PopSugar

Do You Drink Strong Alcohol?

partysugar — Fri, 24 Oct 2008 11:45:31 -0700

The other day I made a martini with Absolut's 100-proof, black-label vodka.

I've never considered myself a lightweight, but you could definitely notice the difference in strength!

How about you? Do you ever drink super-strong alcohol? Anyone else tried the Absolut 100?

Alcoholism

FitSugar — Wed, 08 Oct 2008 17:35:36 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Research

Topiramate (Topamax), an anticonvulsant drug used to treat epilepsy, is showing promise as a treatment for alcohol dependence. In a 2007 study published in the Journal of the American Medical Association, patients who took topiramate had fewer heavy drinking days, fewer drinks per day, and more days of not drinking at all than patients who received placebo.

Alcohol and Heart Disease

Heart disease is one of the leading causes of death among people who are heavy drinkers. Alcohol abuse and dependence increase the risks for unhealthy cholesterol levels, high blood pressure, heart failure, and stroke. Although the heart benefits of moderate alcohol use are widely discussed in the popular media, to date there are no definitive scientific studies that prove that alcohol consumption is beneficial to overall health.

The American Heart Association recommends that people who drink alcohol do so in moderation (one to two drinks a day for men, one drink a day for women). If you don’t drink, the American Heart Association advises against starting to drink to reduce the risk of heart disease. The best methods for preventing heart disease are exercise, healthy diet, and avoiding all forms of tobacco exposure.

Alcohol and Cancer

Long-term heavy alcohol use may increase the risks for many types of cancer including stomach, colorectal, mouth, tongue, throat, liver, and breast cancers. To reduce breast cancer risk, the American Cancer Society recommends that women limit their amount of alcohol consumption. Women who are at high risk for breast cancer should consider not drinking at all.

Introduction

Alcoholism is a chronic, progressive, and often fatal disease. It is a primary disorder and not a symptom of other diseases or emotional problems. The chemistry of alcohol allows it to affect nearly every type of cell in the body, including those in the central nervous system. After prolonged exposure to alcohol, the brain becomes dependent on it. The severity of this disease is influenced by factors such as genetics, psychology, culture, and response to physical pain.

Alcoholism is a chronic illness marked by dependence on alcohol consumption. It interferes with physical or mental health, and social, family, or job responsibilities. This addiction can lead to liver, circulatory, and neurological problems. Pregnant women who drink alcohol in any amount may harm the fetus.

Alcoholism, alcohol dependence, and alcohol abuse are associated with the following:

The only indication of early alcoholism may be the unpleasant physical responses to withdrawal that occur during even brief periods of abstinence.
Alcoholics have little or no control over the quantity they drink or the duration or frequency of their drinking.
Alcoholics are preoccupied with drinking, deny their own addiction, and continue to drink even though they are aware of the dangers.
Over time, some alcoholics become tolerant to the effects of drinking and require more alcohol to become intoxicated, creating the illusion that they can "hold their liquor."
Alcoholics may have blackouts after drinking and have frequent hangovers that cause them to miss work and other normal activities.
Alcoholics might drink alone and start their drinking early in the day.
Alcoholics periodically quit drinking or switch from hard liquor to beer or wine, but these periods rarely last.
Severe alcoholics often have a history of accidents, marital and work instability, and alcohol-related health problems.
Episodic violent and abusive incidents involving spouses and children and a history of unexplained or frequent accidents are often signs of drug or alcohol abuse.

Alcoholism can develop insidiously, and often there is no clear line between problem drinking and alcoholism. Eventually alcohol dominates thinking, emotions, and actions and becomes the primary means through which a person can deal with people, work, and life.

In addition to alcohol dependence, experts are now defining alcohol use by levels of harm that it may be causing. This information is useful to determine possible interventions at earlier stages. The following categories of alcohol use and abuse use a definition of one drink as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces (a jigger) of 90-proof liquor.

Moderate Drinking. Moderate drinking, particularly red wine, appears to offer health benefits. Moderate drinking is defined as equal to or less than two drinks a day for men and one drink a day for women.

Hazardous (Heavy) Drinking. Hazardous drinking puts people at risk for adverse health events. People who are heavy drinkers consume:

More than 14 drinks per week, or four to five drinks at one sitting, for men
More than seven drinks per week, or three drinks at one sitting, for women
Frequent intoxication

Harmful Drinking. Drinking is considered harmful when alcohol consumption has actually caused physical or psychologic harm. This is determined by:

Clear evidence that alcohol is responsible for such harm.
The nature of that harm can be identified.
Alcohol consumption has persisted for at least a month or has occurred repeatedly for the past year.

Certain people are at much higher risk for harmful drinking, such as older individuals with high blood pressure or those taking medications for arthritis or pain.

Alcohol Abuse. People with alcohol abuse have one or more of the following alcohol-related problems over a period of 1 year:

Failure to fulfill work or personal obligations
Recurrent use in potentially dangerous situations
Problems with the law
Continued use in spite of harm being done to social or personal relationships

Alcohol Dependence. People who are alcohol dependent have three or more of the following alcohol-related problems over a year:

Increased amounts of alcohol are needed to produce an effect
Withdrawal symptoms or drinking alcohol is used to avoid these symptoms
Drinks more over a given period than intended
Unsuccessful attempts to quit or cut down
Gives up significant leisure or work activities
Continues to drink in spite of the knowledge of its physical or psychological harm to oneself or others

Two-thirds of those with alcohol dependence continued to be dependent on alcohol after 5 years.

Causes

People have been drinking alcohol for about 15,000 years. Drinking steadily and consistently over time can produce dependence and cause withdrawal symptoms during periods of abstinence. This physical dependence, however, is not the sole cause of alcoholism. To develop alcoholism, other factors usually come into play, including biology, genetics, culture, and psychology.

Genetic factors play a significant role in alcoholism and may account for about half of the total risk for alcoholism. The role that genetics plays in alcoholism is complex, however, and it is likely that many different genes are involved. Research suggests that alcohol dependence, and other substance addictions, may be associated with genetic variations in 51 different chromosomal regions.

Researchers are investigating a number of inherited traits that make particular individuals susceptible to this disorder:

The amygdala is an area of the brain thought to play a role in the emotional aspects of craving, which can lead to addiction. Some studies indicate that the amygdala is smaller in subjects with family histories of alcoholism, suggesting that inherited differences in brain structure may affect risk. Other studies suggest that certain brain chemicals (neurotransmitters) and proteins in the amygdala region may be involved in the link between anxiety and alcoholism.
Some studies indicate that people may inherit a lack of the warning signals that ordinarily make people stop drinking. Research suggests this factor may contribute to 40 - 60% of alcoholism cases related to genetic factors. (Even in the absence of genetic factors, repeated exposure to alcohol increases the ability to tolerate larger amounts before experiencing behavioral impairment.)
Some people with alcoholism may have an inherited dysfunction in the transmission of serotonin. Serotonin is a brain chemical messenger (neurotransmitter). It is important for well-being and associated behaviors (eating, relaxation, and sleep). Abnormal serotonin levels are associated with high levels of tolerance for alcohol. They are also linked to impulsivity and aggressiveness. These behaviors can predispose people to drink and can increase the risk for dangerous behaviors and suicide in people who are alcohol dependent.
Dopamine is another neurotransmitter associated with alcoholism and other addictions. Research indicates that high levels of the D2 dopamine receptor may help inhibit behavioral responses to alcohol, and protect against alcoholism, in people with a family history of alcohol dependence.

Even if genetic factors can be identified, however, they are unlikely to explain all cases of alcoholism. It is important to understand that whether they inherit the disorder or not, people with alcoholism are still legally responsible for their actions. Inheriting genetic traits does not doom a child to an alcoholic future. Environment, personality, and emotional factors also play a strong role.

Alcohol has widespread effects on the brain and can affect neurons (nerve cells), brain chemistry, and blood flow within the frontal lobes of the brain. Researchers are particularly interested in systems of neurotransmitters (chemical messengers) in the brain that are affected by alcohol. Some research is focusing on the way these neurotransmitters are employed in the brain after long-term alcohol use in order to adapt to the cravings and pain of withdrawal. Such chemical changes may lead to dependency or to relapse after quitting in two ways:

They increase the need to reduce agitation
They increase the desire to restore pleasurable feelings

When a person who is dependent on alcohol stops drinking, chemical responses create an overexcited nervous system and agitation by changing the level of chemicals that inhibit impulsivity or stress and excitation. High norepinephrine levels, a chemical the brain produces more of when drinking is stopped, in fact, may be the primary factor in withdrawal symptoms, such as an increase in blood pressure and heart rate. This hyperactivity in the brain produces an intense need to calm down and to use more alcohol. One study suggested that the need to relieve agitation may be the more important factor in causing a relapse than restoring mood.

Drinking alcohol stimulates the release of neurotransmitters (serotonin, dopamine, and opioid peptides) that produce pleasurable feelings such as euphoria, a sensation of being rewarded, and a sense of well-being.

Over time, however, heavy alcohol use appears to deplete the stores of dopamine and serotonin. Persistent drinking, therefore, eventually fails to restore mood, but by then the drinker has been conditioned to believe that alcohol will improve spirits (even though it does not).

Between 80 - 90% of people treated for alcoholism relapse, even after years of abstinence. Patients and their caregivers should understand that relapses of alcoholism are analogous to recurrent flare-ups of chronic physical diseases. Factors that place a person at high risk for relapse include:

Frustration and anger
Social pressure
Internal temptation

Mental and Emotional Stress. Alcohol blocks out emotional pain and is often perceived as a loyal friend when human relationships fail. It is also associated with freedom and with a loss of inhibition that offsets the tedium of daily routines. When the alcoholic tries to quit drinking, the brain seeks to restore what it perceives to be its equilibrium. The brain's best weapons to achieve this are depression, anxiety, and stress (the emotional equivalents of physical pain), which are produced by brain chemical imbalances. These negative moods continue to tempt alcoholics to return to drinking long after physical withdrawal symptoms have abated.

It is important to realize that any life change, even changes for the better, may cause temporary grief and anxiety. With time and the substitution of healthier pleasures, this emotional turmoil weakens and can be overcome.

Co-dependency. Many aspects of the ex-drinker's relationships change when drinking stops, making it difficult to remain abstinent:

One of the most difficult problems that occur is being around other people who are able to drink socially without danger of addiction. A sense of isolation, a loss of enjoyment, and the ex-drinker's belief that pity, not respect, is guiding a friend's attitude can lead to loneliness, low self-esteem, and a strong desire to drink again.
Friends may not easily accept the sober, perhaps more subdued, ex-drinker. Close friends and even intimate partners may have difficulty in changing their responses to this newly sober person and, even worse, may encourage a return to drinking.
To preserve marriages, spouses of alcoholics often build their own self-images on surviving or handling their mates' difficult behavior and then discover that they find it difficult to adjust to new roles and behaviors.

In such cases, separation from these "enablers" may be necessary for survival. It is no wonder that, when faced with such losses, even if they are temporary, a person returns to drinking. The best course in these cases is to encourage close friends and family members to seek help as well. Fortunately, groups such as Al-Anon exist for this purpose.

Social and Cultural Pressures. The media portrays the pleasures of drinking in advertising and programming. The medical benefits of light-to-moderate drinking are frequently publicized, giving ex-drinkers the spurious excuse of returning to alcohol for their health. These messages must be categorically ignored and acknowledged for what they are: An industry's attempt to profit from potentially great harm to individuals.

Risk Factors

About 90% of adults in the U.S. drink alcohol. Every day, more than 700,000 Americans are being treated for alcoholism. In addition, up to half of American men have problems that are caused by alcohol.

Some researchers have categorized people with alcoholism as Type 1 or Type 2.

Type 1 individuals are more often women. They typically become alcoholic at a later age, have less severe symptoms or fewer psychiatric problems, and have a better outlook on life than those classified as type 2.
Type 2 people are more likely to be male. They tend to become alcoholic at an early age and have a high family risk for alcoholism, more severe symptoms, and a negative outlook on life.

Not only do these two groups tend to respond differently to psychotherapeutic approaches, but they may also respond differently to medications.

Drinking in Adolescence. About half of under-age Americans have used alcohol. About 2 million people ages 12 - 20 are considered heavy drinkers, and 4.4 million are binge drinkers. Anyone who begins drinking in adolescence is at risk for developing alcoholism. The earlier a person begins drinking, the greater the risk. A 2006 survey of over 40,000 adults indicated that among those who began drinking before age 14, nearly half had become alcoholic dependent by the age of 21. In contrast, only 9% of people who began drinking after the age of 21 developed alcoholism.

Young people at highest risk for early drinking are those with a history of abuse, family violence, depression, and stressful life events. People with a family history of alcoholism are also more likely to begin drinking before the age of 20 and to become alcoholic. Such adolescent drinkers are also more apt to underestimate the effects of drinking and to make judgment errors, such as going on binges or driving after drinking, than young drinkers without a family history of alcoholism.

Drinking in the Elderly Population. Although alcoholism usually develops in early adulthood, the elderly are not exempt. In fact, doctors may overlook alcoholism when evaluating elderly patients, mistakenly attributing the signs of alcohol abuse to the normal effects of the aging process. A survey of adults over 60 reported that 15% of men and 12% of women were hazardous drinkers, and 9% of men and 3% of women were alcohol dependent.

Alcohol also affects the older body differently. People who maintain the same drinking patterns as they age can easily develop alcohol dependency without realizing it. It takes fewer drinks to become intoxicated, and older organs can be damaged by smaller amounts of alcohol than those of younger people. Also, up to one-half of the 100 most prescribed drugs for older people react adversely with alcohol. Medications used for arthritis or pain pose a particular danger for interaction with alcohol.

Most alcoholics are men, but the incidence of alcoholism in women has been increasing over the past 30 years. Studies indicate that about 7% of men and 2.5% of women abuse alcohol. However, studies suggest that women are more vulnerable than men to many of the long-term consequences of alcoholism. For example, women are more likely than men to develop alcoholic hepatitis and to die from cirrhosis, and women are more vulnerable to the brain cell damage caused by alcohol.

Individuals who were abused as children have a higher risk for substance abuse later on. In one study, 72% of women and 27% of men with substance abuse disorders reported physical or sexual abuse or both. They also had worse response to treatment than those without such a history.

Overall, there is no difference in alcoholic prevalence among African-Americans, Caucasians, and Hispanic-Americans. Some population groups, however, such as Native Americans, have an increased incidence of alcoholism while others, such as Jewish and Asian Americans, have a lower risk. Although the biological or cultural causes of such different risks are not known, certain people in these population groups may have a genetic susceptibility or invulnerability to alcoholism because of the way they metabolize alcohol.

Psychiatric Disorders. Severely depressed or anxious people are at high risk for alcoholism, smoking, and other forms of addiction. Likewise, a large proportion of alcohol-dependent people suffer from an accompanying psychiatric or substance abuse disorder. Either anxiety or depression may increase the risk for self-medication with alcohol. Depression is the most common psychiatric problem in people with alcoholism or substance abuse.

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.

Specific anxiety disorders, such as panic disorders and social phobia, may pose particular risks for alcohol and substance abuse. Social phobia causes an intense fear of being publicly scrutinized and humiliated. Panic disorders cause intense anxiety and panic attacks. People with these disorders may use alcohol as a way to become less inhibited in public situations or to calm feelings of panic. While anxiety disorders are found in about 15% of adults overall, over 50% of people with alcohol abuse problems suffer from these conditions. People who have anxiety disorders are more likely to resume drinking after treatment for alcohol dependence. [For more information, see In-Depth Report #28: Anxiety.]

Long-term alcoholism itself may cause chemical changes that produce anxiety and depression. In fact, a study on elderly people with depression reported that when even moderate drinkers reduced consumption, their mood improved. Studies also indicate that alcohol use may promote panic attacks. It is not always clear, then, whether people with emotional disorders are self-medicating with alcohol, or whether alcohol itself is producing mood swings.

Behavioral Disorders and Lack of Impulse Control. Studies are also finding that alcoholism is strongly related to impulsive, excitable, and novelty-seeking behavior, and such patterns are established early on. Children who later become alcoholics or who abuse drugs are more likely to have less fear of new situations than others, even if there is a greater risk for harm than in nonalcoholics. Specifically, children with attention deficit hyperactivity disorder (ADHD), a condition that shares these behaviors, have a higher risk for alcoholism in adulthood. The risk is especially high in children with ADHD and conduct disorder.

Alcoholism is not restricted to any social or economic levels. For example, a thorough 1996 study reported no higher prevalence of alcoholism among adult welfare recipients than in the general population (about 7%). There was also no difference in prevalence between African-Americans and Caucasians in low-income groups. On the other hand, people in low-income groups who drank did display some tendencies that differed from the general population of drinkers. For instance, in one study as many women as men were heavy drinkers in lower income groups. Excessive drinking may also be more dangerous in lower income groups. One study found that alcohol was a major factor in the higher death rate of people, particularly men, in lower socioeconomic groups compared with those in higher groups.

Complications

Alcoholism reduces life expectancy by 10 - 12 years. Next to smoking, it is the most common preventable cause of death in America. Although studies indicate that adults who drink moderately (about one drink a day for women and two drinks a day for men) have a lower mortality rate than their nondrinking peers, their risk for untimely death increases with heavier drinking. The earlier a person begins drinking heavily, the greater their chance of developing serious illnesses later on. Once one becomes dependent on alcohol, it is very difficult to quit.

Alcohol can affect the body in so many ways that researchers have a hard time determining exactly what the consequences are from drinking. Interestingly, although heavy drinking is associated with earlier death, studies suggest it is not from a higher risk of the more common serious health problems, such as heart attack, heart failure, diabetes, lung disease, or stroke. It is well known, however, that chronic consumption leads to many problems that can increase the risk for death:

In general, people who drink regularly have a higher rate of death from injury or violence.
Alcohol overdose can lead to death. This is a particular danger for adolescents who may want to impress their friends with their ability to drink alcohol but cannot yet gauge its effects. However, alcohol overdose doesn't only occur from any one heavy drinking incident, but may also occur from a constant infusion of alcohol in the bloodstream.
Severe withdrawal and delirium tremens. Delirium tremens occurs in about 5% of alcoholics. It includes progressively severe withdrawal symptoms and altered mental states. In some cases, it can be fatal.
Frequent, heavy alcohol use directly harms many areas in the body and produce dangerous health conditions (liver damage, pancreatitis, anemia, upper gastrointestinal bleeding, nerve damage, and impotence).
Alcohol abusers who need surgery have an increased risk of postoperative complications, including infections, bleeding, insufficient heart and lung functions, and problems with wound healing. Alcohol withdrawal symptoms after surgery may impose further stress on the patient and hinder recuperation.

Although not traditionally thought of as a medical problem, a review of studies found that hangovers have significant consequences that include changes in liver function, hormonal balance, and mental functioning and an increased risk for depression and cardiac events. Hangovers can impair job performance, increasing the risk for mistakes and accidents. Interestingly, hangovers are generally more common in light-to-moderate drinkers than heavy and chronic drinkers, suggesting that binge drinking can be as threatening as chronic drinking. Any man who drinks more than five drinks or any woman who has more than three drinks is at risk for a hangover.

Alcohol plays a large role in accidents, suicide, and crime:

Alcohol plays a major role in more than half of all automobile fatalities.
Alcohol-related automobile accidents are the leading causes of death in young people.
Fewer than two drinks can impair the ability to drive. Even one drink may double the risk of injury, and more than four drinks increases the risk by 11 times.
Alcoholism is the primary diagnosis in one-quarter of all people who commit suicide.
Alcohol is implicated in 67% of all murders.

Alcoholic households are less cohesive and have more conflicts, and their members are less independent and expressive than households with nonalcoholic or recovering alcoholic parents. Domestic violence is a common consequence of alcohol abuse.

Effect on Women. Research suggests that for women, the most serious risk factor for injury from domestic violence may be a history of alcohol abuse in her male partner.

Effect on Children. Alcoholism in parents also increases the risk for violent behavior and abuse toward their children. Children of alcoholics tend to do worse academically than others, have a higher incidence of depression, anxiety, and stress and lower self-esteem than their peers. In addition to their own inherited risk for later alcoholism, many children of alcoholics have serious coping problems that may last their entire life.

Adult children of alcoholic parents are at higher risk for divorce and for psychiatric symptoms. One study concluded that the only events with greater psychological impact on children are sexual and physical abuse.

Researchers are finding common genetic factors in alcohol and nicotine addiction, which may explain, in part, why alcoholics are often smokers. Alcoholics who smoke compound their health problems. More alcoholics die from tobacco-related illnesses, such as heart disease or cancer, than from chronic liver disease, cirrhosis, or other conditions that are more directly tied to excessive drinking. Abuse of other substance is also common among alcoholics.

Alcoholic Hepatitis and Cirrhosis. Alcohol is absorbed in the small intestine and passes directly into the liver, where it becomes the preferred energy source. The liver, then, is particularly endangered by alcoholism. In the liver, alcohol converts to toxic chemicals, notably acetaldehyde, which trigger the production of immune factors called cytokines. In large amounts, these factors cause inflammation and tissue injury.

Cirrhosis is a chronic liver disease that causes damage to liver tissue, scarring of the liver (fibrosis; nodular regeneration), progressive decrease in liver function. Consequences of a failing liver include excessive fluid in the abdomen (ascites), bleeding disorders (coagulopathy), increased pressure in the blood vessels (portal hypertension), and brain function disorders (hepatic encephalopathy). Excessive alcohol use is the leading cause of cirrhosis.

Even moderate alcohol intake can produce pain in the upper right quarter of the abdomen -- a possible symptom of liver involvement. In many cases, such symptoms may be an indication of fatty liver or alcohol hepatitis, which are reversible liver conditions.

Between 10 - 20% of people who drink heavily (five or more drinks a day) develop cirrhosis, a progressive and irreversible scarring of the liver that can eventually be fatal. Alcoholic cirrhosis (also sometimes referred to as portal, Laennec’s, nutritional, or micronodular cirrhosis) is the primary cause of cirrhosis in the U.S. [For more information, see In-Depth Report #75: Cirrhosis.]

Not eating when drinking and consuming a variety of alcoholic beverages increase the risk for liver damage. Nevertheless, the amount of alcohol consumed and the patterns of drinking are only weak predictions of risk. Up to 90% of heavy drinkers do not develop advanced irreversible liver disease. Other risk factors have been identified that may increase the danger to the liver in heavy drinkers:

Obesity is a major factor for all stages of liver disease.
Women develop liver disease at lower quantities of alcohol intake than men.
Genetic factors that regulate the immune responses also play role.

Viral Hepatitis B and C. People with alcoholism tend to have lifestyles that put them at higher risk for hepatitis B and C, which are caused by viruses. Chronic forms of viral hepatitis pose risks for cirrhosis and liver cancer, and alcoholism significantly increases these risks. People with alcoholism should be immunized against hepatitis B. They may need a higher-than-normal dose of the vaccine for it to be effective. There is no vaccine for hepatitis C. [For more informaiton, see In-Depth Report #59: Hepatitis.]

Alcoholism can cause many problems in the gastrointestinal tract. Violent vomiting can produce tears in the junction between the stomach and esophagus. Alcoholism poses a high risk for diarrhea and hemorrhoids. It increases the risk for ulcers, particularly in people taking the painkillers known as nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen. It can also lead to swollen veins in the esophagus (esophagitis), called varices, which can lead to bleeding.

Click the icon to see an image of ulcer emergencies.

Alcohol can contribute to serious and chronic inflammation of the pancreas (pancreatitis) in people who are susceptible to this condition. There is some evidence of a higher risk for pancreatic cancer in people with alcoholism, although this higher risk may occur only in people who are also smokers.

Click the icon to see an image of the pancreas.

Moderate amounts (one to two drinks a day) of alcohol can improve some heart disease risk factors, such as increasing HDL (“good cholesterol”) levels. However, at this time there is no definitive proof that moderate drinking improves overall health, and the American Heart Association does not recommend drinking alcoholic beverages solely to reduce cardiovascular risk.

