use of very strong steroid ointments that cover wide skin areas. The flare-ups may be of various psoriatic forms, including guttate, pustular, and erythrodermic psoriasis. Because these drugs are also used to treat psoriasis, this rebound effect is of particular concern.

Medications that cause rashes, a side effect of many drugs, can trigger psoriasis as part of the Köbner response.

Risk Factors

Between 5.8 and 7.5 million Americans have psoriasis. Risk factors for psoriasis include:

Age under 20. About 40% develop the condition before age 20. Psoriasis (most often plaque psoriasis) can even occur in infants.
Climate. Some studies have found that the disorder develops earlier and more frequently in colder climates. For example, psoriasis occurs more frequently in African-Americans and in Caucasians who live in colder climates than in people of any ethnicity who live in Africa.
Ethnicity. Psoriasis is uncommon in Native Americans of either North or South American descent.
Family history of the disease. About 35% of those with psoriasis have one or more family members with the disorder.
Male gender. Some studies have indicated that more men than women have psoriasis.

Diagnosis

A microscopic examination of tissue taken from the affected skin patch is needed to make a definitive diagnosis of psoriasis and to distinguish it from other skin disorders. Usually in psoriasis, the examination will show a large number of dry skin cells, but without many signs of inflammation or infection. Specific changes in the nails are often strong signs of psoriasis.

Several conditions produce symptoms that resemble those of psoriasis. For example:

Seborrheic psoriasis is hard to distinguish from seborrheic dermatitis (dandruff is one form of this condition). Seborrheic dermatitis patches are usually greasy, yellowish, and crusty. Nail involvement may also help differentiate psoriasis.
Generalized erythrodermic psoriasis may be confused with drug allergic reactions, atopic eczema, and symptoms of lymphomas.
Fungal infections, other skin conditions, or circulation problems may also cause nail changes typical of psoriasis.

Symptoms of psoriatic arthritis may also resemble the following:

Rheumatoid arthritis (RA). As in rheumatoid arthritis, psoriatic arthritis can cause pain or tenderness in one or more joints, and morning stiffness is common. People with psoriatic arthritis, however, lack a particular antibody, called rheumatoid factor, which is found in the blood of many people with rheumatoid arthritis.
Systemic lupus erythematosus (SLE). Symptoms of SLE may include both a psoriasis-like rash and arthritis, which could make the diagnosis difficult.
Reiter's disease. Reiter's disease is a syndrome that includes arthritis and inflammation in the eyes and urinary tract. It also causes skin lesions that are very similar to psoriasis, which are usually raised patches on the lips, penis, palms, and soles.
Gout. Gout causes pain, often in the fingers and toes.

Some evidence now indicates that inflammation in psoriatic arthritis may be distinguished from other arthritic conditions by its occurrence in sites where muscle tissue inserts into the bone (called enthesitis) rather than in the joint, which is a common site in other inflammatory arthritic conditions.

Severity of psoriasis itself ranges from one or two flaky inflamed patches to widespread pustular psoriasis that, in rare cases, can be life threatening. To help determine the best treatment for a patient, doctors usually classify the disease as mild to severe. The classification depends on how much of the skin is affected:

Mild psoriasis affects less than 3% of the body surface. Most cases of psoriasis are limited to less than 2% of the skin.
Moderate psoriasis covers 3 - 10% of the skin.
If more than 10% of the body is affected, the disease is considered severe.

The palm of the hand equals 1% of the body. The severity of the disease is also measured by its effect on a person’s quality of life.

However, the National Psoriasis Foundation has proposed a new classification method. The group suggests a new two-tiered system that classifies patients as needing either local or body-wide (systemic) treatment.

While disease severity impacts treatment success, some forms of psoriasis can be very resistant to treatment even though they are not categorized as severe. They include:

Any psoriasis on the palms and soles (hand and foot psoriasis)
Inverse psoriasis (which occurs in the folds of the skin)
Scalp psoriasis
Psoriatic arthritis

Treatment

Many creams, ointments, lotions, and pills are available for the treatment of psoriasis. Many patients require only over-the-counter treatment, or even none at all during relapses.

About a third of patients with psoriasis, however, do not respond to over-the-counter remedies and lifestyle changes, and require aggressive treatments. In some cases, such treatments need to be lifelong.

In general, there are three treatment options for patients with psoriasis.

Topical medications such as lotions, ointments, creams, and shampoos
Body-wide (systemic) medications, which involve pills or injections that affect the whole body, not just the skin
Phototherapy, which uses light to treat psoriasis lesions

Individual requirements vary widely, and treatment selection must be carefully discussed with the doctor.

Giving treatment in a particular order is a strategy for providing both quick relief of symptoms and long-term maintenance. It involves three main steps:

The quick fix, to clear the psoriatic lesions during an acute outbreak (for example, a high-strength topical steroid in mild-to-moderate psoriasis, or an oral immunosuppressant in more severe cases)
The transitional phase, intended to gradually introduce the maintenance drug
Ongoing maintenance therapy

Choices for transitional or maintenance treatments depend on the severity of the condition. Some examples are described in the following sections.

In severe chronic cases, a doctor may recommend rotational therapy. This approach alternates treatments. The goal is to prevent severe side effects or build-up of resistance from long-term use of a single medicine. An example of a rotational schedule may be the following:

The patient gets phototherapy for about 2 years.
The patient then takes one or two powerful body-wide drugs for 1 - 2 years and stops.
Phototherapy starts again, and the cycle repeats.

Some doctors use the Koo-Menter Psoriasis Instrument (KMPI) to decide which patients should receive a pill or an injection. The KMPI’s questions include:

Does psoriasis cover at least 5% of the patient’s body?
Is the patient disabled by psoriasis?
Does psoriasis affect the patient’s quality of life?

If the answer to these questions is "yes," three additional questions are considered:

Is light therapy inappropriate for the patient?
Is the patient’s psoriasis resistant to light therapy?
Does the patient have psoriatic arthritis?

If the answer to these questions is “yes,” a doctor may decide to prescribe a pill or injected drugs.

Doctors increasingly use combinations of pills, creams, ointments, and phototherapy instead of single medications. Combinations of oral treatments are particularly useful, since the doses of each drug can be reduced. This lowers the risk of severe side effects. Thousands of combinations are possible, and the patient and doctor should discuss the best treatment for individual needs.

Topical Medications

Topical medications are those applied only to the surface of the body. They come in the following forms:

Creams
Foams
Gels
Lotions
Occlusive tapes
Ointments
Shampoos
Solutions
Sprays

In general, topical treatments are the first line for mild-to-moderate psoriasis, but they may also be used, alone or in combination, with more powerful treatments for moderate-to-severe cases. Topical medicines rarely produce complete clearance, however.

Corticosteroid topical treatments are the mainstay of psoriasis treatments in the United States. They work for most patients. Such treatments:

Decrease inflammation
Block cell production
Relieve itching

Corticosteroids are available in a wide range of strengths, and are generally given as follows:

Less potent drugs are used for mild-to-moderate psoriasis.
Stronger drugs are reserved for more severe disease.

In the past, topical steroids have been used twice a day. Studies are reporting, however, that certain drugs may work just as well if taken once a day. Most studies have evaluated high-potency steroids, but one study suggested that those of medium strength, such as triamcinolone (Aureocort, Tri-Adcortyl), may be equally beneficial as a once-daily treatment. However, corticosteroids used alone clear psoriasis in only 4 - 36% of patients.

Combination therapy. Combinations with other drugs are often needed. For example, an effective, topical regimen uses the following combination for maintenance therapy:

A high-potency steroid (such as halobetasol) on the weekend
A vitamin D3 topical medication called calcipotriene, twice daily on weekdays

In one study, more than 75% of patients with mild-to-moderate psoriasis remained in remission for at least 6 months with this regimen.

Side Effects. The more powerful the corticosteroid, the more effective it is. But it also has a higher risk for severe side effects. Side effects may include:

Burning
Irritation
Dryness
Acne
Thinning of the skin; skin may become shiny, fragile, and easily cut
Dilated (widened) blood vessels
Loss of skin color

Loss of Effectiveness. In most cases, the patients become tolerant to the effects of the drugs, and the drugs no longer work as they should. Some experts recommend using intermittent therapy (also called weekend or pulse therapy). This type of treatment involves applying a high-potency topical medication for 3 full days each week.

Note: This list is not all inclusive.
Low potency (some are available over the counter)	Desonide (Tridesilon, DesOwen) Flumethasone pivalate (Locorten) Fluocinolone acetonide (Synalar, Derma-Smoothe) Hydrocortisone (Hytone, Penecort, Synacort, Cort-Dome, Nutracort, Westcort) Triamcinolone acetonide (Aristocort)
Low to medium potency	Alclometasone dipropionate (Aclovate) Hydrocortisone (Locoid, Pandel) Hydrocortisone valerate (Westcort) Prednicarbate (Dermatop)
Medium to upper-mid potency	Clocortolone pivalate (Cloderm) Fluticasone propionate (Cutivate) Mometasone furoate (Elocon) Triamcinolone acetonide (Aureocort, Tri-Adcortyl, Kenalog)
High potency	Betamethasone (Diprosone) Amcinonide (Cyclocort) Desoximetasone (Topicort) Diflorasone diacetate (Florone, Maxiflor) Fluocinonide (Lidex) Halcinonide (Halog)
Very high potency	Halobetasol propionate (Ultravate) Betamethasone (Diprolene, Luxiq) Clobetasol propionate (Temovate, Olux) Diflorasone diacetate (Florone, Maxiflor, Psorcon)

Coal tar preparations have been used to treat psoriasis for about 100 years, although their use has declined with the introduction of topical vitamin D3-related medicines. Crude coal tar stops the action of enzymes that contribute to psoriasis, and helps prevent new cell production. Tar is often used in combination with other drugs and with ultraviolet B (UVB) phototherapy.

Side Effects. Preparations have the following drawbacks:

Stains on clothing
Skin irritation
Sun sensitivity and increased risk of sunburn for up to 24 hours after use

Anthralin (Dritho-Scalp, Drithocreme, Micanol) is related to a medication called chrysarobin, in use since the early 1900s. Anthralin slows skin cell reproduction and can produce remissions that last for months. It is recommended only for chronic or inactive psoriasis, not for acute or inflamed eruptions. Persons with kidney problems should use anthralin with caution.

As with tar, its use has also declined with introduction of the topical vitamin D-related medicines, but newer formulations, such as Micanol, have made its use more tolerable. Micanol (Psoriatec) is an anthralin formulated in microcapsules, which dissolve and allow the drug to be delivered directly to the target skin areas. It is particularly useful for scalp psoriasis, and it is less likely to stain.

Side Effects. Anthralin may cause the following side effects:

Skin irritation and burning
Staining of clothes, hair, fabrics, plastics, and other household products

Patients should not use anthralin on their faces. Fair skinned people should generally avoid it. Triethanolamine (CuraStain) is a chemical that can neutralize anthralin and help reduce irritation from short-contact anthralin treatment. It should be applied 1 or 2 minutes before washing off the anthralin. It is then reapplied after drying the skin.

Washing stained items with hypochlorite (Clorox) detergents can help remove stains. Many people use disposable gloves while applying the treatment to avoid staining hands.

Application. Apply anthralin only to the psoriasis plaques. Rub the cream in well, and wipe off any excess. Wash off only with lukewarm water, not soap. Using hot water will trigger the staining action. A technique called short-contact anthralin therapy (SCAT), also called minute therapy, is useful for local areas of psoriasis. In such cases, anthralin is applied for only 10 minutes to an hour.

A topical form of vitamin D3, calcipotriene (Dovonex) is proving to be both safe and effective. It is now available in a foam preparation, which makes compliance even easier. Several other topical vitamin D3 related drugs showing promise include maxacalcitol (Oxarol), tacalcitol, and calcitriol (Silkis).

Calcipotriene appears to:

Block skin cell reproduction
Enhance the maturity of keratinocytes (the impaired skin cells in psoriasis)
Acts as an anti-inflammatory

It works just as well as moderate topical corticosteroids, short-term anthralin, and coal tar in improving mild-to-moderate plaque psoriasis. Unlike steroids, patients do not develop thinning of the skin or tolerance to the drug.

Using the drug in combination with other topical and systemic treatments may improve effectiveness. Calcipotriene doesn't work as well as the highest potency corticosteroids, but products or regimens that combine both medications are proving to be more effective than either one alone. Taclonex, an ointment containing both calcipotriol and betamethasone, was approved by the U.S. Food and Drug Administration (FDA) in January 2006 for the treatment of adults with psoriasis. Studies show the combination works better than either drug alone.

Combining vitamin D ointments with systemic medicines, notably methotrexate, acitretin, or cyclosporine, increases effectiveness and allows lower doses or either medication, thereby reducing side effects.

Studies also report success in some patients who use vitamin D ointments in combination with phototherapy treatment.

Side Effects. Calcipotriene may cause the following side effects:

A possible lowering of vitamin D levels, which may affect bone growth in some children
A possible increase in blood calcium levels (seen in some people who apply calcipotriene to large areas)
Skin irritation in about 20% of patients, particularly on the face and in skin folds

Calcipotriene appears to cause greater skin irritation than potent corticosteroids. Diluting the drug with petrolatum or applying topical corticosteroids to sensitive areas may prevent this problem.

Retinoids are related to vitamin A. They are used for various skin disorders. Tazarotene (Tazorac) is the first topical retinoid found to be effective for mild-to-moderate psoriasis. It is available in cream or gel form.

Unlike steroids, patients do not develop thinning of the skin or tolerance to the drug. Only a very small amount is needed on each lesion. It can be used on the scalp and nails, but it is not recommended for the genital areas or around the eyes. The gel should be used on only 20% of the body at anytime; the cream on up to 35%. (Note: The palm of the hand is about 1% of the body surface.)

Combining topical retinoids with other psoriasis treatments, such as with topical steroids, works better than using the drug by itself.

Side Effects. Tazarotene may cause dryness and irritation of healthy skin. Applying zinc oxide and moisturizer around the treated area can protect the healthy skin.

At levels high enough to be effective for psoriasis, tazarotene can cause severe skin irritation on treated areas. This medicine, then, is usually used in combination with other treatments, therefore allowing a lower dose. Mixing the drug in equal amounts with petroleum jelly (Vaseline) initially and then gradually increasing the amount of tazarotene may help the skin areas become less sensitive. It should be noted that the skin can become very red while it is actually improving.

Vitamin A derivatives (drugs related to vitamin A) have been associated with birth defects and should not be used by women who are pregnant, who wish to conceive, or who are nursing.

Salicylic acid applied to the skin helps remove scaly plaque and enhance the actions of other medications. It should not be used to cover wide areas of the body, since it can cause nausea and ringing in the ears. Combinations with high potency steroids, such as mometasone furoate (Combisor), clobetasol propionate, and betamethasone, are proving to be very helpful. Only Combisor is available in the United States.

Watertight (occlusive) tapes or wrappings may help heal psoriasis. Occlusive tapes are particularly useful for psoriatic cuts on the palms and soles. In such cases, the tape should be applied across the cuts until they heal.

Occlusive tapes retain sweat, which helps restore moisture to the outer skin layer and prevent scaling. They also protect against abrasion and irritation.

High-Potency Corticosteroid Tapes. Applying a corticosteroid beneath an occlusive tape, or using a tape that already has a potent corticosteroid (Cordran Tape) such as flurandrenolide may be especially beneficial. Studies are showing that high-potency corticosteroid-containing tapes are more effective than using high-potency corticosteroid ointments alone.

However, the tapes are expensive and are associated with a high rate of skin irritation, increased secondary infections, and a greater chance of symptoms relapse after treatment is stopped. Infection risk may be reduced by changing tapes every 12 hours.

The use of corticosteroids under occlusive tapes on large areas of psoriasis also increases the risk for adrenal insufficiency, a sometimes dangerous condition that occurs because the body loses its ability to produce natural steroids. Children are especially vulnerable to this effect.

Other Medications with Occlusive Tapes or Wrappings. The tapes may be used in combination with other medications, such as fluorouracil. Occlusive wrappings are not usually used with tazarotene (Tazorac) and should never be used without a doctor's recommendation.

Numerous topical medications are under investigation. One such medication, tacrolimus (Protopic), is an immunosuppressant that is proving to be useful in allergic skin disorders and is being studied for psoriasis. Studies have been mixed on its benefits, although new delivery methods may make it more effective. It may prove to be safe for sensitive areas, such as the face. Pimecrolimus (Elidel), a similar medication, is also being studied.

Systemic Medications

Systemic treatment uses various medications that affect the whole body, not just the skin. Many systemic drugs used for psoriasis are also used for other severe diseases, including autoimmune diseases (especially rheumatoid arthritis) and cancer.

Systemic treatments for psoriasis may be taken by mouth or injection. The medicines can have significant side effects and are generally reserved for severe psoriasis.

At this time, the only systemic medications specifically approved for psoriasis are:

Cyclosporine
Methotrexate
Retinoids

As with all medications for psoriasis, the patient should use the lowest strength medication first. The primary treatment is called a first-line treatment, the next is known as a second-line treatment, and so on. Combinations of medications are often used.

Methotrexate (Rheumatrex) is a biologic drug that interferes with cell reproduction and has anti-inflammatory properties. It is a first line, or primary, systemic drug used to treat adults with severe psoriasis. The medicine is one of the few systemic drugs proven to help patients with psoriatic arthritis.

The drug is taken weekly, not daily. (Deadly reactions have been reported in people who mistakenly took it once a day.)

Side Effects. Common side effects of methotrexate include:

Anemia
Headache
Mild hair loss
Mouth sores
Nausea
Possible muscle aches
Rash
Vomiting

Many of these side effects are due to folic acid deficiency. Patients should ask their doctor if folic acid supplements (generally recommended at 1 - 5 mg daily) are necessary.

More serious side effects include:

Increased risk for infections, particularly shingles and pneumonia. Methotrexate suppresses the immune system. Patients with active infections should avoid this drug.
Infertility, miscarriage, and birth defects. If used during pregnancy, the drug can cause miscarriages or birth defects in the baby. It may harm fertility in men.
Kidney complications.
Liver damage. In one study, 25% of patients taking methotrexate for 5 years developed scarring of the liver. Those with existing liver problems should not take this medicine, if possible. Regular monitoring for liver toxicity, including blood tests and liver biopsies, is important in patients who take the drug.
Lung disease. This side effect can be sudden and severe, and occurs in up to 5% of people who take methotrexate. Risk factors include diabetes, existing lung inflammation, protein in urine, and use of rheumatoid arthritis drugs called DMARDs.
Lymphomas. A few cases have been reported, which are most likely related to the drug's immune-suppressing (lowering) effects. In most instances, the disease has gone into remission when the drug was stopped. Most studies have found no significant risk for cancers in patients taking methotrexate.
Osteoporosis. Low doses of methotrexate do not appear to have any significant effect on bone loss, but long-term studies are needed to confirm this.
Radiation recall: An uncommon side effect in patients who have previously been burned by radiation cancer treatments or sunburns. In such cases, a flare-up of symptoms occurs in the previously affected skin areas.
Severe anemia. Folic acid supplements can offset this effect.
Toxic effects on bone marrow. This can cause reduced blood cell production.

Despite its side effects, some experts view methotrexate as the best therapy for widespread plaque psoriasis. It may also be effective for some patients with other severe forms of the disease, including psoriatic arthritis, generalized erythrodermic, and pustular psoriasis.

Methotrexate appears to be effective in children, but more safety research is needed.

Drug Interactions. Many drugs interact with methotrexate, occasionally with harmful results. For example, the antibiotic trimethoprim-sulfamethoxazole increases the toxicity of methotrexate.

A serious, harmful reaction can occur if methotrexate is taken with common, nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, or naproxen. Other NSAIDs, namely ketoprofen, flurbiprofen, and piroxicam, appear to be safe when given with methotrexate and may be used in patients with psoriatic arthritis. Rheumatoid arthritis (RA) patients who take methotrexate often take NSAIDs as well, but methotrexate doses in psoriasis patients are usually much higher than those in RA.

People Who Should Avoid Methotrexate. Pregnant and nursing mothers should never take methotrexate because it increases the risk for severe, even fatal, birth defects and miscarriage. The drug should be discontinued several months before planning a pregnancy. It may also cause temporary impairment of fertility in men.

Persons with the following conditions should also avoid taking methotrexate:

Alcoholism
Anemia or other blood abnormalities
Immunosuppression
Kidney problems
Liver problems (including hepatitis)
Rheumatoid arthritis
Peptic ulcers

Patients at risk for liver complications include those with diabetes and obesity. Anyone with a history of hepatitis should have a liver biopsy before taking methotrexate.

Oral retinoids are vitamin A-related medications taken by mouth. This group of medicines is also a first-line treatment for adults with severe psoriasis. Oral retinoids used for psoriasis include acitretin (Soriatane) and isotretinoin (Accutane).

Acitretin is the retinoid of choice and may be dramatically effective for severe psoriasis, particularly pustular or erythrodermic variants. When used alone, it is much less effective against more common forms, such as plaque or guttate psoriasis. However, combinations with PUVA phototherapy can markedly improve the response even in these patients.

Accutane, more commonly used to treat acne, is far less potent than acitretin, but may still be effective against pustular psoriasis and also be effective with phototherapy.

Oral retinoids help control cell reproduction and have anti-inflammatory properties. They may even improve arthritis that accompanies psoriasis.

Combination therapy. Acitretin may work the best when combined with other treatments, usually topical drugs and especially phototherapy. Combination therapy allows lower doses of oral retinoids to be used, which diminishes many skin and mucous membrane side effects. Acitretin combined with phototherapy has some of the highest clearance rates of any treatment.

Side Effects. All retinoids have the same potentially serious toxicities as do high doses of vitamin A. Side effects include:

Bone and joint pain
Bruising
Depression and possible suicide risk (with isotretinoin)
Eye problems, including blurred vision, cataracts, conjunctivitis, and a sudden deterioration in night vision
Fatigue
Headache
Increased bone growth, particularly in the ankles, pelvic area, and knees
Increased triglyceride levels
Liver damage
Nail problems
Skin and mucous membrane problems, including dry nose, nosebleeds, dry eyes, chapped lips, thinning hair, dry or "sticky" feeling skin, and peeling of the palms and soles

In rare cases, retinoids, particularly isotretinoin, may cause a condition called benign intracranial hypertension (pseudotumor cerebri), which occurs in the brain. Symptoms include headache, nausea, vomiting, and blurred vision. Patients experiencing these symptoms should call a doctor immediately and stop taking the drug.

Oral retinoids should not be taken during pregnancy.

Despite these side effects, oral retinoids remain among the safest systemic therapies for psoriasis. A low-fat diet, aerobic exercise, and fish oil supplements may help reduce the side effects. Certain cholesterol-lowering drugs, including gemfibrozil (Lopid) or certain statins, such as atorvastatin (Lipitor), may help control triglyceride levels.

Maintenance doses should be as low as possible and should be taken every second or third day.

Taking retinoids during pregnancy significantly increases the risk for severe birth defects in the unborn child. Pregnant or nursing women or those planning to become pregnant should not use these drugs. Women of childbearing age who take retinoids should have regular pregnancy tests.

Doctors recommend that acitretin should not be given to any woman who may become pregnant within 3 years of taking it. Drinking alcohol changes acitretin to a retinoid that is stored in fat cells for 3 years. It may have the potential for causing birth defects during that time. It's important to note that cooking products and over-the-counter preparations, such as cough syrup, may contain alcohol and be inadvertently consumed.
Women who are pregnant or plan to become pregnant should not use isotretinoin. As of December 31, 2005, everyone who takes, prescribes, or dispenses the drug must enroll in a national registry called iPLEDGE.

Cyclosporine (Neoral, Sandimmune, SangCya) blocks certain immune factors and may be effective for all forms of psoriasis. It is also a first line, or primary, systemic drug used to treat adults with severe psoriasis. Neoral is the preparation used most often for psoriasis and clears psoriasis in many patients within 8 - 12 weeks.

Side Effects. Cyclosporine has significant side effects if used for a long time, notably kidney problems and non-melanoma skin cancers. It should be reserved for patients who do not respond to phototherapy or less potent systemic medications (for example, methotrexate or acitretin).

Common and temporary side effects include:

Fatigue
Gingivitis
Gout
Hair growth
Headaches
Joint pain
Tremor

More serious complications may include:

Kidney damage
High blood pressure (Some doctors advise treating high blood pressure with calcium channel blockers, since other standard blood pressure drugs may worsen psoriasis. Calcium channel blockers also help prevent kidney problems.)
High cholesterol and lipid levels
High levels of calcium and low levels of magnesium
Increased risk for infections
Liver problems
Lymphomas
Skin cancers (Patients who have taken cyclosporine after PUVA therapy have a higher incidence of squamous cell skin cancer. According to a 2003 study, the risk is six times that of the general population. The risks are highest with long use and previous use of PUVA, methotrexate, or other immunosuppressants.)

To reduce complications of cyclosporine, the dosage is decreased after improvement occurs. Maintenance therapy is usually limited to a year, although some experts believe that a microemulsion form of Neoral (Neoral-Neo) may be safe for up to 2 years. Patients should be monitored regularly for high blood pressure and signs of kidney or liver problems and skin cancers.

Patients Who Should not Use Cyclosporine. Because the drug suppresses the immune system, people with active infections or cancer should avoid it. Patients with uncontrolled high blood pressure and impaired kidney function should also not use this medication. Cyclosporine therapy for children with psoriasis has not been well studied.

Drug and Food Interactions. Cyclosporine interacts with numerous drugs -- both prescription and over-the-counter preparations -- and also grapefruit and grapefruit juice.

Biological response modifiers, sometimes called "biologics," belong to a new class of drugs that are considered the most exciting development in psoriasis treatment. Biologics are genetically engineered drugs that interfere with specific components of the autoimmune response. Because of their precise targets, these drugs do not damage the entire immune system the way that general immunosuppressants do.

Biologics are considered second- or third-line treatments, and may be used alone or sometimes in combination with first-line systemic drugs.

There are different types of biologics used to treat psoriasis:

T cell blockers block immune cells linked to inflammation.
Tumor necrosis factor (TNF) blockers target the chemical messenger TNF-alpha, which is released during the inflammatory response.

Types of T-cell blockers:

Alefacept (Amevive). This drug is approved for the treatment of moderate-to-severe plaque psoriasis. Studies suggest that the drug produces 50 - 75% improvement in symptoms. Alefacept is given in a doctor's office or clinic. Patients receive weekly injections for 12 weeks. Patients need weekly blood tests to make sure T cell levels do not drop too low. Side effects are generally mild and include sore throat, dizziness, and cough. There have been a few reports of serious infection and cancer.
Efalizumab (Raptiva). This drug is approved for the treatment of moderate-to-severe plaque psoriasis. Many patients experience 50 - 75% improvement in symptoms within 4 - 6 weeks of starting the drug. Patients give themselves shots of this drug for 12 weeks. Some clinical trials suggest that a longer course of treatment (24 weeks) may also be safe and effective for patients with chronic plaque psoriasis. Some patients have flare-ups of psoriatic lesions after stopping efalizumab. Very serious, but rare, side effects include hemolytic anemia and antibiotic-resistant infections.

Types of TNF blockers:

Etanercept (Enbrel) is approved for the treatment of psoriatic arthritis and moderate-to-severe plaque psoriasis. The drug is given either alone or in combination with methotrexate. Side effects include infections and lymphoma, a type of cancer. Patients inject themselves under the skin, once or twice a week for 12 weeks. However, a 2007 study published in the Archives of Dermatology found that continuing etanercept after 12 weeks lowers the severity of disease without increasing infections or side effects. Study participants randomly received 50 milligrams of the drug or a placebo biweekly up to 84 weeks. Strongest improvements were noted at 48 weeks among those who received the drug.
Infliximab (Remicade) is approved for the treatment of psoriatic arthritis. Patients receive three intravenous infusions during the first 6 weeks of treatment. After the initial treatment period, patients receive an infusion every 8 weeks. Therapy takes 2 hours and is given in a doctor’s office or clinic. Patients with a history of infection or heart failure should not take this drug. Several studies have shown that symptoms improve significiantly by week 10 in the majority of patients with severe psoriasis who are treated with infliximab.
Adalimumab (Humira) is being tested in clinical trials for treatment of psoriasis and psoriatic arthritis. Results from a Phase III (late-stage) study show that the drug works better than methotrexate in the treatment of moderate-to-severe psoriasis.
Efalizumab (Raptiva) appears to effectively clear or nearly clear moderate-to-severe hand and foot psoriasis after 12 weeks. This type of psoriasis is often very difficult to control and treat.

Interleukins (IL) being investigated as sources or targets of therapy include IL-4, IL-2, IL-8, IL-11, and IL-12. For example, in a 2003 study, 75% of patients with severe psoriasis who were treated with interleukin-4 (rhuIL-4) experienced improvement rates of more than 68%.

A study of 180 patients with moderate-to-severe plaque psoriasis has shown that an investigational medicine called ABT-874 greatly reduced symptoms in most patients. ABT-874 targets proteins that are responsible for psoriasis-related inflammation.

Leflunomide. Leflunomide (Arava) is a disease-modifying antirheumatic drug (DMARD), which blocks autoimmune antibodies and is a powerful anti-inflammatory medication. It is proving to be active against psoriatic arthritis. Reports of adverse effects are comparable to those with methotrexate. Common problems include nausea, diarrhea, hair loss, and rash. Potentially serious side effects include infections and liver injury.

Sulfasalazine. Sulfasalazine (Azulfidine) is sometimes used for psoriasis. In one major analysis, sulfasalazine and methotrexate were the only medications proven to help patients with psoriatic arthritis. Many people, however, stop taking the drug because of common side effects that include headaches, gastrointestinal complaints, and rash. Benefits, if any, should be apparent in 4 - 6 weeks.

Immunosuppressants. Some immunosuppressants being studied for psoriasis include tacrolimus (Prograf), pimecrolium, and sirolimus. In one study, for example, tacrolimus showed an 83% reduction in symptoms in patients with psoriasis who used the drug. Studies have been limited, however. Side effects of these medications are similar to those of cyclosporine. Pimecrolimus may specifically target the skin and so have fewer side effects. (Some are also being studied as topical treatments.)

Phototherapy

Phototherapy means to treat with light.

When sunlight penetrates the top layers of the skin, this ultraviolet radiation bombards the DNA inside skin cells and injures it. This can cause wrinkles, aging skin, and skin cancers. However, these same damaging effects can destroy the skin cells that form psoriasis patches.

Phototherapy for psoriasis can be given as ultraviolet A (UVA) light in combination with medications, or as variations of ultraviolet B (UVB) light with or without medications. Not everyone is a candidate. For example, it may not be appropriate for patients who should avoid sunlight or those with very severe psoriasis.

Ultraviolet A (UVA) is a main part of sunlight. UVA phototherapy uses a photosensitizing medication (usually psoralen) in combination with UVA radiation to be effective. A photosensitizing medication makes a person more sensitive to light. Treatment with psoralen and UVA is referred to as PUVA. This approach is very powerful and effective in more than 85% of patients who use it. However, it poses a higher risk for skin cancers than UVB.

PUVA treatments cause inflammation and redness in the skin to develop within 2 - 3 days after treatment. Such damage inhibits skin cell proliferation and reduces psoriasis plaque formation.

Forms of psoralen include methoxsalen, 8-methoxypsoralen (8-MOP), or bergapten (5-MOP). The effectiveness of the treatment is based on a chemical reaction in the skin between the psoralen and light, which creates redness and inflammation that prevents the psoriasis disease process.

People should avoid this treatment if they are taking drugs or have conditions that cause them to be light sensitive. They should also take protective measures before, during, and after each treatment.

Initial PUVA Treatment Phase. The initial phase typically follows these steps:

Psoralen is typically taken by mouth in the form of 8-methoxypsoralen (for example, Oxsoralen) 75 minutes to 2 hours before the treatment starts. Psoralen reaches the skin through the bloodstream, where it increases the skin's sensitivity to UVA radiation.
Topical preparations of psoralen are alternatives to pills. They can be "painted on" or applied to the affected areas by soaking or bathing in a psoralen solution. PUVA-bath therapy may be especially useful for persistent psoriasis on the palms and soles or for patients with liver disease or who get severe nausea from taking the pill form. UVA should be given within 15 minutes of using topical psoralen.
The patient enters and stands in a light box, a unit lined with ultraviolet lamps. The initial UVA exposure time is very short (seconds to several minutes), and then increases to 20 minutes or longer. The amount of time a person is exposed to UVA rays depends on the skin type, with the shortest times recommended for fair-skinned patients.
Treatments may be repeated two or three times a week. They should never be performed more frequently than once every other day, since the full effects of the treatments are not evident for 48 hours.

It takes an average of about 25 PUVA treatments for full effect, but during that period, treatment intensity may vary.

If there is no response after 10 treatments, the doctor may increase the UVA energy.
If there is still no response after 15 treatments, the psoralen dosage may be increased.
If a patient's skin does not improve at all or worsens after these changes, the treatment is temporarily stopped. PUVA may be causing a toxic response in such cases, and, often, the condition gradually improves over the following 2 weeks.
If the skin does not improve over the following 2 weeks, PUVA treatment has failed. If skin improves during this resting period, treatment resumes.

Maintenance Phase. Once the psoriasis has improved by about 95%, the patient may be put on a maintenance schedule. Often only one or two treatments a month are needed, but some people may need more frequent treatments. As maintenance continues and the interval between treatments lengthens, the patients may become more susceptible to tanning and sunburn. They should reduce exposure to natural sunlight during this time.

Success Rates. Nearly 90% of patients achieve marked improvement or clearing within 20 - 30 treatment sessions.

Combinations. Combining acitretin, calcipotriene, methotrexate, or tazarotene gel with PUVA may enhance effectiveness or increase response. In addition, combinations may allow for lower doses of radiation or medications to be used, minimizing side effects. Retinoids may also help protect against skin cancers, while methotrexate may increase the risk. In some cases, patients resistant to PUVA or UVB may respond when the phototherapies are combined.

Side Effects and Complications of PUVA.

The psoralen methoxsalen causes a general ill-feeling and nausea in 20% of patients. Dividing up the dose and taking it in 15-minute intervals with food, or taking ginger 20 minutes before taking the drug, may be helpful.
Skin reactions, including itching, sunburn, and blistering, are common. These can generally be avoided with careful administration of PUVA therapy and protective measures. Antihistamines, baths with special oatmeal preparations (Aveeno), and capsaicin ointment (Zostrix) may be helpful.
After treatment, white spots commonly develop where psoriasis plaques had been, particularly in people with naturally darker skin. If they are troublesome, tanning products may help darken them. Small, dark raised spots called PUVA lentigines may also develop in affected areas with long-term treatment
Prolonged standing may trigger fainting in people with certain heart or blood pressure problems.
People with liver disease should discuss using topical psoralens, since oral forms may have adverse effects on the liver.
UVA penetrates the skin more deeply than UVB, so there is a greater danger of deep skin damage, accelerated skin aging, and skin cancers. Anyone who needs to avoid sunlight should not get this treatment.
The procedure increases the risk for cataracts if eyes are not protected for up to 24 hours after treatment.

Special Warning on PUVA and Skin Cancers. It has been known for some time that PUVA can change DNA and cause genetic mutations. PUVA is known to increase the risk for squamous cell skin cancer and slightly increase the risk for basal cell skin cancer, both of which are nearly always curable. One study reported an increased risk of melanoma. The risk for skin cancers is higher in persons who have:

A family or personal history of skin cancer
Light skin and fair or red hair
Received radiation or x-ray treatments or taken immunosuppressant drugs
Received over 200 PUVA treatments

Discussions are under way about discontinuing PUVA for psoriasis. The arguments generally are as follows:

Opponents of PUVA argue that studies suggest a long-term risk for melanoma, starting about 15 years after treatment, particularly in people who receive more than 250 treatments. In one long-term study, only 9 out of 1,380 patients developed melanoma. However, 7 of these cases occurred in the last 5 years of the study, indicating that the danger persists and more patients in this study are likely to develop this serious skin cancer as time goes on.
Supporters of PUVA argue that it is not yet known if the people who developed melanoma experienced sunburn during the procedures or if they already had risk factors for skin cancers. If so, then properly given treatments could still be considered safe for patients without risk factors. They also argue that PUVA is still the most effective treatment for severe psoriasis, and the alternatives are usually very powerful and relatively new drugs that may have even more serious side effects. Furthermore, the addition of retinoids may protect against skin cancers while proving to be a very effective combination.

Side effects of UVA radiation can be severe. Protective measures are needed during, before, and after treatment. Patients should avoid prolonged exposure to the sun for 24 hours before the oral treatment starts.

Protective Measures During Treatment:

Patients should wear specially designed goggles to protect the eyes from UVA radiation.
Sensitive areas, such as genitals, abdominal skin, and breasts, should be covered until tanning occurs in the exposed areas, after about a third of the treatment period. Note that PUVA is associated with a high risk for genital skin cancers, so male genitals must be covered throughout the process.

The following safety features should be available in the PUVA chamber:

Lamps with protective shields
A viewing window for a health professional to check the patient periodically
A door that can be opened by the patient easily and with little pressure
A timer that terminates the session automatically
An accessible alarm device

Protective Measures After Treatment. The drugs used in PUVA increase susceptibility for a natural sunburn for hours after treatment. The patient should take the following precautions:

Patients should wear UVA absorbing wrap-around sunglasses that are designed to completely block out stray radiation. They should begin wearing them as soon as they take the drug, and for at least 12 hours after the treatment. This is important to prevent a PUVA reaction around the eyes that can cause cataracts. There is no need to wear these glasses after sundown.
For about 8 hours after taking the drug, patients must also avoid exposure to daylight, even if the day is cloudy or exposure occurs through windows.
Patients who must go out should wear heavy opaque clothing (clothes that do not let light through), including hats and gloves.
Patients should apply sunblock over all exposed areas, including the lips. The sunblock should have an SPF (sun protection factor) of more than 15 and include ingredients that block both UVB and UVA radiation.
No patient should spend a long time in sunlight for at least 2 days after the combined treatment.

Ultraviolet B is another main part of sunlight, and is the main cause of sunburn. It generally affects the outer skin layers. UVB radiation reduces the abnormally rapid skin cell growth that occurs with psoriasis.

Types of UVB therapy:

Broadband UVB
Narrowband UVB (NB-UVB)
Laser treatments

Broad spectrum or broad band UVB is radiation in the wavelength of 290 - 350 nanometers, and is the standard UVB phototherapy treatment in the United States. It is not as potent as the treatments that use narrow-band UVB or PUVA, and is not useful for chronic psoriasis.

Broadband UVB may be given with or without medications. When used without medication (known as selective ultraviolet phototherapy), UVB treatment generally is given as follows:

Treatment starts in the doctor's office or another medical setting. Once the disease has stabilized, the patient can obtain a prescription for equipment that can be used at home. Even at home, treatment must always be supervised.
In preparation, the patient fully undresses, although unaffected areas may be covered to avoid overexposure.
The initial session may last as little as a few seconds, depending on whether the patient has a lighter or darker skin, with the lightest skin exposed to the briefest session. The duration increases with each treatment until the skin clears or the patient experiences itching or irritation. It should be noted that the condition may worsen initially.
UVB therapy usually requires about 20 - 40 treatments (about three per week). Full results take about 3 weeks.

Use of Medication. UVB was commonly used with coal tar (the Goeckerman regimen) in past decades, and then with anthralin (the Ingram regimen). Other medications are being studied with some success, and may prove to be tolerated better.

The Goeckerman regimen requires daily treatments for up to 4 weeks. The coal tar or anthralin are applied once or twice each day and then washed off before the procedure. Studies indicate that a low-dose (1%) coal tar preparation is as effective as high dose (6%). Such regimens are unpleasant, but still useful for some patients with severe psoriasis, since they can achieve long-term remission (up to 6 - 12 months).

Some evidence suggests that using a simple emollient (such as Vaseline or mineral oil) that enhances UVB light penetration can be effective. This addition to the treatment increases the risk for sunburns, however, and patients must be careful to avoid sun exposure. Researchers are tring combinations of other topical and oral medications. For example, combining UVB with methotrexate, or retinoids such as a tazarotene gel or oral acitretin, is producing positive results. Combinations with any of these drugs, however, must be supervised carefully to avoid serious reactions.

Side Effects of UVB. The treatment can cause itching and redness. UVB radiation from sunlight is known to increase the risk for skin cancers. There is no strong evidence, however, that UVB treatments pose any risk for skin cancers except on male genitalia. This risk, however, can be significant (4.5%) at high doses.

Narrow band radiation may be safer than other approaches, and some experts now believe it should be the first option for patients with chronic plaque psoriasis.

NB-UVB is used without medications and is very strong. Whether it has any affect, however, on the disease process itself is unclear. The light wavelength is between 310 - 312 nanometers, which, theoretically, is the most beneficial part of sunlight.

Exposure times are shorter but of higher intensity than with broadband UVB. This therapy is probably less likely than PUVA to cause skin cancers.

Clearance of 75% typically occurs after 10 - 12 treatments. NB-UVB treatments performed three times a week achieve results that are equal to twice-weekly PUVA treatments. Weekly NB-UVB treatments are not effective. Studies so far are mixed on whether NB-UVB remission rates are equal to those of PUVA.

Patients prefer NB-UVB over other PUVA treatments because they do not have to wear protective eyewear, take medications, or experience unpleasant side effects, notably nausea. It is also safe for pregnant women and children.

Combinations with topical medications, such as tazarotene or psoralens, may help NB-UVB therapy work better.

Laser UVB Treatment. A recent variation of a device called an excimer laser (Xtrac) delivers a precise UVB wavelength of 308 nanometers. The laser is more effective than narrow-band UVB for localized psoriasis, since it allows very specific areas of skin to be targeted. (Note: The therapy is not suitable for the scalp.) Generally, 8 - 10 treatments given twice a week will clear psoriasis. Remission rates are similar to NB-UVB, but the excimer laser can clear the psoriasis faster and at lower doses. It also spares the healthy skin around it. Blistering is a common side effect. More comparison studies are needed to determine risk and benefits compared to NB-UVB, particularly any long-term risk for skin cancer.

Pulsed-Dye Lasers. Pulsed-dye lasers give off high-intensity yellow light, which destroys the tiny blood vessels that make up psoriatic plaques. This treatment has been used for years to remove birthmarks, such as port wine stains and unsightly blood vessels on the skin. Some studies have reported significant (but not complete) improvement, and remissions that have lasted up to 13 months. Treatment sessions last up to 30 minutes and can feel uncomfortable (similar to being repeatedly snapped with a rubber band). It typically takes up to six sessions to clear the target areas. Bruising is common, and there is a small risk for scarring.

Home tanning devices and tanning salons are not usually recommended, but they may be helpful for patients without access to a medical unit. In a 2003 study, many patients achieved a significant reduction in symptoms when taking acitretin and exposed to a UVB commercial tanning unit (specifically, a Wolff tanning bed).

However, UV outputs can vary widely among tanning beds and salons. Some units emit UVA radiation, which poses a higher risk for skin cancers. Adverse effects of tanning salons that use UVA or UVB radiation are the same as with any UV phototherapies, including a risk for skin cancer.

Managing Psoriasis

Although sunburn carries a risk for skin cancer and can make psoriasis worse, regular exposure to the sun helps clear psoriasis in people with mild-to-moderate conditions. People should cover non-affected areas with clothing or sunscreen and sun bath only until the skin starts to tan.

Vacations in sunny areas, such as Hawaii or the Caribbean, can offer relief. For those who can afford it, a prolonged stay of several weeks at the Dead Sea in Israel has proven to significantly improve or clear 88% of those with psoriasis who go there. The region offers a unique combination of intense but naturally filtered UVA radiation combined with minerals and salts from the sea.

Because of the association between negative emotions and psoriatic flare-ups, relaxation and anti-stress techniques may be helpful. A small 1999 study found that hypnosis aimed at reducing stress may relieve symptoms.

Another study found that some patients with psoriasis had a traumatic or stressful event coincide with the appearance of psoriasis. Talking to a psychiatrist about the issue resulted in significant symptom improvement in 62% of study patients who recalled such an event.

If skin becomes dry and itchy, the patient may try the following:

Soak in a warm bath for about 15 minutes.
Afterward, apply salicylic acid first, which removes scaly skin and may promote the penetration of both moisturizers and topical prescription medications.
Then, apply a thick moisturizer or emollient, such as Vaseline, Cetaphil cream, or Eucerin cream. Lotions are not good enough moisturizers.
Special gloves made of Gore-Tex (DermaPore) may be worn at night over a thick moisturizer cream. These gloves are protective but also allow moisture to escape.

Some experts suggest that many common moisturizers may actually increase water loss in psoriasis, but studies still have to confirm this. In the meantime, if moisturizers help relieve the condition, patients should use them.

Capsaicin (Zostrix) is an ointment prepared from the active ingredient in hot chili peppers. It is used to relieve arthritic pain and may help relieve psoriatic itching. Capsaicin should be handled using a glove and applied to affected areas three or four times daily. The patient will usually have a burning sensation when the drug is first applied, but this sensation lessens with use.

Folic Acid. Patients should be sure they get enough of the B vitamin folate (folic acid). Folate-rich foods include liver, asparagus, fruits, green leafy vegetables, dried beans and peas, orange juice, and yeast. Many types of bread and other commercial grain products now have added folic acid.

Omega-3 Fatty Acids. Omega-3 fatty acids, particularly those found in some fish oil, have anti-inflammatory properties that may benefit some patients with psoriasis and other autoimmune conditions.

Patients with persistent psoriasis may be tempted to try alternative or untested treatments, including herbs and other nontraditional therapies. Researchers at the Medical College of Georgia say green tea slowed the growth of skin cells in animal studies and may one day prove to be useful in treating psoriasis. More research is needed.

Several traditional remedies for psoriasis include various other herbal supplements, but to date no clinical studies have been reported on these substances. No one should use any unproven therapy without consulting a doctor to be sure such treatment is not harmful, and does not interfere with any standard medications they take.

Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been many reported cases of serious and even deadly side effects from herbal products.

The following are special concerns for people taking natural remedies for psoriasis:

Zinc pyrithione is sometimes used, but its effectiveness is doubtful. A number of so-called natural psoriasis products (Skin-Cap, Blue Cap, Miralex) that contain this compound also contain prescription-strength corticosteroids. Such steroids have the same side effects as those in standard psoriasis agents. These products have been banned in the U.S. and Canada, but similar untested medications are available over the Internet.
Gotu Kola (Centella asiatica) is sometimes applied in a cream for psoriasis. The oral form of the herb has serious side effects, however, including increasing the risk for miscarriage in pregnant women.

Outlook

Psoriasis is lifelong and not curable. Although it is also marked by rapid cell growth, psoriasis is neither cancerous nor contagious.

In general, studies report the following features of its course:

The condition almost always relapses. In a few cases, large areas of plaque can persist for years.
Psoriasis nearly always goes into remission, however, often clearing on its own. In one study, 30% of patients reported untreated psoriasis going into remissions that lasted 1 - 54 years.
Psoriasis can improve during pregnancy, especially during the second and third months. Increased levels of estrogen may be responsible for this improvement. Relapse may occur after giving birth.

The emotional and social consequences of psoriasis should not be underestimated.

Many patients suffer severe humiliation and depression if plaques are visible. Some even withdraw from society and become isolated.
Some patients are forced to leave their jobs and go on disability if the condition becomes incapacitating.

Researchers have reported the following:

Surveys of patients with psoriasis report a negative mental and physical impact that is nearly equivalent to that of other major chronic conditions, including cancer, high blood pressure, diabetes, heart disease, and depression.
In one study, 75% of patients reported that psoriasis hurt their confidence.
Another study reported that 8% of people with psoriasis felt their life was not worth living.

Some patients, particularly men, use alcohol and smoking as self-medication to reduce the emotional consequences of psoriasis. In fact, studies have found that people with psoriasis have higher mortality rates, mostly from heavy drinking. Smoking has also been cited as a major risk, particularly for pustular psoriasis. Some experts believe that drinking and smoking may actually cause biological damage that contributes to psoriasis itself.

However, smoking may delay the onset of psoriatic arthritis in some patients, depending on when they started the habit. Psoriatic arthritis tends to occur about a decade after psoriasis develops. The review of 281 psoriasis patients showed that the condition appeared after about 13 years in nonsmokers, compared to 23 years in those who began smoking after the first onset of psoriasis. Psoriatic arthritis appeared after 8 years in people who smoked before developing psoriasis.

Folate Deficiency in Severe Psoriasis. Severe psoriasis can also cause folate deficiency. Folate is a B vitamin that is important for nerve function, preventing birth defects. It also prevents elevations of homocysteine, a factor that may play a critical role in heart disease.

Skin Cancers. In one study, patients with severe psoriasis (who receive medications that affect the whole body) were at higher than normal risk for developing cancers, primarily skin cancers and lymphomas. The risk was not any higher for patients with milder psoriasis. There is some indication, however, that patients with psoriasis have a higher risk for non-melanoma skin cancers regardless of treatments.

Heart Attacks. A study released in October 2006 shows an increased risk of heart attacks in people with psoriasis. The risk was highest in young patients with severe psoriasis.

Other Coexisting Conditions: Studies done in Newfoundland and Germany have also revealed increased cases of diabetes, obesity, arthritis, and cancer in patients with psoriasis. Research is underway to determine if there are genetic links between psoriasis and these conditions.

Increased Risk of Death. Severe psoriasis has been linked to a significant increase in a patient's risk of death. A study of more than 713,000 patients showed that severe psoriasis increased mortality by 50%. Study authors encourage patients to receive comprehensive health examinations to reduce the risk. Study participants were considered to have severe psoriasis if they required systemic treatment.

Impaired Temperature Regulation. Erythrodermic psoriasis, in which psoriasis covers the entire skin, can cause abnormalities in the body's ability to regulate temperature.

Zumbusch Psoriasis. A combination of erythrodermic and pustular psoriasis causes a serious condition called Zumbusch psoriasis:

The condition can develop abruptly.
Symptoms may include fever, chills, weight loss, and muscle weakness.
Patients may develop excessive fluid build-up, protein loss, and electrolyte imbalances. In such cases, hospitalization is required. Fluid and chemical balances must be restored and temperature stabilized as soon as possible.

Zumbusch psoriasis can be life threatening, particularly in the elderly. The condition is very rare in children and, if it occurs, tends to improve more quickly than in adults, possibly even without medication.

Most cases of psoriatic arthritis (PsA) are mild, but complications can occur:

Severe joint deformity and destruction (called arthritis mutilans) may develop, generally in the small joints of the hands and feet. Studies report this happens in about 5 - 16% of patients. Psoriasis patients with other arthritic conditions (osteoarthritis or rheumatoid arthritis) in the joints of the fingers tend to have a higher risk.
People with PsA may have a higher risk for respiratory illnesses.

Some earlier studies indicated that patients with psoriatic arthritis had a shorter lifespan than the general population, but more recent studies found no significant difference.

Resources

www.psoriasis.org -- National Psoriasis Foundation
www.aad.org -- American Academy of Dermatology
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.clinicaltrials.gov -- Find clinical trials

References

Gelfand JM, Neimann AL, Shin DB, et al. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006 Oct 11;296(14):1735-41.

U.S. Food and Drug Administration. CDER Drug and Biologic Approvals for Calendar Year 2006 -- Updated through August 31, 2006. Last accessed on 15 October, 2006.

FDA Announces Strengthened Risk Management Program to Enhance Safe Use of Isotretinoin (Accutane) for Treating Severe Acne. US Food and Drug Administration. Rockville, MD: National Press Office; August 12, 2005.

Anstey AV and Kragballe K. Retrospective assessment of PASI 50 and PASI 75 attainment with a calcipotriol/betamethasone dipropionate ointment. Int J Dermatol. 2006 Aug;45(:970-5.

National Psoriasis Foundation. About Psoriasis: Statistics. Last Accessed 9 October, 2006.

Antoni CE, Kavanaugh A, Kirkham B, Tutuncu Z, Burmester GR, Schneider U. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum. 2005;52(4):1227-1236.

Bowcock AM, Cookson WO. The genetics of psoriasis, psoriatic arthritis and atopic dermatitis. Human Mol Genet. 2004;13 Spec No 1:R43-55.

Feldman SR, Koo JY, Menter A, Bagel J. Decision points for the initiation of systemic treatment for psoriasis. J Am Acad Dermatol. 2005;53(1):101-107.

Murase JE, Chan KK, Garite TJ, Cooper DM, Weinstein GD. Hormonal effect on psoriasis in pregnancy and post partum. Arch Dermatol. 2005;141(5):601-6.

Review Date:
9/19/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Diabetes - type 2

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Screening Tests
Treatment
Lifestyle Changes
Medications
Long-Term Complications
Emergency Complications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

Sitagliptin (Januvia), the first in a new class of diabetes drugs called DPP-4 inhibitors, was approved in 2006.
Janumet, a 2-in-1 pill that contains both sitagliptin and metformin, was approved in 2007.
These drugs are taken by mouth and may be more convenient for patients than exenatide (Byetta), a similar drug. DPP-4 inhibitors do not cause weight gain and may pose a lower risk for hypoglycemia than some other diabetes drugs.

Drug Safety Alert

Rosiglitazone (Avandia) may significantly increase the risk for heart attack, indicates a review published in the Journal of the American Medical Association. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Rosiglitazone and a similar drug, pioglitazone (Actos), are known to significantly increase the risks for heart failure. There is also evidence that these drugs increase the risk for bone fracture.

Anemia Drugs Warning

Patients with anemia associated with end-stage kidney disease, especially those on dialysis, should be aware of new warnings concerning dosing target levels of erythpoiesis-stimulating drugs. In 2007, the FDA warned that darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit) can increase the risk for blood clots, stroke, and heart attacks when excessive doses are given. The FDA has defined target hemoglobin levels and recommends that patients who receive these drugs have frequent blood tests. Patients should also report to their doctors any unusual symptoms.

Genetics Research Breakthroughs

Scientists have now identified 10 genes that are associated with increased risk for type 2 diabetes. Six of these genes were discovered in 2006 and 2007.

Diabetes and Pre-Diabetes

About 20 million Americans have type 2 diabetes, and an additional 54 million have pre-diabetes. According to a 2007 study by the U.S. Centers for Disease Control, the prevalence of type 2 diabetes has been increasing by 5% each year since 1990. Rising rates of obesity may be one factor.
For people with pre-diabetes, lifestyle changes, such as losing weight, appear to work as well as drug treatment in delaying the progression to diabetes, according to a 2007 British Medical Journal study.

Introduction

The two major forms of diabetes are type 1 (previously called insulin-dependent diabetes mellitus, IDDM, or juvenile-onset diabetes) and type 2 (previously called noninsulin-dependent diabetes mellitus, NIDDM, or maturity-onset diabetes).

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It works in the following way:

During and immediately after a meal the process of digestion breaks down carbohydrates into sugar molecules (including glucose) and proteins into amino acids.
Right after the meal, glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise sharply.
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 10 minutes after a meal, insulin rises to its peak level.
Insulin enables glucose and amino acids to enter cells in the body, particularly muscle and liver cells. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. (The brain and nervous system are not dependent on insulin; they regulate their glucose needs through other mechanisms.)
When insulin levels are high, the liver stops producing glucose and stores it in other forms until the body needs it again.
As blood glucose levels reach their peak, the pancreas reduces the production of insulin.
About 2 - 4 hours after a meal, both blood glucose and insulin are at low levels, with insulin being slightly higher. The blood glucose levels are then referred to as fasting blood glucose concentrations.

The pancreas is located behind the liver and is where the hormone insulin is produced. Insulin is used by the body to store and utilize glucose.

Type 2 diabetes is the most common form of diabetes, accounting for 90 - 95% of cases. The disease mechanisms in type 2 diabetes are not wholly known, but some experts suggest that it may involve the following three stages in most patients:

The first stage in type 2 diabetes is the condition called insulin resistance. Although insulin can attach normally to receptors on liver and muscle cells, certain mechanisms prevent insulin from moving glucose (blood sugar) into these cells where it can be used. Most patients with type 2 diabetes produce variable, even normal or high, amounts of insulin. In the beginning, this amount is usually sufficient to overcome such resistance.
Over time, the pancreas becomes unable to produce enough insulin to overcome resistance. In type 2 diabetes, the initial effect of this stage is usually an abnormal rise in blood sugar right after a meal (called postprandial hyperglycemia). This effect is now believed to be particularly damaging to the body.
Eventually, the cycle of elevated glucose further impairs and possibly destroys beta cells, thereby stopping insulin production completely and causing full-blown diabetes. This is made evident by fasting hyperglycemia, in which elevated glucose levels are present most of the time.

In type 1 diabetes, the disease process is more severe and onset is usually in childhood:

Beta cells in the pancreas that produce insulin are gradually destroyed. Eventually insulin deficiency is absolute.
Without insulin to move glucose into cells, blood glucose levels become excessively high, a condition known as hyperglycemia.
Because the body cannot utilize the sugar, it spills over into the urine and is lost.
Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty."
Patients become dependent on administered insulin for survival. [See In-Depth Report #9: Diabetes - type 1.]

Click the icon to see an image of the pancreas.

Conditions that damage or destroy the pancreas, such as pancreatitis, pancreatic surgery, or certain industrial chemicals can cause diabetes. Polycystic ovaries are highly associated with diabetes. Certain drugs can also cause temporary diabetes, including corticosteroids, beta-blockers, and phenytoin. Rare genetic disorders (Klinefelter's syndrome, Huntington's chorea, Wolfram's syndrome, leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetes) and hormonal disorders (acromegaly, Cushing syndrome, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma) are associated with or increase the risk for diabetes.

Causes

Type 2 diabetes is caused by a complicated interplay of genes, environment, insulin abnormalities, increased glucose production in the liver, increased fat breakdown, and possibly defective hormonal secretions in the intestine. The recent dramatic increase indicates that lifestyle factors (obesity and sedentary lifestyle) may be particularly important in triggering the genetic elements that cause this type of diabetes.

The characteristic features of most patients with type 2 diabetes are:

Insulin resistance in muscle cells
Normal or even excessive levels of insulin (to compensate for this resistance), eventually followed by a drop in insulin production

In addition, researchers are trying to determine the factors that might promote insulin resistance:

Both obesity and insulin resistance at different phases are marked by elevated levels of free fatty acids and the hormones resistin and leptin. It is not known yet if elevated levels are simply a product of obesity or play some causal role in diabetes.
Insulin resistance is associated with a chronic low inflammatory response, which involves a number of immune factors, such as TGH-beta 1 and C-reactive protein. Such factors can cause damage over time and may be responsible for the association between insulin resistance and heart disease.

Type 2 diabetes has a genetic component. In 2006 and 2007, major breakthroughs in genetic research identified six new genes associated with type 2 diabetes. Ten genes have now been positively confirmed as increasing the risk for type 2 diabetes: TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11, IGF2B2, CDKAL1, CDKN2A, CDKN2B, and FTO.

Most of these genes play a role in regulating insulin action, including the processes that occur in the pancreas’ insulin-producing beta cells. The FTO gene increases the risk for obesity, which itself is a risk factor for type 2 diabetes. These genes appear to cluster around three genetic regions that include a number of chromosomes. Scientists hope that future research will help uncover how genes influence the progression from pre-diabetes to diabetes, and how lifestyle and medical intervention may help delay or prevent this process.

Risk Factors

Nearly 21 million Americans have diabetes; up to 95% of these cases are type 2. In addition, 26% of Americans age 20 and older (and 40% of Americans age 65 and older) have impaired fasting glucose, a pre-diabetes condition that increases the risk for diabetes. According to the American Diabetes Association, 54 million people have pre-diabetes, bringing a total of 75 million Americans who either have diabetes or are at risk of developing it.

Historically, type 2 diabetes usually developed after the age of 40, but it is now also increasing in children. The prevalence of diabetes in the U.S. has increased by 5% each year since 1990, and experts believe that obesity is the major factor behind this dramatic growth rate. Given the current epidemic of obesity, experts estimate that over a third of all people born in 2002 will eventually develop diabetes. Furthermore, the dramatic increase in diabetes is occurring worldwide as American lifestyles become global. Evidence strongly suggests that healthy lifestyles can prevent most cases of type 2 diabetes. People with pre-diabetes can substantially lower their risk by losing weight through diet and exercise.

Healthy adults age 45 and older should get tested for diabetes. Patients who are younger than age 45 and who are overweight or have other risk factors should also ask their doctors about testing. According to the National Institutes of Health, the following are major risk factors for diabetes and pre-diabetes:

Age 45 or older
Family history of diabetes
Overweight
Inactive lifestyle (exercise less than 3 times a week)
African-American, Hispanic/Latin American, American Indian and Alaska Native, Asian-American, or Pacific Islander ethnicity
High blood pressure (140/90 mm/Hg or higher)
HDL (“good”) cholesterol less than 35 mg/dL or triglyceride level 250 mg/dL or higher
Have had diabetes during pregnancy (gestational diabetes) or have given birth to a baby that weighed more than 9 pounds
Polycystic ovary syndrome (metabolic disorder that affects female reproductive system
Acanthosis nigricans (dark, thickened skin around neck or armpits)
History of disease of blood vessels to the heart, brain, or legs
Diabetes test history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)

Obesity is the number one risk factor for type 2 diabetes. It is estimated that 80 - 95% of the current dramatic increases in type 2 diabetes are due to obesity. Excess body fat appears to play a strong role in insulin resistance, but the way the fat is distributed is also significant. Weight concentrated around the abdomen and in the upper part of the body (apple-shaped) is associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Waist circumferences greater than 35 inches in women and 40 inches in men have been specifically associated with a greater risk for heart disease and diabetes. (People with a "pear-shape" -- fat that settles around the hips and flank -- appear to have a lower risk for with these conditions.) However, obesity does not explain all cases of type 2 diabetes. It is also common among people in countries where weights tend to be low, such as Asia or India.

Metabolic Syndrome. A set of conditions referred to as metabolic syndrome (also called Syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome.

Between 25 - 33% of patients with type 2 diabetes have family members with diabetes. Having a first-degree relative with the disease poses a 40% risk of developing diabetes. One study reported that people with diabetic family histories have a higher risk for developing the disease at an earlier stage and with more severe features. Because families share many lifestyle features (eating and exercise habits) it is difficult to determine when genetics or environment play the major role. When clusters of type 1 and type 2 diabetes appear within families, genetic factors should be strongly suspected.

The risk for type 2 diabetes varies among population groups. Diabetes also seems to pose higher or lower risks for specific complications among ethnic groups. Genetic and socioeconomic factors, or both, seem to be involved in some ethnic differences, but in most cases the observed increase in ethnic groups in Americans is due to changes in traditional lifestyles.

African-Americans. African-American men have twice the risk of developing type 2 diabetes as Caucasian men. African-Americans with diabetes are also at higher risk for amputations than Caucasians. This is most likely due to a higher incidence of high blood pressure and smoking as well as poorer health care in African-Americans. Genetic factors may also play a role. For example, there is some evidence that African-Americans process insulin in the liver differently from Caucasians, which may make them more susceptible to diabetes when other risk factors are present.
Native Americans. The Pima tribe in Arizona has an incidence of type 2 diabetes that is 19 times higher than that of the white population. The risk for diabetic complications among young Pima adults is also very high. Other Native American tribes in North America are also at high risk for type 2 diabetes. The association between diet and diabetes among this population remains critical, however, in assessing the reason for their higher risk. For example, Pimas who live in Mexico exercise more and eat less fat (but consume more calories) than Pima tribes in Arizona. Mexican Pimas have a prevalence of diabetes of only 6%, while half of their Arizona Pima neighbors have diabetes.
Hispanic Americans. The rate of type 2 diabetes is also very high among Mexican-Americans, approximately double that for Caucasians. This group may also be at higher risk for heart problems than other ethnic groups with diabetes.
Asian-Americans. Overweight Asian-Americans and Pacific Islanders are at increased risk for developing type 2 diabetes. The risk for some Asian ethnic groups (such as Native Hawaiians and Filipinos) is twice that of Caucasians.

Smoking increases the risk for diabetes. According to a 2006 study, smokers are more than twice as likely to develop diabetes as people who have never smoked. Another 2006 study found that exposure to second-hand cigarette smoke also increases the risk for diabetes in non-smokers.

Low birth weight is now a recognized risk factor for type 2 diabetes and heart disease in adulthood. The reasons are unclear, although studies suggest it may represent a genetic factor. Studies have observed that babies of fathers with type 2 diabetes and of women who later developed type 2 diabetes tend to weigh less than babies of parents without diabetes. Such studies suggest that some parents may have some specific gene that affects insulin factors, putting both themselves and their children at risk for future diabetes. Theoretically, such a gene might also affect insulin factors in the developing fetus, causing low birth weight. (Of note, mothers of very high-weight babies are also at risk for diabetes -- although in these cases it is most often associated with gestational diabetes.)

Obesity-Related Type 2 Diabetes in Children. Until recent years, diabetes in children was almost always type 1 (an autoimmune disease). Between 1982 - 1994, however, the incidence of type 2 diabetes in children increased 10-fold. By 1996, a study reported that a third of all new diabetes cases in children were type 2. This increase parallels the rising epidemic in childhood obesity that has occurred both in the U.S. and worldwide, notably Europe and Japan. In some areas of Japan, type 2 diabetes has now become the dominant form of diabetes in children and adolescents. Obesity in children is also related to abnormalities in cholesterol, blood pressure, and insulin levels in adults. Administering glucose tolerance tests in overweight children may be helpful in identifying those at high risk for diabetes.

Maturity-Onset Diabetes in Caucasian Youth. Maturity-onset diabetes in youth (MODY) is a rare genetic form of type 2 diabetes that develops only in Caucasian teenagers. It accounts for 2 - 5% of type 2 cases. (This form of type 2 diabetes is not associated with obesity.)

An estimated 5% of pregnant women develop a form of type 2 diabetes, usually temporary, in their third trimester called gestational diabetes.

Gestational diabetes is diabetes that first appears during pregnancy. It usually develops during the third trimester of pregnancy. After delivery, blood sugar (glucose) levels generally return to normal, although 25% of these women develop type 2 diabetes within 15 years.

Who Gets Gestational Diabetes? Estimates for the prevalence of gestational diabetes are generally about 4%. Some studies, however, have suggested significantly higher rates. In one German study, 13% of pregnant women were diagnosed with this form of diabetes, including many who did not have any risk factors.

A pregnant woman's risk factors include:

Family history of diabetes
African-American, Hispanic, Asian, or Pacific Islander ethnicity
Overweight
Older than 25 years
Gestational diabetes with past pregnancy
Having given birth to a child weighing over 9 pounds
Diagnosis of pre-diabetes

Who Should Be Tested for Gestational Diabetes? A number of expert groups recommend that all pregnant women be tested for gestational diabetes between their 24th - 28th week. Pregnant women at high risk for diabetes should be tested earlier. The only women who do not need to be tested are those at very low risk. Generally they have the following characteristics:

Under 25 years old
Normal weight
No first-degree relatives with diabetes
Not belonging to high-risk ethnic groups

Effect of Diabetes on the Fetus. Because glucose crosses the placenta, a woman with diabetes can pass high levels of blood glucose to the fetus. In response, the fetus secretes high level of insulin. Studies indicate that such conditions may affect the developing fetus as soon as it is conceived, placing the unborn child at risk for:

Excessive fetal weight gain, which can lead to complications during delivery
Birth defects
Breathing problems and delayed lung development
Low blood sugar
Higher future risk for obesity and diabetes

Effect of Diabetes on the Pregnant Woman. In addition to endangering the fetus, diabetes also presents risks to the pregnant woman.