Excessive drinking clearly has negative effects on heart health. In fact, heart disease is one of the leading causes of death for alcoholics. Alcohol abuse increases levels of triglycerides (unhealthy fats) and increases the risks for high blood pressure, heart failure, and stroke. In addition, the extra calories in alcohol can contribute to obesity, a major risk factor for many heart problems.

Click the icon to see an image of the heart.

Alcohol abuse and dependence may increase the risk for certain type of cancers. In particular, heavy alcohol use appears to increase the risks for mouth, throat, esophageal, gastrointestinal, liver, colorectal, and breast cancers. Women who are at high risk for breast cancer should consider not drinking at all.

Pneumonia. Over time, chronic alcoholism can cause severe reductions in white blood cells, which increase the risk for community-acquired pneumonia (pneumonia acquired outside of hospitals or nursing homes). Patients who abuse alcoholism have a greater risk for developing severe pneumonia. Doctors recommend that patients with alcohol dependence should receive an annual pneumococcal pneumonia vaccination. The initial signs of pneumococcal pneumonia are high fever, cough, and stabbing chest pains. Immediately contact your doctor if you experience these symptoms.

Click the icon to see an image of pneumonia.

Severe alcoholism is associated with osteoporosis (loss of bone density), muscular deterioration, skin sores, and itching. Alcohol-dependent women seem to face a higher risk than men for damage to muscles, including muscles of the heart, from the toxic effects of alcohol.

Click the icon to see an image of osteoporosis.

Effects Sexual Function and Fertility. Alcoholism increases levels of the female hormone estrogen and reduces levels of the male hormone testosterone, factors that possibly contribute to impotence in men and infertility in women. Such changes may also be responsible for the higher risks for absent periods and abnormal uterine bleeding in women with alcoholism.

Drinking During Pregnancy and Effects on the Infant. Even moderate amounts of alcohol can have damaging effects on the developing fetus, including low birth weight and an increased risk for miscarriage. High amounts can cause fetal alcohol syndrome, a condition that can cause mental and growth retardation. Although there is no specific amount of alcohol intake, the risk of developing the syndrome is increased depending on the time of alcohol exposure during pregnancy, a patter of drinking (four or more drinks per occasion), and how often alcohol consumption occurs.

Moderate alcohol consumption may help protect the hearts of adults with type 2 diabetes. Heavy drinking however is associated with obesity, which is a risk factor for this form of diabetes. In addition, alcohol can cause hypoglycemia, a drop in blood sugar, which is especially dangerous for people with diabetes who are taking insulin. Intoxicated diabetics may not be able to recognize symptoms of hypoglycemia, a potentially hazardous condition.

Drinking too much alcohol can cause immediate mild neurologic problems in anyone, including insomnia and headache. Long-term alcohol use may even physically affect the brain. Depending on length and severity of alcohol abuse, neurologic damage may not be permanent, and abstinence nearly always leads to eventual recovery of normal mental function.

Effect on Mental Functioning. Studies have reported less blood flow in the frontal lobes of the brain, which may reflect links to deeper levels. In one study, even recent high alcohol use (within the last 3 months) was associated with some loss of verbal memory and slower reaction times. Over time, chronic alcohol abuse can impair so-called "executive functions," which include problem solving, mental flexibility, short-term memory, and attention. These problems are usually mild to moderate and can last for weeks or even years after a person quits drinking. In fact, such persistent problems in judgment are possibly one reason for the difficulty in quitting. Alcoholic patients who have co-existing psychiatric or neurologic problems are at particular risk for mental confusion and depression.

Wernicke-Korsakoff Syndrome. Wernicke-Korsakoff syndrome is a serious consequence of severe thiamin (vitamin B1) deficiency in alcoholism. Symptoms of this syndrome include severe loss of balance, confusion, and memory loss. Eventually, it can result in permanent brain damage and death. Once the syndrome develops, oral supplements have no effect, and only adequate and rapid intravenous vitamin B1 can treat this serious condition.

Peripheral Neuropathy. Vitamin B1 deficiencies can also lead to peripheral neuropathy, a condition that causes pain, tingling, and other abnormal sensations in the arms and legs.

Click the icon to see an image of the nervous system.

People with alcoholism should be sure to take vitamin and mineral supplements. Even apparently well-nourished people with alcoholism may be deficient in important nutrients. Deficiencies in vitamin B are particularly health risks in people with alcoholism. Other vitamin and mineral deficiencies, however, can also cause widespread health problems.

Folate Deficiencies. Alcohol interferes with the metabolism of folate, a very important B vitamin, called folic acid when used as a supplement. Folate deficiencies can cause severe anemia. Deficiencies during pregnancy can lead to birth defects in the infant.

Vitamin B1 Deficiencies. Many of the B vitamins are essential for nerve protection. Severe deficiencies are common in alcoholism and can have serious consequences on the central nervous system, notably peripheral neuropathy and, in very severe cases, Wernicke-Korsakoff syndrome.

The effects of many medications are strengthened by alcohol, while others are inhibited. Of particular importance is alcohol's reinforcing effect on anti-anxiety drugs, sedatives, antidepressants, and antipsychotic medications. Alcohol also interacts with many drugs used by people with diabetes. It interferes with drugs that prevent seizures or blood clotting. It increases the risk for gastrointestinal bleeding in people taking aspirin or other nonsteroidal inflammatory drugs (NSAIDs) including ibuprofen and naproxen. Chronic alcohol abusers have a particularly high risk for adverse side effects from consuming alcohol while taking certain antibiotics. These side effects include flushing, headache, nausea, and vomiting. In other words, taking almost any medication should preclude drinking alcohol.

Diagnosis

Even when people with alcoholism experience withdrawal symptoms, they nearly always deny the problem, leaving it up to co-workers, friends, or relatives to recognize the symptoms and to take the first steps toward encouraging treatment. Denial, in fact, may be an important warning signal for alcoholism.

Family members cannot always rely on a doctor to make an initial diagnosis. Although 15 - 30% of people who are hospitalized have alcoholism or alcohol dependence, doctors often fail to screen for the problem. In addition, doctors themselves often do not recognize the symptoms. Even when doctors identify an alcohol problem, however, they are frequently reluctant to confront the patient with a diagnosis that might lead to treatment for addiction.

A doctor who suspects alcohol abuse should ask the patient questions about current and past drinking habits to distinguish moderate from heavy, or hazardous, drinking. Screening tests for alcohol problems in older people should account for possible medical problems or medications that might place them at higher risk for hazardous drinking than younger individuals.

A number of short screening tests are available, which a person can even take on their own. Because people with alcoholism often deny their problem or otherwise attempt to hide it, the tests are designed to elicit answers related to problems associated with drinking rather than the amount of liquor consumed or other specific drinking habits.

CAGE Test. The CAGE test is an acronym for the following questions and is the quickest test:

Attempts to CUT (C) down on drinking
ANNOYANCE (A) with criticisms about drinking
GUILT (G) about drinking
Use of alcohol as an EYE-OPENER (E) in the morning

This test and another called the Self-Administered Alcoholism Screening Test (SAAST) appear to be most useful in detecting possible alcoholism in white, middle-aged males. They are not very accurate for identifying alcohol abuse in older people, white women, and African-Americans and Mexican Americans.

T-ACE Test. The T-ACE test is a four-question test that appears to be quite accurate in identifying alcoholism in both men and women. It asks the following questions:

Does it TAKE (T) more than three drinks to make you feel high?
Have you ever been ANNOYED (A) by people's criticism of your drinking?
Are you trying to CUT DOWN (C) on drinking?
Have you ever used alcohol as an EYE OPENER (E) in the morning?

A positive response to two of these four questions is considered to indicate possible alcohol abuse or dependence.

AUDIT Test. A more effective and important test for most people may be the Alcohol Use Disorders Identification Test (AUDIT), which is the only test specifically designed to identify hazardous or harmful drinking. It asks three questions about amount and frequency of drinking, three questions about alcohol dependence, and four questions about problems related to alcohol consumption.

A Single-Question. One simple question may be as sensitive as the CAGE or AUDIT: "When was the last time you had more than five drinks (for men) or four drinks (for women) in one day?" An answer of "within 3 months" accurately identified about half of people who were problem drinkers. Problem drinking is defined as hazardous drinking within the last month or some alcohol-use disorder during the past year.

Other Screening Tests. Other short screening tests are the Michigan Alcoholism Screening Test (MAST) and the Alcohol Dependence Scale (ADS).

Some symptoms of alcoholism may be attributed to other disorders, particularly in the elderly, where symptoms of confusion, memory loss, or falling may be attributed to the aging process alone. Heavy drinkers may be more likely to complain to their doctors about so-called somatization symptoms, which are vague ailments, such as joint pain, intestinal problems, or general weakness, that have no identifiable physical cause. Such complaints should signal the doctor to follow-up with screening tests for alcoholism.

Alcoholism is particularly less likely to be recognized in elderly women. In fact, only 1% of older women who need treatment for alcoholism are diagnosed accurately and treated appropriately. Instead, they are often diagnosed with depression and may even be prescribed anti-anxiety drugs or antidepressants that can have dangerous interactions with alcohol.

Physical Examination. A physical examination and other tests should be performed to uncover any related medical problems.

Laboratory Tests. Tests for alcohol levels in the blood are not useful for diagnosing alcoholism because they reflect consumption at only one point in time and not long-term usage. Certain blood tests, however, may provide biologic markers that suggest medical problems associated with alcoholism or indications of alcohol abuse:

Carbohydrate-deficient transferrin (CDT). This compound is a marker for heavy drinking and can be helpful in monitoring patients for progress towards abstinence.
Gamma-glutamyltransferase (GGT). This liver enzyme is very sensitive to alcohol and can be elevated after moderate alcohol intake and in chronic alcoholism.
Aspartate (AST) and alanine aminotransaminases (ALT). These are liver enzymes and are markers for liver damage.
Testosterone. Male hormone levels in men with alcoholism may be low. (Such results sometimes persuade men with alcoholism to seek help.)
Mean corpuscular volume (MCV). This blood test measures the size of red blood cells, which increase with alcohol use over time.

Treatment for Alcoholism

Once a diagnosis of alcoholism is made, the next major step is getting the patient to seek treatment. The main reasons alcoholics do not seek treatment are:

Lack of confidence in successful therapies
Denial of their own alcoholism
Social stigma attached to the condition and its treatment

The alcoholic patient and everyone involved should fully understand that alcoholism is a disease. Furthermore, the responses to this disease (need, craving, fear of withdrawal) are not character flaws but symptoms, just as pain or discomfort are symptoms of other illnesses. They should also realize that treatment is difficult and sometimes painful, just as are treatments for other life-threatening diseases, such as cancer, but that treatment is the only hope for a cure.

Interventions by family members, employers, and therapists can be very effective in motivating a person to quit and in reducing drinking over the short term. Even brief interventions from a primary care doctor and self-help information can be helpful in reducing harmful drinking. Studies report, however, that only regular follow-up and reinforcement will sustain quit rates and possibly even improve survival rates.

Personal Intervention Meetings. The best approaches for motivating a patient to seek treatment are interventional group meetings between people with alcoholism and their friends and family members who have been affected by the alcoholic behavior. Using this approach, each person affected offers a compassionate but direct and honest report describing specifically how they have been hurt by their loved one's alcoholism. The family and friends should express their affection for the patient and their intentions for supporting the patient through recovery, but they must strongly and consistently demand that the patient seek treatment. Children may even be involved in this process, depending on their level of maturity and ability to handle the situation.

Employer Intervention. Employers can be particularly effective. Their approach should also be compassionate but strong, threatening the employee with loss of employment if they do not seek help. Some large companies provide access to inexpensive or free treatment programs for their workers. Studies suggest that such interventions are effective at helping the worker at least to cut back on drinking.

The ideal goals of long-term treatment by many doctors and organizations such as Alcoholics Anonymous (AA) are total abstinence. Patients who secure total abstinence have better survival rates, mental health, and marriages, and they are more responsible parents and employees than those who continue to drink or relapse. To achieve this, the patient aims to avoid high-risk situations and replace the addictive patterns with satisfying, time-filling behaviors.

Because abstinence is so difficult to attain, however, many professionals choose to treat alcoholism as a chronic disease. In other words, patients should expect and accept relapse but should aim for as long a remission period as possible. Even merely reducing alcohol intake can lower the risk for alcohol-related medical problems.

AA and other alcoholic treatment groups are greatly worried by treatment approaches that do not aim for strict abstinence, however. Many people with alcoholism are eager for any excuse to start drinking again. There is also no way to determine which people can stop after one drink and which ones cannot.

Evidence strongly suggests that seeking total abstinence and avoiding high-risk situations are the optimal goal for people with alcoholism.

A number of treatment options now exist for alcoholism. It is first important to determine whether inpatient or outpatient care would best benefit the individual. A variety of treatment options exist that do not require overnight stay in a hospital. Structured programs exist that involve anywhere from a couple of hours a day for several days a week to 20 or more hours per week (sometimes called partial hospitalization) of monitoring. Withdrawal and subsequent abstinence monitoring using outpatient visits to a doctor is occasionally tried for select, low-risk patients.

Inpatient care may also be performed in a general or psychiatric hospital or in a center dedicated to treatment of alcohol and other substance abuse. Factors that indicate a need for this type of treatment include:

Coexisting medical or psychiatric disorder
Delirium tremens
Potential harm to selves or others
Failure to respond to conservative treatments
Disruptive home environment

A typical inpatient regimen may include the following stages:

A physical and psychiatric work-up for any physical or mental disorders
Detoxification -- this phase involves initiating abstinence, managing withdrawal symptoms and complications, and ensuring that the patient remains in treatment
On-going treatment with medications in some cases
Psychotherapy, usually cognitive behavioral therapy
An introduction to Alcoholics Anonymous

Some -- but not all -- studies have reported better success rates with inpatient treatment of patients with alcoholism. However, newer studies strongly suggest that alcoholism can be effectively treated in a doctor’s office.

The new approach to outpatient treatment uses “medical management” -- a disease management approach that is used for chronic illnesses such as diabetes. With medical management, patients receive regular 20-minute sessions with a health care provider. The provider monitors the patient’s medical condition, medication, and alcohol consumption.

A medical management approach generally involves one or both of the following:

Drug treatment with naltrexone (ReVia, Vivitrol)
Behavioral counseling with a therapy technique called combined behavioral intervention (CBI)

Outpatient Treatment Options. People with mild-to-moderate withdrawal symptoms are usually treated as outpatients. Treatments are similar to those in inpatient situations and include:

Psychotherapy or counseling
Medications that target brain chemicals involved in addiction
Social support groups such as Alcoholics Anonymous
Cognitive therapies
Quitting smoking (smoking interferes with the brain’s recovery from alcoholism)
Involvement of family and other significant people in patient's life

After-Care and Work Therapy. After-care employs services that help alcoholics maintain sobriety. For example, in some cities, sober-living houses provide residences for people who are trying to stay sober. They do not offer formal treatment services, but the people living there offer each other support and maintain an abstinent environment. One study reported that work therapy improved the outcome for homeless veterans who were being treated for substance abuse.

About 25% of people are continuously abstinent following treatment, and another 10% use alcohol moderately and without problems. Most studies strongly suggest that intensive and prolonged treatment is important for successful recovery, whether the patient is treated within or outside a treatment center.

Certain factors play a role in success or failure. Patients from low-income groups tend to have worse results in general. Their difficulties are often intensified by lack of insurance, low self-esteem, and minimal social support.

Severe alcoholism is often complicated by the presence of serious medical illnesses. People with alcoholism should try at least to maintain a healthy diet and take vitamin supplements. Such deficiencies are a major cause of health problems in people with alcoholism. Women are particularly endangered.

A program called integrated outpatient treatment (IOT) may be specifically helpful for medically ill alcoholics. The patient visits a clinic once a month and receives both intensive alcohol treatment and a physical check-up, which includes tracking factors, such as liver function, that are affected by drinking.

Treatment for patients with both alcoholism and mental illness is particularly difficult. The greater the psychiatric distress a person is experiencing, the more the person is tempted to drink, particularly in negative situations.

There has been some concern that self-help programs, such as Alcoholics Anonymous (AA), are not effective for patients with dual diagnoses of mental illness and alcoholism, because the focus of the organization is on addiction, not psychiatric problems. Studies, however, have reported that they are also effective in many of these patients. (AA may not be as helpful for people with schizophrenia and schizoaffective disorder.) In one study, individuals with a dual diagnosis achieved better abstinence rates after being treated only for alcoholism compared to patients treated for the mental disorder as well. (Cognitive-behavioral therapy was used for both groups.)

Newer antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are proving to be very useful complements to AA or counseling sessions. Anti-anxiety medications are also available for people with anxiety. People with alcoholism and more severe problems such as schizophrenia or severe bipolar disorder may require other types of medications.

Treatment for Alcohol Withdrawal

When a person with alcoholism stops drinking, withdrawal symptoms begin within 6 - 48 hours and peak about 24 - 35 hours after the last drink. During this period, the inhibition of brain activity caused by alcohol is abruptly reversed. Stress hormones are overproduced, and the central nervous system becomes overexcited. Common symptoms include:

Anxiety
Irritability
Agitation
Insomnia

Additional symptoms may include:

Extremely aggressive behavior
Fever
Rapid heartbeat
Changes in blood pressure (either higher or lower)
Mental disturbances
Seizures occur in about 10% of adults during withdrawal. In about 60% of these patients, the seizures are multiple. The time between the first and last seizure is usually 6 hours or less.
Delirium tremens (DTs) are withdrawal symptoms that become progressively severe and include altered mental states (hallucinations, confusion, severe agitation) or generalized seizures. DTs are potentially fatal. They develop in up to 5% of alcoholic patients, usually 2 - 4 days after the last drink, although it may take 2 or more days to peak.

It is not clear if older people with alcoholism are at higher risk for more severe symptoms than younger patients. However, several studies have indicated that they may suffer more complications during withdrawal, including delirium, falls, and a decreased ability to perform normal activities.

Upon entering a hospital due to alcohol withdrawal, patients should be given a physical examination for any injuries or medical conditions. They should be treated, if possible, for any potentially serious problems, such as high blood pressure, anemia, liver damage, or irregular heartbeat.

The immediate goal of treatment is to calm the patient as quickly as possible. Patients should be observed for at least 2 hours to determine the severity of withdrawal symptoms. Doctors may use assessment tests, such as the Clinical Institute Withdrawal Assessment (CIWA) scale, to help determine treatment and whether the symptoms will progress in severity.

About 95% of people have mild-to-moderate withdrawal symptoms, including agitation, trembling, disturbed sleep, and lack of appetite. In 15 - 20% of people with moderate symptoms, brief seizures and hallucinations may occur, but they do not progress to full-blown delirium tremens. Such patients often can be treated as outpatients. After being examined and observed, the patient is usually sent home with a 4-day supply of anti-anxiety medication, scheduled for follow-up and rehabilitation, and advised to return to the emergency room if withdrawal symptoms increase in severity. If possible, a family member or friend should support the patient through the next few days of withdrawal.

Benzodiazepines. Anti-anxiety drugs known as benzodiazepines inhibit nerve-cell excitability in the brain and are considered to be the treatment of choice. They relieve withdrawal symptoms, help prevent progression to delirium tremens, and reduce the risk for seizures. Long-acting drugs, such as chlordiazepoxide (Libritabs, Librium), oxazepam (Serax), and halazepam (Paxipam) are preferred. They pose less risk for abuse than the shorter-acting drugs, which include diazepam (Valium), alprazolam (Xanax), and lorazepam (Ativan).

Assessing symptoms frequently and administering benzodiazepine doses as needed (instead of giving to a fixed dose at regular intervals) may reduce the incidence of withdrawal symptoms and other adverse events, including delirium, seizures, and transfer to the intensive care unit.

Some doctors question the use of any anti-anxiety medication for mild withdrawal symptoms, since these drugs are subject to abuse. Others believe that repeated withdrawal episodes, even mild forms, that are inadequately treated may result in increasingly severe and frequent seizures with possible brain damage. In any case, benzodiazepines are usually not prescribed for more than 2 weeks or administered for more than 3 nights per week. Problems with benzodiazepines include:

Side Effects. Common side effects of benzodiazepines are daytime drowsiness and a hung-over feeling. In rare cases, they actually cause agitation. Respiratory problems may be worsened. The drugs stimulate eating and can cause weight gain. Benzodiazepines can interact with certain drugs, including cimetidine (Tagamet), antihistamines, and oral contraceptives. Benzodiazepines are potentially dangerous when used in combination with alcohol. Overdoses are serious, although rarely fatal. Elderly people are more susceptible to side effects and should usually start at half the dose prescribed for younger people. Benzodiazepines are associated with birth defects and should not be used by pregnant women or nursing mothers.
Loss of Effectiveness and Dependence. The primary problem with these drugs is their loss of effectiveness over time with continued use at the same dosage. As a result, patients may increase their dosage level to prevent anxiety. Patients then can become dependent. In fact, some evidence suggests that people with alcoholism, or even a family history of alcoholism, may be more susceptible to benzodiazepine abuse than nonalcoholics. This is a common danger and can occur after as short a time as 3 months. (These drugs do not cause euphoria, a so-called "high," so such drugs are not addictive in the same way narcotics are.)
Withdrawal Symptoms. People who discontinue benzodiazepines after taking them for even 4 weeks can experience mild rebound symptoms. The longer the drugs are taken and the higher the dose, the more severe the symptoms. They include sleep disturbance and anxiety, which can develop within hours or days after stopping the medication. Some patients experience withdrawal symptoms, including stomach distress, sweating, and insomnia, that can last from 1 - 3 weeks. Sleep changes, in fact, can persist or months or years after quitting and may be a major factor in relapse.

Antiseizure Medications. Antiseizure drugs, such as carbamazepine (Tegretol) or divalproex sodium (Depakote), may be useful for reducing the requirements of a benzodiazepine. When used by themselves, however, they do not appear to reduce seizures or delirium associated with withdrawal.

Other Supportive Drugs. Beta-blockers, such as propranolol (Inderal) and atenolol (Tenormin), are sometimes used in combination with benzodiazepines. They slow heart rate and reduce tremors. They may also reduce cravings.

Note on Treating Alcohol Withdrawal with Alcohol. Some medical centers give patients alcohol to help with withdrawal. Experts do not recommend this approach. There is no evidence that this approach is safe or effective, while there is substantial evidence on the safety and effectiveness of benzodiazepines.

Treating Delirium Tremens. People with symptoms of delirium tremens must be treated immediately. Untreated delirium tremens has a fatality rate that can be as high as 20%. Treatment usually involves intravenous anti-anxiety medications. It is extremely important that fluids be administered. Restraints may be necessary to prevent injury to the patient or to others.

Treating Seizures. Seizures are usually self-limited and treated with a benzodiazepine. Intravenous phenytoin (Dilantin) along with a benzodiazepine may be used in patients who have a history of seizures, who have epilepsy, or in those with ongoing seizures. Because phenytoin may lower blood pressure, the patient's heart should be monitored during treatment. Chlormethiazole, a derivative of vitamin B1, is used in Europe for reducing agitation and seizures.

Psychosis. For hallucinations or extremely aggressive behavior, antipsychotic drugs, particularly haloperidol (Haldol), may be administered. Korsakoff's psychosis (Wernicke-Korsakoff syndrome) is caused by severe vitamin B1 (thiamine) deficiencies, which cannot be replaced orally. Rapid and immediate injection of the B vitamin thiamin is necessary.