The most serious potential complications from gestational diabetes are high blood pressure during pregnancy, a condition called preeclampsia that is potentially dangerous. Because gestational diabetes increases the size of the fetus, it is also increases the likelihood that a woman will require a Cesarean delivery. Gestational diabetes also increases the risk that a woman will later develop type 2 diabetes.

How Is Gestational Diabetes Managed? Some suggestions for preventing complications include:

In most cases, increases in glucose levels can be managed with diet and exercise. Aerobic exercise before and during pregnancy may lower glucose levels and help protect women at risk or those who have gestational diabetes. (Any pregnant woman should check with her doctor before embarking on a vigorous exercise regimen.)
If a woman with gestational diabetes cannot control her glucose with lifestyle measures, she is usually given insulin.

The placenta provides the fetus with oxygen and nutrients and takes away waste, such as carbon dioxide, via the umbilical cord.

Polycystic Ovary Syndrome. Polycystic ovary syndrome (PCOS) is a condition that affects about 6% of women and results in the ovarian production of high amounts of androgens (male hormones), particularly testosterone. It appears to be an important cause of many menstrual disorders. Women with PCOS are at higher risk for insulin resistance, and about half of PCOS patients also have diabetes.

Click the icon to see an image of polycystic ovary syndrome.

Schizophrenia. While no definitive association has been established, research has suggested an increased background risk of diabetes among people with schizophrenia. In addition, many of the new generation of antipsychotic medications may elevate blood glucose levels. Patients taking antipsychotic medications (such as clozapine, olanzapine, risperidone, aripiprazole, quetiapine fumarate, ziprasidone) should receive a baseline blood glucose level test and be monitored for any increases during therapy.

Depression. According to a 2007 study, adults who have severe clinical depression may have a greater risk of developing type 2 diabetes than those who have never experienced depressive symptoms.

Hepatitis C. Patients with hepatitis C have a higher incidence of type 2 diabetes. The reasons for this are unclear.

Symptoms

Type 2 diabetes usually begins gradually and progresses slowly. Symptoms in adults include:

Excessive thirst
Increased urination
Fatigue
Blurred vision
Weight loss
In women, vaginal yeast infections or fungal infections under the breasts or in the groin
Severe gum problems
Itching
Erectile dysfunction in men
Unusual sensations, such as tingling or burning, in the extremities

Symptoms in children are often different:

Most children are obese or overweight
Increased urination is mild or even absent
Many children develop a skin problem called acanthosis, which is characterized by velvety, dark colored patches of skin

Screening Tests

There are no clear-cut guidelines for when to screen for diabetes. Some experts recommend that everyone over age 45 be tested regularly for diabetes, although others do not feel this necessary in people without symptoms or risk factors. In fact, early screening may identify some people with impaired glucose levels that would eventually normalize. Such people might be treated unnecessarily with medications that pose a risk for high blood sugar (hypoglycemia).

Still, given the risk for serious complications with diabetes and the potential value of early treatments, most experts recommend that all adults over 45 be screened and that younger adults be screened if they have one or more of the following conditions:

A weight that is 20% more than ideal body weight
Risk factors for heart disease (high blood pressure, unhealthy cholesterol levels -- especially for patients with low HDL cholesterol and high triglyceride levels
A close relative with diabetes
A high-risk ethnic group background
In women, having delivered a baby weighing over 9 pounds or having a history of gestational diabetes

Some experts recommend that children over age 10 should be tested for type 2 diabetes (even if they have no symptoms), if they are overweight and have at least two of the above mentioned risk factors.

Fasting Plasma Glucose. The fasting plasma glucose (FPG) test is the standard test for diabetes. It is a simple blood test taken after 8 hours of fasting. Results indicate:

FPG levels are considered normal up to 100 mg/dL (or 5.5 mmol/L).
Levels between 100 - 125 mg/dL (5.5 - 7.0 mmol/L) are referred to as impaired fasting glucose or pre-diabetes. These levels are considered to be risk factors for type 2 diabetes and its complications.
Diabetes is diagnosed when FPG levels are 126 mg/dL (7.0 mmol/L) or higher.

The FPG test is not always reliable, so a repeat test is recommended if the initial test suggests the presence of diabetes, or if the test is normal in people who have symptoms or risk factors for diabetes. For example, people who take the test in the afternoon and show normal results may actually have abnormal levels that would be revealed if they were tested in the morning.

A 2005 study suggested that even people with FPG levels in the high end of the normal range (high 90s) may be at increased risk for developing type 2 diabetes. Obesity further increases this risk. Patients with FPG levels in the upper 90s should strive to exercise and lose weight to help lower their FPG levels.

Glucose Tolerance Test. The oral glucose tolerance test (OGTT) is more complex than the FPG and may overdiagnose diabetes in people who do not have it. Some experts recommend it as a follow-up after FPG, if the latter test results are normal but the patient has symptoms or risk factors of diabetes. The test uses the following procedures:

It first uses an FPG test.
A blood test is then taken 2 hours later after drinking a special glucose solution.

The following results suggest different conditions:

OGTT levels are considered normal up to 140 mg/dL.
Levels between 140 - 199 mg/dL are referred to as impaired glucose tolerance or pre-diabetes.
Diabetes is diagnosed when OGTT levels are 200 mg/dL or higher.

Both the FPG and OGTT require that the patient not eat for at least 8 hours prior to the test.

Test for Glycated Hemoglobin. Tests for blood levels of glycated hemoglobin, also known as hemoglobin A1c (HbA1c), are not currently used for an initial diagnosis, but they are useful for determining the severity of diabetes. Some experts think this test can help predict complications in people who have FPG levels between 110 - 139, which are above normal but do not indicate full-blown diabetes.

The basis for its use as a diagnostic measurement in diabetes is as follows:

Hemoglobin is a protein molecule found in red blood cells. When glucose binds to it, the hemoglobin becomes modified, a process called glycosylation.
Glycosylation affects a number of proteins, and elevated levels of glycolated hemoglobin are strongly associated with complications of diabetes.
A glycated hemoglobin level of 1% above normal range identifies diabetes in 98% of patients. Normal HbA1c levels do not necessarily rule out diabetes, but if diabetes is present and levels are normal, the risk for complications is low.

The test is not affected by food intake so it can be taken at any time. A home test has been developed that might make it easier to measure HbA1c. In general, measurements suggest the following:

Normal HbA1c levels should be below 7%.
Levels of 11 - 12% glycolated hemoglobin indicate poor control of carbohydrates. High levels are also markers for kidney trouble.

Screening for Heart Disease. All patients with diabetes should be tested for hypertension and unhealthy cholesterol and lipid levels and given an electrocardiogram. For cholesterol, people with diabetes should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Blood pressure goals should be 130/80 mmHg or lower. Other tests may be needed in patients with signs of heart disease.

The electrocardiogram (ECG, EKG) is used extensively in the diagnosis of heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. Several different types of electrocardiogram exist.

Screening for Kidney Damage. The earliest manifestation of kidney damage is microalbuminuria, in which tiny amounts (30 - 300 mg per day) of protein called albumin are found in the urine. About 20% of type 2 patients show evidence of microalbuminuria upon diagnosis of diabetes. (However, not all people with type 2 diabetes eventually develop kidney disease.) Microalbuminuria typically shows up in patients with type 2 diabetes who have high blood pressure.

The American Diabetes Association recommends that people with diabetes receive an annual microalbuminuria urine test. Patients should also have their blood creatinine tested at least once a year. Creatinine is a waste product that is removed from the blood by the kidneys. High levels of creatinine may indicate kidney damage. A doctor uses the results from a creatinine blood test to calculate the glomerular filtration rate (GFR). The GFR is an indicator of kidney function; it estimates how well the kidneys are cleansing the blood.

Screening for Retinopathy. The American Diabetes Association recommends that patients with type 2 diabetes get an initial comprehensive eye exam by an ophthalmologist or optometrist shortly after they are diagnosed with diabetes, and once a year thereafter. (People at low risk may need follow-up exams only every 2 - 3 years.) The eye exam should include dilation to check for signs of retinal disease (retinopathy).

Screening for Neuropathy. All patients should be screened for nerve damage (neuropathy), including a comprehensive foot exam. Patients who have loss of sensation in their feet should be sure to have a foot exam every 3 - 6 months to check for ulcers or infections.

Screening for Thyroid Abnormalities. Thyroid function tests should be administered.

Treatment

Pre-diabetes precedes the onset of type 2 diabetes. People who have pre-diabetes have fasting blood glucose levels that are 100 - 125 mg/dL -- higher than normal, but not yet high enough to be classified as diabetes. (Pre-diabetes used to be referred to as “impaired glucose tolerance.”) Pre-diabetes greatly increases the risk for diabetes.

Treatment of pre-diabetes is very important. Research shows that lifestyle and medical interventions can help prevent, or at least delay, the progression to diabetes. While insulin-regulating drugs such as metformin (Glucophage) and acarbose (Precose) are sometimes prescribed, evidence indicates that lifestyle changes can be at least as effective as drug therapy. The most important lifestyle treatment for people with pre-diabetes is to lose weight through diet and regular exercise. Even a modest weight loss of 10 - 15 pounds can significantly reduce the risk of progressing to diabetes.

Because people with pre-diabetes have a higher risk for heart disease and stroke, diet and exercise are also very important for heart health, as is quitting smoking. It is also important to have your doctor check your cholesterol and blood pressure levels on a regular basis. Your doctor should also check your fasting blood glucose levels every 1 - 2 years.

The major treatment goals for people with type 2 diabetes are:

Treat all conditions that place the patients at risk for heart disease and stroke, which are the major killers of people with type 2 diabetes.
Control blood glucose levels. The goal is to achieve fasting blood glucose levels of less than 110 mg/dL and glycolated hemoglobin (HbA1c) levels of less than 7%. The objective is to reduce complications in small blood vessels and the nerve damage associated with diabetes.

An intensive multi-pronged approach is critical for reducing complications and improving survival rates in patients with diabetes. Intensive therapy includes:

Healthy lifestyle changes: Regular exercise; heart-healthy diet; quitting smoking.
Controlling blood sugar levels. Monitor blood sugar and hemoglobin HbA1C levels. Oral anti-hyperglycemic drugs such as metformin are first-line drug treatments. Insulin may eventually be needed.
Heart-protective drugs. These medications include various drugs to control high blood pressure (ACE inhibitors, diuretics, others) and cholesterol (statins, fibrates). Controlling high blood pressure is a proven factor in reducing mortality rates. Aspirin may help prevent blood clots and heart attack.

Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions. Treating children with type 2 diabetes depends on the severity of the condition at diagnosis. Metformin is approved for children. Formerly, only insulin was approved for treating children with diabetes.

Lifestyle Changes

A simple heart-healthy diet with weight control and exercise is important for people with pre-diabetes and may be sufficient for some people with type 2 diabetes. Some patients may be able to control their blood sugar with lifestyle measures and not need medication. Even for patients who do need to take drugs, lifestyle plays an essential role in controlling diabetes. Lifestyle changes can be difficult to initiate and sustain, however. Patients should surround themselves with a solid network of doctors, dietitians, family, and friends who understand both their condition and their needs.

Although there are many major dietary approaches for protecting health, experts generally agree on the following recommendations for heart protection:

Choose fiber-rich food (whole grains, legumes, nuts) as the main source of carbohydrates, along with a high intake of fresh fruits and vegetables. High fiber foods help improve blood glucose levels. Whole grain cereals, which are rich in both fiber and magnesium, may also help reduce the risk for diabetes.
Limit saturated fats (found mostly in animal products) to less than 7% of total daily calories and avoid trans fatty acids (found in hydrogenated fats and many commercial products and fast foods). Choose unsaturated fats (particularly omega-3 fatty acids found in vegetable and fish oils).
In selecting proteins, choose soy protein, poultry, and fish over meat. A 2006 study found that soy does not help improve cholesterol. However, experts still recommend it as a heart-healthy food choice.
Weight control, quitting smoking, and exercise are essential components of any diet program.

[See In-Depth Report #43: Heart-healthy diet.]

There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

Healthy eating habits along with good control of blood glucose are the basic goals, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Carbohydrates should provide 45 - 65% of total daily calories. The type and amount of carbohydrate are both important. Best choices are vegetables, fruits, beans, and whole grains. These foods are also high in fiber. Patients with diabetes should monitor their carbohydrate intake either through carbohydrate counting or meal planning exchange lists.
Fats should provide 25 - 35% of daily calories. Monounsaturated (olive, peanut, canola oils; avocados; nuts) and omega-3 polyunsaturated (fish, flaxseed oil, walnuts) fats are the best types. Limit saturated fat (red meat, butter) to less than 7% of daily calories. Choose nonfat or low-fat dairy instead of whole milk products. Limit trans-fats (hydrogenated fat found in snack foods, fried foods, commercially baked goods) to less than 1% of total calories.
Protein should provide 12 - 20% of daily calories, although this may vary depending on a patient’s individual health requirements. Patients with kidney disease should limit protein intake to less than 10% of calories. Fish, soy, and poultry are better protein choices than red meat.

[For detailed information, including diabetic exchange lists and carbohydrate counting, see In-Depth Report #42: Diabetes diet.]

Being overweight is the number one risk factor for type 2 diabetes. Even modest weight loss can help prevent type 2 diabetes from developing. It can also help control or even stop progression of type 2 diabetes in people with the condition and reduce risk factors for heart disease. Patients should aim to lose weight if their body mass index (BMI) is 25 - 29 (overweight) or higher (obese).

The American Diabetes Association recommends that patients aim for a small but consistent weight loss of ½ - 1 pound per week. Most patients should follow a diet that supplies at least 1,000 - 1,200 kcal/day for women and 1,200 - 1,600 kcal/day for men.

Unfortunately, not only is weight loss difficult to sustain, but many of the oral medications used in type 2 diabetes cause weight gain as a side effect. For obese patients who cannot control weight using dietary measures alone, weight-loss drugs, such as orlistat (Xenical) or sibutramine (Meridia), may be helpful. Orlistat may have specific benefits for people with diabetes. It may not only help achieve weight but also improve glucose, cholesterol, and lipid levels. In 2007, the FDA approved a non-prescription form of orlistat (alli). [See In-Depth Report #53: Obesity.]

Sedentary habits, especially TV watching, are associated with significantly higher risks for obesity and type 2 diabetes. Regular exercise, even of moderate intensity (such as brisk walking), improves insulin sensitivity and may play a significant role in preventing type 2 diabetes -- regardless of weight loss. An important study reported a 58% lower risk for type 2 diabetes in adults who performed moderate exercise for as little as 2.5 hours a week.

Aerobic Exercise. Aerobic exercise has significant and particular benefits for people with diabetes. Regular aerobic exercise, even of moderate intensity, improves insulin sensitivity. People with diabetes are at particular risk for heart disease, so the heart-protective effects of aerobic exercise are especially important. Moderate exercise protects the heart in people with type 2 diabetes, even if they have no risk factors for heart disease other than diabetes itself.

For improving glycemic control, the American Diabetes Association recommends at least 150 minutes per week of moderate-intensity physical activity (50 - 70% of maximum heart rate) or at least 90 minutes per week of vigorous aerobic exercise (more than 70% of maximum heart rate). Exercise at least 3 days a week, and do not go more than 2 consecutive days without physical activity.

Strength Training. Strength training, which increases muscle and reduces fat, is also helpful for people with diabetes who are able to do this type of exercise. The American Diabetes Association recommends performing resistance exercise three times a week. Build up to three sets of 8 - 10 repetitions using weight that you cannot lift more than 8 - 10 times without developing fatigue. Be sure that your strength training targets all of the major muscle groups.

Exercise Precautions. The following are precautions for all people with diabetes, both type 1 and type 2:

Because people with diabetes are at higher than average risk for heart disease, they should always check with their doctors before undertaking vigorous exercise. For fastest results, frequent high-intensity (not high-impact) exercises are best for people who are cleared by their doctors. For people who have been sedentary or have other medical problems, lower-intensity exercises are recommended.
Strenuous strength training or high-impact exercise is not recommended for people with uncontrolled diabetes. Such exercises can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet.

Patients who are taking medications that lower blood glucose, particularly insulin, should take special precautions before embarking on a workout program:

Monitor glucose levels before, during, and after workouts (glucose levels swing dramatically during exercise).
Avoid exercise if glucose levels are above 300 mg/dL or under 100 mg/dL.
Inject insulin in sites away from the muscles used during exercise; this can help avoid hypoglycemia.
Drink plenty of fluids before and during exercise; avoid alcohol, which increases the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates prior to exercise, but may need to take an extra dose of insulin after exercise (stress hormones released during exercise may increase blood glucose levels).
Wear good, protective footwear to help avoid injuries and wounds to the feet.
Some blood pressure drugs can interfere with exercise capacity. Patients who use blood pressure medication should consult their doctors on how to balance medications and exercise. Patients with high blood pressure should also aim to breathe as normally as possible during exercise. Holding the breath can increase blood pressure.

[See In-Depth Report #29: Exercise.]

According to the American Diabetes Association, people with diabetes should aim for preprandial (before eating) plasma glucose levels of 90 - 130 mg/dL and postprandial (after eating) plasma glucose levels less than 180 mg/dL. Hemoglobin A1C levels should be less than 7%.

Measuring Blood Glucose. In patients being treated with insulin or insulin-producing or sensitizing drugs, it is important to monitor blood glucose levels carefully to avoid hypoglycemia. Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Blood glucose levels are generally more stable in type 2 diabetes than in type 1, so experts usually recommend measuring blood levels only once or twice a day. For patients who have become insulin-dependent, more intensive monitoring is necessary. Usually, a drop of blood obtained by pricking the finger is applied to a chemically treated strip. The glucose level is read on a standard meter or a small, portable digital display device. For patients who have trouble controlling hypoglycemia (low blood sugar) or fluctuating blood sugar levels, continuous glucose sensor monitors are also available. In 2007, the FDA approved the STS-7 System, which continuously measures glucose levels for up to 7 days through a sensor inserted beneath the skin of the abdomen. Continuous glucose sensor monitors do not replace fingerstick glucose meters and test strips, but are used in combination with them. [See In-Depth Report #9: Diabetes - type 1.]

Measuring Hemoglobin A1C. Hemoglobin A1c (also called HbA1c , HA1c, or A1C) is measured periodically every 2 - 3 months to determine the average blood-sugar level over the lifespan of the red blood cell. Normal A1C levels should be below 7%. Home tests are also available for measuring A1C.

To monitor the amount of glucose within the blood a person with diabetes should test their blood regularly. The procedure is quite simple and can often be done at home.

Some research suggests that not getting enough sleep may impair insulin use and increase the risk for obesity. More research is needed, but it is always wise to improve sleep habits.

Medications

The American Heart Association now recommends that patients should aim for the following test results for intensive control of glucose levels:

Fasting plasma glucose concentrations below 110 mg/dL.
Glycolated hemoglobin (HbA1c) levels of less than 7%. Controlling HbA1c is the most important factor for reducing the risk of complications in patients with diabetes. According to one 2000 study, a 1% reduction in people with elevated glycolated hemoglobin levels lowers the risk for complications by 21%.

Evidence clearly supports strict glycemic control for reducing complications in the nervous system and blood vessels that occur in both type 1 and type 2 diabetes. Research shows that tight glucose control can help prevent heart disease and complications.

Managing risk factors for heart disease and stroke, particularly strict control of blood pressure, may be more important for improving survival than strict control of blood glucose levels for some patients. Such goals also seem to be more attainable for many patients with type 2 diabetes.

Oral Anti-Hyperglycemic Drugs. Many oral anti-hyperglycemic drugs are available to help patients with type 2 diabetes control their blood sugar levels. Most of these drugs are aimed at using or increasing sensitivity to the patient's own natural stores of insulin. Metformin is the only drug to date that achieves lower mortality rates. Oral type 2 diabetes drugs include:

Biguanides (metformin). Metformin increases tissue sensitivity to available insulin. Metformin also has beneficial effects on cholesterol, blood pressure, and clotting factors. It does not cause weight gain or hypoglycemia. Diarrhea and digestive problems are the most common side effects. Metformin produces lower mortality rates than other drugs, including insulin, and should be considered as first-line therapy for most patients with type 2 diabetes.
Sulfonylureas (glyburide, glipizide, glimepiride, repaglinide). Stimulate insulin secretion but can cause hypoglycemia more than other drugs.
DPP-4 inhibitors (sitagliptin). Also called gliptins, DPP-4 inhibitors were first approved in 2006 and are the newest class of oral diabetes drugs. Like metformin, they do not cause weight gain and have low risks for hypoglycemia.
Meglitinides (repaglinide, nateglinide). Stimulate insulin secretion. These newer drugs are better than sulfonylureas in controlling glucose spikes after meals.
Thiazolidinediones (pioglitazone and rosiglitazone). Reduce insulin resistance. These drugs improve cholesterol levels and may reduce the risk for blood clots. However, they can cause swelling from fluid build-up, which can worsen heart failure or even precipitate it. They may also injure the liver.
Alpha-glucosidase inhibitors (acarbose and miglitol). Slow intestinal absorption of carbohydrates. Have only modest effects on diabetes and have gastrointestinal side effects. Can slightly raise HDL (“good”) cholesterol levels.
Combinations of these drugs, particularly with metformin, are often used to increase effectiveness.

A 2007 review in the Annals of Internal Medicine compared these various classes of medications. The review found that older drugs -- such as metformin and sulfonylureas -- are less expensive than and work as well as newer diabetes drugs. In particular, the review cited metformin as a safe and effective drug because it does not cause weight gain or too-low blood sugar. Metformin can also help lower LDL (“bad”) cholesterol.

Injectable Anti-Hyperglycemic Drugs. In 2005, the FDA approved two new injectable drugs to help patients improve blood sugar control:

Exenatide (Byetta). Exenatide is the first drug in a new class of drugs called incretin mimetics. It lowers blood glucose levels by increasing insulin secretion. Exenatide is used in combination with oral antihyperglycemics, such as metformin or a sulfonylurea drug.
Pramlintide (Symlin). Pramlintide is a first-in-class drug that is a synthetic form of the hormone amylin. The drug is meant for patients who take insulin but still have difficulty controlling their glucose levels.

Insulin Replacement. Insulin replacement may be required when natural insulin reserves are depleted. It is typically started in combination with an oral drug. Eventually, some patients may need to go on full insulin replacement. In addition to injectable forms of insulin, an inhaled insulin product (Exubera) is now available.

Metformin (Glucophage) is a biguanide, which works by reducing glucose production in the liver and by making tissues more sensitive to insulin. Many experts recommend it as a first choice for most patients with type 2 diabetes who are insulin resistant, particularly if they are overweight. Metformin achieves lower mortality rates from diabetes and all causes than other drugs. In one comparison study, it achieved the lowest mortality rates (8%) compared to insulin (28%), a sulfonylurea (16%), and a thiazolidinedione (14%). Combinations with insulin-secreting drugs, other insulin-sensitizing drugs, or insulin itself are particularly effective.

Metformin does not cause hypoglycemia or add weight, so it is particularly well-suited for obese patients with type 2 diabetes. (In some studies, in fact, patients lost weight.) Metformin also appears to have beneficial effects on cholesterol and lipid levels and may help protect the heart. Some research has suggested that it significantly reduces the risk for heart attack. It is also the first choice for children who need oral drugs and is proving to be very effective for women with polycystic ovary syndrome and insulin resistance.

Side Effects. Side effects include:

A metallic taste
Gastrointestinal problems, including nausea, and diarrhea
Interference with absorption of vitamin B12 and folic acid, (which are important for protection against heart disease)
Rare reports of lactic acidosis, a potentially life-threatening condition, particularly in people with risk factors for it. Major studies, however, found no greater risk with metformin than with any of the other drugs used for type 2 diabetes.

Certain people should not use this drug, including anyone with heart failure or kidney or liver disease. It is rarely suitable for adults over age 80.

Sulfonylureas are oral drugs that stimulate the pancreas to release insulin. They are also first-line oral drugs. For adequate control of blood glucose levels, the drugs should be taken only 20 - 30 minutes before a meal. A number of brands are available, including chlorpropamide (Diabinese), tolazamide (Tolinase), acetohexamide (Dymelor), glipizide (Glucotrol), tolbutamide (Orinase), glyburide (Micronase), glimepiride (Amaryl), and repaglinide (Prandin).

Most patients can take sulfonylureas for 7 - 10 years before they lose effectiveness. Combinations with small amounts of insulin or with other oral anti-hyperglycemic drugs (such as metformin or a thiazolidinedione) may extend their benefits. A combination of glyburide and metformin in one pill (Glucovance) is available. Glucovance may be particularly beneficial for patients with unhealthy cholesterol levels and poor control of their blood sugar levels. Some doctors recommend the combination as first-line treatment.

An encouraging 2000 study of patients with severe type 2 diabetes reporting that combinations of insulin with either chlorpropamide or glipizide achieved better glucose control over the long term than insulin alone.

Side Effects and Complications. In general, sulfonylureas should not be used by women who are pregnant or nursing or by individuals who are allergic to sulfa drugs. Side effects may include:

Weight gain (some sulfonylureas, such as glimepiride, may produce less weight gain than others)
Water retention
Although sulfonylureas pose a lower risk for hypoglycemia than insulin does, the hypoglycemia produced by sulfonylureas may be especially prolonged and dangerous. The newer sulfonylureas, such as glimipiride, have much less risk of hypoglycemia than older sulfonylureas.
Some sulfonylureas may pose a slight risk for cardiac events.

Sulfonylureas interact with many other drugs, and patients should be sure to inform their doctor of any medications they are taking, including alternative or over-the-counter drugs.

Meglitinides stimulate beta cells to produce insulin. They include repaglinide (Prandin), nateglinide (Starlix), and mitiglinide. These drugs are rapidly metabolized and short-acting. If taken before every meal, they actually mimic the normal effects of insulin after eating. Patients, then, can vary their meal times with this drug. (Nateglinide appears to work more quickly and is shorter-acting than repaglinide). These drugs may be particularly helpful in combination with metformin or other drugs. They may also be a good choice for people with potential kidney problems.

Side Effects. Side effects include diarrhea and headache. As with the sulfonylureas, repaglinide poses a slightly increased risk for cardiac events. (Newer drugs, such as nateglinide, may pose less of a risk.) People with heart failure or liver disease should use them with caution and be monitored.

Thiazolidinediones, also known as peroxisome proliferator-activated receptor (PPAR) agonists, include rosiglitazone (Avandia) and pioglitazone (Actos). They improve insulin sensitivity by activating certain genes involved in fat synthesis and carbohydrate metabolism. These drugs are usually taken once or twice per day; however, it may take several days before the patient notices any results from them and several weeks before they take full effect. Thiazolidinediones are usually taken in combination with other oral drugs or insulin.

Side Effects. Thiazolidinediones can have serious side effects. They tend to increase fluid-build up, which can cause or worsen heart failure in some patients. Combinations with insulin increase the risk. They should not be used by patients with existing heart failure and should be used cautiously in those with risk factors for heart failure.

In 2007, a study published in the New England Journal of Medicine (NEJM) raised serious concerns that rosiglitazone may increase the risk of heart attack. The study reviewed 42 clinical trials of rosiglitazone. Results suggested that patients who took rosiglitazone were 43% more likely to have a heart attack, and 64% more likely to die from overall heart causes, than patients with diabetes who did not take the drug. A subsequent interim analysis in the NEJM found that while rosiglitazone was definitely associated with increased risk of heart failure, the data were insufficient to determine if the drug increases heart attack risk. The FDA has concluded that rosiglitazone may increase the risk of heart attack and will likely restrict its use. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Patients who take rosiglitazone, especially those who have heart disease or who are at high risk for heart attack, should discuss their treatment options with their doctors.

Thiazolidinediones may cause more weight gain than other diabetes medications or insulin. Any patient who experiences sudden weight gain, water retention, or shortness of breath should immediately call their doctor. These drugs have also been linked to increased risks for bone fracture.

There have been rare reports of rosiglitazone causing or worsening diabetic macular edema. This is an eye condition associated with diabetic retinopathy that causes swelling in the macular area of the retina. Symptoms include blurred vision and decreased color sensitivity. Most patients who had this side effect also had swelling in the feet and legs (peripheral edema). The condition resolved or improved when patients stopped taking the drug.

Thiazolidinediones can also cause liver damage. Patients who take these drugs should have their liver enzymes checked regularly.

Alpha-glucosidase inhibitors, including acarbose (Precose, Glucobay) and miglitol (Glyset), reduce glucose levels by interfering with the absorption of starch in the small intestine. Acarbose tends to lower insulin levels after meals, a particular advantage, since higher levels of insulin after meals are associated with an increased risk for heart disease. Some evidence suggests that early use of these drugs may reduce heart risk factors, including high blood pressure. A 2002 study of acarbose suggested that these drugs may possibly delay the development of type 2 diabetes in high-risk individuals. Alpha-glucosidase inhibitors are not as effective alone as other single oral drugs, but combinations, such as with metformin, insulin, or a sulfonylurea, increase their effectiveness.

Side Effects. These medications need to be taken with meals. Unfortunately, about a third of patients stop taking the drug because of flatulence and diarrhea, particularly after high-carbohydrate meals. The drug may also interfere with iron absorption.

Alpha-glucosidase inhibitors do not cause hypoglycemia when used alone, but combinations with other drugs do. In such cases, it is important that the patient receive a solution that contains glucose or lactose, not table sugar. This is because acarbose inhibits the breakdown of complex sugar and starches, which includes table sugar.

Incretin mimetics belong to a new class of drugs that help improve blood sugar control. Incretins include glucagon-like peptide-1 (GLP-1) inhibitors and DDP-4 inhibitors.

In 2005, the FDA approved exenatide (Byetta), the first GLP-1 inhibitor drug. Exenatide is an injectable drug that is a synthetic version of the hormone found in the saliva of the Gila monster, a venomous desert lizard. Exenatide is injected twice a day, 1 hour before morning and evening meals. It is prescribed for patients with type 2 diabetes who have not been able to control their glucose with metformin or a sulfonylurea drug. It can be taken in combination with these drugs or alone.

Side Effects. Exenatide stimulates insulin secretion only when blood sugar levels are high and so has less risk for causing low blood sugar (hypoglycemia) when it is taken alone. However, the risk for hypoglycemia increases when exenatide is taken along with a sulfonylurea drug. There does not appear to be a risk for hypoglycemia when exenatide is used along with metformin. Other side effects may include nausea, vomiting, and diarrhea.

A 2005 study compared exenatide to insulin for improving glucose control in patients taking metformin and a sulfonylurea. Both insulin and exenatide worked well for glucose control. Patients lost weight with exenatide and gained weight with insulin. However, patients who received exenatide had significantly more problems with nausea, vomiting, and diarrhea than those who received insulin.

Dipeptidyl peptidase-4 (DPP-4) inhibitors, also called gliptins, are the second class of incretin drugs. In October 2006, the FDA approved the first DPP-4 inhibitor -- sitagliptin (Januvia). It can be used alone or in combination with metformin or a thiazolidinedione drug. In April 2007, the FDA approved Janumet, which combines sitagliptin with metformin in one pill. Other DPP-4 drugs being studied include vildagliptin (Galvus) and saxagliptin.

DPP-4 inhibitors work in a similar way to GLP-1 inhibitors. However, unlike exenatide, which is given by injection, DPP-4 inhibitor drugs are taken as pills by mouth.

Like exenatide, DPP-4 inhibitors do not cause weight gain, have low risks for hypoglycemia, and have few severe side effects. The most common side effects include upper respiratory tract infection, sore throat, and diarrhea.

Insulin replacement is the best treatment for strict control of blood glucose and is required once natural insulin reserves are depleted. Because type 2 diabetes is progressive, most patients eventually require insulin, typically starting it in combination with an oral anti-hyperglycemic drug. However, when a single oral drug fails to control blood sugar it is not clear whether it is better to add insulin replacement or to add a second or third oral drug.

Some experts advocate using insulin as early as possible for optimal control. However, in patients who still have insulin reserves, there is concern that extra natural insulin will have adverse effects. Low blood sugar (hypoglycemia) and weight gain are the main side effects of insulin therapy. Some research suggests that insulin may also cause heart complications. A 2006 study reported that insulin therapy increases the risk of developing high blood pressure (hypertension). It is still not clear if insulin replacement improves survival rates compared to oral drugs, notably metformin.

One approach is to combine insulin with metformin, which achieves blood glucose control without added weight gain. Newer forms of insulin analogues, such as glargine, may be especially helpful for people with type 2 diabetes and reduce the risk for hypoglycemia.

Fortunately, studies to date have not reported any adverse cardiac effects in patients with type 2 diabetes who take insulin. In fact, insulin has been associated, in some cases, with improvement in heart risk factors. More research is needed to clarify these important issues.

Forms of Insulin. Experts are working toward administering insulin so that it closely mimics the daily pattern of insulin, which responds to blood sugar levels by surging after meals and then falling to a steady base level afterward. To achieve this, doctors may use two insulin types:

Fast-Acting Insulins for Surges. Insulin lispro and aspart are fast-acting insulins. They mimic insulin's response to food intake. They are taken before meals, and their short action reduces the risk for hypoglycemia afterward.
Slower Insulins for Base Levels. Intermediate forms (including NPH and lente) and long-acting forms (glargine, ultralente) were developed to provide a steady level of insulin throughout the day. To date, glargine (Lantus) seems to be the most successful in achieving this goal in type 2 diabetes.

In 2006, the FDA approved the first non-injected form of insulin. Exubera is an inhaled form of insulin. It is approved for adults but should not be used by patients who smoke or have quit smoking within the past 6 months. Patients with asthma, bronchitis, or emphysema should also not use inhaled insulin. Clinical trials indicate that Exubera can provide sustained blood sugar control over a 2-year period. Patients in the trials who took Exubera experienced half as much weight gain as those who took injected insulin. Scientists are also developing other types of non-injected insulin, including spray formulas.

In a 2005 trial, Exubera improved blood sugar control when it was added to or substituted for combination oral drug therapy (sulphonylurea and thiazolidenedione). However, as with other forms of insulin, Exubera caused more hypoglycemia and weight gain than the oral anti-hyperglycemic drugs.

Pramlintide (Symlin) is a new type of injectable drug that may help patients who take insulin but still need better blood sugar control. The FDA approved this drug in 2005. Pramlintide is a synthetic form of amylin, a hormone that is related to insulin. Pramlintide is used in combination with insulin to lower blood sugar levels in the 3 hours after meals.

[See In-Depth Report #9: Diabetes - type 1.]

Sodium Glucose Uptake Transporter 2 (SGLT-2) Inhibitors. SGLT-2 inhibitors are a new class of drug being investigated for treatment of type 2 diabetes. Preliminary trials for two of these drugs, dapagliflozin and serglifozin, have shown promising results in helping improve blood glucose control. The drugs are being tested in combination with metformin.

Various fraudulent products are often sold on the Internet as “cures” or treatments for diabetes. These dietary supplements have not been studied or approved. In 2006, the FDA and Federal Trade Commission (FTC) launched a crackdown on these scams. The FDA and FTC warn patients with diabetes not to be duped by bogus and unproven remedies.

Long-Term Complications

Patients with diabetes have higher mortality rates than people who do not have diabetes regardless of sex, age, or other factors. Heart disease and stroke are the leading causes of death in these patients. All lifestyle and medical efforts should be made to reduce the risk for these conditions.

People with type 2 diabetes are also at risk for nerve damage (neuropathy) and abnormalities in both small and large blood vessels (vascular injuries) that occur as part of the diabetic disease process. Such abnormalities produce complications over time in many organs and structures in the body. Although these complications tend to be more serious in type 1 diabetes, they still are of concern in type 2 diabetes. All people with diabetes should aim for fasting blood glucose levels of less than 110 mg/dL and hemoglobin HbA1C of less than 7%.

There are two important approaches to preventing complications from diabetes:

Intensive control of blood glucose and keeping glycosylated hemoglobin (HbA1c) levels below 7%. Tight blood glucose and HbA1c control can prevent complications due to vascular (blood vessel) abnormalities and nerve damage (neuropathy) that can cause major damage to organs, including the eyes, kidneys, and heart.
Managing risk factors for heart disease. Control of blood glucose also helps the heart, but its benefits occur over time. It is very important that people with diabetes control blood pressure, cholesterol levels, and other factors associated with heart disease.

Heart attacks account for 60% and strokes for 25% of deaths in patients with diabetes. Diabetes affects the heart in many ways:

Both type 1 and 2 diabetes speed the progression of atherosclerosis (hardening of the arteries). Diabetes can adversely affect blood lipid levels by lowering HDL ("good cholesterol") and increasing triglycerides. This can lead to coronary artery disease, heart attack, or stroke. According to a 2007 study, the risk of stroke doubles within 5 years of type 2 diabetes diagnosis.
Impaired nerve function (neuropathy) associated with diabetes also causes heart abnormalities. Some experts estimate that the mortality rates from neuropathy-related heart conditions range between 15 - 53%.
Women with diabetes are at particularly high risk for heart problems. A 2007 study indicated that while progress has been made in reducing mortality rates among men with diabetes, women with diabetes continue to face a high risk of death from heart disease and overall causes.

Tight blood sugar control may help protect blood vessels and reduce the risk for blood clotting. It is still not known whether intensive control will have a major protective effect on the heart, however. People with diabetes must be sure to use other measures as well to protect the heart.

Aspirin for Reducing the Risk for Blood Clots. Taking a daily aspirin (75 - 162 mg/day) reduces the risk for blood clotting and may help protect against heart attacks and heart disease. In a 2000 study, low-dose aspirin was associated with a 30% lower risk for death from heart disease in adults with type 2 diabetes.

Controlling Blood Pressure. Strict control of blood pressure is critical for preventing complications of diabetes and has proven to improve survival rates. Patients should strive for blood pressure levels of less than 130/80 mm Hg (systolic/diastolic). (Controlling systolic pressure may be especially important for reducing the risk for kidney complications.)

Dozens of anti-hypertensive drugs are available. Most fall into the following categories:

Diuretics rid the body of extra sodium (salt) and water. There are three main types of diuretics: Potassium-sparing, thiazide, and loop.
Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin, a chemical that causes arteries to narrow.
Angiotensin-receptor blockers (ARBs) block angiotensin.
Beta-blockers block the effects of adrenaline and ease the heart’s pumping action.
Calcium-channel blockers (CCBs) decrease the contractions of the heart and widen blood vessels.

The American Diabetes Association (ADA) recommends any of these classes of drugs as first-line treatment for hypertension. New research suggests, however, that beta-blockers are less effective at preventing strokes and heart attacks than other types of blood pressure medications. Many patients require more than one type of drug to control blood pressure. For patients with diabetes who have microalbuminuria, the ADA strongly recommends ACE inhibitors or ARBs. Microalbuminuria is an accumulation of protein in the blood, which can signal the onset of kidney disease (nephropathy).

Anti-hypertensive drugs that block or reduce angiotensin are the first option for many people with diabetes. Angiotensin is a natural chemical that influences all aspects of blood pressure control and also interferes with insulin's normal metabolic signaling. In fact, angiotensin may be the common factor linking diabetes and high blood pressure.

The 2005 landmark Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicated that a thiazide-type diuretic works as well as an ACE inhibitor or CCB for patients with diabetes and high blood pressure. Compared with ACE inhibitors or CCBs, diuretics appeared to be better at lowering systolic blood pressure and preventing heart failure. In addition, the trial suggested that diuretics are especially helpful for African-Americans, by offering greater protection than ACE inhibitors or CCBS in preventing strokes.

Several 2006 studies suggested that anti-hypertensive drugs may increase the risk of developing diabetes. One study found more risk for thiazide diuretics and beta-blockers than ACE inhibitors and CCBs. Another study indicated that the ACE inhibitor ramipril had a lower risk of causing diabetes in African-Americans than a CCB or beta-blocker. A 2007 review in the Lancet also found a higher risk for new-onset diabetes with beta-blockers and diuretics, a medium risk with CCBs, and the lowest risk with ARBs and ACE inhibitors.

Research in this subject is important for patients with pre-diabetes who have high blood pressure. Results of future research may help doctors decide which treatment is most appropriate for patients with high blood pressure who are at high risk for diabetes. [See In-Depth Report #14: High blood pressure.]

Improving Cholesterol and Lipid Levels. Abnormal cholesterol and lipid levels are common in diabetes. High LDL (“bad”) cholesterol should always be lowered, but people with diabetes also often have additional harmful imbalances including low HDL (“good”) cholesterol and high triglycerides. Patients should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL and triglyceride levels below 150 mg/dL. Patients with diabetes and existing heart disease should strive for even lower LDL levels; the American Diabetes Association recommends LDL levels below 70 mg/dL for these patients.

Statins are the best cholesterol-lowering drugs. They include atorvastatin (Lipitor), lovastatin (Mevacor, generics), pravastatin (Pravachol), simvastatin (Zocor, generics), fluvastatin (Lescol), and rosuvastatin (Crestor). These drugs are very effective for lowering LDL cholesterol levels. Recent studies indicate that aggressive high-dose statin therapy may be an important treatment approach for high-risk patients who need to substantially lower their LDL levels. A 2006 study found that patients with diabetes and heart disease who were treated with 80 mg daily of atorvastatin had a 25% lower risk of heart attack and stroke than patients who received the standard 10 mg daily dose.

The primary safety concern with statins has involved myopathy, an uncommon condition that can cause muscle damage and, in some cases, muscle and joint pain. A specific myopathy called rhabdomyolysis can lead to kidney failure. People with diabetes and risk factors for myopathy should be monitored for muscle symptoms

Although lowering LDL is beneficial, statins are not as effective as other medications -- such as fibrates, niacin, ezetimbe, or bile acid sequesters -- in addressing HDL and triglyceride imbalances. This is a common problem in type 2 diabetes. Combinations of statins with one of these drugs may be helpful for people with diabetes who have heart disease, low HDL, and near-normal LDL levels. Although combinations of statins and fibrates or niacin increase the risk of myopathy, both combinations are considered safe if used with extra care. Research presented at the 2007 annual meeting of the American Diabetes Association suggested that statins and fibrates may also help reduce the risk of developing peripheral neuropathy, the diabetes-associated nerve damage that can lead to loss of sensation in the feet.

Gemfibrozil (Lopid) and fenofibrate (Tricor) are usually the first choice for fibrate drugs. Niacin has the most favorable effect on raising HDL and lowering triglycerides of all the cholesterol drugs. However, about 30% of patients who take high-dose niacin experience increased blood glucose levels. Moderate doses of niacin can achieve lipid control without causing serious blood glucose problems. [See In-Depth Report #23: Cholesterol.]

Kidney disease (nephropathy) is a very serious complication of diabetes. With this condition, the tiny filters in the kidney (called glomeruli) become damaged and leak protein into the urine. Over time this can lead to kidney failure. Urine tests showing microalbuminuria (small amounts of protein in the urine) are important markers for kidney damage.

Prevention and Treatment of Nephropathy. Tight control of blood sugar and blood pressure is essential for preventing the onset of kidney disease. Long-term studies report that strict control of these two conditions produces a 60% reduction in new cases of nephropathy and a delay in progression of the disease. ACE inhibitors and ARBs, two classes of blood pressure medications, are very helpful for preventing or slowing the progression of diabetic kidney disease.

A doctor may recommend a low-protein diet for patients whose kidney disease is progressing despite tight blood sugar and blood pressure control. Protein-restricted diets can help slow disease progression and delay the onset of end-stage renal disease (kidney failure). However, patients with end-stage renal disease who are on dialysis generally require higher amounts of protein. [See In-Depth Report #42: Diabetes diet.]

Diabetic nephropathy occurs in about 20 - 40% of patients with diabetes and is the leading cause of end-stage renal disease. If the kidneys fail, dialysis is required. Symptoms of kidney failure may include swelling in the feet and ankles, itching, fatigue, and pale skin color.

Anemia is a common complication of end-stage kidney disease. Patients on dialysis usually require injections of erythropoiesis-stimulating drugs to increase red blood cell counts and control anemia. Dosing target levels of erythropoiesis-stimulating drugs are controversial, especially for patients with chronic kidney disease. In 2006, two important New England Journal of Medicine studies indicated that aggressive dosing to completely normalize hemoglobin levels does not work better than standard dosing that only partially corrects anemia.

In 2007, the FDA issued new warnings on darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit). The warnings describe an increased risk with blood clots, strokes, and heart attacks in patients with end-stage kidney disease when these drugs were given at higher than recommended doses. The FDA has set new dosing and hemoglobin target levels for these drugs.

Another controversy surrounding erythropoiesis-stimulating drugs concerns their overuse at dialysis centers. A 2007 study in the Journal of the American Medical Association suggested that large, for-profit dialysis centers tend to administer higher-than-appropriate doses of these drugs compared to nonprofit facilities. The study suggested that for-profit centers are giving higher doses for financial, not medical, reasons.

The FDA recommends that patients with end-stage kidney disease who receive erythropoiesis-stimulating drugs should:

Maintain hemoglobin levels that do not exceed 12 g/dL
Receive frequent blood tests to monitor hemoglobin levels
Contact their doctors if they experience such symptoms as shortness of breath, pain, swelling in the legs, or increases in blood pressure

[See In-Depth Report #57: Anemia.]

Click the icon to see an image of the pancreas and kidneys.

Diabetes reduces or distorts nerve function, causing a condition called neuropathy. Neuropathy refers to a group of disorders that affect nerves. The two main types of neuropathy are:

Peripheral (affects nerves in the toes, feet, legs, hand, and arms)
Autonomic (affects nerves that help regulate digestive, bowel, bladder, heart, and sexual function)

Peripheral neuropathy particularly affects sensation. It is a common complication that affects nearly half of people with type 1 or type 2 diabetes after 25 years. The most serious consequences of neuropathy occur in the legs and feet and pose a risk for ulcers and, in very severe cases, amputation. Peripheral neuropathy usually starts in the fingers and toes and moves up to the arms and legs (called a stocking-glove distribution). Symptoms include:

Tingling
Weakness
Burning sensations
Loss of the sense of warm or cold
Numbness (if the nerves are severely damaged, the patient may be unaware that a blister or minor wound has become infected)
Deep pain

Autonomic neuropathy can cause digestive problems (constipation, diarrhea, nausea, vomiting), bladder infections, and erectile dysfunction. In some cases, neuropathy may mask angina, the chest pain warning for heart disease and heart attack. Patients with diabetes should be aware of other warning signs of a heart attack, including sudden fatigue, sweating, shortness of breath, nausea, and vomiting.

Blood sugar control is the only treatment for neuropathy. Studies show that tight control of blood glucose levels delays the onset and slows progression of neuropathy. A 2005 study also suggested that heart disease risk factors can increase the likelihood of developing neuropathy. Lowering triglycerides, losing weight, reducing blood pressure, and quitting smoking may help prevent the onset of neuropathy.

Prevention of Neuropathy. Patients with type 2 diabetes should receive regular screenings for loss of sensation in feet and other signs of neuropathy. A 2007 study suggested that statin and fibrate drugs, which are used to control cholesterol, may help protect against diabetic peripheral neuropathy.

Pain Relief for Peripheral Neuropathy. A number of different drugs are used for peripheral neuropathy pain relief. They include:

Nonprescription analgesics such as aspirin, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs). (Patients with stomach or kidney problems should check with their doctors before using these drugs.)
Prescription painkillers, such as tramadol (Ultram). Tramadol is a drug that is similar to opioids. It can help relieve pain but has significant side effects, including nausea, constipation, and headache.
Topical medications, particularly capsaicin (the active ingredient in hot peppers), are applied to the skin to relieve minor local pain. A 5% lidocaine patch has also shown good results in clinical trials.
Tricyclic antidepressants, such as amitriptyline (Elavil) or doxepin (Sinequan), are effective in reducing pain from neuropathy in up to 75% of patients. A combination of doxepin and capsaicin (applied to the skin) may be particularly beneficial. Unfortunately, tricyclics may cause heart rhythm problems.
Duloxetine (Cymbalta) is a serotonin and norepinephrine reuptake inhibitor, a newer type of antidepressant, which was approved in 2004 for treatment of pain associated with diabetic peripheral neuropathy.
The anti-convulsant drug pregabalin (Lyrica) was approved in 2004 for neuropathic pain management. It is classified as a controlled substance (like narcotics), which indicates a potential risk for abuse. Other anti-seizure drugs used for peripheral neuropathy pain relief include gabapentin (Neurontin) and valproate (Depakote).

Treatments under investigation include acetyl-l-carnitine and intravenous alpha-lipoic acid. Patients may also benefit from transcutaneous electrostimulation (TENS), a treatment that involves administering mild electrical pulses to painful areas. Alternative treatments such as hypnosis, biofeedback, relaxation techniques, and acupuncture have helped some patients manage pain. Doctors also recommend lifestyle measures such as walking and wearing elastic stockings.

Treatments for Other Complications of Neuropathy. Neuropathy also impacts other functions, and treatments are needed to reduce their effects. If diabetes affects the nerves in the autonomic nervous system, then abnormalities of blood pressure control and bowel and bladder function may occur. Erythromycin, domperidone (Motilium), or metoclopramide (Reglan) may be used to relieve delayed stomach emptying caused by neuropathy.

Erectile dysfunction is also associated with neuropathy. Evidence shows that phosphodiesterase type 5 (PDE-5) drugs, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), are safe and effective, at least in the short term, for patients with diabetes. Typical side effects are minimal but may include headache, flushing, and upper respiratory tract and flu-like symptoms.

Perhaps the most serious consequences of diabetic neuropathy occur in the lower limbs. An estimated 15% of patients with diabetes experience serious foot problems. They are the leading cause of hospitalizations for these patients.

Diabetes is responsible for more than half of all lower limb amputations performed in the U.S. Each year there are about 88,000 non-injury amputations, 50 - 75% of them due to diabetes. The number is increasing as the prevalence in diabetes type 2 rises. According to a 2005 study in the Lancet, every 30 seconds someone in the world receives a lower limb amputation due to diabetes. About 85% of amputations start with foot ulcers, which develop in about 12% of people with diabetes.

In general, foot ulcers develop from infections, such as those resulting from blood vessel injury. A 2006 study reported that people with diabetes who develop foot infections are 155 times more likely to have an amputation than people who did not develop infections. Foot infections often develop from injuries. Even minor infections can develop into severe complications. Numbness from nerve damage, which is common in diabetes, compounds the danger since the patient may not be aware of injuries. About one-third of foot ulcers occur on the big toe.

A 2003 government survey found that those at higher risk for foot ulcers tend to be people with diabetes who are overweight, smokers, and those with a long history of diabetes. People who have the disease for more than 20 years and are insulin-dependent are at the highest risk. Related conditions that put people at risk include peripheral neuropathy, peripheral artery disease, foot deformities, and a history of ulcers. [See In-Depth Report #102: Peripheral artery disease and intermittent claudication.]

Charcot Foot. Charcot foot or Charcot joint (medically referred to as neuropathic arthropathy) occurs in about 2.5% of people with diabetes. Early changes appear like an infection, with the foot becoming swollen, red, and warm. A seriously affected foot can become deformed. The bones may crack, splinter, and erode, and the joints may shift, change shape, and become unstable. It typically develops in people who have neuropathy to the extent that they cannot feel sensation in the foot and are not aware of an existing injury. Instead of resting an injured foot or seeking medical help, the patient often continues normal activity, causing further damage.

Charcot foot is initially treated with strict immobilization of the foot and ankle; some centers use a cast that allows the patient to move and still protects the foot. A 2001 study in the U.K. concluded that a single dose of pamidronate, a bisphosphonate, reduces bone turnover, symptoms, and disease activity. When the acute phase has passed, patients usually need lifelong protection of the foot using a brace initially and custom footwear.

Measures to Prevent Foot Ulcers. Preventive foot care can significantly reduce the risk of ulcers and amputation. Some tips for preventing problems include:

Patients should inspect their feet daily and watch for changes in color or texture, odor, and firm or hardened areas, which may indicate infection and potential ulcers.
When washing the feet, the water should be warm (not hot), and the feet and areas between the toes should be thoroughly dried afterward. Check water temperature with the hand or a thermometer before stepping in.
Moisturizers should be applied, but not between the toes.
Corns and calluses should be gently pumiced and toenails trimmed short and the edges filed to avoid cutting adjacent toes.
Patients should not use medicated pads or try to shave the corns or calluses themselves.
Well-fitting footwear is very important. People should be sure the shoe is wide enough; according to a 2001 study, 30% of patients with diabetes wear shoes that are too narrow. Patients should also avoid high heels, sandals, thongs, and going barefoot. Shoes with a rocker sole reduce pressure under the heel and front of the foot by 35 - 65% and may be particularly helpful. Custom-molded boots increase the surface area over which foot pressure is distributed. This reduces stress on the ulcers and allows them to heal.
Shoes should be changed often during the day.
Wear socks, particularly with extra padding (which can be specially purchased).
Patients should avoid tight stockings or any clothing that constricts the legs and feet.
Foot pain, numbness, or tingling is worse at night; diphenhydramine (Benadryl) may help.
A specialist in foot care should be consulted for any problems.

People with diabetes are prone to foot problems because the disease can cause damage to the blood vessels and nerves, which may result in decreased ability to sense trauma to the foot. The immune system is also altered, so that the patient cannot efficiently fight infection.

Treating Foot Ulcers in Diabetes. About one-third of foot ulcers will heal within 20 weeks with good wound care treatments. Treatments include:

Antibiotics are generally given. In some cases, hospitalization and intravenous antibiotics for up to 28 days may be needed for severe foot ulcers.
In virtually all cases, wound care requires debridement, which is the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (irrigation) means.
Hydrogels (Nu-Gel, Intrasite Gel, Scherisorb, Clearsite, Duoderm, Geliperm) are helpful in healing ulcers and are noninvasive and soothing.
Felted foam may be helpful in healing ulcers on the sole of the foot. Felted foam uses a multi-layered foam pad over the bottom of the foot with an opening over the ulcer.

Other Treatments for Foot Ulcers. Doctors are also using or investigating other treatments to heal ulcers. These include:

Administering hyperbaric oxygen (oxygen given at high pressure) is showing promise in promoting healing. In one study, patients who had had ulcers that had not responded to treatment for over 3 months received daily treatments that lasted 90 minutes for 2 weeks. About 15 days after completion, patients who received oxygen had significant reduction in ulcers, sometimes with complete healing. Other studies are also demonstrating good results.
Monochromatic near-infrared photo energy (MIRE) uses light therapy to improve sensation in the feet of patients with peripheral neuropathy.
Total-contact casting (TCC) uses a cast that is designed to match the exact contour of the foot and to distribute weight along the entire length of the foot. It is usually changed weekly. It may be helpful for ulcer healing and for Charcot foot. Although it is very effective in healing ulcers, recurrence is common.

Diabetes accounts for 12,000 - 24,000 of new cases of blindness annually and is the leading cause of new cases of blindness in adults age 20 - 74. The most common eye disorder in diabetes is retinopathy. People with diabetes are also at higher risk for developing cataracts and certain types of glaucoma, such as primary-open angle glaucoma (POAG). The risk for POAG is especially high for women with type 2 diabetes. [See In-Depth Report #26: Cataracts and In-Depth Report #25: Glaucoma.]

Description of Retinopathy. Retinopathy is a condition in which the retina in the eye becomes damaged. The two primary abnormalities that occur are a weakening of the blood vessels in the retina and the obstruction in the capillaries -- probably from very tiny blood clots. Retinopathy generally occurs in one or two phases:

Click the icon to see an image of diabetic retinopathy.

The early and more common type of this disorder is called nonproliferative or background retinopathy. The blood vessels in the retina are abnormally weakened. They rupture and leak, and waxy areas may form. If these processes affect the central portion of the retina, swelling may occur, causing reduced or blurred vision.
If the capillaries become blocked and blood flow is cut off, soft, "woolly" areas may develop in the retina's nerve layer. These woolly areas may signal the development of proliferative retinopathy. Often there are no symptoms of progressing retinopathy. In this more severe condition, new abnormal blood vessels form and grow on the surface of the retina. They may spread into the cavity of the eye or bleed into the back of the eye. Major hemorrhage or retinal detachment can result, causing severe visual loss or blindness. The sensation of seeing flashing lights may indicate retinal detachment.

Click the icon to see an animation on diabetic retinopathy.

According to a 2003 study, about 40% of young adults with type 1 diabetes had developed retinopathy within 10 years of diagnosis. (Although this rate is high, it is significantly lower than in previous years when blood glucose control was not as strict.) The risk is lower in patients with type 2 diabetes, although in one study over 20% had signs of retinopathy 6 years after diagnosis. Patients who are newly diagnosed with type 2 diabetes should get a comprehensive eye examination, including dilation. In general, all patients with diabetes should have a yearly eye examination. Patients with no signs of retinal damage or low risk factors for retinopathy may only require screening every 2 - 3 years.

Prevention of Retinopathy. Fortunately, severe and even moderate vision loss is largely preventable with tight control of blood glucose levels. (Intense glucose control can cause early worsening of retinopathy, although this is nearly always counterbalanced by long-term benefits.) Tight control of blood pressure can also help protect against retinopathy. Aspirin therapy does not help prevent retinopathy.

Treatment of Retinopathy. Patients with severe diabetic retinopathy or macular edema (swelling of the retina) should be sure to see an eye specialist who is experienced in the management and treatment of diabetic retinopathy. Once damage to the eye develops, laser eye surgery may be needed. Laser surgery can help reduce vision loss in high-risk patients.

Studies indicate that patients with type 2 diabetes face a higher than average risk of developing dementia caused either by Alzheimer's disease or problems in blood vessels in the brain. Problems in attention and memory can occur even in people under age 55 who have had diabetes for a number of years. In one study of people with type 1 diabetes, high glucose levels (hyperglycemia) were associated with slower brain function, including less verbal fluency and slower ability to do mental arithmetic.

Respiratory Infections. People with diabetes face a higher risk for influenza and its complications, including pneumonia, possibly because the disorder neutralizes the effects of protective proteins on the surface of the lungs. In fact, deaths among people with diabetes increase by 5 - 15% during flu epidemics, and they are six times more likely to be hospitalized with complications from flu than nondiabetic patients who have flu. Everyone with diabetes should have annual influenza vaccinations and a vaccination against pneumococcal pneumonia.

Urinary Tract Infections. Women with diabetes face a significantly higher risk for urinary tract infections, which are likely to be more complicated and difficult to treat than in the general population.

Diabetes doubles the risk for depression. Furthermore, according to one study, depression, in turn, increases the risk for hyperglycemia and complications of diabetes. Restoring mental health, both through medication and psychotherapy, not only improves quality of life but may help patients control their blood sugar levels.

Diabetes changes bone quality and density, but the effects differ, depending on type:

Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fractures. The best medications for bone loss in patients with diabetes are bisphosphonates, such as alendronate (Fosamax) and risedronate (Actonel). They not only help prevent bone loss but may even reduce daily insulin requirements in patients taking insulin. [See In-Depth Report #18: Osteoporosis.]
Type 2 diabetes, on the other hand, is associated with an increased bone density but is also associated with fractures. In such cases, the bone quality itself may be impaired.

Older patients with either type of diabetes are at risk for falling, which compounds the risk for fracture.

Diabetes increases the risk for other conditions, including:

Hearing loss
Periodontal disease
Carpal tunnel syndrome
Nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH), a particular danger for people who are obese
Colorectal cancer
Uterine cancer

Emergency Complications

People with diabetes who need to intensively control glucose levels are at risk for low blood sugar (hypoglycemia). Hypoglycemia, also called insulin shock, develops if blood sugar levels fall below normal. It may also be caused by insufficient intake of food, excess exercise, or alcohol intake. The condition is usually manageable, but occasionally it can be severe or even life threatening, particularly if the patient fails to recognize the symptoms. Mild hypoglycemia is common among people with type 2 diabetes, but severe episodes are rare, even among those who are taking insulin. Still, all patients who intensively control blood sugar (glucose) levels should be aware of warning symptoms.

Risk Factors for Severe Hypoglycemia. People at highest risk for severe hypoglycemia are those who intensively control blood glucose and also have one or more of the following conditions:

Long-term diabetes
Less education on their condition
A previous history of severe hypoglycemia
Hypoglycemia unawareness

Hypoglycemia unawareness is a condition in which people become insensitive to hypoglycemic symptoms. It affects about 25% of patients who use insulin, nearly always people with type 1 diabetes. In such cases, hypoglycemia appears suddenly, without warning, and can escalate to a severe level. Even a single recent episode of hypoglycemia may make it more difficult to detect the next episode. With vigilant monitoring and by rigorously avoiding low blood glucose levels, patients can often regain the ability to sense the symptoms. However, even very careful testing may fail to detect a problem, particularly one that occurs during sleep.

Symptoms. Mild hypoglycemia symptoms usually occur at moderately low and easily correctable levels of blood glucose. They include:

Sweating
Trembling
Hunger
Rapid heartbeat

Severely low blood glucose levels can cause neurologic symptoms, such as:

Confusion
Weakness
Disorientation
Combativeness
In rare and worst cases, coma, seizure, and death

Preventive Measures. The following tips may help avoid hypoglycemia or prepare for attacks:

Patients are at highest risk for hypoglycemia at night. Bedtime snacks may be helpful.
Patients who intensively control their blood sugar should monitor blood levels as often as possible, four times or more per day. This is particularly important for patients with hypoglycemia unawareness.
In adults, it is also particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients who use medications that put them at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes designed for individuals with diabetes.

Family and friends should be aware of the symptoms and be prepared:

If the patient is helpless (but not unconscious), family or friends should administer three to five pieces of hard candy, two to three packets of sugar, half a cup (four ounces) of fruit juice, or a commercially available glucose solution.
If there is inadequate response within 15 minutes, additional oral sugar should be provided or the patient should receive emergency medical treatment, including intravenous administration of glucose.
Family members and friends can learn to inject glucagon, a hormone, which, in contrast to insulin, raises blood glucose.

Click the icon to see a glucagon kit.

Diabetic ketoacidosis (DKA) is a life-threatening complication caused by insulin depletion. Until recently, it was a complication almost exclusively of type 1 diabetes. In such cases, it is nearly always due to noncompliance with insulin treatments. However, DKA is being reported increasingly in type 2 diabetes, especially among Hispanic- and African-Americans. It is not clear what causes total insulin depletion in these patients. Researchers are trying to learn which individuals are at particular risk.

Diabetic ketoacidosis often develop as follows:

The process is usually triggered in insulin-deficient patients by a stressful event, most often pneumonia or urinary tract infections. Other triggers include alcohol abuse, physical injury, pulmonary embolism, heart attacks, or other illnesses.
Severely low insulin levels cause excessive amounts of glucose in the bloodstream (hyperglycemia).
Fat breakdown then accelerates and increases the production of fatty acids.
These fatty acids are converted into chemicals called ketone bodies, which are toxic at high levels.

Symptoms and complications may include:

Nausea and vomiting
Abnormally deep and rapid breathing with frequent sighing
Rapid heartbeat
If the condition persists, coma and, eventually, death, may occur; however, over the past 20 years, death from DKA has decreased to about 2% of all cases.
Other serious complications from DKA include aspiration pneumonia and adult respiratory distress syndrome.

Life-saving treatment uses rapid rehydration with a saline solution followed by low-dose insulin and potassium replacement.

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.americanheart.org -- American Heart Association
www.kidney.org -- National Kidney Foundation
www.nei.nih.gov -- National Eye Institute
www.medicalert.org -- Medic Alert
www.eatright.org -- American Dietetic Association
http://limaye.ecri.org -- Limaye Center

References

American Diabetes Association (ADA). Standards of medical care in diabetes. IV. Prevention/delay of type 2 diabetes. Diabetes Care. 2007 Jan;30(Suppl 1):S7-8.

American Diabetes Association (ADA). Standards of medical care in diabetes. V. Diabetes care. Diabetes Care. 2007 Jan;30(Suppl 1):S8-15.

American Diabetes Association (ADA). Standards of medical care in diabetes. VI. Prevention and management of diabetes complications. Diabetes Care. 2007 Jan;30(Suppl 1):S15-24.

Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007 July 11;298:194-206.

Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE, et al. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006 Dec;29(12):2632-7.

Bolen S, Feldman L, Vassy J, Wilson L, Yeh H-C, Marinopoulos S, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007 Jul 17; 147(6). [Epub ahead of print]

Carnethon MR, Biggs ML, Barzilay JI, Smith NL, Vaccarino V, Bertoni AG, et al. Longitudinal association between depressive symptoms and incident type 2 diabetes mellitus in older adults: the cardiovascular health study. Arch Intern Med. 2007 Apr 23;167(:802-7.

Charbonnel B, Karasik A, Liu J, Wu M, Meininger G; Sitagliptin Study 020 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006 Dec;29(12):2638-43.

Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006 Nov 16;355(20):2071-84.

Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007 Jan 20;369(9557):201-7.

Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR, et al. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med. 2006 Jul 20;355(3):241-50.

Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007 May 11;316(5826):889-94. Epub 2007 Apr 12.

Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007 Feb 10;334(7588):299. Epub 2007 Jan 19.

Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006 Mar;38(3):320-3. Epub 2006 Jan 15.

Gregg EW, Gu Q, Cheng YJ, Narayan KM, Cowie CC. Mortality trends in men and women with diabetes, 1971-2000. Ann Intern Med. 2007 Jun 18; [Epub ahead of print]

Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP, et al. Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis. N Engl J Med. 2007 Jul 5;357(1):28-38. Epub 2007 Jun 5.

Jeerakathil T, Johnson JA, Simpson SH, Majumdar SR. Short-term risk for stroke is doubled in persons with newly treated type 2 diabetes compared with persons without diabetes: a population-based cohort study. Stroke. 2007 Jun;38(6):1739-43. Epub 2007 May 3.

Lee AJ, Hiscock RJ, Wein P, Walker SP, Permezel M. Gestational diabetes mellitus: clinical predictors and long-term risk of developing type 2 diabetes: a retrospective cohort study using survival analysis. Diabetes Care. 2007 Apr;30(4):878-83.

Pasquale LR, Kang JH, Manson JE, Willett WC, Rosner BA, Hankinson SE. Prospective study of type 2 diabetes mellitus and risk of primary open-angle glaucoma in women. Ophthalmology. 2006 Jul;113(7):1081-6. Epub 2006 Jun 6.

Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007 Jun 14;356(24):2457-71. Epub 2007 May 21.

Psaty BM, Furberg CD. Rosiglitazone and cardiovascular risk. N Engl J Med. 2007 Jun 14;356(24):2522-4. Epub 2007 May 21.

Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H. Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis. Arch Intern Med. 2007 May 14;167(9):956-65.

Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007 Jun 1;316(5829):1341-5. Epub 2007 Apr 26.

Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006 Nov 16;355(20):2085-98.

Thamer M, Zhang Y, Kaufman J, Cotter D, Dong F, Hernen MA. Dialysis facility ownership and epoetin dosing in patients receiving hemodialysis. JAMA. 2007 Apr 18;297(15):1667-74.

Vardi M, Nini A. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus. Cochrane Database Syst Rev. 2007 Jan 24(1):CD002187.

Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007 Jun 1;316(5829):1336-41. Epub 2007 Apr 26.