Therapy

Standard forms of therapy for alcoholism include:

Cognitive-behavioral therapy
Combined behavioral intervention
Interactional group psychotherapy based on the Alcoholics Anonymous (AA) 12-step program

Comparison studies have reported that these approaches are equally effective when the program is competently administered. Specific people may do better with one program than another. One study, for example, examined the differences in success rates on type 1 or type 2 alcoholics:

People in the type 1 group did well with the 12-step approach. They did not do as well with cognitive-behavioral therapy. (Type 1 individuals become alcoholic at a later age, have less severe symptoms or fewer psychiatric problems, and have a better outlook on life than those classified as type 2. They are more likely to be women.)
The people in the type 2 group tended to do better with cognitive-behavioral therapy. (Type 2 people are more likely to be male, become alcoholic at an early age, have a high family risk for alcoholism, have more severe symptoms, and have a negative outlook on life.)

This difference in response to the two forms of treatment held up after 2 years. Other studies have also reported that people with fewer psychiatric problems do best with the AA approach.

AA, founded in 1935, is an excellent example of interactional group psychotherapy and remains the most well-known program for helping people with alcoholism. It offers a very strong support network using group meetings open 7 days a week in locations all over the world. A buddy system, group understanding of alcoholism, and forgiveness for relapses are AA's standard methods for building self-worth and alleviating feelings of isolation.

AA's 12-step approach to recovery includes a spiritual component that might deter people who lack religious convictions. Prayer and meditation, however, have been known to be of great value in the healing process of many diseases, even in people with no particular religious assignation. AA emphasizes that the "higher power" component of its program need not refer to any specific belief system. Associated membership programs, Al-Anon and Alateen, offer help for family members and friends.

We admit we were powerless over alcohol -- that our lives have become unmanageable.
We have come to believe that a Power greater than ourselves could restore us to sanity.
We have made a decision to turn our will and our lives over to the care of God, as we understand what this Power is.
We have made a searching and fearless moral inventory of ourselves.
We have admitted to God, to ourselves and to another human being the exact nature of our wrongs.
We are entirely ready to have God remove all these defects of character.
We have humbly asked God to remove our shortcomings.
We have made a list of all persons we had harmed and have become willing to make amends to them all.
We have made direct amends to such people wherever possible, except when to do so would injure them or others.
We have continued to take personal inventory and when we were wrong promptly admitted it.
We have sought through prayer and meditation to improve our conscious contact with God as we understand what this higher Power is, praying only for knowledge of God's will for us and the power to carry that out.
Having had a spiritual awakening as the result of these steps, we have tried to carry this message to alcoholics and to practice these principles in all our affairs.

Cognitive-behavioral therapy (CBT) uses a structured teaching approach and may be better than AA for people with severe alcoholism. Patients are given instruction and homework assignments intended to improve their ability to cope with basic living situations, control their behavior, and change the way they think about drinking. The following are examples of approaches:

Patients might write a history of their drinking experiences and describe what they consider to be risky situations.
They are then assigned activities to help them cope when exposed to "cues" (places or circumstances that trigger their desire to drink).
Patients may also be given tasks that are designed to replace drinking. An interesting and successful example of such a program was one that enlisted patients in a softball team. This gave them the opportunity to practice coping skills, develop supportive relationships, and engage in healthy alternative activities.

CBT may be especially effective when used in combination with opioid antagonists, such as naltrexone. CBT that addresses alcoholism and depression also may be an important treatment for patients with both conditions.

Combined behavioral intervention (CBI) is a new form of therapy that uses special counseling techniques to help motivate people with alcoholism to change their drinking behavior. CBI combines elements from other psychotherapy treatments such as cognitive behavioral therapy, motivational enhancement therapy, and 12-step programs. Patients are taught how to cope with drinking triggers. Patients also learn strategies for refusing alcohol so that they can achieve and maintain abstinence. In a 2006 study in the Journal of the American Medical Association, CBI -- combined with regular doctor’s office visits (medical management) -- worked as well as naltrexone in successfully treating alcoholism.

Partners of people with alcoholism can also benefit greatly from behavioral approaches that help them cope with their mate. Children of an alcoholic mother or father may do better if both parents participate in couples-based therapy, rather than just treating the parent with alcoholism.

Nearly all patients who are alcohol dependent suffer from insomnia and sleep problems, which can last months to years after abstinence. Sleep disturbances may even be important factors in relapse. Available therapies include sleep hygiene, bright light therapy, meditation, relaxation methods, and other nondrug approaches. Many medications for inducing sleep are not recommended in people with alcoholism. [For more information, see In-Depth Report #27: Insomnia.]

Some people try alternative methods, such as acupuncture or hypnosis. Such approaches are not harmful. In one study, acupuncture reduced the desire for alcohol in nearly half of people, although it was not significantly more helpful than conventional treatments.

Medications

In the U.S., three drugs are specifically approved to treat alcohol dependence:

Naltrexone (ReVia, Vivitrol)
Acamprosate (Campral)
Disulfiram (Antabuse)

Naltrexone and acamprosate are categorized as anticraving drugs. Disulfiram is an aversion drug. Other types of medications, such as antidepressants, may also be used to treat patients with alcoholism.

Anticraving drugs are opioid antagonists. These drugs reduce the intoxicating effects of alcohol and the urge to drink

Naltrexone. Naltrexone (ReVia, Vivitrol) is approved for the treatment of alcoholism and helps reduce alcohol dependence in the short term for people with low-to-moderate alcohol dependency. ReVia is a pill that is taken daily by mouth. In 2006, the FDA approved Vivitrol, a once-a-month injectable form of naltrexone.

Naltrexone is usually prescribed along with psychotherapy. The most common side effect is nausea, which is usually mild and temporary. High doses can cause liver damage. The drug should not be given to anyone who has used narcotics within 7 - 10 days. For ReVia, it is important that patients take the pill on a daily basis. Because many patients have difficulty sticking to this daily regimen, a monthly injection of Vivitrol may be an easier option.

Naltrexone does not work in all patients. Some studies suggest that people with a specific genetic variant may respond better to the drug than those without the gene. The gene regulates receptors that affect the response to opioids. A 2005 study indicated that naltrexone works best for patients who have a family history of alcoholism, began drinking at an early age, and abuse other drugs.

Research is being conducted on the effects of combining naltrexone with acamprosate (Campral), particularly for individuals who have not responded to single drug treatment. In a 2006 study in the Journal of the American Medical Association that examined various outpatient drug and behavioral treatments, naltrexone worked as well as psychotherapy in preventing relapse to heavy drinking for patients who had recently abstained from alcohol. However, the study showed no benefit for acamprosate either when combined with naltrexone or used alone.

Acamprosate. Acamprosate (Campral) is the newest drug to be approved for treatment of alcoholism. Acamprosate calms the brain and reduces cravings by inhibiting the transmission of the neurotransmitter gamma aminobutyric acid (GABA). Studies indicate that it reduces the frequency of drinking and, in concert with psychotherapy, improves quality of life even in patients with severe alcohol dependence. One study reported that 60% of patients remained abstinent for 12 weeks, and in another 43% were still abstinent after nearly a year. The drug may cause occasional diarrhea and headache. It also can impair certain memory functions but does not alter short-term working memory or mood. People with kidney problems should use acamprosate cautiously. For some patients, combination therapy with naltrexone or disulfiram may provide greater benefit than acamprosate alone.

Disulfiram. Some drugs have properties that interact with alcohol to produce distressing side effects. Disulfiram (Antabuse) causes flushing, headache, nausea, and vomiting if a person drinks alcohol while taking the drug. The symptoms can be triggered after drinking half a glass of wine or half a shot of liquor and may last from half an hour to 2 hours, depending on dosage of the drug and the amount of alcohol consumed. One dose of disulfiram is usually effective for 1 - 2 weeks. Overdose can be dangerous, causing low blood pressure, chest pain, shortness of breath, and even death. The drug is more effective if patients have family or social support, including AA "buddies," who are close by and vigilant to ensure that they take it.

Topiramate. Topiramate (Topamax) is an anti-seizure drug used to treat epilepsy. It also helps control impulsivity. Studies indicate it may be a promising treatment for alcohol dependence. In one well-designed study, patients who took topirimate had fewer heavy drinking days, fewer drinks per day, and more continuous days of abstinence than patients who received placebo. Side effects included burning and itching skin sensations, change in taste sensation, loss of appetite, and difficulty concentrating.

Resources

www.niaaa.nih.gov -- National Institute on Alcohol Abuse and Alcoholism
www.samhsa.gov -- Substance Abuse and Mental Health Services Administration
www.ncadi.samhsa.gov -- National Clearinghouse for Alcohol and Drug Information
www.aca-usa.org -- American Council on Alcoholism
www.ncadd.org -- National Council on Alcoholism
www.alcoholics-anonymous.org -- Alcoholics Anonymous
www.al-anon-alateen.org -- Al-Anon Family Group Headquarters
www.nofas.org -- National Organization on Fetal Alcohol Syndrome

References

Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006 May 3;295(17):2003-17.

Chudley AE, Conry J, Cook JL, Loock C, Rosales T, LeBlanc N. Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. CMAJ. 2005 Mar 1;172(5 Suppl):S1-S21.

de Roux A, Cavalcanti M, Marcos MA, Garcia E, Ewig S, Mensa J, et al. Impact of alcohol abuse in the etiology and severity of community-acquired pneumonia. Chest. 2006 May;129(5):1219-25.

Gazdzinski S, Durazzo T, Jahng GH, Ezekiel F, Banys P, Meyerhoff D. Effects of chronic alcohol dependence and chronic cigarette smoking on cerebral perfusion: a preliminary magnetic resonance study. Alcohol Clin Exp Res. 2006 Jun;30(6):947-58.

Hingson RW, Heeren T, Winter MR. Age at drinking onset and alcohol dependence: age at onset, duration, and severity. Arch Pediatr Adolesc Med. 2006 Jul;160(7):739-46.

Johnson C, Drgon T, Liu QR, Walther D, Edenberg H, Rice J, et al. Pooled association genome scanning for alcohol dependence using 104,268 SNPs: Validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism. Am J Med Genet B Neuropsychiatr Genet. 2006 Aug 7; [Epub ahead of print]

McKenna W. In: Goldman L and Ausiello DA, eds. Cecil Medicine. 23rd edition. Saunders; 2007.

O'Connor PG. In: Goldman L and Ausiello DA, eds. Cecil Medicine. 23rd edition. Saunders; 2007.

Volkow ND, Wang GJ, Begleiter H, Porjesz B, Fowler JS, Telang F, et al. High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors. Arch Gen Psychiatry. 2006 Sep;63(9):999-1008.

Review Date:
12/28/2007
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., 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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Alcoholism

FitSugar — Wed, 08 Oct 2008 17:35:44 -0700

Overview

Signs and Symptoms
Risk Factors
Diagnosis
Preventive Care
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Alcoholism is a chronic, often progressive disease in which a person craves alcohol and drinks despite repeated alcohol-related problems (like losing a job or a relationship). Alcoholism involves a physical dependence on alcohol, but other factors include genetic, psychological, and cultural influences.

Becoming addicted to alcohol is a gradual process that happens as alcohol changes the level of chemicals in your brain, especially gamma-aminobutyric acid or GABA (which stops you from being impulsive) and dopamine (which is linked with pleasurable feelings). As the levels of these chemicals change, you crave alcohol to make yourself feel good again.

About 18 million people in the United States abuse alcohol, and estimates suggest that more than 70 million Americans have dealt with alcoholism in their family. Alcohol is involved in almost half or all traffic deaths in the U.S.

Alcoholism is characterized by craving for alcohol and a loss of control over drinking, along with a physical dependence (meaning that the person experiences withdrawal symptoms when not drinking) and a tolerance for alcohol (meaning the person needs to drink greater amounts to feel “good”). Before entering recovery, most alcoholics will deny they have a problem. People who abuse alcohol but are not dependent on it may have similar symptoms, but they don’t feel the same craving to drink and usually don’t experience withdrawal symptoms.

Signs and Symptoms

Drinking by yourself or in secret
Craving alcohol
Not being able to control the amount you drink
Blackouts (not remembering events or conversations)
Becoming irritable when you can’t get a drink at your regular time
Having legal problems or an inability to sustain a relationship or a job
Withdrawal symptoms, such as nausea, sweating, shakiness, and anxiety, when you stop drinking
Needing more alcohol to feel its effects
Liver disease

Risk Factors

If you have a family history of alcohol abuse, you are more likely to develop the condition than someone without a family history. Other factors that may increase your risk include:

Beginning to drink early, by age 16 or sooner
Drinking more than one to two drinks per day
Smoking cigarettes (particularly teenagers)
Being under a lot of stress
Having a preexisting psychiatric disorder (such as depression or anxiety)

Diagnosis

If you or someone you care for is experiencing symptoms associated with alcoholism, you should see your doctor. He or she can help make a diagnosis and guide you in determining which treatment or combination of therapies will work best. You should know that, because most alcoholics deny they have a problem, they are often unlikely to seek treatment by themselves. Friends and family members may have to convince them to seek help.

Your doctor will take a history and do a physical exam. Questions that he or she may ask include:

Have you ever thought that you needed to cut back on the amount of alcohol you drink?
Has a spouse, friend or coworker ever annoyed you by asking you to drink less?
Do you ever feel guilty about the amount that you drink?
Do you ever drink in the morning or early in the day to soothe a hangover, get the day started, or get rid of the shakes?

Blood tests generally aren’t helpful because they only show recent alcohol consumption. But your doctor may order liver function tests to see if there has been damage to your liver from alcohol..

Preventive Care

If you drink, do so only in moderation - no more than two drinks per day if you are a man and no more than one drink per day if you are a woman.

Early intervention is key, especially with teenagers. To prevent teen drinking, consider the following:

Stay involved and interested in your teenager's life.
Talk openly to your children, especially pre-teens and teens, about the widespread presence and dangers of alcohol and drugs.
Have clear, non-negotiable rules about not using alcohol and drugs.
Act as a role model – don’t drink excessively, use other drugs, or smoke.
Strongly urge your children to not smoke.
Encourage your children to become active in sports, music, the arts, or other activities.
Know where your children and teens are at all times and make sure that there is always adult supervision.
Monitor your teenager for aggressive behavior, feelings of anger or depression, and poor school performance. If any of these develop, consider whether alcohol may be a reason.
Never drink and drive or allow your teenager to be driven in the car by someone who has been drinking.

Treatment Approach

The first and most important step in getting treatment for alcoholism is recognizing that you have a problem. Often, family members and close friends may urge treatment for the person with the addiction.

Treatment and ongoing recovery must address both physical and psychological addiction and may include inpatient treatment and/or Alcoholics Anonymous (AA). In an inpatient or residential program, the person generally stays in a hospital or center for 28 days, undergoing first detoxification (usually four to seven days) and then individual and group therapy emphasizing abstinence. Talk to a doctor about what is best for you or your loved one.

Lifestyle

Attend Alcoholics Anonymous.
Family members should attend Al-Anon to learn how to help the person with the addiction and to get help and support themselves.
Exercise regularly to help reduce cravings.

Medications

Your provider may prescribe the following medications.

For alcohol withdrawal

Benzodiazepines - tranquilizers used during the first few days of treatment to help you withdraw safely from alcohol. These drugs include

Diazepam (Valium)
Chlordiazepoxid (Librium)
Lorazepam (Ativan)
Oxazepam (Serax)

Anticonvulsants - may also help with withdrawal symptoms and don’t have the potential for abuse (as benzodiazepines do). They include

Carbamazepine (Tegretol)
Valprioc acid (Depakote)
Phenytoin (Dilantin)
Gabapentn (Neurontin)

To prevent relapse

Naltrexone (Revia, Vivitrol) - used in combination with counseling, may lessen the craving for alcohol and help prevent a return to drinking. Taking Revia or Vivitrol blocks receptors in your brain so that you don’t get “high” from drinking. It is only used after detoxification – that is, once you are no longer physically addicted to alcohol.

Acamprosate (Campral) - may help restore the chemical balance in the brain. It is best used in combination with counseling.

Disulfiram (Antabuse) - an older medication that discourages drinking by causing nausea, vomiting, and other unpleasant physical reactions when alcohol is used.

Nutrition and Dietary Supplements

Because chronic use of alcohol decreases your appetite and keeps your body from absorbing vital nutrients, you may be deficient in a number of vitamins and minerals. Your doctor may tell you to take supplements while you are regaining your health. Beneficial supplements may include vitamin B complex, vitamin C, selenium, magnesium, and zinc. A combination of amino acids –carnitine, glutamine, and glutathione – may help reduce cravings, blood sugar fluctuations, and stress related to alcohol use.

Thiamine (vitamin B1) - Your doctor may prescribe a thiamine supplement during withdrawal. Heavy use of alcohol causes thiamine deficiency, which can lead to a serious brain disorder called Wernicke-Korsakoff syndrome.

People who abuse alcohol are often deficient in vitamin A, but should take extra supplements (beyond the recommended daily allowance) only under their doctor’s supervision. High doses of vitamin A can damage the liver and may causes alcoholic liver disease to develop more quickly in people who drink heavily.

Herbs

The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, can trigger side effects and can interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care, under the supervision of a healthcare practitioner. However, herbs alone should not be used to treat alcoholism; counseling and peer groups such as AA are also needed.

Milk thistle (Silybum marianum) - Milk thistle is often used to treat liver problems, and some studies looking at milk thistle to treat alcoholic liver disease have found significant improvements in liver function. People with the mildest form of alcohol-related liver damage seem to improve the most. Milk thistle is less effective for those with severe liver disease such as cirrhosis, which is characterized by scarring and permanent, non-reversible damage to the liver. However, there are no studies looking at whether milk thistle is useful for alcohol withdrawal.
Kudzu (Pueraria lobata) - Animal studies suggest that kudzu, used in traditional Chinese medicine to treat alcohol abuse, might help reduce cravings. However, one study in humans failed to show any benefit.
Dandelion (Taraxacum officinale) - Dandelion is used traditionally for liver-related problems, although there is evidence that it helps alcohol withdrawal symptoms. It is often combined with milk thistle.

Homeopathy

There have been few studies examining the effectiveness of specific homeopathic remedies. Professional homeopaths, however, may recommend a treatment for alcoholism based on their knowledge and clinical experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type. In homeopathic terms, a person's constitution is his or her physical, emotional, and intellectual makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for a particular individual. Homeopathy alone should not be used to treat alcoholism, but can be a supportive therapy along with counseling and groups such as AA. The following are a few examples of remedies that an experienced homeopath might consider for symptoms related to alcohol abuse or withdrawal:

Arsenicum album - for anxiety and compulsiveness, with nausea, vomiting, and diarrhea

Nux vomica - for irritability and compulsiveness with constipation, nausea, and vomiting

Lachesis - for cravings for alcohol, headaches, and difficulty swallowing

Staphysagria - for angry individuals who tend to suppress their emotions and may have been abused physically, sexually, or psychologically in the past

Mind/Body Medicine

Cognitive-behavioral therapy with a psychologist or psychiatrist is a very effective treatment approach for alcohol addiction. This type of therapy, which is geared toward changing your beliefs and thought process about drinking, can help you cope with stress and control your behavior. Talk to your doctor about finding a qualified cognitive-behavioral therapist.

Acupuncture

In some cases, acupuncture may be a useful supportive therapy for addiction. Some but not all studies of acupuncture for the treatment of alcohol abuse have shown that it can reduce cravings and symptoms of withdrawal. However, acupuncture alone should not be used to treat alcohol addiction, but used in combination with counseling and groups such as AA.

Other Considerations

Pregnancy

Drinking alcohol while pregnant can seriously damage the baby, causing a condition known as fetal alcohol syndrome. Fetal alcohol syndrome causes irreversible physical and mental disabilities. The only safe way to protect against damage to the baby is not to drink during pregnancy or even if you are trying to become pregnant.

Prognosis and Complications

Possible complications associated with heavy alcohol use include:

Mental confusion or delirium
Severe amnesia
An unsteady gait
Loss of sperm cells
Repeated vomiting, ulcers, gastointestinal bleeding
Pancreatitis

In addition, long-term use of alcohol decreases life expectancy by about 15 years and puts you at significant risk for:

Liver damage, even liver failure (called cirrhosis)
High blood pressure, heart disease, and heart failure
Brain and nerve damage
Certain types of cancer including mouth, throat, laryngeal (voice box), esophageal, and breast
Osteoporosis
Nutritional deficiencies
Infections, including pneumonia and tuberculosis

The good news is, however, that even though alcohol abuse is a serious condition with potentially dire consequences, it is treatable. If you or someone you love has a problem, seek the help and advice of a health care professional as early as possible.

Supporting Research

Ambrose, ML, Bowden SC, Whelan G. Thiamin treatment and working memory function of alcohol-dependent people: preliminary findings. Alcohol Clin Exp Res. 2001;25(1):112-116.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision. Washington, DC: American Psychiatric Association; 2000.

Assanangkornchai S, Srisurapanont M. The treatment of alcohol dependence. Curr Opin Psychiatry. 2007 May;20(3):222-7. Review.

Bullock ML, Umen MS, Culliton PD, Olander RT. Acupuncture treatment of alcoholic recidivism: a pilot study. Alcohol Clin Exper Res. 1987;11(3):292-295.

Bullock ML, Culliton PD, Olander RT. Controlled trial of acupuncture for severe recidivist alcoholism. Lancet. 1989;1:1435-1439.

Carai MAM, Agabio R, Bombardelli E, et al. Potential use of medicinal plants in the treatment of alcoholism. Fitoterapia. 2000;71:538-542.

Ermalinski R, Hanson PG, Lubin B, Thornby JI, Nahormek PA. Impact of a body-mind treatment component on alcoholic inpatients. J Psychosoc Nurs Ment Health Serv. 1997;35:39-45.

Cooney JL, Cooney NL, Pilkey DT, Kranzler HR, Oncken CA. Effects of nicotine deprivation on urges to drink and smoke in alcoholic smokers. Addiction. 2003;98(7):913-921.

Das UN. Essential Fatty acids - a review. Curr Pharm Biotechnol. 2006 Dec;7(6):467-82. Review.

Ferri M, Amato L, Davoli M. Alcoholics Anonymous and other 12-step programmes for alcohol dependence. Cochrane Database Syst Rev. 2006 Jul 19;3:CD005032. Review.

Gurevich MI, Duckworth D, Imhof JE, Katz JL. Is auricular acupuncture beneficial in the inpatient treatment of substance-abusing patients? A pilot study. J Subst Abuse Treat. 1996;13(2):165-171.

Johnson JL, Leff M. Children of substance abusers: overview of research findings. Pediatrics. 1999;103(5).

Kunz S, Schulz M, Lewitzky M, Driessen M, Rau H. Ear acupuncture for alcohol withdrawal in comparison with aromatherapy: a randomized-controlled trial. Alcohol Clin Exp Res. 2007 Mar;31(3):436-42.

Moner SE. Acupuncture and addiction treatment. J Addict Dis. 1996;15(3):79-100.

Oh SH, Soh JR, Cha YS. Germinated brown rice extract shows a nutraceutical effect in the recovery of chronic alcohol-related symptoms. J Med Food. 2003;6(2):115-121.

Otto KC. Acupuncture and substance abuse: a synopsis, with indications for further research. Am J Addict. 2003;12(1):43-51.

Overstreet DH, Keung WM, Rezvani AH, Massi M, Lee DY. Herbal remedies for alcoholism: promises and possible pitfalls. Alcohol Clin Exp Res. 2003;27(2):177-185.

Purohit V, Abdelmalek MF, Barve S, Benevenga NJ, Halsted CH, Kaplowitz N, et al. Role of S-adenosylmethionine, folate, and betaine in the treatment of alcoholic liver disease: summary of a symposium. Am J Clin Nutr. 2007 Jul;86(1):14-24. Review.

Rezvani AH, Overstreet DH, Perfumi M, Massi M. Plant derivatives in the treatment of alcohol dependency. Pharmacol Biochem Behav. 2003;75(3):593-606.

Rogers J. Homeopathy and the treatment of alcohol-related problems. Complement Ther Nurs Midwifery. 1997;3(1):21-28.