Review Date:
7/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Preparing for pregnancy

FitSugar — Wed, 08 Oct 2008 17:34:51 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Preparing for Pregnancy

What can you do to prepare yourself and your body for pregnancy ahead of time? The key is to live a healthy lifestyle. Evaluate your daily habits and take some time to make the necessary changes for you and your future baby. Emotionally, you should be ready to commit to a lifetime of parenthood.

If you have ongoing medical conditions, it is important for those conditions to be stable before getting pregnant. If you have any of the following medical problems, plan to see your doctor or midwife before you conceive:

Arthritis
Asthma
Cancer
Deep vein thrombosis
Diabetes
Epilepsy
Heart disease
Hepatitis
Herpes
High blood pressure
Hypo- or hyperthyroidism
Kidney disease
Lupus
Sickle cell trait or disease
Urinary tract infections

Obviously, you should report any other medical condition that might have an impact on you and the baby.

You will also be asked about your family history because some medical conditions are inherited, such as sickle cell anemia, cystic fibrosis, and muscular dystrophy. If these conditions, or any other medical problems, run in your family, you may be referred to a genetic counselor.

Your doctor will also discuss your current medications and health history, including you and your partner's history of any sexually transmitted diseases.

Stop Smoking

Smoking is bad for unborn babies. Studies have shown that women who smoke during pregnancy are more likely to have babies with lower birth weights. Smoking also increases the risk of miscarriage, premature birth, stillbirths, cleft lip or palate, asthma, preterm labor, and sudden infant death syndrome (SIDS).

It is best to stop smoking before you get pregnant, rather than waiting to quit once you become pregnant.

Alcohol Abuse

Alcohol can have damaging effects on a developing fetus, even in small quantities. When you have a drink, the alcohol rapidly reaches your baby through your bloodstream and across the placenta. Women who have two or more drinks a day are at greater risk for giving birth to a baby with severe long-term effects, such as mental retardation, behavioral problems, learning disabilities, and facial and heart defects. Finally, alcohol may decrease your ability to get pregnant. We don’t know what amount of alcohol is safe in pregnancy, so it’s best to avoid drinking altogether.

What to Eat

A balanced diet is always important and you should try to make the appropriate changes to your diet before you get pregnant. Consider reducing your intake of empty calories, artificial sweeteners, and caffeine. Balancing your diet with foods high in protein, fruits and vegetables, grains, and dairy products will make you healthier before you get pregnant. It is not a good idea to try to lose weight during pregnancy; however, being overweight during pregnancy may increase your chances of having complications such as high blood pressure or diabetes during pregnancy. If you are underweight or overweight, it is best to try to reach your ideal weight before you get pregnant.

Vitamins and Folic Acid

Most doctors recommend that women begin taking a multi-vitamin supplement and at least 400 micrograms (mcg) of folic acid a day before getting pregnant. Taking folic acid is thought to reduce a baby's risk of developing birth defects of the spine, such as spina bifida. Ideally, you should start taking a multivitamin with 400-800 mcg of folic acid two months before you get pregnant.

Exercise Before Getting Pregnant

Exercising before you get pregnant may help your body deal with all of the changes that you will go through during the pregnancy and labor. The amount of exercise you are able to do during pregnancy will be determined by your overall health and how active you were before you got pregnant.

Stress, Rest, and Relaxation

While you are trying to get pregnant, it is important to try to relax and be as stress-free as possible. Practicing stress reduction techniques and getting plenty of rest and relaxation may make it easier for you to become pregnant.

Stopping Birth Control Pills

Women who are planning pregnancy should stop taking birth control a month before they are planning to try to get pregnant. When stopping the pill, you may have irregular periods for a while and this can make it hard to tell when you are fertile or ovulating. It might take longer to become pregnant, but the pill has no impact on fertility. The use of birth control pills before you get pregnant does not cause birth defects, no matter how close you use them to the time you get pregnant.

Review Date:
2/19/2007
Reviewed By:
Douglas A. Levine, MD, Gynecology Service, Memorial Sloan-Kettering Cancer Center, New York, NY. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Pregnancy Center Links

Hypothyroidism

FitSugar — Wed, 08 Oct 2008 17:35:30 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Diagnosis
Risk Factors
Complications
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Congenital Hypothyroidism and Maternal Hyperthyroidism

Thyroid-lowering medications used for treating Graves’ disease, the most common cause of hyperthyroidism (overactive thyroid), can cause babies to be born with hypothyroidism (underactive thyroid). Research presented at the 2006 annual meeting of the American Thyroid Association suggests that hyperthyroidism can be effectively managed during pregnancy without causing newborn hypothyroidism. The researchers suggest that:

Pregnant women with Graves’ disease should take the lowest possible dose of their thyroid medication
It is safe for women with Graves’ disease to maintain thyroid levels in the upper-normal range while pregnant

Low-Normal Thyroid and Metabolic Syndrome

Thyroid levels in the low-normal range may increase the risk of unhealthy cholesterol levels, high blood sugar, and abdominal obesity -- indicators of metabolic syndrome -- according to a 2006 study in the Journal of Clinical Endocrinology and Metabolism.
Metabolic syndrome is a cluster of conditions, (including abdominal obesity, high blood sugar, and unhealthy cholesterol levels), which increases the risk for heart disease. However, many experts do not believe that treating subclinical hypothyroidism (mildly underactive thyroid) can help prevent heart problems. More research is underway.

Subclinical Hypothyroidism and Mood

A large study of elderly people, published in the Annals of Internal Medicine, suggests that subclinical hypothyroidism does not cause depression, anxiety, or impaired cognition. The study included nearly 6,000 people age 65 years and older.

Introduction

The thyroid is a small, butterfly-shaped gland located in the front of the neck that produces hormones, notably thyroxine (T4) and triiodothyronine (T3), which stimulate vital processes in every part of the body. These thyroid hormones have a major impact on the following functions:

Growth
Use of energy and oxygen
Heat production
Fertility
The use of vitamins, proteins, carbohydrates, fats, electrolytes, and water
Immune regulation in the intestine

These hormones can also alter the actions of other hormones and drugs.

The thyroid gland, a part of the endocrine (hormone) system, plays a major role in regulating the body's metabolism.

Regulating thyroid function is a complex and important process that involves several factors, including iodide and four thyroid hormones. Any abnormality in this intricate system of hormone synthesis and production can have far-reaching consequences on health.

Iodide. An understanding of the multi-step thyroid hormone process begins with iodide, a salt that is extracted from the blood and trapped by the thyroid gland. Iodide is converted to iodine in the thyroid gland. (Eighty percent of the body's iodine supply is stored here.) Iodine is the material used to make the hormone thyroxine (T4).

Thyroid Hormones. Four hormones are critical in the regulation of thyroid function:

Thyroxine (T4) and Triiodothyronine (T3). Thyroxine (T4) is the key thyroid hormone. Low levels of T4 produce hypothyroidism, and high levels produce hyperthyroidism. Thyroxine converts to triiodothyronine (T3), which is a more biologically active hormone. Only about 20% of triiodothyronine is actually formed in the thyroid gland. The rest is manufactured from circulating thyroxine in tissues outside the thyroid, such as those in the liver and kidney. Once T4 and T3 are in circulation, they typically bind to substances called thyroid hormone transport proteins, after which they become inactive.
Thyrotropin. Thyrotropin (also called thyroid-stimulating hormone or TSH) is another very important hormone in the process. Secreted by the pituitary gland, this hormone directly influences the process of iodine trapping and thyroid hormone production. When thyroxine levels drop even slightly, the pituitary gland goes into action to pump up secretion of thyrotropin so that it can stimulate thyroxine production. So, when T4 levels fall, TSH levels increase.
Thyrotropin-releasing hormone (TRH), the final critical thyroid hormone, is produced in a region in the brain called the hypothalamus, which monitors thyrotropin levels.

Click the icon to see an image of the pituitary gland.

Click the icon to see an image of the pituitary gland and TSH.

Hypothyroidism occurs when thyroxine (T4) levels drop so low that body processes begin to slow down. Hypothyroidism was first diagnosed in the late nineteenth century when doctors observed that surgical removal of the thyroid resulted in the swelling of the hands, face, feet, and tissues around the eyes. They named this syndrome myxedema and correctly concluded that it was the outcome of the absence of substances, thyroid hormones, normally produced by the thyroid gland. Hypothyroidism is usually progressive and irreversible. Treatment, however, is nearly always completely successful and allows a patient to live a fully normal life.

Subclinical hypothyroidism (mildly underactive thyroid), also called early-stage hypothyroidism, is a condition in which thyrotropin (TSH) levels have started to increase in response to an early decline in T4 levels in the thyroid. However, blood tests for T4 are still normal. The patient may have mild symptoms (usually slight fatigue) or none at all. Mildly underactive thyroid is very common (affecting about 10 million Americans) and is a topic of considerable debate among professionals because it is not clear how to manage this condition.

For instance, mildly underactive thyroid does not progress to the full-blown disorder in most people. Experts estimate that each year approximately 2 - 5% of people with mildly underactive thyroid will go on to develop overt hypothyroidism. Other factors associated with a higher risk include being an older woman (up to 20% of women over age 60 have subclinical hypothyroidism), having a goiter (enlarged thyroid gland) or thyroid antibodies, or harboring immune factors that suggest an autoimmune condition.

Mildly underactive thyroid is determined on the basis of the TSH laboratory blood tests. According to a 2004 consensus statement from the American Thyroid Association, the American Association of Clinical Endocrinologists, and the Endocrine Society, the normal range of TSH concentration falls between 0.45 and 4.5 mU/L. Patients with mildly underactive thyroid have TSH levels between 4.5 mU/L and 10mU/L. Patients with levels greater than 10mU/L are considered to have overt hypothyroidism and should be treated with medication.

For patients in the mildly underactive thyroid range, treatment decisions are less clear. The consensus committee recommended against routine treatment for patients with mildly underactive thyroid , but did suggest repeat screenings of thyroid function every 6 - 12 months to detect any changes in TSH levels. However, these are general guidelines, and individual cases and risk factors may differ. Patients should discuss with their doctor the course of action that is most appropriate for them.

Causes

Many permanent or temporary conditions can reduce thyroid hormone secretion and cause hypothyroidism. About 95% of hypothyroidism cases occur from problems that originate in the thyroid gland. In such cases, the disorder is called primary hypothyroidism. (Secondary hypothyroidism is caused by disorders of the pituitary gland. Tertiary hypothyroidism is caused by disorders of the hypothalamus.)

The two most common causes of primary hypothyroidism are:

Hashimoto's thyroiditis. This is an autoimmune condition in which the body's immune system attacks its own cells.
Overtreatment of hyperthyroidism (an overactive thyroid).

Hashimoto's thyroiditis, atrophic thyroiditis, and postpartum thyroiditis are all autoimmune diseases of the thyroid. An autoimmune disease occurs when the immune system mistakenly attacks the body's own healthy cells. In the case of autoimmune thyroiditis, a common form of primary hypothyroid disease, the cells under attack are in the thyroid gland.

All forms of thyroid autoimmunity typically start with T and B cells:

Important immune factors called T and B cells infiltrate the thyroid gland in equal numbers. These white blood cells are the primary infection-fighting immune cells. T cells identify invasive molecules, such as viral proteins, and help B cells to produce antibodies that are designed specifically to attack these invaders.
In cases of autoimmunity, T cells are tricked into classifying molecules on the body's own cells as invaders. In such cases, B cells then produce antibodies, called autoantibodies, which attack those cells.
In most cases of thyroid autoimmunity, the autoantibodies launch an attack on a thyroid protein called thyroid peroxidase; this attack appears to destroy thyroid cells.

Experts do not know why the immune system starts the process that injures the thyroid. Some theories follow:

One theory starts with a virus that has a protein resembling a thyroid protein. During an infection, T cells induce B cells to secrete specific antibodies that attack the invasive viral protein. Unfortunately, the T cells are also tricked into inducing a B-cell attack on the similar thyroid protein.
Genetic factors most likely play some role in autoimmune thyroiditis. For example, many patients with Hashimoto's thyroiditis express a gene called the Fas gene, which interacts with thyroid cells and triggers a process called apoptosis, in which the cells begin to self-destruct. The Fas gene is linked to genes that regulate tumor necrosis factors, which are products of the immune system that trigger a damaging inflammatory response in cells.
In some women, thyroid autoimmunity may have developed while they were pregnant. In such cases, some evidence suggests that fetal cells accumulated in the mother's thyroid gland, triggering an immune attack.
In some cases of Hashimoto's thyroiditis, antibodies block a receptor on thyroid cells that bind to thyrotropin (TSH). This effect is more likely to be involved in worsening the disorder, but does not explain initial destruction.
Some evidence suggests that excess iodine intake triggers the process leading to Hashimoto's thyroiditis.

Hashimoto's Thyroiditis. The most common form of hypothyroidism in the U.S. is Hashimoto's thyroiditis, a genetic disease named after the Japanese doctor who first described thyroid inflammation. It occurs in about 0.3 - 5 people per 1,000 per year, and women are 15 - 20 times more likely than men to develop this disease.

Click the icon to see an image of Hashimoto's thyroiditis.

An enlargement of the thyroid gland, called a goiter, is almost always present and may appear as a cyst-like or fibrous growth in the neck. Hashimoto's thyroiditis is permanent and requires lifelong treatment. Both genetic and environmental factors appear to play a role in its development.

One theory proposes that Hashimoto's thyroiditis and Graves' disease (a form of hyperthyroidism) are caused by a similar immunologic dysfunction. Similar immune system substances called antibodies are present in both diseases, and some experts believe that the predominance of one or another antibody determines which of the diseases become manifest. The two diseases, then, are essentially two sides of a single coin.

Click the icon to see an image of Grave's disease.

Atrophic Thyroiditis. Atrophic thyroiditis is similar to Hashimoto's thyroiditis, except a goiter is not present.

Riedel's Thyroiditis. Riedel's thyroiditis is a rare autoimmune disorder, in which scar tissue progresses in the thyroid until it produces a hard stony mass that suggests cancer. Hypothyroidism develops as the scar tissue replaces healthy tissue. Surgery is usually required, although early stages may be treated with tamoxifen, corticosteroids, or other immunosuppressive drugs.

Autoimmune Thyroiditis Due to Pregnancy. Hypothyroidism may also occur in women who develop antibodies to their own thyroid during pregnancy, causing an inflammation of the thyroid after delivery.

Subacute thyroiditis is a temporary condition that passes through three phases: hyperthyroidism, hypothyroidism, and a return to normal thyroid levels. Patients may exhibit symptoms of both hyperthyroidism and hypothyroidism (rapid heartbeat, nervousness, weight loss), and they can feel extremely sick. Symptoms last about 6 - 8 weeks and then resolve in most patients, although each form carries some risk for becoming chronic. Experts estimate that subacute thyroiditis is responsible for 10% of all cases of hypothyroidism.

The three forms of subacute thyroiditis follow a similar course:

Painless Postpartum Subacute Thyroiditis. Postpartum thyroiditis is an autoimmune condition that occurs in up to 10% of pregnant women and tends to develop between 4 - 12 months after delivery. In most cases, a woman develops a small, painless goiter. Although 80% of women with this condition have normal thyroid function within a year, some evidence suggests that half of women with this condition develop permanent hypothyroidism within 7 years. Women who have had recurrent episodes after previous pregnancies and women who have other autoimmune disorders are at higher risk for this form of subacute thyroiditis. It is generally self-limiting and requires no therapy unless the hypothyroid phase is prolonged. In such cases, therapy may be thyroxine replacement for a few months. A doctor will prescribe beta blockers if the hyperthyroid phase requires treatment.

Painless Sporadic, or Silent, Thyroiditis. This painless condition is very similar to postpartum thyroiditis except it can occur in both men and women and at any age. About 20% of patients with silent thyroiditis may develop chronic hypothyroidism. Treatment considerations are the same as for postpartum subacute thyroiditis.

Painful, or Granulomatous, Thyroiditis. This condition comes on suddenly with flu-like symptoms and severe neck pain and swelling. It generally occurs in the summer and is five times more common in women. It recurs in about 2% of patients. Hypothyroidism persists in about 5%. Treatments typically include pain relievers and, in severe cases, corticosteroids.

Up to half or more of patients who receive radioactive iodide treatments for an overactive thyroid develop permanent hypothyroidism within a year of therapy. This is the standard treatment for Graves' disease, which is the most common form of hyperthyroidism, a condition caused by excessive secretion of thyroid hormones.

By the end of 5 years, about 65% of treated patients have developed hypothyroidism, after which the rate of this condition levels off to about 1% a year. Such patients need to take thyroid hormones for the rest of their lives. Other forms of treatment for overactive thyroid glands using either antithyroid drugs or surgery may also result in hypothyroidism.

Too much or too little iodide can cause hypothyroidism. If there is a deficiency of iodide, the body cannot manufacture thyroxine. About 200 million people around the world have hypothyroidism because of insufficient iodine in their diets. Too much iodide is a signal to inhibit the conversion process of thyroxine to T3. The end result in both cases is inadequate production of thyroid hormones. Some evidence suggests that excess iodine triggers the process leading to Hashimoto's thyroiditis.

Complete removal (total thyroidectomy) of the thyroid to treat thyroid cancer requires a lifetime of treatment with an appropriate dosage of thyroid hormone. Removing one of the two lobes of the thyroid gland (hemithyroidectomy), usually because of benign growths on the thyroid gland, rarely produces hypothyroidism. The remaining thyroid lobe will generally enlarge so that it can produce sufficient amounts of thyroid hormone for normal function. Many doctors recommend thyroid hormone treatment, however, to prevent the formation of additional nodules.

Click the icon to see an illustrated series detailing thyroid removal.

A small percentage of Graves disease patients who require surgery to remove most of both thyroid lobes (subtotal thyroidectomy) may develop hypothyroidism. It is important to find an experienced surgeon for this procedure and to have the thyroid checked at 6- or 12-month intervals.

Researchers have identified several additional syndromes that also cause hypothyroidism. These generally involve abnormalities in thyroid hormone itself or genetic deficiencies in certain proteins that impair thyroid hormone conversion processes or responses.

Lithium. Lithium, a drug widely used to treat psychiatric disorders, has multiple effects on thyroid hormone synthesis and secretion. Up to 50% of patients who take lithium develop a goiter, with 20% developing symptomatic hypothyroidism, and another 20 - 30% developing hypothyroidism without symptoms.

Amiodarone. The drug amiodarone (Cordarone), which is used to treat abnormal heart rhythms, contains high levels of iodine and can induce hyper- or hypothyroidism, particularly in patients with existing thyroid problems. Hypothyroidism occurs in 20% of patients and is the more common effect in the U.S. and other countries where dietary iodine is abundant. Hyperthyroidism is a less common effect in these regions.

Other Drugs. Drugs used for treating epilepsy, such as phenytoin and carbamazepine, can reduce thyroid levels. Certain antidepressants may cause hypothyroidism, although this is rare. Interferons and interleukins are used for treating hepatitis, multiple sclerosis, and other conditions. Evidence suggests that these drugs increase antibodies that put patients at risk for hypo- or hyperthyroidism. Some drugs used in cancer chemotherapy, such as sunitinib (Sunent) or imatinib (Gleevec), can also cause or worsen hypothyroidism.

High-dose radiation for cancers of the head or neck and for Hodgkin's disease causes hypothyroidism in up to 65% of patients within 10 years after treatment.

In rare instances, usually due to a tumor, the pituitary gland will fail to produce thyrotropin (TSH), the hormone that stimulates the thyroid to produce its hormones. In such cases, the thyroid gland withers. When this happens, secondary hypothyroidism occurs.

Hypothyroidism in newborns (known as congenital hypothyroidism) occurs in one in every 3,000 - 4,000 births, making it the most common hormonal disorder in infants. In 90% of these cases, it persists throughout life.

Permanent Congenital Hypothyroidism. In up to 85% of permanent congenital hypothyroidism cases, the thyroid gland is missing, underdeveloped, or not properly located. In most cases the cause or causes of these conditions are unknown. In about 10 - 15% of cases, processes involved in hormone production are impaired, most likely because of genetic abnormalities. In less than 5% of cases, the pituitary or hypothalamus function abnormally.

Temporary Hypothyroidism in Infants. Temporary hypothyroidism can also occur in infants. In about 20% of cases, the cause remains unknown. The known causes stem from various immunologic, environmental, and genetic factors, including those in the mother:

Hypothyroidism. Women who have an underactive (“low”) thyroid, including those who develop the problem during pregnancy, are at increased risk for delivering babies with congenital (newborn) hypothyroidism. Maternal hypothyroidism can also cause premature delivery and low-birth weight.
Hyperthyroidism. Graves disease is the most common cause of maternal hyperthyroidism (overactive or “high” thyroid). Some of the drugs used to treat hyperthyroidism can cause hypothyroidism in the infant. Some research indicates that using the lowest possible dose of thyroid-lowering medication can minimize the risk of congenital hypothyroidism. (The research also suggests that it is safe for women with Graves’ disease to remain in a mildly hyperthyroid state during pregnancy.
Iodine deficiency. This may cause temporary hypothyroidism. (Exposure to too much iodine immediately after birth, for example, from iodine-containing disinfectants or medicines, can also cause thyroid dysfunction.)
Being premature.
Kidney disease. Temporary hypothyroidism in infants can occur in premature babies and, rarely, in those with kidney disease.
The central nervous system connections between the hypothalamus and pituitary gland may also mature late; this condition generally resolves 4 - 16 weeks after birth.

Children with temporary congenital hypothyroidism should be followed-up regularly during adolescence and adulthood for possible thyroid problems. The risk for further thyroid problems is highest in these adult women during pregnancy. Newborn siblings of these children should also be screened for possible thyroid defects.

Symptoms

Early Symptoms. Early symptoms of hypothyroidism are subtle and, in older people, can be easily mistaken for symptoms of stress or aging. They include:

Chronic fatigue
Sensitivity to cold
Headache
Muscle and joint aches
Weight gain, despite diminished appetite
Constipation
Dry skin

In premenopausal women, early symptoms can interfere with fertility. They may experience heavy periods or, in rare cases, a milky discharge from the breasts. A history of miscarriage may be a sign of impending hypothyroidism. Studies suggest that even if thyroid levels are normal, women who have a history of miscarriages often have antithyroid antibodies during early pregnancy and are at risk for developing autoimmune thyroiditis over time.

Later Symptoms. As free thyroxine levels fall over the following months, other symptoms may develop:

Impaired mental activity, including concentration and memory, particularly in the elderly.
Depression. Some experts believe that even mild thyroid failure may increase susceptibility to major depression.
Muscle weakness, numbness, pain, and cramps. This can cause an unsteady gait. Muscle cramps are common, and carpal tunnel syndrome or symptoms similar to arthritis sometimes develop. In some cases, the arms and legs may feel numb.
Numbness in the fingers.
Hearing loss.
Husky voice.
Continuing weight gain and possible obesity, in spite of low appetite.
Some people experience less sweating, and their skin becomes pale.
Skin and hair changes. Skin becomes pale, rough, and dry. Patients may sweat less. Hair coarsens and even falls out. Nails become brittle.
Snoring and obstructive sleep apnea (a condition in which in the soft palate in the throat collapses at intervals during sleep, thereby blocking the passage of air).

Secondary hypothyroidism, caused by tumors or other growths on the pituitary, produces the usual symptoms of primary hypothyroidism. In addition, sexual drive and fertility may be impaired in both men and women. Patients may also feel exhausted, crave salt, and have low blood pressure. Headaches and visual disturbances may develop, which are directly related to the pituitary tumor.

Hypothyroidism occurs when the thyroid gland is underactive. The condition may affect all body functions. The rate of metabolism slows, causing mental and physical sluggishness. Myxedema, a medical emergency, is the most severe form of hypothyroidism. A problem with the thyroid itself (primary) or malfunction of the pituitary gland (secondary) or hypothalamus (tertiary) can cause hypothyroidism.

All babies are now screened for hypothyroidism in order to prevent retardation that can occur if treatment is delayed. Symptoms of hypothyroidism in children vary depending on when the problem first develops.

Most children who are born with a defect that causes congenital hypothyroidism have no obvious symptoms. Symptoms that do appear in newborns may include jaundice (yellowish skin), noisy breathing, and an enlarged tongue.
Early symptoms of undetected and untreated hypothyroidism in infants include feeding problems, failure to thrive, constipation, hoarseness, and sleepiness.
Later on, symptoms in untreated children include protruding abdomens; rough, dry skin; and delayed teething. Rarely, in advanced cases, yellow raised bumps (called xanthomas) may appear under the skin, the result of cholesterol build-up.
If they do not receive proper treatment in time, children with hypothyroidism may be extremely short for their age, have a puffy, bloated appearance, and have below-normal intelligence. Any child whose growth is abnormally slow should be examined for hypothyroidism.

Diagnosis

Advances in diagnostic methods now make it possible to detect hypothyroidism in almost all cases before severe symptoms develop. Doctors can diagnosis hypothyroidism after completing a history and physical exam of the patient and performing sensitive laboratory tests on the patient's blood.

The doctor will check the heart, eyes, hair, skin, and reflexes for signs of hypothyroidism.

Goiter. The presence of a goiter (an enlarged thyroid), especially a rubbery, painless one, may be an indication of Hashimoto's disease. If the thyroid is tender and enlarged but not necessarily symmetrical, the doctor may suspect subacute thyroiditis. A diffusely enlarged gland may occur in hereditary hypothyroidism, in postpartum patients, or from use of iodides or lithium. Goiters may also develop in people with iodide deficiency.

Thyroid Neck Check. Women who are experiencing menopausal symptoms that may be masking those of hypothyroidism should perform a simple self-examination called the Thyroid Neck Check:

Hold a mirror in front of the area of the neck where the thyroid gland is located. This area is just below the Adam's apple and right above the collarbone. (Note: The Adam's apple is not the thyroid location.)
Tip the head back.
Take a drink of water and swallow, watching the neck during the process.
Check for any bulging or protrusions. If any is detected, call a doctor for a check up.

In diagnosing hypothyroidism, blood tests measuring hormone levels are needed to make a correct diagnosis. In some cases, antibody tests are also helpful.

Thyroxine (T4). Hypothyroidism is a condition marked by low thyroxine (T4) hormone levels, and a test can measure levels of this hormone in the blood. However, this test is usually inadequate for the following reasons:

T4 levels can be normal early in the disease process leading to hypothyroidism. If hypothyroidism is suspected, other tests are needed.
T4 levels can be low in patients who do not have hypothyroidism. For instance, thyroxine can be extremely variable in very elderly or seriously ill patients and during pregnancy.

Measuring thyroxine is usually performed using a process called a T3 resin uptake to correct for the presence of medications (such as birth control pills, aspirin, and others) that could distort the results. Other tests are needed to confirm a diagnosis of hypothyroidism.

Thyrotropin (Thyroid-Stimulating Hormone or TSH). Measuring TSH is the most sensitive indicator of hypothyroidism. (As with thyroxine levels, however, TSH levels can vary in pregnant women and patients who are ill with other conditions.) In general, results indicate the following:

TSH levels over 10mU/L. This is a clear indicator of hypothyroidism if T4 levels are low -- and, in most cases, even if they are normal. Patients usually require thyroxine (T4) replacement therapy. They should also be tested for high cholesterol levels and antithyroid antibodies.
Levels between 4.5 mU/L - 10 mU/L. Patients with signs and symptoms of hypothyroidism usually need thyroxine replacement therapy. Patients without symptoms have subclinical hypothyroidism and should be rechecked every 6 - 12 months. Antibody tests may also be performed.
TSH levels between 0.45 mU/L - 4.5 mU/L. These indicate normal thyroid function. (Abnormally low levels suggest hyperthyroidism, which is overactive thyroid.)
Specific TSH measurement -- even if it is significantly higher than 10 mU/L -- is not associated with the severity of the condition. This can be determined only by measuring thyroxine levels and evaluating the patient's symptoms.

Antithyroid Antibodies. If TSH levels suggest hypothyroidism or subclinical hypothyroidism, the doctor may choose to perform a blood test for specific antithyroid antibodies that act against a factor called thyroperoxidase (TPO). Tests can also check for antibodies to thyroglobulin. Results depend on the patient's condition:

Patients with confirmed hypothyroidism (TSH levels over 10 mU/L). Positive test results in such patients confirm the need for thyroxine replacement therapy. (Even if antibody results are negative, these patients usually require thyroxine replacement therapy.) About 90% of patients with Hashimoto's thyroiditis test positive for antibodies to thyroperoxidase, and up to half have thyroglobulin antibodies.
Patients with subclinical hypothyroidism (TSH between 4.5 mU/L - 10 mU/L). If antibody levels are high, thyroxine therapy is usually warranted, since it indicates an underlying autoimmunity condition that poses a high risk for later thyroid failure. If the tests are negative, but patients have thyroid-related problems (such as high cholesterol, female infertility), they should be monitored annually with hormone tests.

About 10% of the American population and 25% of women over 60 years old carry these antibodies, and the majority of these women have no thyroid problems. Only about 0.5% have full-blown hypothyroidism, and 10% have subclinical hypothyroidism. In one 10-year study, however, people with normal thyroid results and high levels of antibodies still had an annual risk of 2 - 4% for developing hypothyroidism.

Other Hormone Tests Used for Thyroid Function. Other hormone tests are done if hyperthyroidism is suspected. They include tests for triiodothyronine (T3) and thyroglobulin (also called thyroid binding globulin). Such measurements, however, may also be helpful in detecting sudden temporary increases in thyroid hormone (thyrotoxicosis) that can precede certain forms of autoimmune thyroiditis.

Thyroid Scintigraphy. Thyroid scintigraphy tests scan the thyroid and pick up images highlighted by small amounts of radioactive substances. Thyroid scans can be used to determine whether the thyroid is producing normal amounts of hormone. The patient drinks a small amount of radioactive iodine or technetium and waits until the substance has passed through the thyroid. Images of a properly functioning thyroid would show uniform levels of absorption throughout the gland. Overactive areas show up white, and underactive areas appear dark. Thyroid scans are usually unnecessary unless the doctor needs to rule out suspected cancer.

Ultrasound. Ultrasound has limited value, but it can visualize the thyroid and specific abnormalities, such as nodules. (It cannot measure the thyroid gland's function, however.)

Click the icon to see an image of thyroid ultrasound.

More Advanced Imaging Tests. If laboratory tests suggest that a pituitary or hypothalamus problem is causing hypothyroidism, the doctor will usually order brain imaging procedures using computed tomography (CT) scans or magnetic resonance imaging (MRI). MRIs may also be used for determining the extent of thyroid cancers and of goiters. MRIs are also being used for investigating hypothyroidism in infants and for determining widespread effects of autoimmune thyroiditis (such as Hashimoto's hypothyroidism).

Needle aspiration biopsy is used to obtain thyroid cells for microscopic evaluation. It may be useful to rule out thyroid cancer in patients with suspected Hashimoto's hypothyroidism, especially if they have difficulty swallowing or develop a goiter. Much like drawing blood, the doctor injects a small needle into the thyroid gland and draws cells from the gland into a syringe. The cells are put onto a slide, stained, and examined under a microscope.

Cholesterol levels need to be checked. Other blood tests may be performed to detect levels of calcitonin, calcium, prolactin, and thyroglobulin and to check for anemia and liver function, all of which may be affected by hypothyroidism.

Screening in Older Adults. Some doctors believe that because thyroid problems are so common in the elderly and thyroid hormone tests are so inexpensive, blood tests for thyroid function should be routine. Undiagnosed hypothyroidism in elderly patients can develop into a serious and even life-threatening situation. Hyperthyroidism also poses many health risks. In fact, during the period around menopause, the symptoms of menopause and hypothyroidism are similar and can easily be confused with each other.

Professional organizations differ widely on screening recommendations. Most do not recommend widespread screening for healthy adults:

The American College of Physicians recommends that women over 50 years old be screened for thyroid disorders every 5 years. The American Academy of Family Physicians believes that adults do not have to be screened until they are over 60.
The American Thyroid Association, however, recommends that all adults, both men and women, begin their screening at age 35 and every 5 years thereafter. Experts in this organization argue that such early screening is inexpensive and would prevent progression to hypothyroidism, and therefore possibly heart disease, in people with subclinical hypothyroidism. Such an approach would also eliminate the need for expensive anti-cholesterol drugs.

Screening in Pregnant Women. Untreated hypothyroidism in a pregnant woman, particularly in the first trimester, may cause premature delivery and birth defects. Birth defects can affect a baby’s intelligence, mental development, and motor skills. Subclinical hypothyroidism also increases the risk for premature delivery and birth defects.

Some experts propose that screening be done on any woman who is planning a pregnancy to help determine those who may be at increased risk for hypothyroidism and, if needed, begin treatment as early as possible during the critical first trimester. Women who have a personal or family history of hypothyroidism should have their thyroid checked within the first weeks of pregnancy and should be retested during each trimester.

Screening in Infants. It is very difficult to diagnose hypothyroidism in newborns by symptoms alone. Fortunately, almost all newborns with hypothyroidism are identified shortly after birth through an effective national screening program using a thyroid blood test.

Because the symptoms of hypothyroidism are so similar to common conditions, including aging, diagnosis can be difficult.

Conditions That Cause Thyroid Abnormalities. Some conditions may cause thyroid abnormalities without symptoms and must be differentiated from subclinical hypothyroidism. They include, although are not limited to:

Inadequate response to thyroid therapies in people with hypothyroidism
Recovery from a severe illness that is unrelated to thyroid disorders
Chronic kidney failure
Failure of the adrenal gland

Aging-Related Disorders. Some symptoms of hypothyroidism and aging are very similar. Menopausal symptoms often resemble hypothyroidism. Many other problems related to aging -- such as vitamin deficiencies, Parkinson's and Alzheimer's diseases, and arthritis -- also have characteristics that can mimic hypothyroidism.