Russel RM. Vitamin A and zinc metabolism in alcoholism. Am J Clin Nutr. 1980;33(12):2741-2749.

Sachan DA, Rhew TH. Lipotropic effect of carnitine on alcohol-induced hepatic stenosis. Nutr Rep Int. 1983;27:1221-1226.

Sachan DS, Rhew TH, Ruark RA. Ameliorating effects of carnitine and its precursors on alcohol-induced fatty liver. Am J Clin Nutr. 1984;39:738-744.

Sapir-Weise R, Berglund M, Frank A, Kristenson H. Acupuncture in alcoholism treatment: a randomized out-patient study. Alcohol Alcohol. 1999;34(4):629-635.

Shebek J, Rindone JP. A pilot study exploring the effect of kudzu root on the drinking habits of patients with chronic alcoholism. J Alt Compl Med. 2000;6:45-48.

Shwartz M, Saitz R, Mulvey K, Brannigan P. The value of acupuncture detoxification programs in a substance abuse treatment system. J Subst Abuse Treat. 1999;17(4):305-312.

Singh AK, Jiang Y, Benlhabib E, Gupta S. Herbal mixtures consisting of puerarin and either polyenylphosphatidylcholine or curcumin provide comprehensive protection against alcohol-related disorders in P rats receiving free choice water and 15% ethanol in pure water. J Med Food. 2007 Sep;10(3):526-42.

Sukul NC, Ghosh S, Sinhababu SP, Sukul A. Strychnos nux-vomica extract and its ultra-high dilution reduce voluntary ethanol intake in rats. J Altern Complement Med. 2003;7(2):187-193.

Trumpler F, Oez S, Stahli P, Brenner HD, Juni P. Acupuncture for alcohol withdrawal: a randomized controlled trial. Alcohol Alcohol. 2003;38(4):369-375.

Ventegodt S, Clausen B, Langhorn M, Kromann M, Andersen NJ, Merrick J. Quality of life as medicine III. A qualitative analysis of the effect of a five-day intervention with existential holistic group therapy or a quality of life course as a modern rite of passage. Scientific World J. 2004;4:124-133.

Worner TM, Zeller B, Schwarz H, Zwas F, Lyon D. Acupuncture fails to improve treatment outcome in alcoholics. Drug Alcohol Depend. 1992;30:169-173.

Xu BJ, Zheng YN, Sung CK. Natural medicines for alcoholism treatment: a review. Drug Alcohol Rev. 2005 Nov;24(6):525-36. Review.

Review Date:
12/26/2007
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

A News Study Shows Alcoholics Misread Facial Cues

TresSugar — Wed, 19 Aug 2009 06:00:00 -0700

They don’t call it getting blotto for nothing.

You’ve probably heard the claim that alcohol kills brain cells. A new study makes this a little more concrete: long-time alcoholics’ brains (even those who are now sober) are not good at recognizing facial expressions. Specifically, their brain’s limbic system (which supports emotion, long-term memory and the ability to smell things) does not register facial expressions of joy, sadness or disappointment as intensely for them.

Making sure that the two test groups were matched in IQ, socioeconomic status and education, researchers showed 15 now-sober alcoholics and 15 nonalcoholics pictures of faces asking, “How intelligent do you think this person is?” The pictures represented a face that was positive, negative or neutral. Using an MRI to check out how the respective groups’ limbic systems were operating, they saw strong activity in the nonalcoholics’ brains in response to the emotion-expressing photos, but for the abstaining alcoholics - it was all the same to them.

Without being able to read a person’s expressions, even the recovering alcoholic (to say nothing of a practicing alcoholic), will have more difficulty with interpersonal situations - with coworkers, significant others and family members. They may misread what's happening and overreact or underreact. All this may cause more strife for them, which could lead to more drinking. What researchers aren’t clear about it is which came first - emotional insensitivity and hence alcoholism, or alcohol-induced emotional insensitivity?

Cirrhosis

FitSugar — Wed, 08 Oct 2008 17:35:41 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Lifestyle Changes
Abdominal Infections
Encephalopathy
Ascites
Bleeding Episodes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration approved HepaGram B, an injectable immune globulin that can help prevent recurrence of hepatitis B following liver transplantation.

Primary Biliary Cirrhosis

Primary biliary cirrhosis is an autoimmune liver disease that increases the risk for liver cancer. According to a 2007 study, specific risk factors may help predict which patients with primary biliary cirrhosis are at particularly high risk of developing liver cancer. These risk factors include older age, being male, history of blood transfusion, and any signs of portal hypertension (high pressure of the blood in the portal vein, which leads to the liver) or cirrhosis.

Hepatitis C and Cirrhosis

Patients with cirrhosis who are infected with a particular hepatitis C genotype (1b) have a high risk of developing liver cancer, indicates a 2007 study. These patients should receive regular monitoring so that liver cancer can be detected in its earliest stages.
Interferon drug therapy can help reduce -- but not entirely eliminate -- the risk of liver cancer developing in patients with hepatitis C-related cirrhosis.

Hemochromatosis

Hemochromatosis, also called “iron overload,” is an iron disorder that increases the risk for cirrhosis. Hereditary hemochromatosis is one of the most common genetic diseases in the United States, and experts have debated whether all people should get screened for it. In 2006, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines concerning hemochromatosis screening. The USPSTF does not recommend routine screening in the general population. However, people who have family histories of hemochromatosis, or who show signs or symptoms of this disorder, should get tested.

Encephalopathy

Lactulose, a drug that helps remove ammonia from the body, can help improve cognitive function and quality of life for people with hepatic encephalopathy, suggests a 2007 study. Hepatic encephalopathy, a complication of liver disease, affects the brain and nervous system.

Introduction

Cirrhosis is an irreversible result of various disorders that damage liver cells over time. Eventually, damage becomes so extensive that the normal structure of the liver is distorted and its function is impaired.

Cirrhosis is a chronic liver disease that causes damage to liver tissue, scarring of the liver (fibrosis - nodular regeneration), progressive decrease in liver function, excessive fluid in the abdomen (ascites), bleeding disorders (coagulopathy), increased pressure in the blood vessels (portal hypertension), and brain function disorders (hepatic encephalopathy). Excessive alcohol use is the leading cause of cirrhosis.

The disease process often takes the following path:

Scarring. The main damage in cirrhosis is triggered by scarring (fibrosis) that occurs from injuries due to alcohol, viruses, or other assaults. Normal clumps and form nodules around the scarred areas. The scar tissue and regenerated nodules act like small dams and alter the flow of blood and bile in and out of the liver.

Altered Blood and Bile Flow. The changes in blood and bile flow have significant consequences, with both the liver and other organs responding to the altered flow:

The spleen overproduces nitric oxide, a gas that causes blood vessels in the spleen to relax and open.
The small blood vessels and bile ducts in the liver itself, however, narrow (constrict). (Blood vessels in other organs, including the kidney, also narrow.)
Blood flow coming from the intestine into the liver is slowed by the narrow blood vessels. It backs up through the portal vein and seeks other routes.
New, abnormally twisted and swollen veins called varices form in the stomach and lower part of the esophagus in order to compensate for the backup blood.
Bile also builds up in the bloodstream, resulting in high levels of bilirubin, which causes a yellowish cast in the skin called jaundice.
Fluid buildup also occurs in the abdomen (called ascites), and swelling in the arms and legs is common.

Changes in Liver Size. The liver enlarges in the first phases of the disease. In advanced stages, the liver sometimes shrinks, a condition called postnecrotic cirrhosis.

The liver is the largest organ in the body. In the healthy adult, it weighs about 3 pounds. The liver is wedge-shaped, with the top part wider than the bottom. It is located immediately below the diaphragm and occupies the entire upper right quadrant of the abdomen.

Vital Functions. The liver performs over 500 vital functions. Damage to the liver can impair these and many other processes. Among them are the following:

Processing Healthful Nutrients. It processes all of the nutrients the body requires, including proteins, glucose, vitamins, and fats.

Bile Production. The liver produces bile, a green-colored fluid that helps the body absorb fats and fat-soluble vitamins. Bile is formed from bilirubin, a yellow-green pigment produced from the breakdown of hemoglobin, the oxygen-carrying component in red blood cells. Bile contains bile salts, fatty acids, cholesterol, and other substances. Bile travels from the liver to the gallbladder, where it is stored until after a meal. It is then secreted into the intestines where it helps digest fat.

Eliminating Toxins. One of the liver's major functions is to render harmless potentially toxic substances, including alcohol, ammonia, nicotine, drugs, and harmful by-products of digestion.

Recycling Blood. The liver and spleen removes old red blood cells from the blood. The iron contained in them is recycled in the bone marrow to make new red blood cells.

The Liver's Architecture. The vital processes the liver performs rely on well-organized liver architecture.

The Building Blocks. The basic building blocks of the liver are the following structures:

Bile ducts
Blood vessels
Working liver tissue (called the parenchyma)
Supportive (connective) tissue

The Architecture. The liver is a built on a framework of lobes:

The lobes. The liver is divided into two major lobes, a right and a smaller left, that are separated by tough, fibrous connective tissue.
The lobules. The liver's two major lobes contain about 100,000 smaller lobes, called lobules. Each lobule contains microscopic columns of liver cells and blood vessels. Bracing the corners of each lobule column are an artery and a vein that carry blood and a bile duct that drains bile.
The arteries and veins. The arteries bring oxygen-rich blood to nourish the liver cells. The veins supply the liver cells with blood containing the nutrients and toxins that the liver cells process. A central vein runs through each column and collects the processed blood from both sources. These veins join to form the hepatic vein.
The bile ducts. The bile ducts in the column corners collect bile draining from tiny canals around the liver cells. These ducts eventually join to form the large common bile duct that leads from the liver to the gallbladder.

The Liver's Blood Supply. The liver is rich in blood. It holds about a pint, or 13% of the body's supply. It is furnished with blood from two large vessels, the hepatic artery and the portal vein, and is drained of blood by the hepatic vein. (The word "hepatic" derives from the Latin word for liver.)

The hepatic artery. This artery supplies blood from the heart directly to the liver. This blood nourishes the liver.

The portal vein. The portal vein carries to the liver blood that has been circulating through the stomach, spleen, and intestine. The liver processes this blood, extracting nutrients and toxins.

The hepatic vein. This vein carries blood from the liver and connects to the inferior vena cava, a large vein that carries blood back to the heart.

Click the icon to see an image of the liver.

Causes

Several processes can lead to cirrhosis.

Alcoholism particularly endangers the liver. Alcoholic cirrhosis (also sometimes referred to as portal, Laennec's, nutritional, or micronodular cirrhosis) is the primary cause of cirrhosis in the U.S. It is estimated to be responsible for 44% of deaths from cirrhosis in North America. Some experts believe this estimate is low. One Canadian study found alcohol to be the major contributor in 80% of all cirrhosis deaths.

The relationship between alcohol and cirrhosis is generally as follows:

Alcohol is absorbed from the small intestine, and the blood carries it directly into the liver, where it becomes the preferred energy source.
In the liver, alcohol converts to toxic chemicals, such as acetaldehyde (AcH), which trigger the production of powerful immune factors called cytokines. These molecules in large amounts can cause inflammation and tissue injury. They are proving to be major culprits in the destructive process in the liver. AcH is particularly being researched because it plays a role in most actions of alcohol, including damaging effects on the liver that may lead to cirrhosis.
The injured liver eventually is unable to break down fatty acids, compounds that make up fat. Over time, then, fat accumulates, further impairing the liver's ability to absorb oxygen and increasing its susceptibility to injury. During the initial phase, the fat-laden liver becomes greatly enlarged, but it eventually shrinks as cirrhosis develops.

Chronic hepatitis, both hepatitis B and hepatitis C, is the second leading cause of cirrhosis. Chronic hepatitis C is the more dangerous form and accounts for one-third of all cirrhosis cases. About 5 - 20% of patients with chronic hepatitis C, and 5 - 10% of patients with chronic hepatitis B, eventually develop cirrhosis over the course of several decades. The longer a patient has had chronic hepatitis, the greater the risk for eventually developing cirrhosis. A 2005 study indicated that cirrhosis develops in 70% of patients who have had hepatitis C for more than 60 years.

The hepatitis virus can produce inflammation in liver cells, causing injury or destruction. If the condition is severe enough, the cell damage becomes progressive, building a layer of scar tissue over the liver. In advanced cases, as with alcoholic cirrhosis, the liver shrivels in size, a condition called postnecrotic or posthepatic cirrhosis.

Hepatitis C is a virus-caused liver inflammation which may lead to jaundice, fever, and cirrhosis. The people most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs and health care workers or emergency workers who may be exposed to contaminated blood.

Autoimmune liver diseases include autoimmune hepatitis and primary biliary cirrhosis. Like other autoimmune disorders, these conditions most likely develop because a genetically defective immune system attacks the body's own cells and organs. People who have one of these liver diseases also often have other autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, scleroderma, inflammatory bowel disease, glomerulonephritis, and hemolytic anemia.

Autoimmune Hepatitis. Autoimmune chronic hepatitis occurs when an abnormal immune response causes an attack on the liver cells. It accounts for about 20% of all chronic hepatitis cases. Autoimmune chronic hepatitis typically occurs in women age 20 - 40 who have other autoimmune diseases. Some research indicates that the postmenopausal period may be another peak in incidence of AIH among women. About 30% of patients are men, however, and in both genders there is often no relationship to another autoimmune disease. In general, no major risk factors have been discovered for this condition.

Suspects for triggering this hepatitis include the measles virus, a hepatitis virus, or the Epstein-Barr virus, which causes mononucleosis. It is also possible that a reaction to a drug or other toxin that affects the liver also triggers an autoimmune response in some people.

Click the icon to see an image of mononucleosis.

Primary Biliary Cirrhosis. Up to 95% of primary biliary cirrhosis (PBC) cases occur in women, usually around age 50. In people with PBC, the immune system attacks and destroys cells in the liver’s bile ducts. Like many autoimmune disorders, the causes of PBC are unknown. Recent research indicates the following risk factors:

Family history of PBC
Family history of Sjögren syndrome (another autoimmune disorder)
Individual history of urinary tract infections (UTI)
History of smoking
History of nail polish use
Hormone replacement therapy
Exposure to toxins from hazardous waste sites

This research suggests that environmental factors (chemicals, cigarette smoke) or infectious organisms (bacteria that causes UTI) may trigger PBC in patients who are genetically susceptible to the disease. Women who have never been pregnant appear less likely to develop PBC.

Nonalcoholic fatty liver disease (NAFLD) resembles alcoholic liver disease, but it occurs in people who do not drink a lot of alcohol. Obesity and type 2 diabetes are the two main causes of a fatty liver. Some evidence suggests that insulin resistance (the primary problem in type 2 diabetes) is a major factor in development of a fatty liver. A diet high in fatty foods may also be a risk factor, as dietary fat accumulates in the liver. Due to the recent rise in childhood obesity, NAFLD is increasingly occurring in children. In fact, NAFLD is now the most common liver disease in American children.

Nonalcoholic fatty liver disease can lead to nonalcoholic steatohepatitis (NASH). Liver inflammation and injury, as well as a fatty liver, characterize NASH. NASH occurs in about half of people with diabetes and up to 75% of obese people.

Nonalcoholic fatty liver disease is usually benign and very slowly progressive. But, in certain patients it can lead to cirrhosis, liver failure, or liver cancer. About 8 - 20% of people with nonalcoholic steatohepatitis go on to develop cirrhosis. A 2006 study indicated that NASH-related cirrhosis causes fewer deaths than cirrhosis that is caused by chronic hepatitis C. However, many patients with NASH have coronary artery disease and heart failure and have a high risk of dying from heart disease.

Weight reduction and diabetes and cholesterol management are the primary approaches to controlling these diseases.

Hemochromatosis is a disorder of iron metabolism. This disease interferes with the way the body normally gets rid of iron. People with hemochromatosis absorb too much more iron from the food that they eat. The iron overload accumulates in organs in the body. When excess iron deposits accumulate in the liver, they can cause cirrhosis.

There are two main forms of hemochromatosis:

Primary hemochromatosis, also called hereditary hemochromatosis, is an inherited genetic disease.
Secondary hemochromatosis results from other conditions, such as anemia and alcoholism.

Hereditary hemochromatosis is one of the most common genetic diseases, especially among Caucasians. About 1 in every 200 Americans carries the gene that causes this disease. Although experts do not recommend that everyone get screened for hemochromatosis, people who have a family history of this disease, or who show symptoms (joint pain, fatigue, abdominal pain), should get tested. Left untreated, hemochromatosis can lead to serious damage of the liver, heart, and pancreas.

Hemochromatosis is treated with phlebotomy, a procedure that involves removing about a pint of blood once or twice a week. Starting phlebotomy treatment before organ damage occurs can help prevent cirrhosis. If, however, cirrhosis has already developed, patients have a high risk for developing liver cancer even if iron levels are normalized.

Inherited Diseases. Cirrhosis can be caused by several inherited diseases, including:

Cystic fibrosis
Alpha-1 antitrypsin deficiency
Galactosemia
Glycogen storage diseases
Wilson's disease

Other Rare Causes. Rare causes of cirrhosis include:

Schistosomiasis, caused by a parasite found in the Far East, Africa, and South America.
Small intestine bypass surgery (rarely, if ever, performed anymore).
Long-term or high level exposure to certain chemicals and drugs can cause cirrhosis, including arsenic, methotrexate, and toxic doses of vitamin A.

Cancers that have metastasized to the liver, blood clots in the hepatic or portal vein, or obstructions in the bile duct can cause changes that resemble cirrhosis.

Risk Factors

Cirrhosis affects about 3 million Americans a year. However, because about 2.7 - 4 million people harbor hepatitis C, the rates of cirrhosis could dramatically increase over the next few years.

Only 10% of heavy drinkers develop advanced liver disease. Not eating when drinking and consuming a variety of alcoholic beverages are factors that increase the risk for liver damage. Still, the amount of alcohol consumed and the patterns of drinking are only weak predictions of risk. Other risk factors have been identified that may increase the danger to the liver:

Obesity is a major factor for all stages of liver disease.
Women develop liver disease at lower quantities of alcohol intake than men. The reason for this may be due to women's inability to metabolize alcohol as quickly as men, so it stays in the bloodstream longer.
Genetic factors that regulate the immune responses in the intestine also play a role in increasing the risk for liver injury from alcoholism.

Risk Factors for Developing Cirrhosis from Hepatitis C. Overall, between 10 - 15% of patients with chronic hepatitis C develop cirrhosis. The risk varies widely, however. The following conditions put people with hepatitis C at higher risk for liver damage:

Overall the risk for progression is highest in men -- particularly African-Americans -- who were older at the time of infection. The risk is much lower in women and children (2 - 4%).
Moderate-to-heavy alcohol users. (Even one or two alcoholic drinks a day increase the risk for liver injury in hepatitis C patients.)
Having a specific genetic type of the virus. There are six main genetic types and more than 90 subtypes, which can differ significantly in their effects and response to treatment. Genotype 1 is the most serious and is the cause of up to three quarters of the cases in the U.S. The other common forms are types 2 (15%) and 3 (7%), which pose less danger.
Co-infection with hepatitis B. Co-infection with B significantly affects the outcome of these patients and may be more common than previously believed. This co-condition may cause superinfections with very serious consequences, reduce these patients' responses to interferon therapy, and increase their risk of liver cancer. Patients with hepatitis C should be immunized against hepatitis B.
Co-infection with HIV.
A history of transfusions. (In one report, the risk in middle-aged patients with a history of transfusions was 20 - 30%).
Being diabetic and overweight, particularly if fat is distributed in the abdomen (an apple-shape). This condition poses a higher risk for nonalcoholic fatty liver disease (NASH), which in turn is apt to become scarred and cirrhotic.

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

Having large iron stores in the liver.
High exposure to toxic chemicals or environmental contaminants.

Because there are millions of Americans now infected with chronic hepatitis C, doctors have been justifiably concerned that there will be a significant number of cases of liver failure and liver cancer in the coming years. Computer analyses have suggested that mortality rates from hepatitis C-related cirrhosis or liver cancer will double or triple over the next 20 years. Fortunately, improved therapies may significantly reduce these discouraging estimates.

Researchers are working on developing a genetic test to identify patients with chronic hepatitis C who are most at risk of developing cirrhosis. In 2007, scientists announced they had made progress on a test that measures variations in seven genes to calculate a “Cirrhosis Risk Score.” The researchers hope that this experimental test may eventually help doctors decide which patients should receive early treatment with alpha-interferon and ribavirin.

Risk Factors for Developing Cirrhosis from Hepatitis B. The great majority of people with chronic persistent hepatitis B have a good long-term outlook. Between 5 - 10%, however, become carriers of the virus, and 5 - 10% of these individuals eventually develop cirrhosis. The addition of hepatitis D is a particular danger and increases the risk for cirrhosis. Seven genetic types of hepatitis B virus (designated A to G) have now been identified, which may help researchers determine the patients who may have a better outlook than others. Genotype C is the most common form and is more aggressive than genotype B, which also responds better to treatment.

Primary biliary cirrhosis accounts for only 0.6 - 2% of deaths from cirrhosis. In patients with chronic persistent autoimmune hepatitis, the outlook is very favorable, and survival rates are equal to the general population. If it becomes active, it must be treated. Left untreated, the 5-year survival rates of primary biliary cirrhosis are 50%.

Obesity increases the risk for nonalcoholic fatty liver disease (NAFLD), a condition that can lead to nonalcoholic steatohepatitis (NASH). Studies estimate that 8 - 20% of people with NASH eventually develop cirrhosis. A 2006 study found that people with NAFLD and elevated liver enzymes have a high risk of developing end-stage liver disease. People with NASH had an especially poor prognosis for survival. Losing weight is important for overweight people with NASH and may help to delay disease progression. A 2003 study of more than 11,000 patients indicated that obesity increases the risk of death from cirrhosis in people who drink little or no alcohol, but not among those who drink alcohol.

Symptoms

Many people experience few symptoms at the onset of cirrhosis.

Early symptoms include:

Fatigue and loss of energy.
Loss of appetite and nausea.
Spider angiomas may develop on the skin. These are pinhead-sized red spots from which tiny blood vessels radiate.

Patients in later stages may develop the following symptoms:

Jaundice. This yellowish cast to the skin and eyes occurs because the liver cannot process bilirubin for elimination from the body.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

The palms of the hands may be reddish and blotchy, a condition known as palmar erythema.
Loss of body hair.
Abnormalities in hormone-affected organs. In men with alcoholic cirrhosis, the testicles may atrophy, and their breasts may become swollen, sometimes painfully.
Ascites. A swollen belly is a sign of ascites, the most common major complication of cirrhosis, which occurs when fluid accumulates in the abdomen. Fever, abdominal pain, and tenderness when the belly is pressed indicate that the fluid is infected, but infection can occur without any symptoms.
Fluid buildup and swelling (edema) in legs.

People with primary biliary cirrhosis may have severe generalized itching and often develop small fatty yellow lumps called xanthomas on the eyelids, hands, and elbows. They may have an unpleasant condition called steatorrhea, in which the feces contain excessive fat, causing them to float and to be very foul smelling.

Click the icon to see an image of a xanthoma.

Complications

Cirrhosis is the eleventh leading cause of death by disease in the United States, killing more than 25,000 people each year. A damaged liver affects almost every bodily process, including the functions of the digestive, hormonal, and circulatory systems. The most serious complications are those associated with so-called decompensation, which occur when cirrhosis progresses. They include the following:

Bleeding and fluid buildup (ascites).
Infections.
Damage to the brain (encephalopathy). Impaired brain function occurs when the liver cannot detoxify harmful substances.

Liver cancer is also a long-term risk with cirrhosis.

Cirrhosis is irreversible, but the rate of progression can be very slow, depending on its cause and other factors. Five-year survival rates are about 85% and can be lower or higher depending on severity.