Obesity. Many people who are overweight believe that they have an underactive thyroid gland, but only a very small percentage of obese people actually have hypothyroidism. Patients with hypothyroidism generally show only a moderate weight increase of 5 - 10 pounds, mainly from accumulation of fluid, and in fact they often have a decreased appetite.

Depression. A lack of interest in personal relationships, drowsiness, an increase in sleep, slowing of speech, and general apathy are signs of clinical depression as well as hypothyroidism. The two disorders often coexist, particularly in older women, so diagnosing one does not rule out the presence of the other.

Diseases of Muscles and Joints. Joint and muscle aches may be the first symptoms of hypothyroidism. Most likely, however, such pain is not caused by hypothyroidism if other thyroid symptoms remain absent. Numerous conditions can cause muscle and joint pain, and if thyroid levels are normal the doctor should look for other causes.

Risk Factors

About 15 million Americans have unrecognized thyroid disease, mostly subclinical hypothyroidism (mildly underactive thyroid). Less than 2% of the U.S. population has full-blown hypothyroidism.

Women. Women have 10 times the risk of hypothyroidism as men, with the difference being significant after age 34. In one study, nearly 6% of women over 60 had hypothyroidism, and some experts estimate that as many as 20% of women in this age group have a subclinical condition. Because the symptoms of hypothyroidism and menopause are so similar, hypothyroidism may easily be missed.

Pregnancy is a major factor in the higher risk in women. It affects the thyroid in a number of ways and poses a high risk for hypothyroidism, both during pregnancy and afterward. For one, iodine requirements are high in both the mother and the fetus. Changes in reproductive hormones also cause changes in thyroid hormone levels. In addition, some women develop antibodies to their own thyroid during pregnancy, causing a condition known as postpartum autoimmune, or subacute, thyroiditis. This occurs in up to 10% of pregnant women and tends to develop between 4 - 12 months after delivery. It is a limited condition and nearly always clears up. However, it does pose a risk for the development of permanent hypothyroidism later on.

Age. The elderly are most susceptible, but hypothyroidism can affect people of all ages. For example, 1 in every 3,000 - 4,000 infants is born with congenital hypothyroidism. Female infants are at higher risk than males.

Ethnicity. African-Americans may be less likely to have thyroid disease than Caucasians and Asians.

Genetics plays a role in many cases of underactive and overactive thyroid. The genetics involved with hypothyroidism are complicated, however. Certain genetic features, for example, appear to play a role in Hashimoto's thyroiditis and postpartum thyroiditis in Caucasians, but others affect different ethnic groups. Thyroid disease will often skip generations. For example, someone with an underactive thyroid may have healthy parents but have grandparents who had thyroid troubles. Some people inherit a tendency to thyroid problems but never become ill, while others become very sick.

Smoking significantly increases risk for thyroid disease, particularly autoimmune Hashimoto's thyroiditis and postpartum thyroiditis. Chemicals in cigarette smoke called thiocyanates appear to have especially harmful effects on the thyroid. Smoking also increases the negative effects of hypothyroidism, notably on the arteries and heart.

People with certain medical conditions have a higher risk for hypothyroidism. These conditions include:

Autoimmune diseases. People with many autoimmune diseases have a higher risk for hypothyroidism. Type 1 (insulin-dependent) diabetes poses a higher risk and is a special problem since hypothyroidism can affect insulin requirements. Women with other autoimmune diseases, including systemic lupus erythematosus, pernicious anemia, and rheumatoid arthritis, are also at higher risk for hypothyroidism. Pregnant women with autoimmune conditions have a 25% risk for hypothyroidism during gestation.
Breast cancer. There may be a link between breast cancer and thyroid levels, but the evidence is unclear. Some studies have indicated that women with breast cancer may be more susceptible to hypothyroidism. Other studies suggest the opposite. Several studies indicate that hypothyroidism itself may protect against breast cancer. In addition, when women with hypothyroidism develop breast cancer, it is often a less aggressive and more easily treated form.
Gout. Hypothyroidism and gout often coexist and may have biologic mechanisms in common.
Addison's disease.
Myasthenia gravis.
Polycystic ovarian syndrome.
Anorexia or bulimia. People with eating disorders are at risk for hypothyroidism. In these cases, however, reduced thyroid function may be an adaptation to malnutrition and, therefore, some experts think that only the eating disorder should be treated, not hypothyroidism.
Turner syndrome. As many as half of patients with Turner syndrome have hypothyroidism, usually in the form of Hashimoto's thyroiditis. This inherited condition is one of the most common genetic diseases in women.
Glaucoma. A 2004 study of male veterans suggested that hypothyroidism may be associated with increased risk for developing open-angle glaucoma.

Click the icon to see an animation about gout.

Click the icon to see an image of polycystic ovarian syndrome.

Many drugs affect the thyroid, so anyone being treated for a chronic disease, patients who are taking thyroid medication, and those who are at risk for a thyroid disorder should discuss the impact these drugs may have on their thyroid.

Hypothyroidism is associated with premature gray hair and left-handedness.

Complications

Hypothyroidism carries serious physical and mental risks for all ages. Studies indicate that subtle adverse health effects occur even with subclinical hypothyroidism, a condition in which the patient has no symptoms but blood tests indicate hypothyroidism. Fortunately, hypothyroidism is now easily diagnosed, and treatment will restore normal thyroid function and relieve symptoms and physical signs of the disease. With treatment, a patient should expect to live a normal life, free of harmful consequences. Iodine deficiency and goiter are still major problems in less developed nations and cause varying degrees of mental retardation in millions of people.

Myxedema Coma. Myxedema coma is a rare, life-threatening complication of untreated hypothyroidism. Symptoms include a severe drop in body temperature (hypothermia), delirium, reduced lung function, slow heart rate, constipation, urine retention, seizures, stupor, fluid build-up, and finally coma. It is uncommon, but may develop in untreated patients subjected to severe stress, such as infection, surgery, or extreme cold. Certain drugs (such as sedatives, painkillers, narcotics, amiodarone, and lithium) may increase the risk. Emergency treatment is required. Mortality rates are high (between 30 - 60%) with the highest risks in older patients and those with persistent hypothermia or heart problems.

Suppurative Thyroiditis. Suppurative thyroiditis is a life-threatening infection of the thyroid gland. It is very rare, since the thyroid is normally immune to infection. People with pre-existing thyroid diseases, such as Hashimoto's thyroiditis, however, may be at higher than average risk for it. It often begins with an upper respiratory infection. Symptoms include fever, neck pain and rash, and trouble swallowing and speaking. Immediate treatment is critical.

Thyroid hormones, notably triiodothyronine (T3), affect the heart directly and indirectly. They are closely linked with heart rate and heart output. T3 provides particular benefits by relaxing the smooth muscles of blood vessels. This helps keep the blood vessels open so that blood flows smoothly through them.

Hypothyroidism is associated with:

Unhealthy cholesterol levels. Hypothyroidism raises levels of total cholesterol, LDL (the so-called bad cholesterol), triglycerides, and other lipids (fat molecules) associated with heart disease. Treating the thyroid condition with thyroid replacement therapy can significantly reduce these levels.
Mild high blood pressure. Hypothyroidism may slow the heart rate to less than 60 beats per minute, reduce the heart's pumping capacity, and increase the stiffness of blood vessel walls. All of these effects may lead to high blood pressure. Indeed, patients with hypothyroidism have triple the risk of developing hypertension. All patients with chronic hypothyroidism, especially pregnant women, should have their blood pressures checked regularly.
Heart failure. Hypothyroidism can affect the heart muscle’s contraction and increase the risk of heart failure in people with existing heart disease.

The evidence for subclinical hypothyroidism and heart disease is mixed. Some studies suggest that subclinical hypothyroidism increases the risks for coronary artery disease and heart failure. A 2007 study indicated that low-normal thyroid function may increase the risk for metabolic syndrome (a cluster of symptoms that include abdominal obesity, high blood sugar, and unhealthy cholesterol levels). However, a 2006 study in the Journal of the American Medical Association found that while subclinical hypothyroidism was associated with atrial fibrillation (irregular heart beat), it was not associated with other types of heart disease. Many experts believe that treatment of subclinical hypothyroidism will not help prevent or improve heart problems. More research is underway.

Depression. Depression is common in hypothyroidism and can be severe. Some psychiatrists suspect that even subclinical hypothyroidism may contribute to depression. The two disorders may have some common physiological basis. Adding thyroid hormones to antidepressants may hasten a depressed patient's recovery, even in some patients who have not been diagnosed with hypothyroidism. Hypothyroidism should be considered as a possible cause of any chronic depression, particularly in older women.

Mental and Behavioral Impairment. Untreated hypothyroidism can, over time, cause mental and behavioral impairment and eventually, even dementia. Whether treatment can completely reverse problems in memory and concentration is uncertain, although many experts believe that only mental impairment in hypothyroidism that occurs at birth is permanent.

A 2006 study of nearly 6,000 people age 65 years and older concluded that subclinical hypothyroidism is not associated with depression, anxiety, or mental impairment in elderly patients.

The following medical conditions have been associated with hypothyroidism. Often the causal relationship is not clear in such cases:

Iron deficiency anemia.
Respiratory problems.
Kidney function.
Glaucoma. (Some research has associated hypothyroidism with an increased risk for glaucoma.)
Headache. (Hypothyroidism may worsen headaches in people predisposed to them.)
Thyroid lymphoma. (Patients with Hashimoto's thyroiditis are at higher risk for this rare form of cancer.)
Joint stiffness. (Women with hypothyroidism may actually have fewer problems with joint stiffness than women with normal thyroid.)

Most women with hypothyroidism fail to produce eggs, and many younger women with hypothyroidism are diagnosed with the condition for the first time during a fertility evaluation. A pregnant woman with hypothyroidism has a fourfold risk for miscarriage. In one study, nearly 40% of women with a history of miscarriages and normal thyroid levels had antithyroid antibodies (immune factors that attack thyroid tissue). Those who continue to have hypothyroidism near the time of delivery are in danger of developing high blood pressure and premature delivery. They are also prone to postpartum thyroiditis, which is said to be a contributor to postpartum depression.

Children of Untreated Mothers. Children born to untreated pregnant women with hypothyroidism are at risk for impaired mental performance, including attention problems and verbal impairment. Studies on the effects on children of women with subclinical hypothyroidism are less clear, with some reporting lower IQs in such children and others reporting no significant problems.

Effects of Hypothyroidism During Infancy. Transient hypothyroidism is common among premature infants. Although temporary, severe cases can cause difficulties in neurologic and mental development.

Infants born with permanent congenital (inborn) hypothyroidism need to receive treatment as soon as possible after birth to prevent mental retardation, stunted growth, and other aspects of abnormal development (a syndrome referred to as cretinism). It has been estimated that untreated infants can lose up to three to five IQ points per month during the first year. An early start of lifelong treatment avoids or minimizes this damage. Even with early treatment, however, mild problems in memory, attention, and mental processing may persist into adolescence and adulthood.

Effects of Childhood-Onset Hypothyroidism. If hypothyroidism develops in children older than 2 years, mental retardation is not a danger, but physical growth may be slowed and new teeth delayed. If treatment is delayed, adult growth could be affected. Even with treatment, some children with severe hypothyroidism may have attention problems and hyperactivity.

Two million Americans, mostly children, received x-ray treatments to the head or neck between 1920 - 1960 for acne, enlarged thymus gland, recurrent tonsillitis, or chronic ear infections. The risk of developing thyroid nodules and thyroid cancers is increased in these individuals, especially if they have hypothyroidism. Cancer can develop as late as 40 years after the original treatment. Everyone who has had head and neck radiation should be sure to have their thyroid glands examined regularly.

Treatment

Various tests are used when deciding whether to treat a patient for hypothyroidism:

First, an elevated TSH (thyrotropin) level should be confirmed and thyroxine (T4) level determined.
Testing for antithyroid antibodies and determining cholesterol levels is also important.

Treating Hypothyroidism. Patients with full-blown hypothyroidism, indicated by clear symptoms and blood tests that show high TSH (generally 10 mU/L and above) and low thyroxine (T4) levels, must be treated with thyroid replacement.

Treating Subclinical Hypothyroidism. Considerable debate exists about whether to treat patients with subclinical hypothyroidism (slightly higher than normal TSH levels, normal thyroxine levels, and no obvious symptoms). Some doctors opt for treatment because of the following benefits, although evidence remains uncertain:

Preventing progression to full-blown hypothyroidism. Treating subclinical hypothyroidism will prevent progression to overt hypothyroidism. Only a minority of people with subclinical hypothyroidism go on to develop the active condition, however.
Preventing heart disease. Some studies have shown that treating subclinical hypothyroidism lowers cholesterol levels and may improve other heart functions, including blood pressure, endothelial function, and heart rate. However, current research from 2006 suggests that subclinical hypothyroidism poses little risk for heart disease and that untreated subclinical hypothyroidism will not increase heart disease risks.
Improving well-being. Some studies report that treating subclinical hypothyroidism may improve mild psychological symptoms, such as impaired mental functioning and depression. About 25% of patients with subclinical hypothyroidism report feeling better after taking thyroid medication even if they have not previously reported symptoms.

It is not clear, then, if the benefits of treating subclinical hypothyroidism outweigh the higher costs of testing and treatments. Experts against treatment argue that thyroid levels can vary widely, and subclinical hypothyroidism may not persist. In such cases, overtreatment leading to hyperthyroidism is a real risk.

In spite of such uncertainties, three out of four major medical organizations recommend treatment for subclinical hypothyroidism, particularly in patients who have:

High total or LDL cholesterol levels
Blood tests that show autoantibodies indicating a future risk for Hashimoto's thyroiditis or other forms of other autoimmune hypothyroidism·
Blood tests that show TSH levels greater than 10 mU/L
Goiter

Experts also recommend treating subclinical hypothyroidism in:

Pregnant women
Women with infertility that may be associated with subclinical hypothyroidism

Treatment is optional in patients with subclinical hypothyroidism who have no obvious symptoms and normal cholesterol levels. If they forego treatment, however, they should be tested yearly for TSH and thyroxine.

Treating Patients with Hypothyroidism Symptom and Normal Thyroid Tests. Some doctors treat patients who have a normal or below normal thyroid function test. Some experts believe it is irresponsible to treat such patients with thyroid replacement since such symptoms can occur with many physical and psychological conditions. In any case, studies have not found any benefits from T4 replacement therapies in this group.

In the 19th century, doctors observed the relationship between myxedema (swelling of the hands, face, feet, and tissues around the eyes) and surgical removal of the thyroid gland. Some doctors began to feed patients with myxedema with whole or powdered extracts of animal thyroid glands. Using thyroid hormone to treat hypothyroidism was one of the first successful medical treatments based on careful scientific observation. With only some modifications, this approach has varied little for over a century.

A synthetic thyroid hormone called levothyroxine is currently the treatment of choice for hypothyroidism. This drug is a synthetic derivative of T4 (thyroxine), and it normalizes blood levels of TSH, T4, and T3. Nevertheless, the therapeutic principle for hypothyroidism is the same as it was more than 100 years ago: To provide the body with replacement thyroid hormone when the gland is not able to produce enough itself.

Brand Names. A number of levothyroxine brands are available in the U.S. and overseas. Synthroid is the oldest brand and has been used for over 40 years. In the past, manufacturers of levothyroxine have not had to meet as strict standards as in the production of other drugs. This resulted in thyroid products with varying quality. The FDA has issued stronger requirements that have largely corrected this problem.

Generics versus Brand-Name Products. Generic brands are available and are subject to the same guidelines as brand-name products. There is still considerable debate over whether generic thyroid preparations are as effective as brand products.

In addition, the amount of T4 in some generic products is outside the FDA range, which requires additional testing of thyroid hormone levels. Many doctors, then, prefer to use brand-name products, noting that the cost difference between brand and generic thyroid drugs is not substantial. Regardless of which type is used, once a patient has been stabilized, doctors generally recommend sticking with one type or brand since potency often varies from one drug to the next.

Natural Thyroid Hormone. Dried powdered thyroid hormone (Armour Thyroid, S-P-T, Thyrar, Thyroid Strong) is made from animal glands. It was once the most common form of thyroid therapy but is no longer generally recommended because potency varies. Some people argue that with stricter FDA regulations, this natural form is better controlled and may even reduce the risk of developing autoimmunity factors. Dried thyroid also contains both T3 and T4 and is favored as a natural treatment by many alternative practitioners. However, studies need to be conducted to evaluate its benefits.

T3 and T4 Combinations. Triiodothyronine (T3), the other important thyroid hormone, is not ordinarily prescribed except under special circumstances. Most patients respond well to thyroxine (T4) alone, which is converted in the body into T3. In addition, the use of T3 may cause disturbances in heart rhythms. Some patients treated only with thyroxine continue to have mood and memory problems or other symptoms.

Combination products containing T4 and T3, such as liotrix (Thyrolar), are available, but there is some controversy concerning their benefits. Several 2005 studies suggested that although some patients may prefer combination therapy, T3 and T4 together do not work better than T4 alone. Patients might like the combined drugs because they cause more weight loss, or a placebo effect may be involved. It does not appear that combination products offer any advantage for normalizing TSH levels.

Levothyroxine only needs to be taken once a day. It is slowly assimilated by body organs, so it usually takes up to 6 weeks before symptoms improve in adults. Nevertheless, many patients feel better after 2 - 3 weeks of treatment. The speed at which specific symptoms improve varies:

Weight loss, less puffiness, and improved pulse usually occur early in the treatment.
Improvements in anemia and skin, hair, and voice tone may take a few months.
High LDL ("bad cholesterol") levels decline very gradually. HDL ("good cholesterol") levels are not affected by treatment.
Goiter size declines very slowly, and some patients may require high-dose thyroid hormone (called suppressive thyroid therapy) for a short period.

Levothyroxine reduces blood pressure in about half of hypothyroid patients with hypertension, although blood pressure medications may still be needed.

Appropriate Dosage Levels. Initial dosage levels are determined on an individual basis and can very wide depending on a person's age, medication condition, other drugs they are taking, and, in women, whether they are pregnant or not. For example, pregnant women with hypothyroidism may require higher than normal doses.

Starting out. Most individuals need to build up gradually until they reach a maintenance dose. In uncomplicated cases, the dose typically starts at 50 micrograms per day, which then increases in 3- to 4-week intervals until thyroid hormone levels are normal. Seniors and those with heart disease may start at 12.5 - 25 micrograms per day. On the other hand, young adults with a short history of hypothyroidism might be able to tolerate a full maintenance dosage right away.
Maintenance dose. Maintenance dose for most patients averages 112 micrograms but it can vary between 75 - 260 micrograms. If conditions such as pregnancy, surgery, or other drugs alter hormone levels, the patient's thyroid needs will have to be reassessed.

Daily Regimen. Because thyroid replacement is usually lifelong, setting up a regular daily routine is helpful. Here are some tips to remember:

Establish a habit of taking the medication at the same time each day. This may help prevent missed doses.
Levothyroxine is very forgiving. The hormone remains in the body for several days, so one missed dose should not cause a noticeable decline in well-being. The patient can safely take two doses the next day.
Fiber and common daily supplements, such as calcium, may interfere with thyroxine absorption. Although levothyroxine can be taken at any time of day either with or without food, some experts recommend taking thyroid hormone upon awakening and at least 30 minutes before consuming anything, including breakfast or supplements.

Annual Evaluation. Thyroid failure is an ongoing process and so is its treatment. Many factors can cause changes that require modifying the thyroxine dosages.

A dose that is appropriate for 1 year may be too low the next. To maintain normal thyroid levels, some patients may need to take gradually increasing doses of thyroid hormone every year or two. Experts recommend that patients be reevaluated 6 months after normal TSH levels have been reached and then once a year thereafter.

Specific factors, such as changes in health or diet, new medications for other conditions, or simply switching brands, can also cause changes in thyroid hormone levels that require different doses. If patients change dose levels or thyroxine brands then they should be checked again at least 6 weeks later.

Because levothyroxine is identical to the thyroxine the body manufactures, side effects are rare. Over- or under-dosing, however, is fairly common, although rarely serious in the short term.


Under-Dosing	Over-Dosing
Sluggishness	Heart symptoms (rapid heart beat, palpitations, and wide variations in pulse; possible angina or congestive heart failure)
Mental dullness	Agitation (tremor, nervousness, insomnia, excessive sweating)
Feeling cold	Pain (headache and muscle pain)
Muscle cramps	Intestinal and metabolic symptoms (change in appetite, diarrhea, weight loss)
	Fever and intolerance to heat

No Symptom Improvement When Normal Thyroid Levels Are Reached. Some patients fail to feel significantly better even when their thyroid levels become normal after taking thyroid replacement.

Some experts argue that many patients become symptom-free only if their thyroid replacement achieves high-normal T4 and low-normal TSH levels (rather than just normal levels). They believe that slightly higher thyroxine levels will not be harmful. Research is needed to confirm these claims.

Some patients with persistent symptoms may benefit from triiodothyronine (T3), the other important thyroid hormone. In such cases, either a combination of a lower-dose of thyroxine with a small amount of T3 or natural dried thyroid hormone, which contains T3, may be helpful.

Side Effects of Under-Dosing. If the levothyroxine dose is not sufficient to restore normal thyroid levels, or if the patient frequently forgets to take the medication, the patient may continue to experience symptoms of hypothyroidism. Even mild hypothyroidism without any symptoms can eventually lead to an increase in cholesterol levels. In a 2000 study, 40% of people taking thyroid medication still had abnormal levels of TSH. To avoid these problems, patients should take the proper dosage of levothyroxine as prescribed and have regular check-ups that include measurement of blood TSH.

Side Effects of Over-dosing: Thyrotoxicosis. Over-dosing can cause thyrotoxicosis, or the symptoms of hyperthyroidism. A patient with too much thyroid hormone in the blood is at an increased risk for abnormal heart rhythms, rapid heartbeat, congestive heart failure, and possibly a heart attack if the patient has underlying heart disease. Excess thyroid hormone is particularly dangerous in newborns, and their drug levels must be carefully monitored to avoid brain damage.

Side Effects of Long-Term Treatment. Patients with hypothyroidism usually receive lifelong levothyroxine therapy. There has been some concern that long-term use will increase the risk of osteoporosis, as suppression therapy does. Studies indicate that postmenopausal women who are taking long-term normal replacement thyroxine have no out-of-the-ordinary risk for osteoporosis.

Drug Interactions with Levothyroxine. Many drugs interact with levothyroxine and may either enhance or interfere with its absorption. These drugs include amphetamines, anticoagulants (blood thinners), tricyclic antidepressants, anti-anxiety drugs, arthritis medications, aspirin, beta-blockers, insulin, oral contraceptives, digoxin, and certain cancer drugs. Large amounts of dietary fiber may also reduce the drug’s effectiveness. People whose diets are consistently high in fiber may require larger doses of the drug. Since thyroid hormones regulate the metabolism and can affect the actions of a number of medications, dosages may also need to be adjusted if a patient is being treated for other conditions. Even changing thyroxine brands can have a different effect.

Suppressive thyroid therapy involves taking levothyroxine in doses that are high enough to block the production of natural TSH but too low to cause hyperthyroid symptoms. It may used for patients with large goiters or thyroid cancer.

Suppressive thyroid therapy places patients, particularly postmenopausal women, at risk for accelerated osteoporosis, a disease that reduces bone mass and increases risk of fractures. Some researchers suggest, however, that such bone loss is too slight to pose any significant risk for fracture. Furthermore, the cholesterol-lowering benefits of suppressive therapy outweigh this small risk. A small study found that premenopausal women taking suppressive therapy for more than 10 years were also at increased risk of bone loss by the time they reach menopause, although more research is needed to confirm this.

Bone density loss can be reduced or avoided by taking no higher a dose of thyroxine than necessary to restore normal thyroid function. In any case, doses of T4 must be continuously and carefully tailored in all patients to avoid adverse effects on the heart.

A number of medications are also available that can help preserve bone in postmenopausal women. Women on hormone replacement therapy may need to increase their dose of thyroid hormone.

Drugs that Inhibit Thyroid Hormone

Drugs that are Enhanced by Thyroid Hormone

Drugs that are Suppressed by Thyroid Hormone

Drugs that Reduce Natural Thyroid Hormone Levels and May Cause Hypothyroidism

Iron supplements (even low doses found in multivitamins)

Calcium carbonate supplements

Aluminum-containing antacids (Maalox)

Drugs used to reduce cholesterol levels by binding bile acids (colestipol and cholestyramine)

Estrogens in oral contraceptives and hormone replacement therapy (may need to increase thyroid hormone while taking estrogen)

Raloxifene (Evista), a designer-estrogen used for osteoporosis

Sucralfate (Carafate)

Epinephrine (adrenaline) injections. Thyroid hormone may increase the risk of serious side effects in heart disease patients given this drug.

Warfarin, a blood thinner. Doses of this medication may need to be reduced if thyroid treatment is started after blood thinning treatments have begun.

Many antidepressants. In some cases, potency of both antidepressants and thyroid hormones may increase.

Diabetes drugs. Patients taking thyroid hormone may need additional insulin or oral hypoglycemic drugs. Stopping or reducing thyroid hormone may increase the risk of low blood sugar.

Digoxin. Patients with heart disease may need to increase their dosage of digoxin.

Lithium. This drug, used for bipolar disorder, has multiple effects on thyroid hormone synthesis and secretion.

Amiodarone (Cordarone). This drug, used to treat abnormal heart rhythms, contains iodine and can induce hyper- or hypothyroidism, particularly in patients with an existing thyroid problem.

Antiseizure drugs used for epilepsy, including phenytoin and carbamazepine.

Interferons and interleukins used in hepatitis, multiple sclerosis, and other conditions.

Rifampin, used for tuberculosis.

Some drugs used for cancer chemotherapy.

Interferon.

Large doses of selenium, a dietary supplement.

Treating the Elderly and Patients with Heart Disease. Thyroid dysfunction is common in elderly patients, with most having subclinical hypothyroidism. There is no evidence that this condition poses any great harm in this population, and some experts recommend treating only high-risk patients. One study suggested many elderly patients have been treated unnecessarily for hypothyroidism for years. In the study, half the patients taking thyroid hormone were taken off the medication successfully. Such patients may have been inappropriately diagnosed years ago, when testing was less accurate. More sensitive tests available now should reduce this risk.

Elderly patients, particularly people with heart conditions, usually start with lower doses of thyroid replacement, since a large initial dose may be a shock to the heart. Thyroid treatment may aggravate angina in about 20% of patients with the heart condition. About 40% of patients who have heart disease must take lower-than-average maintenance doses. Experts do not recommend treatment for subclinical hypothyroidism in elderly patients with heart disease whose test show only minimal thyroid hormone abnormalities and who have no anti-thyroid antibodies. Such patients should be closely monitored, however.

Preliminary research indicates that in patients undergoing cardiac bypass surgery, administration of triiodothyronine at the time of surgery may improve blood flow, heart rate, and cardiac output. Patients with advanced heart failure may also benefit from supplementary thyroid hormone.

Treating the Mentally Ill. Patients with psychiatric illness often forget to take their medications regularly. In these patients, once- or twice-weekly dosing of thyroid medications is often safe and effective and may improve compliance.

Treating Newborns and Infants with Hypothyroidism. Babies who are born with hypothyroidism (congenital hypothyroidism) should be treated with levothyroxine (T4) as soon as possible to prevent complications. Early treatment can help improve IQ and other developmental factors. However, even with early treatment, mild problems in mental functioning may persist into adulthood. In general, children who are born with milder forms of hypothyroidism will fare better than those who have more severe forms.

Single oral doses of levothyroxine (T4) can usually restore normal thyroid hormone levels within 1 - 2 weeks. It is critical that normal levels are achieved within a 2-week period. If thyroid function is not normalized within 2 weeks, it can pose greater risks for developmental problems. Some experts urge treating newborns at slightly higher than recommended doses for the first 2 weeks and then reducing the dosage once normal thyroid levels have been reached. Infants should continue to be monitored closely to be sure that thyroxine levels remain as consistently close to normal as possible. These children need to continue lifelong thyroid hormone treatments.

Treatment During Pregnancy and for Postpartum Thyroiditis. Women who have hypothyroidism before becoming pregnant may need to increase their dose of levothyroxine during pregnancy. In very rare cases, women may develop hypothyroidism while pregnant and need to be treated with levothyroxine in full replacement doses to reduce the risk of stillbirth. The developing baby is not affected when the pregnant woman takes thyroid hormones. The pregnant woman with hypothyroidism should be monitored regularly and doses adjusted as necessary. If postpartum thyroiditis develops after delivery, any thyroid medication should be reduced or temporarily stopped during this period.

Treatment for Myxedema Coma. Myxedema coma is an emergency situation, and the patient should be given intravenous doses of thyroid hormone, which could be triiodothyronine, levothyroxine, or both. Lower doses may be safer in elderly patients. Oftentimes, hydrocortisone, a corticosteroid, is also administered. Any other accompanying critical condition, including low body temperature, slow heart rate, low blood sugar, and difficulty in breathing, should also be treated immediately.

Treatment of Secondary Hypothyroidism. The small percentage of patients who have hypothyroidism due to a pituitary or hypothalamus problem should take levothyroxine along with their other medication to treat the primary disorder. In secondary hypothyroidism, the adrenal gland is often impaired. This means that the increased activity in the metabolic rate that occurs after thyroid replacement therapy may trigger a severe and even life-threatening condition called addisonian crisis, which is caused by a sudden demand for the depleted stress hormones secreted by the adrenal gland. Before administering thyroid replacement, the doctor should initiate a test that stimulates release of ACTH, one of the hormones secreted by the adrenal gland. If there is insufficient ACTH, then before thyroid replacement is started, the patient is usually treated with cortisone acetate, a stress hormone.

In one study of those taking thyroid hormone, 12% of women and 29% of men took it inappropriately. In some cases of infertility, women with menstrual problems and repeated miscarriages and men with low sperm counts have been treated with thyroid hormones even when there was no evidence of thyroid abnormalities. (Women showing high levels of TSH, however, may benefit from levothyroxine therapy.)

Other inappropriate uses for thyroid hormones are for weight loss and to reduce high cholesterol levels. Thyroid hormones have also been given to treat so-called metabolic insufficiency. Vague symptoms suggesting low metabolism, such as dry skin, fatigue, slight anemia, constipation, depression, and apathy, should not be treated indiscriminately with thyroid hormone. No evidence exists that thyroid therapy is beneficial unless the patient has proven hypothyroidism. Indiscriminate use of thyroid hormones can weaken muscles and, over the long term, even the heart. One exception is the use of thyroxine to enhance drugs used for the treatment of severe depression.

Treating Hypothyroidism and Iodide Deficiency. People who are iodide deficient may be able to be treated for hypothyroidism simply by using iodized salt. In addition to iodized salt, seafood is a good source. Except for plants grown in iodine-rich soil, most other foods do not contain iodine. The current RDA for iodide is 150 micrograms for both men and women, with an upper limit of 1,100 micrograms to avoid thyroid injury.

Iodine Restriction in Patients with Hashimoto's Thyroiditis. Some evidence suggests that excess iodine triggers Hashimoto's thyroiditis. Small studies report that restricting iodine intake restored thyroid levels to normal in up to 75% of these patients. More research is needed.

Resources

www.aace.com -- American Association of Clinical Endocrinologists
www.thyroid.org -- American Thyroid Association
www.tsh.org -- Thyroid Foundation of America
www.endo-society.org -- Endocrine Society

References

Desai J, Yassa L, Marqusee E, George S, Frates MC, Chen MH, et al. Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med. 2006 Nov 7;145(9):660-4.

Roberts LM, Pattison H, Roalfe A, Franklyn J, Wilson S, Hobbs FD, et al. Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med. 2006 Oct 17;145(:573-81.

Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab. 2007 Feb;92(2):491-6.

Review Date:
3/20/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Depression

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Complications of Depression...
Diagnosis
Treatment
Antidepressants and Drug Tr...
Psychotherapy
Other Treatments
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration (FDA) approved the atypical antipsychotic drug aripiprazole (Abilify) for treatment of major depression in adults. Aripiprazole is used for treatment of schizophrenia and bipolar disorder. For depression, it is used in combination with antidepressant drug therapy. Researchers are also investigating other atypical antipsychotics for major depression treatment.

Antidepressants and Suicide Risk

In 2007, the FDA proposed adding new information to antidepressant warning labels concerning the increased risk for suicidal thinking and behavior among young adults ages 18 - 24 during the initial months of drug therapy.
The benefits of antidepressants for children and adolescents outweigh their potential risks, suggests a 2007 study in the Journal of the American Medical Association.

Antidepressants During Pregnancy

Most selective serotonin reuptake inhibitors (SSRIs) do not significantly increase the risk for birth defects when taken during early pregnancy, indicate several 2007 studies in the New England Journal of Medicine. However, some SSRIs -- such as paroxetine (Paxil) -- carry a higher risk than others. Researchers are still studying the overall safety of SSRIs during pregnancy. Women with depression should discuss with their doctors all potential risks and benefits.

Introduction

Everyone experiences some unhappiness, often as a result of a change, either in the form of a setback or a loss, or simply, as Freud said, "everyday misery." The painful feelings that accompany these events are usually appropriate, necessary, and transitory, and can even present an opportunity for personal growth. However, when depression persists and impairs daily life, it may be an indication of a depressive disorder. Severity, duration, and the presence of other symptoms are the factors that distinguish normal sadness from a depressive disorder.

Depression has been alluded to by a variety of names in both medical and popular literature for thousands of years. Early English texts refer to "melancholia," which was for centuries the generic term for all emotional disorders.

Depression is now referred to as a mood disorder, and the primary subtypes are major depression, dysthymia (chronic and usually milder depression), and atypical depression. Other important forms of depression are premenstrual dysphoric disorder (PDD or PMDD) and seasonal affective disorder (SAD).

Depression is defined as a mood disorder, and there are several subtypes. Bipolar disorder, also known as manic-depressive illness, is considered in a separate category.