For example, alcoholics with cirrhosis who abstain can have a 5-year or more survival rate of as high as 85%. For those who continue drinking, the chance for living beyond 5 years is no higher than 60%.
In patients with hepatitis B or C, the 5-year survival rate after a diagnosis of cirrhosis is 71 - 85%.
About two-thirds of patients with primary biliary cirrhosis never develop symptoms and can have a normal lifespan. Once symptoms of liver damage, such as jaundice, occur, however, the average survival time declines. In one study of women diagnosed with primary biliary cirrhosis, about 36% developed symptoms over an 11-year period, and 11% either died or required liver transplantation.

Unfortunately, doctors are usually unable to determine when cirrhosis first occurred, which makes it difficult to determine prognosis.

In cirrhosis, liver cell damage slows down blood flow. This causes a backup of blood through the portal vein, a condition called portal hypertension. The effects of portal hypertension can be widespread and serious, including fluid buildup and bleeding.

Ascites and Fluid Buildup. Ascites is fluid buildup in the abdomen. It is uncomfortable and can reduce breathing function and urination. Ascites is usually caused by portal hypertension, but it can result from other conditions. Swelling can also occur in the arms, legs, and spleen. Although ascites itself is not fatal, it is a marker for severe progression. Once ascites occurs, only half of patients survive after 2 years. Some doctors refer to the phases of cirrhosis as preascitic and ascitic. Some doctors even believe that ascites signals the need for liver transplantation, particularly in alcoholic cirrhosis.

Variceal Bleeding. One of the most serious repercussions of portal hypertension is the development of varices, blood vessels that enlarge to provide an alternative pathway for blood diverted from the liver. In about two-thirds of patients, they form in esophagus. Varices pose a high risk for rupture and bleeding because of the following characteristics:

They are thin-walled.
They are often twisted.
They are subject to high pressure.
Internal bleeding from these varices (variceal bleeding) occurs in 20 - 30% of patients with cirrhosis. The risk of death from a single episode can reach 70%.

Bleeding commonly recurs within 2 weeks of the first episode, but after 6 weeks, the risk for recurrence is the same as for patients who have not had a bleeding event.

Factors that predict variceal bleeding include:

Ascites
Encephalopathy
Large veins

Factors that can increase the danger for a bleeding episode in high-risk individuals include the following:

Moderate-to-intense exercise
Bacterial infection
Certain times of the day. Eating increases portal pressure, and there is a greater risk for bleeding in the evening. A lesser but still significant risk occurs in the early morning.

It is important for patients to be screened for esophageal varices and treated with preventive beta blockers if they show signs of risk. Between 30 - 40% of patients with cirrhosis have bleeding. The risk of dying from this complication is 20 - 35%. Some doctors recommend that all newly diagnosed patients be screened using endoscopy. Screening should also be considered for all previously diagnosed patients who have not been screened but would benefit from preventive treatments.

Portal hypertension can cause several secondary complications, including kidney failure. Non-steroidal anti-inflammatory drugs, such as naproxen, may increase the risk for kidney failure.

Gastrointestinal bleeding can occur from abnormal blood clotting, which can be a result of a combination of complications associated with cirrhosis. They include vitamin K deficiencies and thrombocytopenia -- a drop in platelets (the blood cells that normally initiate the clotting process). Some research now suggests that thrombocytopenia itself may be associated with more advanced liver failure.

Bacterial infections are very common in advanced cirrhosis, and may even increase the risk for bleeding. Most bacterial infections, including those in the urinary, respiratory, or gastrointestinal tracts, develop when patients are in the hospital. Abdominal infections are a particular problem in cirrhosis and occur in up to 25% of patients with cirrhosis within a year of diagnosis.

Mental impairment is a common event in advanced cirrhosis. In severe cases, the disease causes encephalopathy (damage to the brain), with mental symptoms that range from confusion to coma and death. A combination of conditions associated with cirrhosis causes this serious complication:

Buildup in the blood of harmful intestinal toxins, particularly ammonia.
An imbalance of amino acids that affect the central nervous system.

Encephalopathy is often triggered by certain conditions, including:

Gastrointestinal bleeding
Constipation
Excessive dietary protein
Infection
Surgery
Dehydration

Alcoholics with cirrhosis are believed to be at higher risk for this complication than are nonalcoholic cirrhosis, but one study suggested that alcoholics simply tend to have more severe cirrhosis. Even minimal hepatic encephalopathy (MHE) can have detrimental effects on functional ability. One study suggested that MHE impairs the ability to safely drive a car, and that all patients with cirrhosis be tested for MHE.

Symptoms of Encephalopathy. Early symptoms of hepatic encephalopathy include forgetfulness, unresponsiveness, and trouble concentrating. Sudden changes in the patient's mental state, including agitation or confusion, may indicate an emergency condition. Other symptoms include bad fruity-smelling breath and tremor. Late stage symptoms of encephalopathy are stupor and eventually coma.

Hepatorenal syndrome occurs if the kidneys drastically reduce their own blood flow in response to the altered blood flow in the liver. It is a life-threatening complication of late-stage liver disease that occurs in patients with ascites. Symptoms include dark colored urine and a reduction in volume, yellowish skin, abdominal swelling, mental changes (delirium, confusion), jerking or coarse muscle movement, nausea, and vomiting.

People with cirrhosis have an increased risk for liver cancer. Hepatitis B and C themselves increase the risk for liver cancer, regardless of the presence of cirrhosis. Hepatitis B infection is the leading cause of liver cancer.

For hepatitis C-related cirrhosis, a 2007 study indicated that patients with cirrhosis who are infected with genotype 1b hepatitis C have a greater risk of developing liver cancer than patients infected with other types of hepatitis C genotypes. (Genotype 1 is the most common type of hepatitis C in the United States.)

People with primary biliary cirrhosis also face a high risk of liver cancer. According to a 2007 study, several factors can indicate the increased likelihood of developing liver cancer. These factors include older age, male gender, history of blood transfusion, and signs of portal hypertension or cirrhosis.

About 30% of patients with chronic liver disease develop osteoporosis (loss of bone density), which is twice the usual incidence. Patients with primary biliary cirrhosis have a particularly high risk for osteoporosis. Treating osteoporosis in patients with cirrhosis can be complicated. One study found that calcitriol (a form of vitamin D) is especially helpful in preventing bone loss in patients with cirrhosis.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Regular exercise and vitamin and mineral supplements may reduce and even reverse loss of bone density.

Nearly all patients with cirrhosis are insulin resistant. Insulin resistance is a primary feature in type 2 diabetes and occurs when the body is unable to use insulin. This hormone is important for delivering blood sugar and amino acids into cells and helps determine whether these nutrients will be burned for energy or stored for future use.

One study reported that nearly a quarter of patients with cirrhosis had gallstones.

Click the icon to see an image of gallstones.

They may also face a higher than average risk for certain abnormal heart rhythms. Peptic ulcers, sleep disorders, and respiratory problems are also more common in people with cirrhosis than in the general population.

Diagnosis

A physical examination may reveal the following in a patient with cirrhosis:

The cirrhotic liver is firm and often enlarged. The liver may feel rock-hard. (In advanced stages of cirrhosis, the liver may become small and shriveled.)
The left side can often be felt by the doctor when pressing on the abdomen.

If the abdomen is swollen, the doctor will check for ascites by tapping the flanks and listening for a dull thud and feeling the abdomen for a shifting wave of fluid.

Measuring Liver Enzymes (Aminotransferases). Enzymes known as aminotransferases, including aspartate (AST) and alanine (ALT), are released when the liver is damaged. Measurements of these enzymes, particularly ALT, are the least expensive and most noninvasive tests for determining severity of the underlying liver disease and monitoring treatment effectiveness. Enzyme levels vary, however, and are not always an accurate indicator of disease activity. (For example, they are not useful in detecting progression to cirrhosis.)

Radioimmunoassays. To identify a particular virus that may be causing hepatitis, blood tests called radioimmunoassays are performed. Typically, radioimmunoassays identify particular antibodies, which are molecules in the immune system that attack specific antigens. (Antigens are any molecules that the body considers threatening or dangerous, and can be targeted by antibodies.)

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

Some of these tests can pinpoint hepatitis antigens directly. These tests, however, have limitations:

There may not be enough antibodies for blood tests to detect for up to weeks or months after hepatitis develops. Blood tests that are taken too early, then, may miss these signs of infection.
Antibodies also persist after patients recover, so a positive antibody test can indicate a previous infection but does not necessarily determine if the infection is active.

The assays for individual hepatitis viruses may differ.

Polymerase Chain Reaction. In some cases of hepatitis C, a polymerase chain reaction (PCR), may be performed. A PCR is able to make multiple copies of the genetic material (the RNA) of the virus to the point where it is detectable.

Screening for Hepatitis C Virus. In 2004, the U.S. Preventive Services Task Force (USPSTF) recommended against routine screening for the hepatitis C infection in the general population due to low prevalence of the disease. In addition, it "found no evidence that screening for HCV infection in adults at high risk leads to improved long-term health outcomes" and found insufficient evidence to recommend for or against such screening. However, the USPSTF did advise testing in those with signs or symptoms of liver disease. The failure to recommend testing in the high-risk population goes against current recommendations made by the Centers for Disease Control and Prevention, the National Institutes of Health, and other professional organizations. In response to the study, published in the Annals of Internal Medicine, the American Association for the Study of Liver Diseases issued a statement saying that halting such screening would be a "terrible mistake with grave consequences," pointing out that the study itself underscored some key infection-related data that strongly emphasizes the need for screening in high-risk populations.

A liver biopsy is the only definite method for diagnosing cirrhosis. It also helps determine its cause, treatment possibilities, the extent of damage, and the long-term outlook. For example, hepatitis C patients who show no significant liver scarring when biopsied appear to have a low risk for cirrhosis.

The biopsy may be performed using various approaches, including:

Percutaneous Liver Biopsy. This approach uses a needle inserted through the abdomen to obtain a tissue sample from the liver. Various forms of needles are used, including those that use suction or those that cut out the tissue. If cirrhosis is suspected, a cutting needle is the better tool. This approach should not be used in patients with bleeding problems, and it must be used with caution in patients with ascites or severe obesity.

Click the icon to see an image of liver biopsy.

Transjugular Liver Biopsy. This approach uses a catheter (a thin tube) that is inserted in the jugular vein in the neck and threaded through the hepatic vein (which leads to the liver). A needle is passed through the tube, and a suction device collects liver samples. This procedure is risky but may be used for patients with severe ascites.
Laparoscopy. This procedure requires a small abdominal incision through which the doctor inserts a thin tube that contains small surgical instruments and a tiny camera to view the surface of the liver. This is generally reserved for staging cancer or for ascites with unknown causes.

Biopsies can be dangerous, so they cannot be performed on patients who have test results that indicate clotting problems, on those who have had previous liver biopsies, or who have ascites.

Certain blood tests are used to determine liver function. They include the following:

Serum albumin concentration. Serum albumin measures protein in the blood (low levels indicate poor liver function).
Prothrombin time (PT). The PT test measures in seconds the time it takes for blood clots to form (the longer it takes the greater the risk for bleeding).
Bilirubin. One of the most important factors indicative of liver damage is bilirubin, a red-yellow pigment that is normally metabolized in the liver and then excreted in the urine. In patients with hepatitis, the liver cannot process bilirubin, and blood levels of this substance rise, sometimes causing jaundice.

The results of these tests along with the presence of specific complications (ascites and encephalopathy) are used for calculating the Child-Pugh Classification. This is a staging system (A to C) that helps doctors determine the severity of cirrhosis.

Very high levels of serum alkaline phosphatase, an enzyme produced in the liver, and high levels of immune factors called mitochondrial antibodies are usually present in blood tests of patients with primary biliary blood cirrhosis. Bilirubin measurements appear to be important factors in determining its severity.

Fatty liver is suspected when a patient has elevated liver enzymes. The doctor will take imaging tests of the liver using ultrasound, computed tomography, or magnetic resonance imaging. A liver biopsy is the standard test for confirming a diagnosis of fatty liver disease and for distinguishing NAFLD from nonalcoholic steatohepatitis (NASH). Several studies in 2006 and 2007 suggested that a blood test for cytokeratin-18 (CK-18), a protein found in liver cells, may be an effective noninvasive approach for diagnosing NASH. Doctors hope that this simple blood test may eventually be able to replace liver biopsy.

Several imaging tests can be used to diagnose cirrhosis and its complications.

Imaging Techniques. Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound are all imaging techniques that are useful in detecting and defining the extent of cirrhosis. Such tests can reveal ascites, an enlarged spleen, an irregular liver surface, reversed portal vein blood flow, and liver cancer. Sometimes they can even detect abnormally large blood vessels in the liver. In some cases, images from ultrasound and CT can be misinterpreted as cancer. MRI is most useful for ruling out or confirming cancer.

Click the icon to see an image of an MRI scan.

Click the icon to see an image of a CT scan.

Liver Scans. Sometimes liver scans are performed using a small radioactive tracer and a special camera that records information provided by the tracer as it passes through the liver:

Arteriography uses dye injected into the hepatic arteries that show up on x-ray.
Splenoportography uses dye injected into the spleen, which allows the doctor to measure portal vein pressure. This procedure is risky.

Hepatic vein wedge pressure involves insertion of a catheter into the hepatic veins. The blood pressure in the veins of the liver is then measured. The result is an indicator of portal vein pressure. If pressure is high, cirrhosis is likely. A low measurement is a favorable sign.

Endoscopy. Some doctors recommend endoscopy for patients newly diagnosed with mild-to-moderate cirrhosis in order to screen for esophageal varices. (These are abnormal blood vessels in the esophagus that increase the risk for bleeding). In this test, a fiber optic tube is inserted down the throat. The tube contains tiny cameras to view the inside of the esophagus, where varices are most likely to develop. Endoscopy is the only procedure for detecting varices, but it is not clear if screening for varices in patients without severe cirrhosis is any more beneficial than simply putting them immediately on preventive drugs -- whether or not varices have been identified.

Paracentesis. If ascites is present, paracentesis is performed to determine its cause. This procedure involves using a thin needle to withdraw fluid from the abdomen. The fluid is tested for different factors to determine the cause of ascites:

Bacteria cultures and white blood cell counts. (These are used to determine the presence of infection.)
Protein levels. Low levels of protein in the fluid plus a low white blood cell count suggest that cirrhosis is the cause of the ascites.

The appearance of the fluid is helpful in determining problems:

A cloudy fluid plus a high white blood cell count means an infection is present.
Bloody fluid suggests the presence of a tumor.

Screening for Liver Cancer. Patients with cirrhosis are usually screened for liver cancer using ultrasound and tests for a substance called alpha-fetoprotein (AFP). It is not known whether such screening has much impact on survival, because it is not very sensitive and has a high rate of false positives (suggesting the presence of cancer when it is not actually present). Screening is not necessary in patients without cirrhosis.

Treatment

The only treatment for alcoholic cirrhosis is to stop drinking. Individuals with alcoholic cirrhosis are typically malnourished and require increased calories and rigorous nutritional support, which can improve survival rates.

Interferons Alone and in Combination with Ribavirin. Pegylated interferon combined with ribavirin is the gold standard treatment for chronic hepatitis C in both adults and children. It achieves response rates of up to 50% for patients infected with HCV genotype 1 (the most common genotype form in the U.S.) and up to 80% for patients infected with genotypes 2 or 3. Interferon alone is usually reserved for patients who cannot tolerate ribavarin.

A 2005 clinical trial of patients with chronic hepatitis C and cirrhosis found that interferon treatment reduced the risk of liver cancer and significantly improved chance of survival. The study emphasizes the importance and substantial benefits of interferon therapy. A 2007 study of patients with hepatitis C-related cirrhosis also indicated that interferon therapy can help reduce the risk of liver cancer and overall risk of death from liver disease.

A number of natural and synthetic interferons are available:

Natural interferons include interferon alfa-2a (Intron) and interferon alfa-2b (Roferon).
Pegylated interferons (PegINF) are long-acting formulations of interferon. They include alfa-2b (Peg-Intron) or alfa-2a (Pegasys). These drugs are used in combination with ribavarin (Copegus, Rebetol).
Alfacon-1 (Infergen), also called consensus interferon, is a genetically modified interferon. A combination of alfacon-1 with ribavirin is proving to help some patients who had been resistant to ribavirin with interferon.

A 2005 study suggested that some patients with hepatitis C genotypes 2 or 3 may be able to benefit from a shorter course of combination treatment (12 weeks) than the standard 24-week treatment duration. A shorter treatment time may reduce the risk of side effects. However, a 2007 study in the New England Journal of Medicine found that 16 weeks of combination therapy in patients with these genotypes did not work as well as the 24-week regimen. Given the significant side effects associated with combination pegylated interferon and ribavarin treatment, particularly anemia, researchers are actively investigating how to identify which patients may be able to succeed with shorter treatment duration.

PegINF combinations are proving to slow progression of scarring, and have even achieved improvement in some patients who already have cirrhosis. Whether the combination treatment protects against future liver cancer is still unclear. (A higher total dose, rather than a longer duration of treatment, may be the critical factor for protection.)

Side Effects of Combination Treatment. The side effects of the combination include those of both interferon and ribavirin. Interferon side effects may occur more often in the combination treatment. Combination treatment side effects may include:

Anemia occurs in about 22% of patients who take combination treatment versus 1% who take interferon alone. This complication is reversible and usually stabilizes after 1 - 2 months of treatment. However, some patients may become so anemic that they have to stop the medication. Since anemia can worsen heart disease, patients with a history of significant heart problems should not be treated with ribavirin. Other nucleoside analogues are being investigated that may have a lower risk for anemia than ribavirin.
Flu-like symptoms, such as fever, headaches, and muscle aches, are the most common side effect.
Reduced white blood cell count.
Skin disorders, such as dry skin and rash.
Coughing and shortness of breath.
Gastrointestinal symptoms (nausea, indigestion, lack of appetite).
Emotional and psychological symptoms, such as severe sleep disturbances, depression, irritability, and anxiety.
Combination treatment in pregnant women poses a very high risk for birth defects.

The current drugs used for hepatitis C still do not meet the needs of all patients. They are expensive, have significant side effects, do not work in half the patients who take them, and are unsuitable in many others. Investigation is ongoing to find better solutions. Drugs showing promise include:

Albinterferon alfa-2b (Albuferon). This long-acting form of interferon-alfa may have fewer side effects and require less dosing than pegylated interferons. It is currently being tested in combination with ribavarin in Phase II trials for patients with genotype 1 chronic hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a peptide derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It is being used for hepatitis B and is under investigation for hepatitis C in combination with interferon.
Celgosivir. Celgosivir is a new type of antiviral drug, which blocks alpha-glucosidase, an enzyme involved in viral replication. Celgosivir is being studied in combination with pegylated interferon alfa-2b and ribavirin. The drug is derived from the Australian chestnut tree.
Eltrombopag (Revolade). Thrombocytopenia, reduced production of blood platelets, is a condition that affects patients with hepatitis C and cirrhosis. Patients with thrombocytopenia cannot tolerate standard antiviral therapy. Researchers hope that eltrombopag, a drug that stimulates platelet production, may help normalize platelet levels so that they can start antiviral drug treatment.
Statins. Statin drugs are used for the treatment and management of cholesterol. Researchers are studying whether they may help improve liver enzyme levels in patients with hepatitis C.

Of interest are studies using phlebotomy (which is simply drawing blood) to reduce iron levels. In one study, maintenance therapy with this procedure reduced liver inflammation and possibly slowed progression of cirrhosis.

An ounce of prevention is worth a pound of cure, and the phrase resoundingly holds true in the case of hepatitis B. Today, a vaccine against hepatitis B is available. It can prevent hepatitis B and, therefore, also prevent liver cancer. The American Academy of Pediatrics and the Centers for Disease Control and Prevention currently recommend that all babies born in the United States receive a hepatitis B vaccine at birth.

Six drugs are currently approved in the United States for treatment of chronic hepatitis B:

Peginterferon alfa-2a (Pegasys)
Interferon-alfa-2b (Intron)
Adefovir (Hepsera)
Lamivudine (Epivir)
Entecavir (Baraclude)
Telbivudine (Tyzeka)

These drugs block the replication of hepatitis B in the body. Some also help boost the immune system. A doctor will decide which drug to prescribe based on a patient’s age, disease severity, and other factors. Each drug has various advantages and disadvantages in terms of cost, efficacy, side effects, and likelihood of drug resistance. A combination of drugs may also be prescribed.

Peginterferon alfa-2a. Peginterferon alfa-2a (Pegasys) was approved in 2005 for treatment of chronic hepatitis B. (Peginterferon is also called pegylated interferon.) The drug was previously approved in 2002 for treatment of chronic hepatitis C. Pegasys prevents the hepatitis B virus from replicating and also helps boost the immune system. It is given as a weekly injection. Peginterferon is sometimes prescribed in combination with lamivudine (Epivir).

Interferon Alpha. For many years, interferon alfa-2b (Intron) was the standard drug for hepatitis B. The drug is usually taken by injection every day for 16 weeks. (It does not appear to help hepatitis D.) Unfortunately, even in hepatitis B, the virus recurs in almost all cases, although this recurring mutation may be weaker than the original strain. Administering the drug for longer periods may produce sustained remission in more patients while still being safe. Interferon is also effective in eligible children, although long-term effects are unclear.

Lamivudine, Entecavir, and Telbivudine. These drugs are classified as nucleoside analogs. Lamivudine (Epivir or 3TC) is an antiretroviral drug that is used to treat human immunodeficiency virus (HIV) as well as hepatitis B. Studies suggest that lamivudine reduces viral count in over half of hepatitis B patients who take it as sole therapy for about a year. It is less expensive than interferon-alfa and has fewer side effects, but may not work as well as interferon-alfa for long-term therapy. A major problem with lamivudine is the development of mutated viral strains that become resistant to the drug, particularly in areas where the virus is common. About 20% of patients who take lamivudine develop drug resistance.

In 2005, the Food and Drug Administration (FDA) approved entecavir (Baraclude) for treatment of adults with chronic hepatitis B. In clinical trials, entecavir worked better than lamivudine for treating hepatitis B. Entecavir appears to have less risk of drug resistance than lamivudine. Studies also suggest that it may be a good alternative treatment for patients who have developed resistance to lamivudine. Questions have been raised about the drug’s possible cancer risks. Ongoing studies are evaluating this risk.

In 2006, the FDA approved telbivudine (Tyzeka), the newest nucleoside analog drug, for treatment of chronic hepatitis B.

Adefovir. Adefovir (Hepsera) belongs to a class of antiviral drugs called nucleotide analogs. (Nucleotides are related to nucleosides but have a slightly different chemical structure.) Nucleotide analogs block an enzyme involved in the replication of viruses. Adefovir costs more than lamivudine, but may be effective against lamivudine-resistant strains of hepatitis B. The drug must be taken on a long-term basis. A 2006 study indicated that when patients stopped taking adefovir after 48 weeks, the hepitatis B virus resumed replication. Patients who took the drug for a longer period (144 weeks) continued to benefit from treatment. Another 2006 study indicated that for some patients, adefovir remains effective for up to 5 years, although resistance occurs in about 20% of patients.

Drug Warnings. In 2004, the FDA issued two drug warnings for patients with hepatitis B. The HIV drug tenofovir (Viread) should not be used to treat patients with HIV who are co-infected with hepatitis Bas the drug may increase hepatitis severity. The lymphoma drug rituximab (Rituxan) may reactivate hepatitis B. Patients with lymphoma should be screened for hepatitis B. In 2007, the FDA revised the label for entecavir (Baraclude); patients who are co-infected with hepatitis Band HIV should take entecavir only if they are also taking antiviral HIV drugs.