The other major mood disorder is bipolar disorder, or manic-depressive illness, which is characterized by periods of depression alternating with episodes of excessive energy and activity. Bipolar disorder is not discussed in this report. [For more information, see In-Depth Report #66: Bipolar disorder.]

In major, or acute, depression, at least five of the symptoms listed below must occur for a period of at least 2 weeks, and they must represent a change from previous behavior or mood. Depressed mood or loss of interest must be present. Symptoms include:

1. Depressed mood on most days for most of each day -- irritability may be prominent in children and adolescents

2. Total or very noticeable loss of pleasure most of the time

3. Significant increases or decreases in appetite, weight, or both

4. Sleep disorders, either insomnia or excessive sleepiness, nearly every day

5. Feelings of agitation or a sense of intense slowness

6. Loss of energy and a daily sense of tiredness

7. Sense of guilt or worthlessness nearly all the time

8. Inability to concentrate occurring nearly every day

9. Recurrent thoughts of death or suicide

In addition, other criteria must be met:

The symptoms listed above do not follow or accompany manic episodes (such as in bipolar disorder or other disorders).
They impair important normal functions (such as work or personal relationships).
They are not caused by drugs, alcohol, or other substances.
They are not caused by normal grief.

A long-term study found that episodes of major depression usually last about 20 weeks. Between 30 - 40% of depressed patients experience sudden attacks of anger that they describe as uncharacteristic and inappropriate.

Click the icon to see an image of childhood depression.

Dysthymia, or chronic depression, afflicts 3 - 6% of the general population and is characterized by many of the same symptoms that occur in major depression. Symptoms of dysthymia are less intense and last much longer, at least 2 years. The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities. Possibly because of the duration of the symptoms, patients who suffer from chronic minor depression do not exhibit marked changes in mood or in daily functioning, although they have low energy, a general negativity, and a sense of dissatisfaction and hopelessness.

Double Depression. Often, symptoms become more severe over time. In one long-term study, nearly all patients with dysthymia suffered at least one episode of major depression superimposed over chronic depression (sometimes called double depression) at some time in their life. Some experts believe that such double depression should be considered as part of the natural course of dysthymic disorder. Women may be more susceptible to double depression. In one study, more than one-third of those who recovered from dysthymia relapsed within 5 years.

About a third of patients with depression have atypical depression. Symptoms include overeating and oversleeping. Such patients tend to have a feeling of being weighed down and react strongly to rejection. It tends to occur more in women, unmarried people, and those with other emotional disorders, such as anxiety or substance abuse. It also may impair functioning more severely than ordinary depression does.

Seasonal affective disorder (SAD) is characterized by annual episodes of depression during fall or winter that remit in the spring or summer. Other SAD symptoms include fatigue and a tendency to overeat (particularly carbohydrates) and oversleep in winter. A minority of individuals with SAD has the more common depressive symptoms of undereating and being sleepless. SAD tends to last about 5 months in those who live in the northern part of the U.S.

Seasonal changes affect many people's moods, regardless of gender and whether or not they have SAD. Simply being mildly depressed during the winter does not mean that one has SAD. Living in a northern country with long winter nights does not guarantee a higher risk for depression. Changes in light may not be the only contributor to SAD.

Causes

The causes of depression are not fully known. Most likely a combination of genetic, biologic, and environmental factors are at work.

Because depression runs in families, and has a strong genetic component, compelling evidence suggests that depression is a biologic phenomenon. Data from family, twin, adoption, and genetic studies have confirmed this. Studies have found that first-degree relatives of patients with depression are two to six times more likely to develop the problem than individuals without a family history.

Evidence supports the theory that depression has a biologic basis. The basic biologic causes of depression are strongly linked to abnormalities in the delivery of certain key neurotransmitters (chemical messengers in the brain). These neurotransmitters regulate mood and associated behaviors. Scientists hope that by identifying the gene mutations that code the regulation of these neurotransmitters, they may eventually be able to predict which patients are most likely to respond to specific antidepressant drugs.

Serotonin. Perhaps the most important neurotransmitter in depression is serotonin. Among other functions, it is important for feelings of well-being. Imbalances in the brain’s serotonin levels can trigger depression and other mood disorders.
Other Neurotransmitters. Other neurotransmitters possibly involved in depression include acetylcholine and catecholamines, a group of neurotransmitters that consists of dopamine, norepinephrine, and epinephrine (also called adrenaline). Corticotropin-releasing factor (CRF), which is believed to be a stress hormone and a neurotransmitter, is thought to be involved in depression and anxiety. Increased CRF concentrations appear to interact with serotonin and have been detected in patients with either depression or anxiety.

Endocrine glands release hormones into the bloodstream that are transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which allows the body to regulate levels of sugar in the blood. The thyroid gets instructions from the pituitary gland to secrete hormones that determine the pace of chemical activity in the body. The more hormone in the bloodstream, the faster the chemical activity; the less hormone, the slower the activity.

The degree to which these chemical messengers are disturbed is determined by other factors, such as light, structural abnormalities in the brain, sleep disorders, or genetic susceptibility. For example, researchers have identified a defect in the gene known as SERT, which regulates serotonin and has been linked to depression.

Reproductive Hormones. In women, the female hormones estrogen and progesterone most likely play a role in depression.

Women, regardless of nationality or socioeconomic level, have significantly higher rates of depression than men. The causes of such higher rates appear to be a mix of biologic and cultural factors.

Social and Economic Factors. The role that work, marriage, and children play in a woman's depression is complex. Many women feel that they must be everything to everyone and at the same time feel as if they are no one at all. Such a self-image is common and should be strongly considered as a major contributor to depression in many women, particularly those who work and have small children.

Hormonal Fluctuations and Life Stages. Extreme hormonal shifts can trigger emotional swings in all women. The role of hormones in depression is not clear, however, and is mostly based on observations of depression during specific stages in female development. Female hormones undoubtedly play some role in premenstrual dysphoria, postpartum depression, and SAD. These forms of depression recede or stop after menopause.

Early Puberty. Girls who go through puberty early (reaching the midpoint at 11 years or younger) are more likely to experience depression during adolescence than girls who mature later.

Premenopause. Premenopausal women ages 20 - 45 are most susceptible to depression, with 22% of this age group reporting symptoms of major depression. Specifically, premenstrual dysphoric disorder (severe depression before a period) affects an estimated 3 - 8% of women during their reproductive years. [For more information, see In-Depth Report # 79: Premenstrual syndrome.]

Perimenopause. Depression often occurs around menopause (the perimenopausal period), when, in addition to hormonal changes, other factors such as cultural pressures favoring young women, sudden recognition of aging, and sleeplessness are involved.

Postmenopause. Once women pass into the postmenopausal period, studies suggest that average depression scores are nearly as low as those in premenopausal women. In fact, many women report that after menopause, previous bouts of depression, particularly when caused by seasonal changes or premenopausal syndrome, recede or stop completely.

Premenstrual Dysphoric Disorder. The syndrome of severe depression, irritability, and tension before menstruation is known as premenstrual dysphoric disorder (PDD or PMDD), also called late-luteal dysphoric disorder. It affects an estimated 3 - 8% of women in their reproductive years. A diagnosis of PDD depends on having five or more standard symptoms of major depression that occur during most menstrual cycles, with symptoms worsening a week or so before the menstrual period and resolving afterward. PMDD has features of both anxiety and depression disorders, although experts increasingly believe it is a distinct disorder with specific biochemical abnormalities. [For more information, see In-Depth Report #79: Premenstrual disorder.]

Depression During Pregnancy. Pregnancy is certainly an occasion of great celebration for most women most of the time. However, emotions during that time are not always straightforward, and depression is a common (although most often a temporary) companion. Prenatal depression can affect a mother's sleep, physical activity, adherence to care, and appetite.

Miscarriage. Miscarriage poses a very high risk for depression, particularly in the first month after the loss. Older women with no previous successful pregnancies and those with a history of depression are at particular risk during this time. (Despite some concern that depression increases the risk for miscarriage in the first place, there is no evidence to support this.)

Postpartum Depression. Most new mothers experience weeping, irritability, and confusion for a few days following childbirth. Such symptoms, known as the "baby blues," are not considered signs of postpartum depression unless they persist in severe form nearly every day for more than 1 - 2 weeks.

Women are most likely to develop postpartum depression and other mental disorders in the first 3 months following delivery. (The risk is highest for first-time mothers, especially in the 10 - 19 days after delivery.) Other studies have reported that 8 - 20% of women have diagnosable postpartum depression within that 3-month period. In one study, 5% of these women had suicidal thoughts.

Studies have not found any association between a higher risk for postpartum depression in women and the following:

Educational level
Gender of the child
Whether or not the woman breast-feeds
Whether or not the pregnancy was planned
Whether the delivery was vaginal or cesarean

The rapid decline of reproductive hormones that accompany childbirth is likely to play the major role in postpartum depression in susceptible women. Fluctuating thyroid hormones can also contribute to depression. Studies suggest that women who are more sensitive to hormone fluctuations are at greater risk for postpartum depression if they have one or more of the following conditions:

A history of prior depressive episodes
A family history of mood disorders
Stressful life events (such as being a new mother and having an infant with medical problems)
Lack of social support or feeling as if it is lacking

Depressed children often suffer in silence, and depression may be evident only from reports of problems in school. It is also often difficult for adults to believe that children can be chronically depressed. Symptoms for depression in children often differ from those in adults and may include the following:

An inability to enjoy favorite activities
Persistent sadness
Increased irritability
Complaints of physical problems, such as headaches and stomachaches
Poor performance in school
Persistent boredom
Low energy
Poor concentration
Changes in eating and/or sleeping patterns
A greater tendency to bully others -- anxious children are more often bullied.

Risk Factors for Depression in Children and Adolescents. Depression can occur in children of all ages, including preschoolers, although adolescents have the highest risk (about 20%). Risk factors for depression in young people include having parents, particularly mothers with depression. Early negative experiences and exposure to stress, neglect, or abuse also pose a risk for depression. Sometimes depression develops after a physical illness. In adolescents, feeling alienated from parents is a strong predictor for depression.

Outlook for Future Emotional Problems. Adolescents who have depression are at significantly higher risk for substance abuse, recurring depression, and other emotional problems (such as bipolar disorder) in adulthood.

Risk for Suicide in Adolescents. Suicide is the third most common cause of death among adolescents, and is one of the most devastating events than can happen to a family. Suicide is most commonly associated with depression in young people but it is also linked with anxiety, psychosis, substance abuse, or impulsivity. More girls attempt suicide but more boys succeed, most often because they choose guns or violent methods while girls tend to overdose, which is more treatable. Nevertheless, attempts are major risk factors for a later suicide. Any expression of suicidal intent should be treated very seriously.

The following are danger signs in young people:

Withdrawal from friends
Sudden decrease in school performance
Loss of interest in activities that were previously pleasurable
Unusual irritability
Unusual changes in sleep or eating habits

Risk factors for suicide include a history of neglect or abuse, history of deliberate self-harm, a family member who committed suicide (nearly always one who shared a common mood disorder), access to firearms, and living in communities where there have been recent outbreaks of suicide in young people. A romantic break-up is often the trigger for a suicidal attempt in teenagers. Feeling connected with parents and family protected young people with depression in one study, regardless of gender or ethnicity.

Adolescents may fail to seek help for suicidal thoughts for the following reasons:

They believe nothing would help
They are reluctant to tell anyone they had problems
They think it is a sign of weakness to seek help
They do not know where to go

Parents should not hesitate to seek professional help for their children if they suspect they are thinking about killing themselves. This is a medical emergency and requires immediate treatment.

Behavioral therapies and antidepressants are promising treatments for preventing suicide but need study. There has been a decline in adolescent suicides over the past decade, which some experts attribute to the increased use of antidepressants in this population. However, recent evidence has indicated that antidepressants can also raise the risk for suicidality (suicidal thoughts and behavior) in some people. Children, adolescents, and young adults who are prescribed antidepressant medication should be carefully monitored by both their parents and doctor, especially during the first few months of treatment, for any worsening of depression symptoms or changes in behavior. [See Suicide Risk and Antidepressant Medications in Medication section.]

Although depression in the elderly is very common, the aging process itself is unlikely to be the cause in most cases. An Italian study, for example, indicated that the very old (people who lived beyond 90 years of age) were no more likely to be depressed than younger adults. (The rate was 10% in both groups.) Studies on the cause or extent of depression in the elderly are not clear.

The severity of depression in elderly patients is strongly associated with poor health and less ability to function. In one study of older adults undergoing rehabilitation, half of whom were depressed, as their function improved so did their mood.

Anyone who experiences cumulative negative life events, physical illness, the death of a loved one, impaired functioning, or loss of independence can become deeply depressed. The elderly are at highest risk for such events.

Diagnosing Depression in the Elderly. Because of the complex relationship between depression, drug interactions, and serious physical illness in the elderly, an accurate diagnosis in this group is important but not always straightforward. The characteristic symptoms of depression are not always present or readily apparent in older people:

Some older people may be aware of their depression but believe that nothing can be done about it.
Many elderly people who are depressed may report only physical symptoms (aches and pains) or other mood states (confusion, agitation, anxiety, and irritability) related to depression rather than depression itself.
Often they are unable or unwilling to express their feelings or are even unaware that they are depressed.
Their symptoms are often ignored or confused with other ailments common in the elderly, including Parkinson's or Alzheimer's disease, dementia, thyroid disorders, arthritis, stroke, cancer, heart disease, and other chronic conditions.
Depression is also a side effect of many drugs that are commonly prescribed for the elderly. It is often very difficult, then, to determine if the patient's depression is a psychologic reaction to the illness, caused by the disease itself, or completely independent from the medical condition. Both physical and emotional conditions should be considered in making a diagnosis in older people.

Many studies suggest strong associations between even mild depression and poorer quality of life as well as a shorter lifespan.

Risk for Suicide in the Elderly. Suicide in the elderly is the third-leading cause of death related to injury. Men account for 81% of these suicides, with divorced or widowed men at highest risk.

Effects of Depression on the Ability to Function. Even mild depressive symptoms in people aged 65 and above are associated with a higher risk of becoming disabled and having a lower chance of recovery.

Heart Disease and Heart Attacks. Depression increases the severity of a heart attack and may even impair a patient's response to medication for heart disease. Although people with heart disease may certainly become depressed, this does not explain entirely the link between the two problems. Data suggest that depression itself may be a true risk factor for heart disease as well as its increased severity. A number of studies indicate that depression has biologic effects on the heart, including a higher risk for blood clotting, changes in heart rate, and impaired blood flow to the heart (particularly in response to mental stress). The more severe the depression, the more dangerous to the health, although even mild depression, including feelings of hopelessness, experienced over many years, may harm the heart, even in people with no early signs of heart disease.

Mental Decline. Depression in the elderly is associated with a decline in mental functioning, regardless of the presence of dementia. Depression may be a predictor or even a cause of Alzheimer's disease. Brain scans in the elderly, for example, have reported greater atrophy in the brains of depressed individuals than in those of nondepressed ones.

Risk Factors

According to a major surveys, more than 13% of Americans have major depression disorder over the course of their lifetimes. Furthermore, an estimated 18 million Americans experience major depression each year. Depression is second only to high blood pressure as a chronic condition encountered by primary care doctors. Depression is an illness that can afflict anyone, regardless of age, race, class, or gender. A third of all depressed people consider suicide, and 9% attempt it.

Depression in Women. At any given time, 5 - 9% of women are depressed, compared to 1 - 3% of men. In one study, nearly half of all women surveyed had experienced depression at some point in their lives and over half of those who suffered from it had sought treatment. Women are also more apt to have multiple types of depression (dysthymia and major depression). [For more information, see Depression in Women.]

Depression in Men. Depression is not rare in men. In fact, prepubescent boys are more likely than girls of the same age to be depressed. Older men are also at much higher risk for suicide and, as with women, they are at risk for health complications of depression. Some evidence suggests that men are more apt than women to mask their depression by using alcohol, which may result in a lower reported (but not actual) incidence of depression in men. Some experts suggest that men with depression might be identified with the following indicators:

Low tolerance to stress
Behaviors such as "acting out" and being impulsive
A history of alcohol or substance abuse
A family history of depression, alcohol abuse, or suicide

Depression is less reported in the male population, but this may be caused by male tendency to mask emotional disorders with behavior such as alcohol abuse.

Depression in Children and Adolescents. Children ages 12 - 16 are at high risk for depression. Studies suggest that 3 – 5% of children and adolescents suffer from depression, and 10 – 15% have some depressive symptoms. Depression before puberty is more likely to occur in boys and after puberty in girls.

Depression in Adults. Surveys indicate that depression usually begins around the age of 30, although people do not generally seek treatment until they are about 33 years old. Statistics also suggest that depression is becoming more common among middle-aged people ages 45 - 64. According to a 2005 survey, middle-aged adults have the highest lifetime risk for depression.

Depression in the Elderly. Studies suggest that 5 – 14% of the elderly population suffer from some form of depression. In addition, the elderly are highly vulnerable to suicide. Elderly people comprise 13% of the U.S. population but account for 18% of all suicide deaths.

The role of society and economics has specific implications for women. [See Depression in Women.] Being in a low socioeconomic group is a major risk factor for depression in anyone. Money, of course, allows greater access to good medical care, but this factor does not fully explain the higher rates of depression in impoverished people. People at any income level are likely to be depressed if they have poor health and are socially isolated. Some studies suggest that Western cultural attitudes that link income to social status may play a significant role in the connection between poverty and depression:

In one British study, actual poverty or unemployment increased the duration of any existing depression, but it did not appear to play any important causal role. Feelings of financial insecurity, however, both caused and prolonged depression.
Another study reported that Mexican adults who immigrated to America had half the psychiatric illnesses as did Mexican-Americans born in the U.S., regardless of their income. But the longer the immigrants lived in the U.S., the greater their risk for psychiatric problems. Traditional influences of Mexican culture and social ties appeared to protect newly arrived immigrants from mental illness, even when they were poor. Eventually, however, the consequences of Americanization added to poverty and led to feelings of alienation and inferiority.

Depression in family members increases the risk for depression in other family members. Studies report that depression for even 1 - 2 months in a mother increases the risk for depression in her children. The more severe the maternal depression, the higher the risk for depression in the children. In a perpetuating cycle, being depressed as a child increases the risk for depression during adulthood. In such cases, genetic or environmental factors or both may be responsible. Spouses of partners with depression are themselves at higher risk for depression.

Patients who have had serious bouts of depression usually cite a stressful life event as the precipitating factor for their illness. Adverse events during childhood pose a higher risk for depression in adulthood. In one study, parental divorce, physical abuse, and frightening experiences were particularly associated with onset of depression in adulthood. Only divorce was associated with recurrence, however.

Adverse events in adulthood also trigger depression. Losing a spouse through divorce or death is a major risk factor for depression in anyone. In fact, recent loss of a loved one is the most frequently reported precipitant of acute depression. All major (and even minor) losses, however, cause grief reactions. People who develop acute or chronic depression after a loss may have predisposing factors, including genetic or biologic ones, which make them more vulnerable. The existence or absence of a strong social network of family, friends, or both also has a major positive or negative effect, respectively, on recovery. Most people are able to cope with the emotional pain and eventually move beyond it without becoming chronically depressed. [See Ruling out Grief and Loneliness in the diagnosis section of this report.]

Traumatic events such as abuse or even natural disasters can cause severe immediate or delayed depression from which recovery takes a long time.

Severe or Chronic Medical Conditions. Any chronic or serious illness that is life-threatening or out of a person's control can lead to depression.

Thyroid Disease. Hypothyroidism (a condition caused when the thyroid gland does not produce enough hormone) can cause depression. However, hypothyroidism may also be misdiagnosed as depression and go undetected.

Chronic Pain Conditions. Studies have reported a strong association between depression and headaches, including chronic tension-type and migraine. Some experts believe that a syndrome of migraine headaches (and also possibly tension-type), anxiety, and depression is caused by common factors, such as abnormalities in chemical messengers, particularly dopamine or serotonin. Fibromyalgia and other chronic pain syndromes are also associated with depression.

Stroke and Other Neurological Conditions. Having a stroke increases the risk of developing depression. Also, patients with Parkinson's disease, spinal cord injuries, and other similar problems that impair movement or thinking are associated with depression.

Heart Failure. Patients with heart failure or patients who have suffered a heart attack may also suffer from depression.

A number of drugs taken for chronic problems cause depression. Among them are pain relievers for arthritis, cholesterol-lowering drugs, medications for high blood pressure and heart problems, and bronchodilators used for asthma and other lung disorders.

There is a significant association between cigarette smoking and a susceptibility to depression. People who are prone to depression face a 25% chance of becoming depressed when they quit smoking, and this increased risk persists for at least 6 months. What's more, depressed smokers are unlikely to stop smoking. Only about 6% remain smoke-free after a year. Smokers with a history of depression are not encouraged to continue smoking, but rather to keep a close watch on recurrence of depressive symptoms if they do stop smoking. The antidepressant bupropion (Wellbutrin), which is approved for helping people quit smoking (marketed under the name Zyban), is proving to be very useful in helping smokers to quit.

Chronic depression is a frequent companion to anxiety disorders. In one study, up to 96% of patients with depressive disorders experienced concurrent anxiety. More than two-thirds of people with obsessive-compulsive disorder, a common anxiety disorder, also suffer from depression.

Some evidence suggests that certain personality styles, which include an intense need for close relationships and concern for disapproval or need for control, pose a high risk for depression, particularly after an adverse life event. In line with these findings, the following specific personality disorders have been associated not only to a first episode of depression, but also to relapses:

A person with borderline personality disorder acts impulsively and has a poor self-image and unstable relationships. In one study, patients with borderline personality disorder and major depression were more likely than those with either condition alone to plan and attempt suicide.
An individual with an avoidant personality avoids strangers and unfamiliar situations.

(Personality disorders, as opposed to emotional disorders, are those with abnormal behavioral patterns rather than abnormal emotions.)

Sleep abnormalities are an integral part of depressive disorders, with more than 90% of depressed patients experiencing insomnia. Although stress and depression are major causes of insomnia, insomnia may also increase the activity of the hormones and pathways in the brain that can produce emotional problems. Even modest alterations in waking and sleeping patterns can have significant effects on a person's mood. Persistent insomnia may even predict the future development of emotional disorders. Some experts think that some psychiatric disorders can be prevented by early recognition and treatment of insomnia.

Seasonal affective disorder (SAD) affects about one in 20 adults. About 80% of people who suffer from SAD are women. People who live in the north are more apt to experience SAD than people who live in southern latitudes.

Complications of Depression

Depression is often chronic, with episodes of recurrence and improvement. About one-third of patients with a single episode of major depression will have another episode within 1 year after discontinuing treatment, and more than 50% will have a recurrence at some point in their lives. Depression is more likely to recur if the first episode was severe or prolonged, or if there have been recurrences. To date, even newer antidepressants have failed to achieve permanent remission in most patients with major depression, although the standard medications are very effective in treating and preventing acute episodes.

About 90% of suicides are due to treatable disorders, most commonly depression or substance abuse. People with depression have up to a 15% risk for suicide, with the highest risk in patients who are hospitalized for depression. Some studies indicate that atypical depression poses a higher risk for suicide than typical depression and that dysthymia may pose a higher risk than episodic major depressive disorder. Depressed men are more likely to commit suicide than depressed women. Around the world, suicide is most common in men older than 60. Suicidal preoccupation or threats of suicide should always be treated seriously in anyone, however. [See Depression in the Elderly or Depression in Children in this report.]

Major depression in the elderly or in people with serious illness seems to reduce their survival rates, even independently of any accompanying illness. Decreased physical activity and social involvement certainly play a role in the association between depression and illness severity.

Effect on Heart Disease and Other Age-Related Problems. Many studies report strong associations between depression and a worse and even shorter old age. Depression is also associated with mental decline in older people.

Studies are now showing that depression may contribute to poor outcomes for patients with heart disease.

Obesity. Both obesity and depression are increasing in Americans. Adolescents who are depressed have a high risk for obesity. Conversely, obese people are about 25% more likely than non-obese people to develop depression or other mood disorders. The conditions may have common risk factors. For example, being in a lower social and economic group increases the risk for both obesity and depression. Low physical activity may also be a common factor.

Increasing Sensations of Pain. Depression coincides with increased pain in people with conditions such as those arthritis or fibromyalgia.

Cancer. The relationship between depression and cancer has been explored for years with only a few clear-cut associations. Certainly depression and anxiety can have a profound impact on quality of life in cancer patients.

Effects of Parental Depression on Children. Depression in parents can have profound effects on their children and may increase the risk for childhood depression.

Effects on Marriage. In one survey, nearly half of people who suffered from psychiatric disorders before or during their first marriage were divorced, compared to a divorce rate of 36% in those who never suffered from emotional disorders. Spouses of partners with depression are themselves at higher risk for depression.

Effect on Work. Depression is well-known to adversely affect a person's work life. It significantly increases the risk for unemployment and lower income. Nearly half of the nation's excess lost productive time (in most cases because of reduced performance at work) may be a result of depression. Workers with depression also lose significantly more time due to ill health than non-depressed workers. Such lost time is estimated to cost the country billions of dollars each year.

Alcohol and Drug Abuse. About 14% of people with major depression also have an alcohol use disorder and 5% have drug abuse problems. Studies on the connections between alcohol dependence and depression have still not resolved whether one causes the other or if they both share some common biologic cause.

Smoking. Depression is a well-known risk factor for smoking, and 26% of people with major depression are nicotine dependent. Nicotine may stimulate receptors in the brain that improve mood in certain people with genetically induced depression.

Diagnosis

Most people who are depressed do not seek psychiatric help and must rely on their family doctor. Unfortunately, it is often difficult for a primary care doctor to recognize the problem if the patient does not bring it up directly.

Patients themselves may be unable to sense or admit their own depression. In one study, although 21% of patients who visited their family doctors were depressed, only 1% described their problem as depression.

Depression can also be confused with other medical illnesses. Weight loss and fatigue, for example, accompany many conditions, some serious, but they can also occur with depression.

Although not all patients who visit their doctor should be screened for depression, individuals who have certain factors might ask their doctor if they should be screened for depression. For example, the following people may be at higher risk and therefore warrant a screening test:

People with a family or personal history of depression
Patients with multiple medical problems
Patients with physical symptoms that have no clear medical cause
Patients with chronic pain
Individuals who visit their doctor more frequently than expected

A mental health specialist, such as a psychiatrist, social worker, or psychologist, is the best source for a diagnosis of depression. Such health professionals may administer a screening test such as the Beck Depression Inventory or the Hamilton Rating Scale, both of which consist of about 20 questions that assess the individual for depression. Studies are finding that even computerized phone interviews are valuable as screening tools for depression. However, most mental health professionals generally diagnose depression based on symptoms and other criteria.

Specific ethnic groups may present different symptoms of depression. People from non-Western countries are more apt to report physical symptoms (such as headache, constipation, weakness, or back pain) related to the depression, rather than mood-related symptoms.

Grief. The symptoms of grief (bereavement) and depression have much in common; indeed, it may be difficult to separate the two. Grief, however, is considered to be a healthy and important emotional response for dealing with loss, and it generally follows a characteristic path:

Grief normally has a limited duration. In people without any co-existing emotional disorder, bereavement usually lasts between 3 - 6 months.
The grieving person typically endures a succession of emotions that include shock and denial, loneliness, despair, social alienation, and anger.
The recovery period following this process, during which the individual becomes re-involved with life, takes about the same amount of time as the bereavement cycle.

If the grief is still severe after this period, however, it may affect a person's health or increase the risk for on-going depression. Some experts suggest that such a severe persistent grieving state be categorized as a separate psychologic diagnosis, termed complicated grief disorder, which would be related to post-traumatic stress syndrome and require special treatment.

Loneliness. Like grief, loneliness is a condition that may often be mistaken for depression. In fact, while loneliness and depression often go hand in hand, some researchers believe that some people with loneliness may be effectively treated for depression. Of course, every person feels loneliness now and then. Debilitating loneliness, however, is often characterized by misery, a feeling of hollowness, unrealistic expectations for one's life, and feeling removed from others. Shy people may be more prone to loneliness. Psychotherapy of various kinds may help people address and allay loneliness.

Treatment

Depression is a treatable illness, with many therapeutic options available. Increasingly, professionals are viewing major depression as a chronic illness (the condition nearly always returns when treatment is stopped). Therefore, medical intervention and help must be ongoing.

Patients with chronic depression have a number of options, including psychotherapy, antidepressants, or both. In general, the treatment choice depends on the degree and type of depression and other accompanying conditions. It also may depend on age, pregnancy status, or other individual factors.

Unfortunately, many Americans with major depression receive either inadequate treatment or no treatment at all. Reasons may include treatment by providers who may not have sufficient information or training on dosages or specific drugs that would be best suited for individual cases, lack of recognition of depression symptoms by providers, poor access to health care services, lack of health insurance, and poor compliance with medications.

Patients with Major Depression. Numerous studies support a combination of cognitive behavioral therapy (CBT) plus antidepressants, typically a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI). Although some people may feel better after taking antidepressants for a few weeks, most people need to take medication for at least 6 - 12 months to ensure a full response. Research indicates that patients respond better to medications when drug therapy is combined with CBT. Exercise is also important in helping relieve depressive symptoms.

For patients who are not helped by SSRIs or SNRIs, other types of antidepressants are available. Sometimes an atypical antipsychotic drug may be given in combination with an antidepressant for patients with severe major depressive disorder.

Brain stimulation techniques, such as electroconvulsive therapy (ECT) and vagus nerve stimulation, are also options. In recent years, experimental procedures, such as repetitive transcranial magnetic stimulation, have also been found to help in some cases of treatment-resistant depression. Researchers are also investigating new types of drugs (such as ketamine), which may provide a rapid, if temporary, improvement for these patients. In general, the more treatment strategies that patients need, the less likely they are to recover completely from depression.

Patients with Minor Depression. Patients with minor depression (fewer than five symptoms that persist for fewer than 2 years) may respond well to watchful waiting to see if antidepressants are necessary. Some studies indicate that antidepressants do not work that well for mild depression. Counseling or cognitive behavioral therapy may be helpful, as is regular exercise.

Patients with Depression and Other Psychiatric Problems. Other psychiatric problems often coexist with depression. If patients also suffer from anxiety, treating the depression first often relieves both problems. More severe psychiatric problems, such as bipolar disorder or schizophrenia, require specialized treatments.

Patients with Depression and Medical Conditions. Depression can worsen many medical conditions and may even increase mortality rates from some disorders, such as heart attack and stroke. Depression, then, should be aggressively treated in anyone with a serious medical problem.

Patients with Depression and Substance Abuse Problems. Treating depression in patients who abuse alcohol or drugs is important and can sometimes help patients quit. However, absence from substance abuse is considered essential for adequate treatment of depression.

Most people with depression can be treated in an office setting by a psychiatrist or other therapist. Infrequently, the level of dysfunction may be serious enough to warrant hospitalization to provide protection from further deterioration or self-harm.

Health professionals who can prescribe antidepressants include:

Doctors, including psychiatrists
Some nurse clinicians

Although other mental health professionals cannot prescribe drugs, most therapists have arrangements with a psychiatrist for providing medications to their patients. In general, mental health professionals are categorized by their training:

Psychoanalysts tend to have a degree in psychiatry, psychology, or social work as well as several years of training at a psychoanalytic institute.
Psychologists have received a Ph.D, including an internship in a mental healthcare facility.
A clinical social worker has a master's degree and 2 years of supervised experience in mental health and human services.
Advanced-practice psychiatric nurses have a master's degree and can provide therapeutic services.

Tips for Selecting a Therapist:

Patients can locate a mental health professional in their area by asking their doctor for a referral or by contacting a mental health organization. [See Resources.]
The patient should describe problems briefly but specifically over the phone to any prospective therapist to get a sense of whether he or she will suit the patient's needs.
An advanced degree does not necessarily guarantee quality therapy. The patient's belief in their health care provider may be the most important component in recovery.
Patients should not be shy about considering a change in their therapist if they lack confidence in their current one.

Although a mother's depression during and after pregnancy can have serious effects on her child, researchers are still trying to determine the best methods for preventing and treating pregnancy-related depression.

The use of antidepressants during pregnancy is controversial, especially for women with major depression who regularly take antidepressant medication. Most doctors advise women to avoid, if possible, any medications during pregnancy and nursing. But, women with depression who stop taking antidepressants during pregnancy may be likely to have a relapse of depression. Women who are pregnant or thinking about becoming pregnant should not stop taking antidepressants without first talking to their doctors.

Some research suggests that certain serotonin reuptake inhibitors (SSRIs) may increase risks for the fetus. The strongest evidence concerns the SSRI paroxetine (Paxil), which can cause major birth defects -- including heart abnormalities -- if taken during the first trimester of pregnancy. In 2006, the American College of Obstetricians and Gynecologists recommended that doctors should not prescribe paroxetine to women who are pregnant or planning on becoming pregnant.

Other research indicates that first-trimester use of SSRIs may increase the risk for rare skull and neural tube defects. Venlafaxine (Effexor), a dual inhibitor antidepressant, has been associated with birth complications when taken during the last trimester. In addition, some studies have shown that babies may experience withdrawal symptoms if their mothers take SSRIs late in pregnancy. However, the overall evidence indicates that there is a very low overall risk for antidepressant-associated birth defects and problems. Still, women should discuss all potential risks with their doctors.

In terms of non-drug treatment of postpartum depression, a review of 15 clinical trials suggested that postpartum depression is best treated by intensive and individualized psychotherapy within a month after a woman gives birth. The researchers found that women are too busy in the weeks before birth to attend prenatal classes that focus on preventing postpartum depression.

Some experts recommend only psychotherapy or attention intervention for elderly patients with mild depression. In many older patients, a regular exercise program may be sufficient to improve mood. Ideally, elderly people with more serious depression should be treated with a combination of psychotherapy and antidepressants on an ongoing basis, even after their depressive symptoms are relieved.

The use of antidepressants in the elderly is problematic:

Tricyclics are as effective as, and less expensive than, SSRIs, but they have more side effects. Specifically, they pose a higher risk for adverse effects on the heart and possibly the lungs. (The older tricyclics, such as amitriptyline and imipramine, have other severe side effects in older adults.)
SSRIs have fewer side effects than tricyclics. However, SSRIs may not pose any lower risk for falls than the older tricyclic antidepressants. In addition, researchers are investigating whether SSRIs are associated with an increased rate of osteoporosis (“thin bones”) and fractures in older adults.

About 2% of American primary school-age children and 4 - 8% of adolescents suffer from depression. Studies suggest that when children or adolescents are treated, up to 80% recover. Still, 25 - 50% of these young people have a recurrence of depression within 2 years of their first episode of depression.

It is important to recognize that childhood depression differs from adult depression and that children may respond differently than adults to antidepressant medication. These variances are due to childhood brain development processes as well as age-related differences in drug metabolism. Children may experience medication side effects not seen in adults, and some antidepressants that are effective for adults may not work for children.

Mild-to-Moderate Depression. The pediatrician may want to monitor a child with mild depression for 6 - 8 weeks before deciding whether to prescribe psychotherapy, antidepressant medication, or a referral to a mental health professional. Once medication has been started, the doctor will decide if the dosage needs to be increased after another 6 - 8 weeks. Medication may need to be continued for 1 year after the symptoms have resolved, and the doctor should continue to monitor the child on a monthly basis for 6 months after full remission of depression. For psychotherapy, cognitive therapy may be the best approach for children and adolescents with depression. Some studies suggest that other types of psychotherapy, such as family therapy and supportive therapy, can also be very effective.

Severe Depression. The American Academy of Child and Adolescent Psychiatry recommends an SSRI antidepressant for children and adolescents with very severe depression that does not respond to psychotherapy. Tricyclic antidepressants do not tend to help adolescents and children and these drugs have many side effects. MAOIs are also not commonly prescribed.

Many SSRIs appear to be safe and effective, but at this time fluoxetine (Prozac) is the only one approved for children over age 7 and for adolescents. The FDA strongly advises against the use of specific SSRIs, such as paroxetine (Paxil), due to concerns about an increased risk for suicidal behavior as well as the lack of any evidence supporting the drug's efficacy in pediatric patients. On an encouraging note, a 2007 review in the Journal of the American Medical Association indicated that the overall benefits of antidepressants for children and adolescents appear to be much greater than the risks for suicidal behavior. Still, the study found that antidepressants have only modest benefits for major depressive disorder, which underlines the importance of adjunctive psychotherapy.

For optimal results, SSRIs should be combined with either cognitive-behavioral or interpersonal psychotherapies. A study of adolescents with depression reported that combination treatment with fluoxetine and cognitive behavioral therapy was more effective than either treatment alone.

Due to potential suicide risks, children and adolescents should be monitored regularly during the initial months of antidepressant treatment. [For more detailed information, see Suicide Risk and Antidepressant Medications.]

Antidepressants and Drug Treatment Guidelines

Major classes of antidepressants include:

Selective serotonin-reuptake inhibitors (SSRIs). These have become the standard antidepressants. They target the brain chemical (neurotransmitter) serotonin. They are effective and have very moderate side effects. Some may be beneficial in treating anxiety and certain subtypes of depressive disorders unresponsive to previous drugs, including premenstrual dysphoric disorder and seasonal affective disorder, atypical depression, and recurrent brief depression.
Other neurotransmitter inhibitors. These drugs target neurotransmitters other than or in addition to serotonin, such as norepinephrine. Many are proving to be effective in patients who do not respond to standard antidepressants or in specific patients, such as smokers who want to quit or patients with chronic pain.
Tricyclic antidepressants (TCAs). These drugs are effective but can have severe adverse effects, particularly in older people.
Monoamine oxidase inhibitors (MAOIs). These drugs include newer selective MAOIs. MAOIs are the most effective antidepressants for atypical depression, but have some severe side effects and require restrictive dietary rules.
St. John's wort and other herbal remedies are included in the Lifestyle section of this report.

Approach and Duration of Initial Treatment. The guidelines for the duration of an initial antidepressant regimen is as follows:

Patients should start at a low dose, which is increased over a period of 5 - 10 days.
Patients should see their doctor every 1- 2 weeks until substantial improvement occurs. It may take 4 - 8 weeks before a patient experiences the effects of any antidepressant.
Side effects usually diminish within 1 - 4 weeks. (Exceptions may be weight gain and sexual dysfunction.)
If no improvement occurs, an alternative drug may be tried. More than 80% of patients respond to some antidepressant, although specific drugs are helpful for only about half of patients. This suggests that if one medication fails, another has a good chance of being helpful. In general, the fewer drug treatment strategies required, the better a patient’s chances of recovering completely from depression. Patients who become symptom-free have the best chance for complete recovery compared to patients whose symptoms merely improve.
In general, patients should continue taking antidepressants for at least 6 months after symptom relief to help prevent relapse. (Patients who improve within 2 weeks of taking medications may not require lengthy treatment.)

Treating Recurrence. Recurrence of depression is very common. About a third of patients will relapse after a first episode within a year of ending treatment, and more than half will experience a recurring bout of depression at some point during their lives. Among those at highest risk for early relapse and who may require ongoing antidepressants are:

Patients with at least two episodes of major depression or major depression that lasts for 2 years or longer before initial treatment.
Patients who continue to have low-level depression for 7 months after starting antidepressant treatments.

Patients may need maintenance therapy. Experts disagree, however, on the optimal length or the appropriate dosage of maintenance therapy. Some patients may need to stay on antidepressants for 1 - 2 years -- or even indefinitely. Some experts recommend withdrawing from medication after a year. (This should be done gradually, over 2 - 3 months.) If depression recurs, the patient should go back on the antidepressants.

There is no risk for addiction with current antidepressants, and many of the common antidepressants, including most standard SSRIs, have been proven safe when taken for a number of years.

Common Side Effects of Most Antidepressants. No matter how well a drug treats depression, the ability of the patient to tolerate its side effects strongly influences their compliance with therapy. Lack of compliance is probably the major barrier to success. Side effects can be avoided or moderated if any regimen is started at low doses and built up over time. Although specific side effects are discussed under individual drugs, there are a few that are common to many of them:

Sexual dysfunction is a common side effect of many of the standard antidepressants and some of the newer drugs. These side effects can be particularly distressing for patients on maintenance treatment who otherwise feel well. Some of the newer antidepressants, such as bupropion, may be effective alternatives without as high a risk for this problem. Sildenafil (Viagra), used for erectile dysfunction in men, may help reverse sexual dysfunction from antidepressants. It does not heighten sexual interest, however.
An increased risk of oral health problems caused by dry mouth is associated with long-term use of most antidepressants. Patients can increase salivation by chewing gum, taking vitamin C tablets, using saliva substitutes, and rinsing the mouth frequently.
Virtually all antidepressants have complicated interactions with other drugs; some are very important. Patients should inform the doctor of any drugs they are taking, including over-the-counter medications and herbal remedies.
Nearly all antidepressants are metabolized in the liver, so anyone with liver abnormalities should use them with caution.
Abrupt withdrawal from many antidepressants can produce severe side effects; no antidepressant should be stopped abruptly without consultation with a doctor.

In recent years, there has been concern that SSRI antidepressants may increase the risk for suicidal behavior. Of particular concern is a greater risk for suicide in young people taking these medications. While depression is itself the major risk factor for suicide, and antidepressant medication may revitalize suicidal attempts in patients who were too despondent before treatment to make the effort, evidence suggests that in some cases the medication itself can cause suicidal behavior. One specific SSRI, paroxetine (Paxil), has been definitely linked with suicidal behavioral risk in adults ages 18 - 30. In May 2006, the drug’s manufacturer warned doctors that all patients, and particularly young adults, should be carefully monitored during paroxetine therapy.

The U.S. Food and Drug Administration (FDA) has been conducting in-depth research on suicide risk and antidepressant medications. In October 2004, after careful review of scientific evidence, the FDA issued a public health advisory instructing drug manufacturers to include a "black box" warning explaining the association between antidepressant use and increased risk for suicidality (suicidal thoughts and behavior) in children and adolescents. In May 2007, the FDA proposed that the labels of antidepressant medications should include additional warnings about the risk of suicidal thoughts and behavior in young adults (ages 18 - 24) during the first 1 - 2 months of treatment. The FDA also notes there is a decreased risk of suicidality for adults age 65 years and older taking antidepressants.

The FDA based its recommendations for children and adolescents on a review of 24 clinical trials of nine antidepressant drugs. These trials enrolled over 4,400 pediatric patients and tested the safety and efficacy of SSRIs as well as other classes of antidepressants. The data suggested a greater risk for suicidality within the first few months of treatment. The average risk was minimal. Children and adolescents treated with these drugs had a 4% risk for suicidality compared with 2% for patients who received placebo. No patients in these studies actually committed suicide.

Based on these findings, the FDA recommends that caregivers monitor children being treated with antidepressants for sudden behavioral changes, and immediately notify their doctor if such changes occur. These behavioral signs include:

Agitation
Irritability
Anxiety
Panic attacks
Insomnia
Aggressiveness
Impulsivity
Hyperactivity in actions and speech
Worsening of depression
Increased thoughts of suicide

The FDA’s guidelines for medication usage recommend that patients see their doctor regularly after initiating drug treatment. The recommended schedule is:

Once per week for 4 weeks (1st month)
Every 2 weeks for the next month (2nd month)
At the end of week 12 following the start of drug treatment (3rd month)
More frequently if changes in mood or behavior occur
Patients should also be closely monitored if their drug dosage is changed.

Patients should immediately contact their doctor if depression symptoms worsen or if suicidal thoughts or behavior increase.

Selective serotonin-reuptake inhibitors (SSRIs) are now the first-line treatment of major depression. They work by increasing levels of serotonin in the brain. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro). There are no significant differences among SSRI brands in effectiveness for treating major depressive disorder, although individual drugs may have different side effects or benefits for specific patients. At this time, fluoxetine is the only one of these drugs to be approved for children over age 7 and adolescents.

Because they act specifically on serotonin, SSRIs have fewer side effects than older antidepressants, which have more widespread effects in the body.

Candidates for SSRIs. SSRIs appear to help people with the following conditions:

Mild to moderately severe major depression
Seasonal affective disorder
Dysthymia
Severe premenstrual syndrome and premenstrual dysphoric disorder (PMDD) -- a repackaged form of fluoxetine (Sarafem) is the first SSRI specifically FDA-approved for PMDD. Other SSRIs and newer antidepressants are also proving to be effective
Anxiety disorders
Bulimia
Impulsive and aggressive behaviors in psychiatric patients and in people with no mental health problems

Duration of Effectiveness and Use. SSRIs take, on average, 2 - 4 weeks to be effective in most adults. They may take even longer, up to 12 weeks, in the elderly and in those with dysthymia. By 14 weeks, depression should be in remission in everyone who responds to the drugs. Unfortunately, recurrence is common once the drugs are stopped. Studies indicate that the standard SSRIs are generally safe, although it is still unclear which patients would most benefit from on-going medication. Some doctors recommend withdrawing from medication after a year. If depression recurs, then the patient should go back on the antidepressant.

Side Effects of SSRIs. Side effects may include:

Nausea and gastrointestinal (GI) symptoms usually wear off over time.
Agitation, insomnia, mild tremor, and impulsivity occur in 10 - 20% of people who take SSRIs. These symptoms may be particularly problematic in patients who also suffer from anxiety, sleeplessness, or both.
Drowsiness affects about 20% of SSRI-treated patients. Newer SSRIs, such as escitalopram (Lexapro), may have fewer of these adverse effects.
Dry mouth is a common side effect.
Patients may lack motivation, feel tired, be confused, and experience mental dullness, but this side effect is fairly rare.
Headache and flu-like symptoms may occur.
Heart palpitations and chest pain may occur.
Weight gain varies depending on the SSRI. For example, in one study patients who took paroxetine (Paxil) experienced five times the weight gain as those who took citalopram (Celexa). Patients should be encouraged to maintain a low-calorie diet and to exercise. They should be aware that some of the weight-loss medications, notably sibutramine (Meridia), can have serious interactions with SSRIs.
Sexual side effects include delayed or loss of orgasm and low sexual drive. They are a well-known side effect of SSRIs. Taking a supervised drug "holiday" on the weekend may improve sexual function during that time. Some of the newer SSRIs or other antidepressants may cause less severe impairment of sexual function.
Paroxetine (Paxil) may cause birth defects if taken during the first 3 months of pregnancy. Most reported defects have been heart-related. The most common heart abnormalities are ventricular septal defects, which are holes in the muscular wall that separate the main pumping chambers of the heart. Venlafaxine (Effexor) has also been associated with birth defects. Still, recent research suggests that most types of SSRI-associated birth defects are rare and the overall risks are low. Pregnant women who are being treated for major depression should not stop taking antidepressants without first talking to their doctors. [For more information on antidepressant treatment guidelines during pregnancy, see Treating Depression During and After Pregnancy in Treatment section.]

Drug Interactions. SSRIs can interact with other antidepressants such as tricyclics and, in particular, monoamine oxidase inhibitors (MAOIs). SSRIs should never be taken in combination with an MAOI or within 2 weeks after discontinuing MAOI treatment. Other serious interactions have occurred with meperidine (Demerol) and illegal substances (such as LSD, cocaine, or ecstasy). People who take SSRIs may drink alcohol in moderation, although the combination may compound any drowsiness experienced with SSRIs, and some SSRIs increase the effects of alcohol.

Withdrawal Symptoms. Cognitive problems, sleep disturbances, increase in depressive symptoms, and electric shock-like symptoms have been known to occur with sudden discontinuation of SSRIs. The symptoms are more likely to occur with antidepressants with shorter half-lives as compared with fluoxetine, which has a long half-life. The dose of the antidepressant should be slowly reduced before stopping.

These newer antidepressants target other neurotransmitters, such as norepinephrine or dopamine, alone or in addition to serotonin. In general, the advantages of the new designer antidepressants are:

They may be better tolerated than the older tricyclic compounds and even some SSRIs, although long-term side effects are not fully known in this group.
Most of these drugs have fewer adverse effects than SSRIs on sexual function.
They may be more effective than SSRIs for severely depressed patients.
Some of these drugs are helpful for additional problems -- such as insomnia, fibromyalgia and similar chronic pain syndromes, or smoking -- that may affect people with depression.

They do share some side effects with other antidepressants, including dizziness and dry mouth.

Dual Inhibitors. Dual inhibitors act directly on two neurotransmitters -- norepinephrine and serotonin. These drugs are also known as serotonin norepinephrine reuptake inhibitors (SNRIs). The following SNRIs are approved for treatment of major depression in adults:

Venlafaxine (Effexor) is similar to Prozac in effectiveness and tolerability for most patients. As with SSRIs, venlafaxine may impair sexual function. The drug can increase blood pressure and heart rate and should be used with caution in patients with high blood pressure or heart disease. It can also cause uterine and vaginal bleeding unrelated to menstruation. Venlafaxine should not be taken during the last trimester of pregnancy as it can cause complications in newborn infants. Some patients report severe withdrawal symptoms, including dizziness and nausea. In 2006, the drug’s manufacturer warned of an increased overdose risk and advised doctors to prescribe their patients only small amounts of venlafaxine pills.
Duloxetine (Cymbalta) also acts on both serotonin and norepinephrine. Side effects are generally mild and include dry mouth, nausea, and sleepiness. Patients with narrow-angle glaucoma or patients with liver or kidney diseases should not take duloxetine. Because duloxetine can cause liver damage, patients who drink large quantities of alcoholic beverages should not take it. Signs of liver damage include itching, dark urine, yellowing of skin and eyes (jaundice), and fatigue. Patients should immediately contact their doctor if they experience these symptoms.
Mirtazapine (Remeron) can cause sleepiness, increased appetite, weight gain, and dizziness.

Other Antidepressants with Effects on Multiple Neurotransmitters. Bupropion (Wellbutrin, Zyban) affects the reuptake of serotonin, norepinephrine, and dopamine -- a third important neurotransmitter. In addition to depression, bupropion is also approved for smoking cessation and for treating seasonal affective disorder (SAD). Bupropion causes less sexual dysfunction than SSRIs. About 25% of patients experience initial weight loss. Side effects include restlessness, agitation, sleeplessness, headache, and stomach problems. Bupropion has a risk for seizures, which increases with higher doses. High doses may also cause dangerous heart arrhythmias.

Before the introduction of SSRIs, tricyclics were the standard treatment for depression.

Tricyclics are sometimes grouped into two categories:

Tertiary amines include amitriptyline (Elavil, Endep) and imipramine (Tofranil).
Secondary amines include desipramine (Norpramin) and nortriptyline (Pamelor, Aventyl). Secondary amines may have fewer side effects, including drowsiness, than tertiary amines, but they are as toxic in high amounts.

Less commonly used tricyclics include doxepin (Sinequan), amoxapine (Asendin), maprotiline (Ludiomill), protriptyline (Vivactil), trimipramine (Surmontil), mianserin (Bolvidon), and dothiepin (Prothiaden).

Tricyclics are as effective for treating depression but they have many side effects. They may offer benefits for many people with dysthymia, who generally do not respond to SSRIs. They may also be prescribed in lower dosages to be taken at night to help with insomnia.

Side Effects of Tricyclics. Side effects are common with these medications. In fact, in an analysis of studies, more tricyclic users discontinued their drugs due to side effects than did SSRI or MAOI users. Those most often reported include:

Dry mouth
Constipation
Blurred vision
Sexual dysfunction
Weight gain
Difficulty urinating
Drowsiness
Dizziness -- blood pressure may drop suddenly when sitting up or standing.

Tricyclics can have serious, although rare, side effects:

They tend to cause disturbances in heart rhythm, which can pose a danger for some patients with certain heart diseases. Care should be taken when these medications are prescribed to the elderly and to those at risk of overdose.
Also of concern are reports that tricyclics, particularly imipramine as well as mianserin and dothiepin, may increase the risk for a lung disease called idiopathic pulmonary fibrosis (IPF), which can cause lung inflammation and scarring. Initial symptoms are breathlessness and dry cough.
Tricyclics can be fatal with an overdose.
Protriptyline can cause sun sensitivity. People who take this drug should take precautions against sunlight when they go outdoors.

Monoamine oxidase inhibitors (MAOIs) block monoamine oxidase, an enzyme which has negative effects on many of the neurotransmitters that are important for well-being. MAOIs include phenelzine (Nardil), isocarboxazid (Marplan), and tranylcypromine (Parnate). Because these drugs can have very severe side effects, they are usually prescribed only when other types of antidepressants do not help. Research indicates that MAOIs are an effective option for atypical and treatment-resistant depression.

Newer MAOIs, such as selegiline (Eldepryl, Movergan), target only one form of the MAOI enzyme. They may cause fewer side effects than older MAOIs. In 2006, a skin patch form of selegiline (Emsam) was approved for treatment of major depressive disorder in adults.

Candidates for MAOIs. MAOIs may be effective for the following conditions:

Atypical depression
Eating disorders
Post-traumatic stress disorder
Borderline personality

Side Effects. MAOIs commonly cause the following side effects:

Orthostatic hypotension (a sudden drop in blood pressure upon standing)
Drowsiness or insomnia
Dizziness
Sexual dysfunction
The most serious side effect is severe hypertension (high blood pressure), which can be brought on by eating certain foods having high tyramine content. Such foods include aged cheeses, most red wines, sauerkraut, vermouth, chicken livers, dried meats and fish, canned figs, fava beans, and concentrated yeast products.
MAOIs can cause birth defects and should not be taken by pregnant women.

Very dangerous side effects, such as serotonin syndrome, can occur from interactions with other antidepressants, including SSRIs. Serotonin syndrome is a potentially fatal condition that is caused by the interaction of serotonergic drugs. Symptoms include confusion, agitation, sweating and shivering, and muscle spasms. There should be at least a 2-week break between taking MAOIs and other antidepressants. MAOIs can have serious interactions with other drugs as well, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctors any other medications they are taking.

If patients fail to respond to antidepressants, doctors may try adding on a different type of drug. (This combination strategy is called “augmentation” or “adjunctive treatment”.) Atypical antipsychotics are drugs that are usually prescribed for schizophrenia or bipolar disorder, but they can also play a role in the treatment of severe depression. In 2007, aripiprazole (Abilify) was approved in combination with antidepressant therapy for treatment of adults with major depressive disorder. Investigators are also studying whether combination treatment with the atypical antipsychotic risperidone (Risperdal) can help patients with major depression achieve remission.

Ketamine. Ketamine, an anesthetic drug, may be helpful for patients with severe treatment-resistant depression. In a small preliminary study, a single intravenous dose of ketamine helped patients quickly recover from depression within 2 hours, and some patients sustained benefits for up to a week. (Standard antidepressant drugs usually take about 8 weeks to have an effect.) Ketamine blocks the NMDA brain protein receptor, which is involved in glutamate regulation. Glutamate is a brain chemical that is thought to be involved in depression.

Psychotherapy

Among the various psychotherapies, cognitive-behavioral therapy appears to be the most effective approach. If psychotherapy is used alone without medications, benefits should be evident within 8 weeks and symptoms should be fully resolved by 12 weeks. If these conditions are not met, then the patient should strongly consider antidepressant drugs.

In a major analysis of four randomized comparative studies, cognitive behavior therapy worked as well as antidepressants in treating severe depression for many patients. Much of the success of psychologic therapy depends on the skill of the therapist. Many studies suggest that combining cognitive therapy with antidepressants offer the greatest benefits for many patients, particularly for dysthymia (chronic depression).

Medical evidence also has found that the benefits of cognitive therapy persist after treatment has ended. Cognitive behavioral therapy has been shown to help prevent future suicide attempts in patients with a history of suicidal behavior.

Best Candidates. Cognitive therapy may be particularly helpful for the following patients:

Patients with atypical depression
Adolescents with mild symptoms of major depression
Women with non-psychotic postpartum depression
Children of parents with the disorder -- in this case, therapy should involve the whole family.
Cognitive therapy does not appear to be as beneficial as antidepressants for most patients with dysthymia.

Approach. This approach focuses on identification of distorted perceptions that patients may have of the world and themselves, on changing these perceptions, and on discovering new patterns of actions and behavior. These perceptions, known as schemas, are negative assumptions developed in childhood that can precipitate and prolong depression. Cognitive therapy works on the principle that these schemas can be recognized and altered, thereby changing the response and eliminating the depression.

First, the patient must learn to recognize depressive reactions and thoughts as they occur, usually by keeping a journal of feelings about, and reactions to, daily events.
The patient is often given "homework" that tests old negative assumptions against reality and demands different responses.
Then, the patient and therapist examine and challenge these entrenched and automatic reactions and thoughts.
As the patient begins to understand the underlying falseness of the assumptions that cause depression, they can begin substituting new ways of coping.

Over time, such exercises help build confidence and eventually alter behavior. Patients may take group or individual cognitive therapy. Cognitive therapy is a time-limited treatment, typically lasting 12 - 14 weeks. Extending this period, however, may help prevent relapse. In one study, therapy was continued for 10 sessions over an additional 8 months. This extended treatment significantly reduced the risk of recurrence. In fact, some experts believe that short-term therapy is not effective for patients with chronic or relapsing psychiatric disorders.

Based in part on psychodynamic theory, interpersonal therapy acknowledges the childhood roots of depression, but focuses on symptoms and current issues that may be causing problems. IPT is not as specific as cognitive or behavioral therapy, and all work is done during the sessions. The therapist seeks to redirect the patient's attention, which has been distorted by depression, toward the daily details of social and family interaction. The goals of this treatment method are improved communication skills and increased self-esteem within a short period (3 - 4 months of weekly appointments) of time. Among the forms of depression best served by IPT are those caused by distorted or delayed mourning, unexpressed conflicts with people in close relationships, major life changes, and isolation.

The intent of supportive psychotherapy or attention intervention is to provide the patient with a nonjudgmental environment by offering advice, attention, and sympathy. Supportive therapy appears to be particularly helpful for improving compliance with medications by giving reassurance, especially when setbacks and frustration occur.

Other Treatments

Electroconvulsive therapy (ECT) is commonly called shock treatment. It has received bad press, in part for its potential memory-depleting effect. Since its introduction in the 1930s, ECT has been significantly refined, and is now considered an effective and safe treatment for severe depression in the appropriate situation. It is especially effective for patients with severe depression who experience delusions and hallucinations. Maintenance ECT may also help prevent relapse.

Candidates for ECT. ECT may be helpful for the following patients with severe depression:

Patients who cannot, for any reason, take antidepressant drugs
Suicidal patients
Elderly patients who are psychotic and depressed
Pregnant women with severe depression
Patients with certain heart problems
Young patients who fit the adult criteria for ECT

The Procedure. In general, hospitalization is not necessary. ECT involves the following steps:

The patient receives a muscle relaxant and short-acting anesthetic.
A small amount of electric current is sent to the brain, causing a generalized seizure that lasts for about 40 seconds.
Most patients receive 6 treatments, spaced every 2 - 5 days. Others receive up to 15 treatments, followed by 6 - 12 additional treatments spaced every other week or longer for another 2 - 4 months.

Side Effects. Side effects of ECT may include temporary confusion, memory lapses, headache, nausea, muscle soreness, and heart disturbances. Concerns about permanent memory loss appear to be unfounded.

Transcranial magnetic stimulation (TMS) uses high frequency magnetic pulses that target affected areas of the brain. This investigational treatment is similar to electroconvulsive therapy (ECT) but, unlike ECT, it is more precise. However, it is not yet clear whether it as effective as ECT. Researchers are continuing to refine rTMS techniques to improve treatment outcomes.

Vagus nerve stimulation (VNS) is a procedure that is effective for certain patients with epilepsy, and is now showing some success in patients with treatment-resistant depression

VNS involves implanting a battery-powered device under the skin in the upper left of the chest. The neurologist programs the device to deliver mild electrical stimulation to the vagus nerve. The two vagus nerves are the longest nerves in the body. They run along each side of the neck, then down the esophagus to the gastrointestinal tract. The vagus nerve travels to areas of the brain that control functions such as sleep and mood.

Studies report response rates of 35 - 46% in appropriate candidates with treatment-resistant depression. VNS is approved by the FDA for long-term treatment of chronic depression in adults who have not responded to typical treatments for their major depressive episode. Patients who use VNS may continue to show improvement in both their depression symptoms and quality of life.

Vagal stimulation can cause shortness of breath, hoarseness, sore throat, coughing, ear and throat pain, or nausea and vomiting. These side effects can be reduced or eliminated by reducing the intensity of stimulation. Long-term studies on patients with epilepsy have reported no serious adverse side effects, although the treatment may cause lung function deterioration in some people with existing lung disease.

The vagus nerves branch off the brain on either side of the head and travel down the neck, along the esophagus to the intestinal tract. They are the longest nerves in the body, and affect swallowing and speech. The vagus nerves also connect to parts of the brain involved in seizures. In many seizures disorders, electrical stimulation of the vagus nerves may help relieve symptoms.

Phototherapy is recommended as treatment for seasonal affective disorder (SAD), particularly for patients who do not wish to try antidepressants.

The Procedure. The procedure is noninvasive and simple. It is best performed immediately after waking in the morning. The patient sits a few feet away from a box-like device that emits very bright fluorescent light (10,000 lux) for about 30 minutes every day.

Some people report mood improvement as early as 2 days after treatment. In others, depression may not lift for 3 - 4 weeks. If no improvement is experienced after that, depressive symptoms will be unlikely to respond to phototherapy. Phototherapy may work best when combined with cognitive behavioral therapy.

Side Effects. Side effects include headache, eye strain, and irritability, although these symptoms tend to disappear within a week. Patients taking light-sensitive drugs (such as those used for psoriasis), certain antibiotics, or antipsychotic drugs should not use light therapy. Patients should be examined by an ophthalmologist before undergoing this treatment.

A surgical technique called cingulotomy interrupts the cingulate gyrus, a bundle of nerve fibers in the front of the brain, by applying heat or cold. A variation of this procedure using MRI scans to guide the surgeon produced long-term improvement in 53 - 78% of patients with severe intractable depression. The procedure is generally safe with few serious complications. It does not affect intellect or memory.

Some small studies have suggested that acupuncture may help in relieving depression. Larger studies are required to confirm its benefits.

Lifestyle Changes

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

St. John's wort (Hypericum perforatum) is an herbal remedy that may help some patients with mild-to-moderate depression. It does not appear to help patients with moderate or severe depression.

The herb St. John's wort is believed to be helpful in relieving mild-to-moderate depression, but should only be taken under a doctor's supervision. Manufacturers of herbal supplements do not need FDA approval to sell the products.

This herbal substance is not regulated, and there is no guarantee of quality in any brands currently available. In fact, in a 2003 study, only 2 of 54 St. John's products bought in Canada and the U.S. contained concentrations of the active ingredients that fell within 10% of the claims on the labels.

The following guidelines are recommended:

People with depression should not use St. John's wort without consulting a doctor. Children and pregnant or nursing women should not take this substance.
People should purchase brands only from well-established manufacturers.
Although no specific dose levels have been established, evidence suggests taking 900 mg daily (300 mg taken 3 times a day or 450 mg taken twice a day).
It takes between 2 - 3 weeks for the herb to have an effect.
St. John's wort should not be combined with other antidepressants. This herb may also interact with other types of medications and increase or decrease their potency. St. John's wort can increase the risk for bleeding when used with blood-thinning drugs. It can also reduce the strength of certain drugs including cancer and HIV treatments.

Side Effects. Side effects are uncommon but may include nausea, dry mouth, allergic reactions, and fatigue. This herb may increase sensitivity to light (photosensitivity). Some people have reported temporary nerve damage after sun exposure, specifically pain and tingling on sun-exposed areas.

Carbohydrates and Tryptophan. Some people report relief from depression by eating foods or diet supplements that boost levels of tryptophan, an amino acid involved in the production of serotonin. There are high-carbohydrate drinks available over the counter that increase tryptophan levels and may alleviate depression associated with premenstrual syndrome for about 3 hours. Simply eating a high amount of carbohydrates, however, is not a solution for depression.

Impurities found in diet supplements containing L-tryptophan itself have caused cases of eosinophilia-myalgia syndrome, a condition that elevates certain white blood cells and can be fatal. Supplements containing L-tryptophan are currently banned in the U.S. by the FDA.

Fish Oil. Some evidence suggests that an imbalance in the ratio of specific fatty acids (omega-6 to omega-3) may increase the risk for depression. Both are polyunsaturated fats, but omega-6 fatty acids are mostly found in corn, safflower, soybean, and sunflower oil whereas omega-3 fatty acids are found in fish oil, canola oil, soybeans, flaxseed, and certain nuts and seeds.

The bottom line may be to increase intake of omega-3 rich foods, such as fish, nuts, and canola oil, and reduce consumption of foods containing omega-6 fatty acids, such as corn and sunflower oils. Such a dietary approach is healthy in any case. Researchers are studying whether eating fish or taking fish oil supplements can reduce depression. Small preliminary studies suggest that these dietary approaches may be helpful for some patients. Scientists are also investigating which type of fish oil compound -- eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) -- provides the greatest benefit.

Omega-3 fatty acids, found in oily fish and flaxseed and canola oils, may be beneficial to people with depression.

Vitamins and Other Supplements. Certain B vitamins have been associated with some protection against depression.

Vitamin B-3 (niacin) is important in the production of tryptophan and is produced from processing vitamin B3 (niacin). Dietary sources of niacin include oily fish (such as salmon or mackerel), pork, chicken, dried peas and beans, whole grains, seeds, and dried fortified cereals.
Vitamin B-12 and calcium supplements may help reduce depression that occurs before menstruation. One study also suggested that calcium might help prevent postpartum depression.
Low levels of folate, a B vitamin, may be associated with depression. Researchers are studying whether folate supplements may help enhance the effectiveness of SSRIs and other antidepressants.

Increasingly studies are reporting major benefits from exercise for people with depression.

Aerobics. Either brief periods of intense training or prolonged aerobic workouts can raise chemicals in the brain, such as endorphins, adrenaline, serotonin, and dopamine that produce the so-called runner's high. And, of course, weight loss and increased muscle tone can boost self-esteem.

Yoga. Yoga practice, which involves rhythmic stretching movements and breathing, may help improve and stabilize mood.

Click the icon to see an image depicting the practice of yoga.

A strong network of social support is important for both prevention and recovery from depression. Support from family and friends must be healthy and positive. One study of depressed women showed, however, that overprotective as well as very distant parenting was associated with a slow recovery from depression. Studies indicate that people with strong spiritual faiths have a lower risk for depression. Such faith does not require an organized religion. People with depression might find solace from less structured sources, such as those that teach meditation or other methods for obtaining spiritual self-fulfillment.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.dbsalliance.org -- Depression and Bipolar Support Association
www.fda.gov/cder/drug/antidepressants -- FDA Antidepressant Use in Children, Adolescents, and Adults
www.parentsmedguide.org -- American Psychiatric Association-sponsored information on pediatric antidepressants
www.nami.org -- National Alliance on Mental Illness
www.nmha.org -- Mental Health America
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.psych.org -- American Psychiatric Association
www.apa.org -- American Psychological Association
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.postpartum.net -- Postpartum Support International
www.mentalhealth.samhsa.gov -- National Mental Health Information Center
www.mentalhealth.samhsa.gov/suicideprevention/concerned.asp -- National Strategy for Suicide Prevention (if contemplating suicide, call 1-800-273-TALK)
www.suicidology.org -- American Association of Suicidology

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Review Date:
12/25/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

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