Emtricitabine is a nucleoside analog drug used to treat HIV and AIDS. It is being investigated for chronic hepatitis B.
Pegylated interferon alfa-2b (Peg-Intron) and alfa-2a (Pegasys) are approved for treatment of chronic hepatitis C. They are being investigated alone and in combination with other drugs, such as ribavirin (Copegus, Rebetol), for treatment of hepatitis B. The combination of pegylated interferon and ribavirin is the standard treatment for hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a substance derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It appears to be safe for hepatitis B patients when used alone or in combination with interferon. It is approved in many countries, but not the United States.

Ursodeoxycholic Acid (UDCA) and Drugs Used to Slow Progression. At this time no medication can cure primary biliary cirrhosis. Ursodiol, ursodeoxycholic acid (Actigall), or UDCA has been the standard drug used for primary biliary cirrhosis. Several studies have reported that it slows progression and helps prevent the need for liver transplantation.

It has no effect on symptoms, including itching and fatigue. Some drugs, such as colchicine, corticosteroids, or immunosuppressants, are being investigated for use in combination with UDCA. Long-term controlled trials are needed to determine the value of UDCA alone or with other drugs.

Drugs for Itching. Itching is a major problem with this disease. Cholestyramine, taken with meals, is the first choice for relieving itching. Several other drugs have been used or investigated, including low doses of the drug naltrexone and phototherapy.

Drugs for Impaired Fat Absorption. Because primary biliary cirrhosis affects fat absorption, patients may need high doses or injections of important fat-soluble vitamins, including K, D, A, and E.

Treatment of Nonalcoholic Fatty Liver Disease. Weight loss is the most important method for managing nonalcoholic fatty liver disease (NAFLD) and preventing progression to nonalcoholic steatohepatitis (NASH) and, eventually, cirrhosis. Diabetes and cholesterol control are also important. Investigators are studying whether various drugs used to treat type 2 diabetes may help treat NAFLD and NASH.

Other research is focusing on antioxidant vitamins, such as vitamin E.

In 2005, the National Institutes of Health launched two trials to study treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitisin adults and children. Children with NAFLD will receive vitamin E, metformin, or placebo. In the adult trial, patients with NASH will receive vitamin E, pioglitazone, or placebo.

Secondary Biliary Cirrhosis. Secondary biliary cirrhosis caused by blockage in the bile ducts can be relieved by surgery.

Autoimmune Hepatitis. Autoimmune hepatitis is treated with the corticosteroid prednisone and also sometimes immunosuppressants, such as azathioprine (Imuran).

Hemochromatosis. For hemochromatosis, weekly bleedings (phlebotomies) may be performed until iron levels are normal, then repeated as needed. If treatment is given before cirrhosis develops, life expectancy may be normal.

Wilson's Disease. D-penicillamine is the drug most used for Wilson's disease.

There are no current safe and effective therapies for liver scarring (fibrosis). However, recent insights into the cellular and molecular mechanisms responsible for scarring have led to the development of specific, antifibrotic drugs that target the primary injury and inhibit abnormal cell mechanisms. Such drugs, now in very early testing, could one day help prevent or reduce the progression of liver scarring or the progression to liver cancer.

Liver transplantation may be indicated for the following:

Patients who have developed life-threatening cirrhosis and who have a life expectancy of more than 12 years.
Patients with liver cancer that has not spread beyond the liver.

Survival rates after transplantation are similar among those who have hepatitis B, hepatitis C, or alcoholic liver disease. Current 5-year survival rates after liver transplantation are about 75%. Patients also report improved quality of life and mental functioning after liver transplantation. Patients should seek medical centers that perform more than 50 transplants per year and produce better-than-average results.

Unfortunately, there are many more patients waiting for liver transplants than there are available organs. Fortunately, more procedures are now being performed using liver tissue from a living donor. In these cases, surgeons replace the patient’s diseased liver with a part of the liver taken from a donor. The donor’s liver regenerates to full size within a few weeks of surgery, and the recipient’s liver also regrows.

Transplantation surgery generally takes 4 - 12 hours to perform, and patients stay in the hospital for up to 3 weeks after the surgery. Most patients return to normal or near-normal activities 6 - 12 months following the transplant. For the rest of their lives, patients need to take immunosuppressive medication to prevent rejection.

Liver Transplantation in Patients with Hepatitis. One of the primary problems with many hepatitis patients is recurrence of the virus after transplantation.

One study of patients with hepatitis C reported 5-year risks of 80% for viral recurrence and 10% for cirrhosis. A 2004 study found that the hepatitis C virus recurs with more severity with liver donations from living donors than livers taken from cadavers.
Viral recurrence is also high in patients with hepatitis B. In 2007, the FDA approved HepaGram B, an immune globulin, to prevent recurrence of hepatitis B after transplantation. Patients need to receive HepaGram B injections on a lifelong basis.

Liver Transplantation in Autoimmune Liver Diseases. Patients who require transplantation for primary biliary cirrhosis are those who develop major complications of portal hypertension and liver failure or who have poor quality of life and short survival without the procedure. Survival rates after transplantation are excellent.

The outlook is also good for patients who have autoimmune hepatitis who require a transplant. Survival rates are about 90% after 1 year, and 70 - 80% after 5 years. Rejection usually occurs in those patients whose immune systems are very compromised.

Liver Transplantation in Alcoholism. There is considerable controversy over whether liver transplantation should be performed in alcoholics with cirrhosis who are unlikely to abstain. One French study reported no differences in survival, transplant rejection, and other indicators of success and failure after transplantation between alcoholics and non-alcoholics and between alcoholics who abstained and those who relapsed after the procedure.

Click the icon to see an illustrated series detailing a liver transplant.

Lifestyle Changes

A healthy lifestyle is particularly important for people with cirrhosis.

Healthy Foods. Because important antioxidant vitamins are depleted in the cirrhotic liver, patients should maintain a diet rich in fresh fruits, vegetables, and whole grains.

Coffee and Tea. Coffee appears to help lower the risk of cirrhosis, especially among heavy drinkers. A 2006 study indicated that people who drank 1 - 3 cups of coffee a day reduced their risk of alcoholic cirrhosis by 40%. Those who drank 4 or more cups reduced their risk by 80%. Researchers think that there is some ingredient in coffee (other than caffeine) that is responsible for this apparent protection. Studies on tea have been mixed. Some studies report that tea also lowers the risk of chronic liver disease, while others have found no effect.

Antioxidant Supplements. There is some preliminary laboratory evidence that various antioxidant supplements -- including vitamin E, selenium, and S-adenosylmethionine (SAMe) -- may help protect against liver damage and cirrhosis. Supplements, however, are not recommended for people with liver disease except with the advice of a doctor. Some vitamins, such as vitamins D and A, are metabolized in the liver and can be toxic.

Iron Restrictions. Elevated iron levels have been associated with cirrhosis from many causes. Patients should avoid iron-rich foods, such as red meats, liver, and iron-fortified cereals, and should avoid cooking with iron-coated cookware and utensils.

Supplemental Nutritional Products. Supplemental nutritional beverages may be helpful, particularly for patients with both alcoholism and cirrhosis. In one study, patients with both alcoholism and cirrhosis drank Ensure every day as a supplement to their regular diet. After 6 months they showed significant improvement in many signs of overall health compared to those who did not consume the beverage.

Vitamin B1 (Thiamine). Thiamine binds to iron and helps reduce iron load in the liver. One small study suggested it may be helpful for patients with chronic hepatitis B. It is not known if it has any benefit for cirrhosis. Pork is high in the vitamin, but more healthful sources include dried fortified cereals, oatmeal, corn, nuts, cauliflower, sunflower seeds and vitamin pills.

Like most vitamins, vitamin B1 may be obtained in the recommended amount with a well-balanced diet, including some enriched or fortified foods.

Omega-3 Fatty Acids. Some research suggests that supplements of omega-3 fatty acids (found in fish oil and evening primrose oil) may help protect the diseased liver.

Click the icon to see an image of omega-3 fatty acids.

Protein and Soy. High-quality dietary protein may be especially helpful for patients with ascites and for repairing muscle mass, but excessive protein loads may trigger encephalopathy. Protein solutions have been devised that provide beneficial amino acids without including those that increase this risk. There is no limit on vegetable proteins, such as those from soy.

Salt Restriction. Restricting salt consumption to less than 2,000 mg a day is particularly important for patients with ascites. The less salt the better.

Zinc. In some studies, taking zinc supplements have lowered ammonia levels in some patients who were zinc-deficient, a common problem in cirrhosis. Zinc replacement may reduce frequency and severity of muscle cramps and may even help protect against encephalopathy.

Fluid restriction is not usually necessary, but patients with severe ascites should discuss limiting fluid with their doctors.

Exercise increases the risk for portal pressure and variceal bleeding. One study reported that taking a beta-blocker may reduce this risk, although patients should discuss this with their doctor.

Infections can have a severe impact on the liver. Although most respiratory infections generally affect only the lungs, one small study suggested influenza may directly affect the liver in patients with cirrhosis and exacerbate the disease process. Researchers in the study advise annual flu shots for people with cirrhosis.

Patients should be aware that 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 several reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Among the natural substances being investigated for liver disease are ginseng, glycyrrhizin (a compound in licorice), catechin (found in green tea), SAMe, and silymarin (found in milk thistle).

Silymarin. Silymarin is a chemical found in the milk thistle herb. It is one of the most popular, and most studied, herbal remedies for liver disease. Some studies have indicated that silymarin may help improve liver enzyme levels. However, a 2005 review found that milk thistle did not help reduce deaths from liver disease caused by alcohol or hepatitis.

S-adenosylmethionine. S-adenosylmethionine (SAMe) is a chemical found in all parts of the body, which declines with age. It has been investigated for years in Europe for arthritis, depression, and liver disease. Some preliminary studies suggest it may provide some protection against liver damage and scarring and may improve survival rates in alcoholic patients with cirrhosis. It is very expensive, however, and as with all unregulated products, long-term side effects, drug interactions, and other factors are not fully known.

The following warnings are of particular importance for people with liver disease:

Kava kava (an herb used for anxiety and tension) can be toxic to the liver and cause severe hepatitis and even liver failure if taken excessively.

Abdominal Infections

Antibiotics are administered when fluid examination and tests for ascites indicate infection. For a first episode, the antibiotic cefotaxime is typically administered intravenously, requiring hospitalization. Treatment usually lasts 10 days, but research indicates that 5 days may be sufficient for certain patients. Some research indicates that the oral antibiotic ofloxacin may work as well with fewer complications, allowing patients to be treated at home.

In advanced cirrhosis, the risk for serious abdominal infection is high, and the antibiotic norfloxacin is often prescribed preventively against specific organisms that infect the abdominal cavity. One study reported, however, that patients who took norfloxacin became susceptible to Staphylococcal infections. Long-term treatments with norfloxacin or similar antibiotics may increase the risk for fungal infections after liver transplantation.

Encephalopathy

The first step in managing encephalopathy (damage to the brain) is to treat any precipitating cause, such as:

High ammonia levels
Bleeding
Low oxygen
Dehydration
Infection
Use of sedatives

Some studies indicate that manganese poisoning may be partially responsible for encephalopathy in cirrhosis. Studies are needed to determine if drugs that remove manganese improve this complication.

Ammonia is the leading toxin in causing encephalopathy related to cirrhosis. Mild encephalopathy is managed by directing therapy toward eliminating ammonia in the intestine:

The first step is to restrict animal protein, substituting meats and dairy products with vegetable protein, such as soy, and amino acid supplements.
Enemas, which clean out the intestine, may be effective.
Lactulose (Cephulac, Chronulac, Constulose, Duphalac, Enulose) and lactitol, known as disaccharides, help lower blood ammonia levels and have been shown to be effective in improving cognitive function and quality of life in people with mild encephalopathy.
Antibiotics, such as metronidazole, rifamycin, or neomycin, are effective in reducing levels of ammonia-producing bacteria in the intestine, although long-term use of these drugs can cause toxic side effects. Rifaximin (Xifaxan), another antibiotic, was approved in 2005 for treatment of hepatic encephalopathy.
L. acidophilus is the probiotic found in live culture yogurt. Researchers are studying whether L. acidophilus food or supplements can aid in improving liver and cognitive functions.
Researchers are investigating whether exercise can help remove ammonia from the body and improve encephalopathy.

Investigational Drugs. Certain drugs, such as rifaximin (Xifaxan) and flumazenil (Mazicon, Romazicon), are under investigation for treating encephalopathy. Flumazenil is typically administered to counteract the effects of sedatives.

Ascites

Nearly all patients with ascites (fluid accumulation in the abdomen) can benefit from the following measures:

Abstaining from alcohol. (Sometimes abstaining from alcohol is enough to improve this complication.)
Restricting salt.
Taking diuretics, usually spironolactone (Aldactone) and furosemide (Lasix). Previously, spironolactone was usually given alone, but experts now use it by itself only in patients with minimal fluid buildup. Patients should be monitored carefully for excessive and too-fluid loss, which can set off complications, including hypokalemia (dangerously low potassium levels), kidney failure, or encephalopathy. Weight loss from diuretics usually should not exceed 1 - 2 pounds per day, but there is no limit for patients with massive swelling.

Doctors often recommend bed rest for patients with ascites, but studies do not support its benefits. Restricting fluid is not usually necessary unless sodium levels in the blood are very low.

Patients with recurring ascites, or ascites that does not respond to standard diuretics after a month (refractory ascites), may require procedures to reduce fluid.

Large-Volume Paracentesis. Large-volume paracentesis is the current standard procedure and involves the following:

Large volumes of fluid are removed through a tube in the abdomen. Research indicates that 4 - 6 liters are usually effective and safe.
Albumin (protein) may be administered intravenously. This helps prevent a sudden drop in blood flow in the arteries. One study suggested that terlipressin, a drug that constricts blood vessels, may be as effective.
If the ascites does not respond to treatments, the patient may need paracentesis every 2 weeks or more frequently, and up to 10 liters may need to be removed.

Patients who need this procedure are probably not complying with dietary requirements.

Transjugular Intrahepatic Portosystemic Shunt. Studies have been mixed on whether transjugular intrahepatic portosystemic shunt (TIPS) improves survival without transplantation compared to large-volume paracentesis. An important 2003 study reported that although TIPS reduced the number of paracenteses, there was no improvement in survival rates. In addition, patients who were given TIPS had a higher risk for encephalopathy than those given large-volume paracentesis. In general, TIPS should be a second-line option for ascites that does not respond to diuretics.

Peritoneovenous Shunting. Peritoneovenous shunting is an older, more invasive, procedure involving insertion of a tube, or shunt, under the skin that routes the fluid from the abdomen into the jugular vein. The procedure can have serious complications, including infection, blood clots, encephalopathy, and rupture of blood vessels in the esophagus. It is now generally reserved for patients who are not candidates for repeat paracentesis or liver transplantation.

Hepatorenal syndrome can occur in patients with ascites. This is a life-threatening condition in which the kidneys fail in trying to compensate for altered blood flow in the liver. Studies suggest that terlipressin may be an effective treatment in combination with albumin for hepatorenal syndrome.

Researchers are testing certain drugs that may correct the imbalances in circulation that lead to portal hypertension and ascites. Of particular interest are drugs called nonpeptide vasopressin antagonists, also referred to as aquaretics. They may reverse the dilation in blood vessels that lead to salt and fluid retention.

The prognosis for patients with ascites is poor, even with intensive procedures. Liver transplantation should be considered for patients when ascites does not respond to treatments and when poor liver function or other complications, such as peritonitis or kidney failure, are present.

Bleeding Episodes

Preventing an Initial Bleeding Episode. About half of patients with mild-to-moderate cirrhosis have esophageal varices (enlarged veins in the esophagus). In such patients, the risk for bleeding within 2 years is as high as 35%. Bleeding is fatal in half of these patients. In general, experts recommend preventive drugs for such patients, even if they have not been screened with endoscopy -- the procedure needed to actually detect varices. Beta-blockers are the only medications to date that have some preventive effects, but others are under investigation.

Guidelines for Treating Bleeding Episodes. The doctor should first be certain that bleeding is caused by portal hypertension and ruptured varices and not by other conditions. For example, patients with cirrhosis are also at higher than average risk for bleeding peptic ulcers.

Saline or Ringers solution (a fluid and electrolyte replenisher) followed by red blood cells and plasma is administered immediately to replace lost blood.

The next step is to immediately achieve normal blood clotting (hemostasis) in order to stop the current bleeding episode and prevent early recurrence, which typically occurs 3 - 5 days after a bleeding episode.

In general it is a two-pronged approach using drugs and endoscopy procedures.

Drugs. Either octreotide or vasopressin are typically used to reduce portal pressure and blood flow.
Endoscopy. Endoscopy involves insertion of a thin tube containing a tiny camera followed by surgery to make repairs. Endoscopic sclerotherapy is the most common procedure. Emergency sclerotherapy is often used as first-line therapy for variceal bleeding, but a major 2002 analysis suggested that it is no more effective than drugs for stopping bleeding, and it has potentially serious adverse effects.

A combination of drugs and endoscopy is the best approach for stopping bleeding compared to endoscopy alone. It is not clear if there is any difference in long-term survival, however.

Prevent Bleeding Recurrence. Rebleeding is common after an episode. Beta-blocker drugs are typically used, although they are not effective for many patients.

Preventing Complications. The patient who is experiencing a bleeding episode is at high risk for other complications, including pneumonia, bacterial infections, and hepatic encephalopathy. Bacterial infections can also impair blood clotting. Preventive oral antibiotics are often problematic in these patients. One study suggested that intravenous ciprofloxacin may be helpful.

Beta-Blockers. Beta-blockers, typically propranolol (Inderal) or nadolol (Corgard), reduce the heart rate and can lower portal vein pressure in many patients and so reduce variceal bleeding. Carvedilol (Coreg), a newer drug, may be even more effective, but more research is needed. Beta-blockers are also used as a primary approach for prevention of recurring bleeding. Nevertheless, they fail to reduce portal pressure in nearly 40% of patients with cirrhosis. They may not be appropriate for patients with type 1 diabetes, asthma, emphysema, and chronic bronchitis. They must be taken for at least 2 years and most likely longer to sustain a survival advantage.

Other Drugs. Other drugs are being used or investigated, mostly in combination with beta-blockers, to reduce recurrence rates.

Isosorbide mononitrate is a nitrate, a type of drug commonly used for angina. Combinations with beta-blockers appear to prevent rebleeding more effectively than beta-blockers alone. It is not clear if the combination improves any other aspects of the disease. The nitrate may also be an alternative drug for patients who cannot tolerate beta-blockers. Studies have failed to show any survival advantage, however, when isosorbide mononitrate is used alone.
The diuretic spironolactone may be helpful in combination with a beta-blocker for reducing both ascites and rebleeding after an initial episode.
Angiotensin II receptor antagonists, including losartan (Cozaar), are being studied for lowering portal pressure.

Somatostatinand Similar Drugs. Somatostatin is a natural hormone that constricts blood vessels. This drug or synthetic derivatives (octreotide and vapreotide) may be more effective than the common procedure, endoscopic sclerotherapy, for controlling bleeding. No single drug is more effective than another. Their benefits for improving overall survival, however, are still uncertain, and a major analysis of current studies found no effects on survival rates with either octreotide or somatostatin.

Somatostatin, the natural hormone, controlled variceal bleeding in 87% of patients in one study, but it is short acting.
Octreotide (Sandostatin) is a derivative of somatostatin and is longer acting. It has largely replaced the older drug. It is very safe, even for heart patients, and has few serious side effects.
Vapreotide (Octastatin) also resembles somatostatin. One study concluded that a combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone for controlling bleeding, but the combination therapy did not improve mortality rates at 42 days. The study suggested that these drugs should be taken for 5 days.

Vasoconstrictors. Vasoconstrictors narrow the blood vessels and reduce flow in the spleen. They are particularly effective when used with nitroglycerin.

Vasopressin (Pitressin) is the most commonly used vasoconstrictor. It poses a risk to the heart, however, and it is not clear whether it is actually helpful.
Terlipressin is a synthetic version of vasopressin that is proving to be as effective as sclerotherapy in controlling bleeding. It also lacks vasopressin's side effects and may prove to prolong survival and serve as a bridge for patients waiting for liver transplantation.

Endoscopic procedures use a tube inserted down through the esophagus, containing microcameras and tiny instruments. Endoscopy is used both to diagnose the disease and stop bleeding. The two standard procedures are band ligation and sclerotherapy. In general, a combination of drug therapies and an endoscopic procedure is the usual approach for preventing a bleeding recurrence.

Endoscopic Band Ligation. In endoscopic band ligation, latex bands are wrapped around the bleeding varices, shutting off the blood supply. It is the method of choice to control of bleeding and, in weekly sessions, to prevent rebleeding, because it has a lower risk for complications than sclerotherapy. Recurrence rates are higher with band ligation, however. Studies are mixed on whether weekly treatments with band ligation are any more effective in preventing rebleeding than beta-blockers plus isosorbide mononitrate. A combination of medications plus band ligation is under investigation.

Investigators are studying argon plasma coagulation (APC) after band ligation to prevent variceal recurrence and rebleeding. This procedure uses argon gas to deliver electric currents that coagulate and stop bleeding.

Endoscopic Sclerotherapy. Endoscopic sclerotherapy is only effective against bleeding in the esophagus. The endoscopic tube is inserted through the mouth. A sclerosant (a solution that toughens the tissue around the variceal blood vessels) is injected to stop the bleeding. The procedure is repeated over a period of 2 - 3 months. Repeat treatments appear to reduce rebleeding and death. Minor complications (usually ulcers in the mucus membranes) are common, and serious complications can occur (narrowing or perforation of the esophagus and leakage at the injection site.)

Balloon tamponade has been available for years, but it is now used only for bleeding that cannot be controlled by drugs or endoscopy. It uses a tube inserted through the nose and down through the esophagus until it reaches the upper part of the stomach. A balloon at the tube's end is inflated and positioned tightly against the esophageal wall. It is usually deflated in about 24 hours. Serious complications can occur, the most dangerous being rupture of the esophagus. Recurrence of bleeding is common.

Shunts are used for patients who are still bleeding in the esophagus after endoscopic sclerotherapy or who are bleeding in the stomach. Choices include the following:

Transjugular intrahepatic portosystemic shunt (TIPS)
A surgical shunt

Shunt operations usually eliminate variceal bleeding, but encephalopathy and shunt failure are frequent complications. Doctors do not recommend shunts as elective surgery for high-risk patients who are candidates for liver transplantation, since shunts make this operation more difficult.

Transjugular Intrahepatic Portosystemic Shunt.A transjugular intrahepatic portosystemic (or portal-systemic) shunt (TIPS) involves the following:

The patient only requires a local anesthetic and a sedative.
A long needle is inserted into the jugular vein in the neck and passed down through the vena cava, a large vein that conducts blood back to the heart. This serves to widen the vein.
The surgeon makes an incision in the hepatic vein in the liver and creates a connection to the portal vein.
A cylindrical wire-mesh stent is inserted into this connecting vein.
The stent now acts as a shunt, which reroutes blood around the scarred liver.

TIPS is a good choice for bleeding that is not controlled by endoscopy, particularly when it is performed shortly after a bleeding episode. It also reduces ascites.

It is not useful as the first choice for stopping an initial bleeding episode or for preventing rebleeding, however, since it poses a high risk for encephalopathy. This complication outweighs its benefits compared to endoscopy for initial treatment and to beta-blockers for preventing recurrence. Blockage or closure of the shunt can develop over time.

TIPS is generally recommended for only patients who:

Cannot tolerate sclerotherapy
Are unlikely or unable to comply with the repeated procedures necessary for sclerotherapy
Have poor blood circulation

Surgical Shunts. There are two types of surgical shunts:

A portal shunt, or portal systemic shunt. It was introduced in 1945 and was the first significant treatment for bleeding varices. It relieves pressure in the portal vein by surgically joining it to the inferior vena cava, a large vein that conducts blood back to the heart. It poses a high risk for encephalopathy and does not appear to improve survival, so is not used often.
A variation called the H-graft portacaval shunt is a partial shunt that is proving to be effective for treating bleeding. It controls bleeding in 90% of patients and has a lower encephalopathy rate than the complete portal shunt or TIPS. In fact, early studies report that it may have lower rates for transplantation and death than TIPS.
A distal splenorenal shunt (DSRS) preserves blood flow through the portal vein while relieving pressure on the varices by joining the left kidney vein to the splenic vein. (The splenic vein returns blood from the spleen and is one of two veins that form the portal vein.) Studies show that DSRS has similar mortality rates compared to the portal shunt but lower rates of encephalopathy afterwards. Patients with alcoholic cirrhosis fare worse with DSRS than nonalcoholic patients. It is probably best used as an elective operation in patients with good liver function who continue to bleed in spite of endoscopy.

Resources

www2.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.aasld.org -- American Association for the Study of Liver Diseases
www.liverfoundation.org -- American Liver Foundation
www.gastro.org -- American Gastrointestinal Association
www.cdc.gov/ncidod/diseases/hepatitis -- Centers for Disease Control and Prevention, Hepatitis
www.hepfi.org -- Hepatitis Foundation International
www.pbcers.org -- Primary Biliary Cirrhosis Organization
www.organdonor.org -- National Transplant Society
www.unos.org -- United Network for Organ Sharing
www.organdonor.gov -- US government organ donor site

References

Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU. Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: A seventeen-year prospective cohort study. Hepatology. 2007 Aug 6; [Epub ahead of print]

Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnu L, Mazzella G, et al. Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology. 2007 Mar;45(3):579-87.

Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006 Oct;44(4):865-73.

Huang H, Shiffman ML, Friedman S, Venkatesh R, Bzowej N, Abar OT, et al. A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C. Hepatology. 2007 Aug;46(2):297-306.

Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. Lactulose improves cognitive functions and health-related quality of life inpatients with cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007 Mar;45(3):549-59.

Suzuki A, Lymp J, Donlinger J, Mendes F, Angulo P, Lindor K. Clinical predictors for hepatocellular carcinoma in patients with primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2007 Feb;5(2):259-64. Epub 2006 Dec 15.

U.S. Preventive Services Task Force. Screening for hemochromatosis: recommendation statement. Ann Intern Med. 2006 Aug 1;145(3):204-8.

Whitlock EP, Garlitz BA, Harris EL, Beil TL, Smith PR. Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2006 Aug 1;145(3):209-23.

Review Date:
8/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Ask a Writer: Help With My Boyfriend's Kidney-Stealing Parents!

TresSugar — Mon, 08 Jun 2009 04:00:00 -0700

Conventional Wisdom is a different kind of advice column. Your questions will be answered by people from all walks of life rather than by advice experts. Today, a nonfiction writer will offer her common sense advice. You can submit questions here.

Today's Question: My boyfriend and I have been together for over three years. We live together and plan on getting married someday so you better believe I love him.

His parents are alcoholics. I have always said I knew what alcoholics were like, but after meeting them, I realized I had no idea. His mother drinks nothing but alcohol and barely eats. She weighs 90 lbs and refuses to get help. His dad actually encourages her.

Recently his dad got ill and was put on dialysis but continues to drink and eat bad things and always ends up back in the ER. He was on the list to receive a kidney donation but due to his poor behavior, he was taken off the list. He can, however, be given a kidney if someone he knows will donate. So who have they turned to? Their three sons. They are now pressuring my boyfriend and his brothers to go get tested to see if they are the same blood type.

I am furious about this. Besides the fact that they are alcoholics (and yes, I know it's an illness), they are mean. Their sons break their necks to please them and get nothing in return. My boyfriend and his brothers had a horrible childhood and I can only hope the rest of his parents' lives are half as bad as what they put their kids through. I know that if his dad receives a kidney, he will go back to drinking and not take his meds and it will have all been for nothing. How can I intervene? Or should I?

- Worried For My Boyfriend's Kidneys and Sanity

To hear a nonfiction writer's advice, read more.

Dear Worried,

What a painful situation for both you and your boyfriend to be in. Of course you feel protective of the man you love. Unfortunately, this is a true life or death situation involving his father, who for better or worse is one of your boyfriend’s most significant relationships. You did not mention whether your boyfriend is seriously considering giving his father his kidney, or if he has asked for your advice. I will assume so, since you’ve written this letter.

My first instinct is to tell you to be very careful about putting yourself between your boyfriend and his family. If you encourage him not to do this (or even consider it) and he later comes to regret that choice, it could damage your relationship and your future together.

Your role is to love and support him while he makes this difficult choice, regardless of what he decides to do. Don’t come down too strongly against his parents, even though it sounds clear that they have been abusive to their children. Being raised in an alcoholic family is very psychologically complex, often leaving children with feelings of guilt and responsibility that seem confusing to others. Groups like Al-Anon exist for the people that love alcoholics to help give them perspective and support by talking to one another in a safe place. You could encourage him to find a local chapter and attend a meeting. Perhaps they could help your boyfriend explore why he would be willing to get radical surgery to help a man who is not helping himself.

Rather than building a case against his family, you could help your boyfriend gather and process information about the surgery. He needs to seriously consider the physical and emotional risks he would experience by giving up a kidney. He should meet with his father's doctor to find out what his own health risks would be, what the procedure would be like, and what his father's prognosis would be if he does continue to drink. Maybe you could accompany him to that meeting.

Sometimes the best way we can help the people we love is by helping them help themselves.

Signed, A Nonfiction Writer

Source

Anxiety disorders

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Complications
Diagnosis
Treatment
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, duloxetine (Cymbalta) was approved for treatment of generalized anxiety disorder. Duloxetine is a dual inhibitor antidepressant.

Anxiety Disorders Under-Recognized and Under-Treated

About 41% of patients with an anxiety disorder do not receive any treatment, indicates a 2007 study in the Annals of Internal Medicine. Anxiety disorders can interfere with daily functioning, and problems worsen when people have more than one type of anxiety disorder. The study’s researchers recommend that screening for anxiety become a regular part of office visits in the same way that primary care doctors screen patients for depression.

Antidepressants and Children

The benefits of antidepressants for treating pediatric anxiety disorders appear to outweigh the risks for suicide, according to a 2007 review in the Journal of the American Medical Association. Researchers also found that antidepressants did not work as well for treating obsessive compulsive disorder compared to other types of anxiety disorders. This review was the largest to date of antidepressant use in children and adolescents. Most doctors recommend cognitive behavioral therapy as the first treatment approach for childhood anxiety disorders.

Psychological Therapies for Post-Traumatic Stress Disorder

Specially designed psychotherapies -- such as trauma-focused cognitive behavioral therapy, eye movement desensitization and reprocessing, and stress management -- are the most effective therapies for patients with post-traumatic stress disorder, according to a 2007 review in the Cochrane Database.

Introduction

Fear and stress reactions are essential for human survival. They enable people to pursue important goals and to respond appropriately to danger. In a healthy individual, the stress response (fight, fright, or flight) is provoked by a genuine threat or challenge and is used as a spur for appropriate action.

An anxiety disorder, however, involves an excessive or inappropriate state of arousal characterized by feelings of apprehension, uncertainty, or fear. The word is derived from the Latin, angere, which means to choke or strangle. The anxiety response is often not attributable to a real threat. Nevertheless it can still paralyze the individual into inaction or withdrawal. An anxiety disorder persists, while a healthy response to a threat resolves, once the threat is removed.

Anxiety disorders have been classified according to the severity and duration of their symptoms and specific behavioral characteristics. Categories include:

Generalized anxiety disorder (GAD), which is long lasting and low-grade
Panic disorder, which has more dramatic symptoms
Phobias
Obsessive-compulsive disorder (OCD)
Post-traumatic stress disorder (PTSD)
Separation anxiety disorder (which is almost always seen in children)

GAD and panic disorder are the most common. Anxiety disorders are usually caused by a combination of psychological, physical, and genetic factors, and treatment is, in general, very effective.

Generalized anxiety disorder (GAD) is the most common anxiety disorder. It affects about 5% of Americans over the course of their lifetimes. It is characterized by the following:

A more-or-less constant state of worry and anxiety, which is out of proportion to the level of actual stress or threat in their lives.
This state occurs on most days for more than 6 months despite the lack of an obvious or specific stressor. (It worsens with stress, however.)
It is very difficult to control worry. For a clear diagnosis of GAD, the specific worries should be differentiated from those that would define other anxiety disorders, such as fear of panic attacks or appearing in public. Moreover, they are not obsessive like people with obsessive-compulsive disorder. (It should be noted, however, that over half of those with GAD also have another anxiety disorder or depression.)
Patients with anxiety may experience physical symptoms (such as gastrointestinal complaints) in addition to, or even in place of, mental worries. (This latter case may be more common in people from non-Western cultures such as those with Asian backgrounds.)
People with GAD tend to be unsure of themselves, overly perfectionist, and conforming.

Given these conditions, a diagnosis of GAD is confirmed if three or more of the following symptoms are present (only one for children) on most days for 6 months:

Being on edge or very restless
Feeling tired
Having difficulty with concentration
Being irritable
Having muscle tension
Experiencing disturbed sleep

Symptoms should cause significant distress and impair normal functioning and not be due to a medical condition, another mood disorder, or psychosis. It should be noted that pure GAD is uncommon. It typically occurs with other mood disorders (anxiety or depression) or substance use.

Panic disorder is characterized by periodic attacks of anxiety or terror (panic attacks). They usually last 15 - 30 minutes, although residual effects can persist much longer. The frequency and severity of acute states of anxiety determine the diagnosis. (It should be noted that panic attacks can occur in nearly every anxiety disorder, not just panic disorder. In other anxiety disorders, however, there is always a cue or specific trigger for the attack.) A diagnosis of panic disorder is made under the following conditions:

A person experiences at least two recurrent, unexpected panic attacks.
For at least a month following the attacks, the person fears that another will occur.

Symptoms of a Panic Attack. During a panic attack a person feels intense fear or discomfort with at least four or more of the following symptoms:

Rapid heart beat
Sweating
Shakiness
Shortness of breath
A choking feeling or a feeling of being smothered
Dizziness
Nausea
Feelings of unreality
Numbness
Either hot flashes or chills
Chest pain
A fear of dying
A fear of going insane

Women may be more likely than men to experience shortness of breath, nausea, and feelings of being smothered. More men than women have sweating and abdominal pain. Panic attacks that include only one or two symptoms, such as dizziness and heart pounding, are known as limited-symptom attacks. These may be either residual symptoms after a major panic attack or precursors to full-blown attacks. (It should be noted that panic attacks can also accompany other anxiety disorders, such as phobias and post-traumatic stress disorder. In such cases, however, additional characteristics differentiate these disorders from panic disorder.)

Frequency of Panic Attacks. Frequency of attacks can vary widely. Some people have frequent attacks (for example, every week) that occur for months; others may have clusters of daily attacks followed by weeks or months of remission.

Triggers of Panic Attacks. Panic attacks may occur spontaneously or in response to a particular situation. Recalling or re-experiencing even harmless circumstances surrounding an original attack may trigger subsequent panic attacks.

Phobias, manifested by overwhelming and irrational fears, are common. In most cases, people can avoid or at least endure phobic situations, but in some cases, as with agoraphobia, the anxiety associated with the feared object or situation can be incapacitating.

Agoraphobia. Agoraphobia has been somewhat misleadingly described as fear of open spaces, the term having been derived from the Greek word agora, meaning outdoor marketplace. In its severest form, agoraphobia is characterized by a paralyzing terror of being in places or situations from which the patient feels there is neither escape nor accessible help in case of an attack. (One patient described the terror of going outside as opening a door onto a landscape filled with snakes.) Consequently, people with agoraphobia confine themselves to places in which they feel safe, usually at home. The patient with agoraphobia often makes complicated plans in order to avoid confronting feared situations and places.

Social Phobia. Social phobia, also known as social anxiety disorder, is the fear of being publicly scrutinized and humiliated and is manifested by extreme shyness and discomfort in social settings. This phobia often leads people to avoid social situations and is not due to a physical or mental problem (such as stuttering, acne, or personality disorders). The incidence of social phobia is about 13% and has been termed "the neglected anxiety disorder" because it is often not properly diagnosed.

The associated symptoms vary in intensity, ranging from mild and tolerable anxiety to a full-blown panic attack. (Unlike a panic attack, however, social phobia is always directly related to a social situation.) Symptoms include sweating, shortness of breath, pounding heart, dry mouth, and tremor.

The disorder may be further categorized as generalized or specific social phobia:

Generalized social phobia is the fear of being humiliated in front of other people during nearly all social situations. People with this subtype are the most socially impaired and also the most likely to seek treatment.
Specific social phobia usually involves a phobic response to a specific event. Performance anxiety ("stage fright") is the most common specific social phobia and occurs when a person must perform in public. These patients usually feel comfortable in informal social situations.

Children with social anxiety develop symptoms in settings that include their peers, not just adults, and they may include tantrums, blushing, or not being able to speak to unfamiliar people. These children should be able to have normal social relationships with familiar people, however.

Specific Phobias. Specific phobias (formerly simple phobias) are an irrational fear of specific objects or situations. Specific phobias are among the most common medical disorders. Most cases are mild and not significant enough to require treatment.

The most common phobias are fear of animals (usually spiders, snakes, or mice), flying (pterygophobia), heights (acrophobia), water, injections, public transportation, confined spaces (claustrophobia), dentists (odontiatophobia), storms, tunnels, and bridges.

When confronting the object or situation, the phobic person experiences panicky feelings, sweating, avoidance behavior, difficulty breathing, and a rapid heartbeat. Most phobic adults are aware of the irrationality of their fear, and many endure intense anxiety rather than disclose their disorder.

Obsessive-compulsive disorder (OCD) has been described as hiccups of the mind. OCD is time-consuming, distressing, and can disrupt normal functioning. Much research suggests that a critical feature in this disorder is an overinflated sense of responsibility, in which the patient's thoughts center around possible dangers and an urgent need to do something about it.

Obsessions are recurrent or persistent mental images, thoughts, or ideas. The obsessive thoughts or images can range from mundane worries about whether one has locked a door to bizarre and frightening fantasies of behaving violently toward a loved one.
Compulsive behaviors are repetitive, rigid, and self-directed routines that are intended to prevent the manifestation of an associated obsession. Such compulsive acts might include repetitive checking for locked doors or unlit stove burners or calls to loved ones at frequent intervals to be sure they are safe. Some people are compelled to wash their hands every few minutes or to spend inordinate amounts of time cleaning their surroundings in order to subdue the fear of contagion.

Over half of OCD-sufferers have obsessive thoughts without the ritualistic compulsive behavior. Although individuals recognize that the obsessive thoughts and ritualized behavior patterns are senseless and excessive, they cannot stop them in spite of strenuous efforts to ignore or suppress the thoughts or actions. OCD often accompanies depression or other anxiety disorders. There is some evidence that the symptoms improve over time and that nearly half will eventually recover completely or have only minor symptoms.

Symptoms in children may be mistaken for behavioral problems (taking too long to do homework because of perfectionism, refusing to perform a chore because of fear of germs). Children do not usually recognize that their obsessions or compulsions are excessive.

Associated Obsessive Disorders. Certain other disorders that may be part of, or strongly associated with, the OCD spectrum include the following:

Body dysmorphic disorder (BDD). In BDD, people are obsessed with the belief that they are ugly, or part of their body is abnormally shaped.
Hypochondriasis. People who have hypochondiasis have an excessive fear of having a serious disease.
Anorexia nervosa. OCD frequently accompanies this eating disorder, where the compulsive behavior focuses on food restriction and thinness.
Trichotillomania. People with trichotillomania continually pull their hair, leaving bald patches.
Tourette syndrome. Symptoms of Tourette syndrome include jerky movements, tics, and uncontrollably uttering obscene words.

Obsessive-Compulsive Personality. OCD should not be confused with obsessive-compulsive personality, which defines certain character traits (being a perfectionist, excessively conscientious, morally rigid, or preoccupied with rules and order). These traits do not necessarily occur in people with obsessive-compulsive disorder.

Post-traumatic stress disorder (PTSD) is a severe, persistent emotional reaction to a traumatic event that severely impairs one’s life. It is classified as an anxiety disorder because of its symptoms. Not every traumatic event leads to PTSD, however. There are two criteria that must be present to qualify for a diagnosis of PTSD:

The patient must have directly experienced, witnessed, or learned of a life-threatening or seriously injurious event.
The patients' response is intense fear, helplessness, or horror. Children may behave with agitation or with disorganized behavior.

Triggering Events. PTSD is triggered by violent or traumatic events that are usually outside the normal range of human experience. There is some evidence that events most likely to trigger PTSD are those that involve deliberate and destructive behavior (murder, rape) and those that are prolonged or physically challenging. Such events include, but are not limited to, experiencing or witnessing sexual assaults, accidents, military combat, natural disasters (such as earthquakes), or unexpected deaths of loved ones. PTSD may also occur in people who have serious illness and receive aggressive treatments or who have close family members or friends with such conditions.

Symptoms of PTSD. There are three basic sets of symptoms associated with PTSD. They may begin immediately after the event or can develop up to a year afterward:

Re-experiencing. In such cases, patients persistently re-experience the trauma in at least one of the following ways: in recurrent images, thoughts, flashbacks, dreams, or feelings of distress at situations that remind them of the traumatic event. Children may engage in play, in which traumatic events are enacted repeatedly.
Avoidance. Patients may avoid reminders of the event, such as thoughts, people, or any other factors that trigger recollection. They tend to have an emotional numbness, a sense of being in a daze or of losing contact with their own identity or even external reality. They may be unable to remember important aspects of the event.
Increased Arousal. This includes symptoms of anxiety or heightened awareness of danger (sleeplessness, irritability, being easily startled, or becoming overly vigilant to unknown dangers).

To further qualify for a diagnosis of PTSD, patients must have at least one symptom in the re-experiencing category, three avoidance symptoms, and two arousal symptoms. Symptoms are chronic (3 months or more). Symptoms should also not be associated with alcohol, medications, or drugs and should not be intensifications of a pre-existing psychological disorder.

Acute Stress Disorder. Experts have identified a syndrome called acute stress disorder, in which symptoms of PTSD occur within 2 days to 4 weeks after the traumatic event. Acute stress disorder can accurately identify up to 94% of victims at risk for PTSD. Between 50 - 80% of these patients actually develop the more chronic and serious disorder. In other words, it is very sensitive for identification of those at highest danger for PTSD but less successful in determining specifically who will or will not recover emotionally.

Long-Term Outlook. The long-term impact of a traumatic event is uncertain. In one study of people who survived a mass killing spree in Texas, less than half of those who suffered PTSD (28% of all survivors) had recovered after a year. In another study, PTSD became chronic in 46% of the subjects. In fact, PTSD may cause physical changes in the brain, and in some cases the disorder can last a lifetime.

Separation anxiety disorder almost always occurs in children. It is suspected in children who are excessively anxious about separation from important family members or from home. For a diagnosis of separation anxiety disorder, the child should also exhibit at least three of the following symptoms for at least 4 weeks:

Extreme distress from either anticipating or actually being away from home or being separated from a parent or other loved one
Extreme worry about losing or about possible harm befalling a loved one
Intense worry about getting lost, being kidnapped, or otherwise separated from loved ones
Frequent refusal to go to school or to sleep away from home
Physical symptoms such as headache, stomach ache, or even vomiting, when faced with separation from loved ones

Separation anxiety often disappears as the child grows older, but if not addressed, it may lead to panic disorder, agoraphobia, or combinations of anxiety disorders.

Studies suggest that an imbalance of certain substances called neurotransmitters (chemical messengers in the brain) may contribute to anxiety disorders. The neurotransmitters targeted in anxiety disorders are gamma-aminobutyric acid (GABA), serotonin, dopamine, and epinephrine. Serotonin appears to be specifically important in feelings of well-being, and deficiencies are highly related to anxiety and depression.

Examples of study findings on some neurotransmitters are:

Abnormalities in the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin may have a particular role in susceptibility to generalized anxiety disorder. GABA helps prevent nerve cells from over-firing and serotonin is a brain chemical important in feelings of well-being.
Serotonin is a major player in OCD.
Changes in serotonin and dopamine have been observed in social phobia.
People with post-traumatic stress disorder have abnormalities in stress hormones (cortisol) and neurotransmitters associated with stress (epinephrine and norepinephrine). Such imbalances could account for the higher anxiety levels and a tendency to startle easily after a threat in people with PTSD.
Corticotropin-releasing factor (CRF), which is believed to be a stress hormone and a neurotransmitter, is thought to be involved in depression and anxiety by causing changes in serotonin levels.

The best way to envision the brain's response to a threat is to imagine a primal situation, such as being chased by a bear.

The Brain's Response to Acute Stress. In response to seeing the bear, a part of the brain called the hypothalamic-pituitary-adrenal (HPA) system is activated.

Release of Steroid Hormones and the Stress Hormone Cortisol. The HPA systems trigger the production and release of steroid hormones (glucocorticoids), including the primary stress hormone cortisol. Cortisol is very important in marshaling systems throughout the body (including the heart, lungs, circulation, metabolism, immune systems, and skin) to deal quickly with the bear.

Release of Catecholamines and Activation of the Amygdala. The HPA system also releases certain neurotransmitters (chemical messengers) called catecholamines, particularly those known as dopamine, norepinephrine, and epinephrine (also called adrenaline).

Catecholamines activate the amygdala, a small structure deep in the brain, which regulates control of major emotional activities, including anxiety, depression, aggression, and affection. In fact, the amygdala is sometimes known as the "fear" center.

Effects on Long- and Short-Term Memory. During the stressful event, catecholamines also suppress activity in areas at the front of the brain concerned with short-term memory, concentration, inhibition, and rational thought. This sequence of mental events allows a person to react quickly to the bear, either to fight or to flee from it. (It also hinders the ability to handle complex social or intellectual tasks and behaviors during that time.)

On the other hand, neurotransmitters at the same time signal the hippocampus (a nearby area in the brain) to store the emotionally loaded experience in long-term memory. In primitive times, this brain action would have been essential for survival, since long-lasting memories of dangerous stimuli (the large bear) would be critical for avoiding such threats in the future.

Response by the Heart, Lungs, and Circulation to Acute Stress. The stress response also affects the heart, lungs, and circulation:

As the bear comes closer, the heart rate and blood pressure increase instantaneously.
Breathing becomes rapid and the lungs take in more oxygen.
The spleen discharges red and white blood cells, allowing the blood to transport more oxygen throughout the body. Blood flow may actually increase 300 - 400%, priming the muscles, lungs, and brain for added demands.

The Immune System's Response to Acute Stress. The effect on the immune system from confrontation with the bear is similar to marshaling a defensive line of soldiers to potentially critical areas. The steroid hormones dampen parts of the immune system, so that specific infection fighters (including important white blood cells) or other immune molecules can be redistributed. These immune-boosting troops are sent to the body’s front lines where injury or infection is most likely, such as the skin, the bone marrow, and the lymph nodes.

The Acute Response in the Mouth and Throat. As the bear gets closer, fluids are diverted from nonessential locations, including the mouth. This causes dryness and difficulty in talking. In addition, stress can cause spasms of the throat muscles, making it difficult to swallow.

The Skin's Response to Acute Stress. The stress effect diverts blood flow away from the skin to support the heart and muscle tissues. (This also reduces blood loss in the event that the bear catches up.) The physical effect is a cool, clammy, sweaty skin. The scalp also tightens so that the hair seems to stand up.

Metabolic Response to Acute Stress. Stress shuts down digestive activity, a nonessential body function during short-term periods of physical exertion or crisis.

The Relaxation Response: the Resolution of Acute Stress. Once the threat has passed and the effect has not been harmful (the bear has not eaten or seriously wounded the human), the stress hormones return to normal. This is known as the relaxation response. In turn, the body's systems also normalize.

Causes

A person's genetics, biochemistry, environment, history, and psychological profile all seem to contribute to the development of anxiety disorders. Most people with these disorders seem to have a biological vulnerability to stress, making them more susceptible to environmental stimuli than the rest of the population.

Abnormalities in the Brain. Scientists are using imaging techniques, particularly magnetic resonance imaging (MRI), to identify different areas of the brain associated with anxiety responses.

An MRI (magnetic resonance imaging) of the brain creates a detailed image of the complex structures in the brain. An MRI can give a three-dimensional depiction of the brain, making location of problems such as tumors or aneurysms more precise.

Important research in anxiety disorders is focusing on changes in the amygdala, which is sometimes referred to as the "fear center." This part of the brain regulates fear, memory, and emotion and coordinates these resources with heart rate, blood pressure, and other physical responses to stressful events. Some evidence suggests that the amygdala in people with anxiety disorders is highly sensitive to novel or unfamiliar situations and reacts with a high stress response.

Obsessive-compulsive disorder (OCD) is the anxiety disorder most strongly associated with specific brain dysfunction. For example, abnormalities in a specific pathway of nerves have been linked to OCD, attention deficit disorder, and Tourette syndrome. The symptoms of the three disorders are similar and they often coexist.

A number of imaging studies have reported less volume in the hippocampus in people with post-traumatic stress disorder. This important region is related to emotion and memory storage.

The influence of the family on anxiety is complicated by both genetic and psychological factors.

Panic Disorder and Family Influence. Certain psychodynamic theories suggest, and a few studies support the idea, that some people may develop panic disorder if they cannot resolve the early childhood conflict of dependence vs. independence. In one study, for example, young adults who had experienced childhood anxiety were more likely to live with their parents until their early to mid-twenties. Many people with panic disorder perceive their parents as being extremely controlling and overly protective while showing little actual affection.

Phobias and Family Influence. Several studies show a strong correlation between a parent's fears and those of the offspring. Although an inherited trait may be present, some researchers believe that many children can "learn" fears and phobias, just by observing a parent or loved one's phobic or fearful reaction to an event. People who have social phobias and severe agoraphobia generally report less parental affection and more strictness, overprotection, and encouragement of dependence than those without these disorders.

Obsessive-Compulsive Disorder and Family Influence. One study found that parental influence played no part in obsessive-compulsive disorder if the OCD patient was also not suffering from depression. However, depression coexists in two-thirds of OCD patients, and in the study patients who had both OCD and depression reported lower levels of parental care and overprotectiveness.

Traumatic events generally trigger anxiety disorders in individuals who are susceptible to them because of psychological, genetic, or biochemical factors. The clearest example is post-traumatic stress disorder. Specific traumatic events in childhood, particularly those that threaten family integrity, such as spousal or child abuse, can also lead to other anxiety and emotional disorders. Some individuals may even have a biological propensity for specific phobias, for instance of spiders or snakes, that have been triggered and perpetuated after a single exposure.

The acronym PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) is a term for an autoimmune condition associated with group A streptococcal infection in children (the cause of "strep throat" and rheumatic fever). Children with PANDAS develop tic-related disorders, including OCD and Tourette syndrome. In such cases, the OCD symptoms develop abruptly soon after the infection. It is unlikely to be an important cause of OCD.

Risk Factors

As many as 25% of all American adults experience intense anxiety sometime in their lives. The prevalence of true anxiety disorders is much lower, although they are still the most common psychiatric conditions in the United States and affect more than 20 million Americans.

Gender. With the exception of obsessive-compulsive disorder (OCD), women have twice the risk for most anxiety disorders as men. A number of factors may increase the reported risk in women, including cultural pressures to meet everyone else's needs except their own, and fewer self-restrictions on reporting anxiety to doctors.

Age. In general, phobias, OCD and separation anxiety show up early in childhood, while social phobia and panic disorder are often diagnosed during the teen years. Studies suggest that 3 - 5% of children and adolescents have some anxiety disorder. Children and adolescents who have an anxiety disorder are at risk of later developing other anxiety disorders, depression, and substance abuse.

Personality Factors. Children's personalities may indicate higher or lower risk for future anxiety disorders. For example, research suggests that extremely shy children and those likely to be the target of bullies are at higher risk for developing anxiety disorders later in life. Children who cannot tolerate uncertainty tend to be worriers, a major predictor of generalized anxiety. In fact, such traits may be biologically based and due to a hypersensitive amygdala -- the "fear center" in the brain.

Family History and Dynamics. Anxiety disorders tend to run in families. Genetic factors may play a role in some cases, but family dynamics and psychological influences are also often at work.

Social Factors. Several studies have reported a significant increase in anxiety levels in children and college students in the past two decades compared to children in the 1950s. In several studies, anxiety was associated with a lack of social connections and a sense of a more threatening environment. It also appears that more socially alienated populations have higher levels of anxiety. For example, a study of Mexican adults living in California reported that native-born Mexican Americans were three times more likely to have anxiety disorders (and even more likely to be depressed) as those who had recently immigrated to the U.S. The longer the immigrants lived in the U.S., the greater their risk for psychiatric problems. Traditional Mexican cultural and social ties seemed to protect recently arrived immigrants from mental illness.

Genetic Factors. Up to 50% of people with panic disorder and 40% of patients with generalized anxiety (GAD) have close relatives with the disorder. (About half of GAD patients also have family members with panic disorder, and about 30% have relatives with simple phobias.)

Obsessive-compulsive disorder (OCD) is also strongly related to a family history of the disorder. Close relatives of people with OCD are up to 9 times more likely to develop OCD themselves. Researchers are making progress in identifying specific genetic factors that might contribute to an inherited risk. Of particular interest are genes that regulate specific neurotransmitters (brain chemical messengers), including serotonin and glutamate. Recent research has suggested that the SLC1A1 gene, which is associated with glutamate regulation, may play an important role in early-onset OCD in boys. Research is also beginning to pinpoint regions on specific chromosomes (1, 3, 7, 6, 9, 15) that may contain genes linked to OCD.

However, there are no genetic tests to date that can identify patients at risk for anxiety disorders.

Medical Conditions. Although no causal relationships have been established, certain medical conditions have been associated with panic disorder. They include migraines, obstructive sleep apnea, mitral valve prolapse, irritable bowel syndrome, chronic fatigue syndrome, and premenstrual syndrome.

GAD affects about 1 - 5% of Americans in the course of their lives and is more common in women than in men. Some experts believe that it is underdiagnosed and more common than any other anxiety disorder. It is certainly the most common anxiety disorder among the elderly. GAD usually begins in childhood and often becomes a chronic ailment, particularly when left untreated. Depression in adolescence may be a strong predictor of GAD in adulthood. Depression commonly accompanies this anxiety disorder in any case.

Age and Panic Disorder. Studies indicate that the prevalence of panic disorder among adults is between 1.6 - 2% and is much higher in adolescence, 3.5 - 9%. Panic disorder usually first occurs either in late adolescence or in the mid-30s.

Gender and Panic Disorder. Women have about twice the risk for panic disorder as men. Panic attacks are very common after menopause. In one study, nearly 18% of older women reported panic attacks within a 6-month period, with over half of these attacks being full-blown. They tended to be associated with stressful life events and poor health. The effects of pregnancy on panic disorder appear to be mixed. It seems to improve the condition in some women and worsen it in others.

Obsessive-compulsive disorder occurs equally in men and women, and it affects about 2 - 3% of people over a lifespan. Most cases of OCD first develop in childhood or adolescence, although the disorder can occur throughout the life span.

Social anxiety disorder is currently estimated to be the third most common psychiatric disorder in the U.S. Studies have reported a prevalence of 7 - 12% in Western nations.

Age and Phobias. The onset of social anxiety disorder is usually during the early teenage years.

Gender and Phobias. Women are more likely to develop social anxiety disorder than men, although equal numbers of men and women seek treatment for it. Most people seeking treatment have had symptoms for at least 10 years.

Studies estimate a lifetime risk for PTSD in the U.S. of up to 8%. People exposed to traumatic events, of course, are at highest risk, but many people can go through such events and not experience PTSD. Studies estimate that 6 - 30% or more of trauma survivors develop PTSD, with children and young people being among those at the high end of the range. Women have the twice the risk of PTSD as men.

Furthermore, PTSD can occur in people not directly involved with a traumatic event. For example, 17% of the U.S. population outside New York City reported some symptoms of post-traumatic stress 2 months after the September 11 attack on the World Trade Towers. (In the city itself, where the attack occurred, an estimated 7.5% of New York's population reported PTSD within the month of the event, which declined to 0.6% at 6 months.)

Researchers are trying to determine factors that might increase vulnerability to catastrophic events and put people at risk for develop PTSD. Some studies report the following may be risk factors:

Pre-existing emotional disorder. People who have a history of an emotional disorder, particularly depression, before the traumatic event are at higher risk for PTSD.
Drug or alcohol abuse
A family history of anxiety
A history of abuse, particularly that which threatens family integrity, such as spousal or child abuse. Studies of individuals who had suffered physical or sexual abuse or neglect as children suggest that up to one-third develop PTSD.
An early separation from parents
Lack of social support and poverty
Sleep disorders. Insomnia and excessive daytime sleepiness even within a month after a traumatic event are important predictors for the development of PTSD. One specific sleep disorder -- sleep apnea -- may even intensify symptoms of PTSD, including sleeplessness and nightmares. Sleep apnea occurs when tissues in the upper throat (or airway) collapse at intervals during sleep, thereby blocking the passage of air. In one study, 91% of crime victims with PTSD had either sleep apnea or a lesser condition that partially blocked the airways during sleep. In fact, in one study treatment of sleep apnea eased PTSD. Sleep apnea has also been associated with a risk for panic disorder. [For more information, see In-Depth Report #65: Sleep apnea.]

Complications

Studies consistently report that all types of anxiety disorders can be very debilitating and seriously affect a person’s quality of life.

Depression. Depression is very common in people with an anxiety disorder, and it is sometimes difficult to distinguish one from the other because either or both can be accompanied by anxious feelings, agitation, insomnia, and problems with concentration.

Depression and nearly every anxiety disorder often go hand in hand, in both the young and old. In fact, the lifetime risk for depression in people with anxiety disorders may be higher than 70%. Furthermore, the combination of depression and anxiety is a major risk factor for both substance abuse and suicide. The following are examples of depression in specific anxiety disorders:

Between 50 - 65% of people with panic disorder also have major depression. Some studies have suggested that treating panic disorder early enough may help prevent major depression later on.
More than two-thirds of OCD patients suffer from depression.
Most patients with GAD will experience at least one episode of significant depression and many develop recurrent episodes. In patients with both disorders, GAD usually precedes the onset of depression.
Social anxiety during adolescence or young adulthood has been associated with a higher risk for depression, and the presence of both increases the chances for severe depression.
People with PTSD are four to seven times as likely to be depressed as are people without PTSD.

Bipolar Disorder. Symptoms of panic disorder are very common in people with bipolar disorder (manic-depression). In fact, people with bipolar have 26 times the rate of panic disorder as in the general population. Furthermore, anxiety worsens bipolar disorder. According to one study, anxiety disorders in teenagers were associated with bipolar disorder in adulthood, while manic behavior in adolescence was linked to later anxiety disorders.

Evidence now strongly supports an association between panic disorder and a risk for suicidal thoughts. Studies report that up to 18% of people with panic disorder attempt suicide and up to 38.5% regularly harbor suicidal thoughts, with the risks being higher in people with both panic disorder and depression. One study reported suicide attempts in about 12% of people with social phobias or OCD. If a person has an anxiety disorder and a mood disorders (such as depression), the risk for suicide is even higher.

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 commonly associated 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, unsuccessful 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.

In one study, adolescents failed to seek help for suicidal thoughts for the following reasons:

They believed nothing would help.
They were reluctant to tell anyone they had problems.
They thought it was a sign of weakness to seek help.
They did 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.

[For more information on suicide, see In-Depth Report #8: Depression.]

Severely depressed or anxious people are at high risk for alcoholism, smoking, and other forms of addiction. Anxiety disorders are highly prevalent among people with alcoholism. Moreover, long-term alcohol use can itself cause biologic changes that may actually produce anxiety and depression.

Risk for Substance Abuse in Specific Anxiety Disorders. The following are some observations on specific anxiety disorders and substance abuse:

Some people with GAD and panic disorders may use alcohol or drugs to self-medicate.
Social phobia appears to pose a particular risk for alcohol abuse. People with this disorder are likely to drink in order to boost confidence. Alcohol itself has no direct beneficial effect on anxiety, but studies suggest that the belief in its effect appears to relieve anxious feelings. (Alcohol or substance abuse is not associated with specific phobias -- such as a fear of flying or spiders.)
Heavy smoking and substance abuse are common in people with PTSD. In adolescents, the disorder not only increases the risk for drug and alcohol use but also for eating disorders.

Studies consistently report that anxiety disorders have negative effects on work and relationships. Some examples:

In one study, more than 10% of patients with GAD missed at least 6 days of work within the previous month.
In a survey of OCD sufferers, 40% reported that they had to stop working because of the disorder. Only 40% worked full-time, while only half were married.
A 2006 study indicated that children with OCD are more likely to be bullied than other children.
Studies report that people with social phobias are less likely to get married, to leave home, and to finish school than those without this disorder. Their outlook worsens if they have other emotional disorders.

Anxiety disorders are associated with many different physical illnesses. Research suggests that people who have both an anxiety disorder and a physical illness have a worse quality of life and greater risk for disability than those who have only a physical illness. Anxiety disorders often tend to occur before the development of physical disorders.

Heart Disease. Anxiety has been associated with several heart problems, including unhealthy cholesterol levels, thicker blood vessels, and high blood pressure. Both anxiety and depression have been associated with a poorer response to treatment in heart patients, including a worse outcome after heart surgery.

Cholesterol is a soft, waxy substance that is present in all parts of the body including the nervous system, skin, muscle, liver, intestines, and heart. It is made by the body and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed for normal body functions including the production of hormones, bile acid, and vitamin D. Excessive cholesterol in the blood contributes to atherosclerosis and subsequent heart disease. The risk of developing heart disease or atherosclerosis increases as the level of blood cholesterol increases.

Some researchers speculate that intense anxiety might trigger abnormal and dangerous heart rhythms in people with existing heart problems. In other studies, panic disorders, post-traumatic stress disorder, and phobias have been associated with a higher rate of sudden death from cardiac events, including heart attack.

Gastrointestinal Disorders. Anxiety frequently accompanies gastrointestinal conditions. Of note, half the cases of irritable bowel syndrome are associated with anxiety.

Headache. Both tension and migraine headaches are associated with anxiety disorders. One study reported that 32% of people with chronic tension headaches met criteria for anxiety. Similarly, another study reported that young girls with anxiety disorders were three times more likely to have chronic headaches than those without the disorder. (Headaches in both studies were also strongly associated with depression.)

Respiratory Problems. Studies report an association between anxiety in patients with obstructive lung conditions (asthma, emphysema, and chronic bronchitis) and more frequent relapses.

Obesity. Anxiety disorders may lead to obesity, and the reverse may also be true. A 2006 study suggested that anxiety disorders and depression in childhood may lead to higher body mass index (BMI) in adult women (but not men). Another 2006 study indicated that obesity is associated with a 25% increased risk of developing anxiety and mood disorders.

Allergic Conditions. Anxiety disorders are associated with numerous allergic conditions including hay fever, eczema, hives, food allergies, and conjunctivitis.

Other Conditions. Other physical conditions associated with anxiety disorders include thyroid problems and arthritis.

People with obsessive-compulsive disorders can experience skin problems from excessive washing, injuries from repetitive physical acts, and hair loss from repeated hair pulling (behavior known as trichotillomania).

Effect of PTSD on the Brain. Studies are reporting that PTSD is associated with shrinkage in the hippocampus, the part of the brain important for memory and learning. Some animal studies indicate that such damage may result from long-term exposure to cortisol, the major stress hormone. In one study, people who had suffered severe trauma scored 40% lower in tests of verbal memory than did the general population. There was no difference in IQ or in scores of other types of memory. Some studies suggest that exposure to chronic stress, common in PTSD patients, may even compromise the function of the brain’s receptors for anti-anxiety medication. On the other hand, a small hippocampal volume may itself increase stress hormone levels, so people with genetically smaller hippocampi may be susceptible to PTSD.

Effects of PTSD on Health. Studies of military veterans who have endured major traumatic events have found a higher risk for health problems. One study of Vietnam veterans reported that PTSD was associated with greater physical limitations, poorer physical health, and a lower quality of life than was found in the general population, regardless of other accompanying emotional or medical disorders. In another study of these veterans, PTSD sufferers had twice the risk for abnormal heart rhythms and four times the risk of a heart attack compared to men without PTSD.

Evidence suggests an association between anxiety in children and recurrent stomach aches. Anxiety has been associated with a higher risk for sleep disorders in children, such as frequent nightmares, restless legs syndrome, and bruxism (grinding and gnashing of the teeth during sleep).

Diagnosis

A physical examination and medical and personal history is essential. Because anxiety accompanies so many medical conditions, some serious, it is extremely important for the doctor to uncover any medical problems or medications that might underlie or be masked by an anxiety attack.

The patient should describe any occurrence of anxiety disorders or depression in the family and mention any other contributing factors, such as excessive caffeine use, recent life changes, or stressful events.

It is very important to be honest with your doctor about all conditions, including excessive drinking, substance abuse, or other psychological or mood states that might contribute to, or result from, the anxiety disorder.

Diagnosing children with an anxiety disorder can be very difficult, since anxiety often results in disruptive behaviors that overlap with attention-deficit hyperactivity or oppositional disorder. Other conditions with symptoms similar to anxiety disorders include pervasive developmental disorders such Asperger syndrome, learning disabilities, bipolar disorder, and depression. Many children have anxiety disorder and a co-occurring condition, which should be treated along with anxiety.

People with anxiety disorders are more likely to see a family doctor before a mental health specialist, since their symptoms are often physical. Symptoms can include muscle tension, trembling, twitching, aching, soreness, cold and clammy hands, dry mouth, sweating, nausea or diarrhea, or urinary frequency. Anxiety attacks can mimic or accompany nearly every acute disorder of the heart or lungs, including heart attacks and angina (chest pain). In fact, nearly all individuals with panic disorders are convinced that their symptoms are physical and possibly life-threatening.

Heart Problems. Studies suggest that up to a third of patients entering the emergency room with chest pain and who are low-to-moderate risk for a heart attack are actually suffering from panic attacks. It is often difficult even for specialists to distinguish between heart conditions and a panic attack:

Women who are having an actual heart attack or acute heart problem are much more likely to be misdiagnosed as having an anxiety attack than are men with similar symptoms.
Mitral valve prolapse, a common and usually mild heart problem, may have symptoms that are nearly identical to those of panic disorder. The two conditions, in fact, frequently occur together.

Mitral valve prolapse is a disorder in which the mitral valve does not close properly when the heart contracts. When the valve does not close properly it allows blood to backflow into the left atrium. Some symptoms can include palpitations, chest pain, difficulty breathing after exertion, fatigue, cough, and shortness of breath while lying down.

People with a heart-rhythm disturbance called paroxysmal supraventricular tachycardia have many of the same symptoms as those with panic attacks.

Asthma. Asthma attacks and panic attacks have similar symptoms and can also coexist.

Hyperthyroidism. Hyperthyroidism can cause many of the same symptoms of generalized anxiety disorder and must be ruled out.

Click the icon to see an image of hyperthyroidism.

Epilepsy. The symptoms of partial seizures and panic attacks often overlap.

Other Medical Conditions. In addition, anxiety-like symptoms are seen in many other medical problems, including hypoglycemia, recurrent pulmonary emboli, and adrenal-gland tumors. Women can also experience intense anxiety attacks with hot flashes during menopause.

Medication Side Effects. Many drugs, including some for high blood pressure, diabetes, and thyroid disorders, can produce symptoms of anxiety. Withdrawal from certain drugs, often those used to treat sleep disorders or anxiety, can also precipitate anxiety reactions.

Substance Abuse. People with anxiety disorders often drink alcohol or abuse drugs in order to conceal or eliminate symptoms, but substance abuse and dependency can also cause anxiety. In addition, withdrawal from alcohol can produce physiologic symptoms similar to panic attacks. Clinicians often have difficulty determining whether alcoholism or anxiety is the primary disorder. Overuse of caffeine or abuse of amphetamines can cause symptoms resembling a panic attack.

Clinicians use various screening tests to determine the causes, type, severity, and frequency of anxiety. Such tests include the Hamilton Anxiety Rating Scale, the Beck Anxiety Inventory, the Penn State Worry Questionnaire, and the Yale-Brown Obsessive Compulsive Scale.

Treatment

Anxiety disorders require treatment. Simply trying to talk oneself out of anxiety is as futile as trying to talk oneself out of a heart or stomach problem. Most anxiety disorders, especially phobias, respond well to treatment. They may, however, require long-term treatment. Many patients have a recurrence and may require additional medications. Nevertheless, most patients do not receive appropriate care for anxiety disorders. Many patients do not receive any treatment at all.

The standard current approach to most anxiety disorders is a combination of cognitive-behavioral therapy (CBT) and an antidepressant medication. A selective serotonin reuptake inhibitor (SSRI) is typically the first choice, with the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine (Effexor) an alternative. If patients do not respond to these drugs, tricyclic antidepressants or monoamine oxidase inhibitors (MAOIs) may be helpful. Benzodiazepines may be recommended for patients who are not helped by antidepressants. A healthy lifestyle that includes exercise, adequate rest, and good nutrition can also help to reduce the impact of anxiety.


Anxiety Disorder	Medications	Cognitive-Behavioral Therapy (CBT) and other Non-Drug Therapies
Generalized Anxiety Disorder	Antidepressants, benzodiazepines, and buspirone are helpful but have varying side effects. Investigational drugs include pregabalin and other anticonvulsants.	Cognitive-behavioral therapy or anxiety management therapy. Anxiety management therapy involves education, relaxation training, and exposure to anxiety-provoking stimuli but does not include cognitive restructuring.
Panic Attacks	SSRIs are treatment of choice. If patients do not respond to SSRIs, short-term treatment with a benzodiazepine may be used, or patients may switch to another type of antidepressant such as venlafaxine or tricyclics.	Cognitive-behavioral therapy, provided in 12 - 16 sessions over 3 - 4 months, focuses on recreating fear symptoms and helping patients change their response to them.
Social Anxiety Disorder	SSRIs or venlafaxine are first-line drug treatments. Benzodiazepines may help patients who do not respond to these antidepressants. In severe cases, an MAOI antidepressant may be prescribed. Anticonvulsants such as gabapentin (Neurontin) and pregabalin (Lyrica) are being investigated.	Cognitive-behavioral therapy can help improve symptoms after 6 - 12 weeks.
Obsessive-Compulsive Disorder	SSRIs are the first choice for adults. Clomipramine (a tricyclic antidepressant) is an alternative for adult patients who do not respond to SSRIs. For children, SSRIs do not seem to work as well for OCD as for other types of anxiety disorders.	Cognitive-behavioral therapy is the first treatment choice for children. For adults, either CBT or drug therapy may be offered as initial treatment. CBT techniques focus on exposure and response prevention (ERP).
Post-Traumatic Stress Disorder	Antidepressants, particularly SSRIs (sertraline and paroxetine approved for PTSD). The atypical antipsychotic olanzapine may be added to an antidepressant for patients who do not respond to a SSRI alone.	Trauma-focused psychological treatments include exposure therapy, trauma-focused cognitive therapy, and eye movement desensitization and reprocessing.
Note: For anxiety disorders in adults, the most effective treatments are usually combinations of drugs and CBT techniques. For children, CBT is usually the first treatment.

Medications

Selective serotonin-reuptake inhibitors (SSRIs), or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine (Effexor), are the primary first-line treatment for anxiety disorders. For patients who are not helped by these drugs, benzodiazepines, either alone or in combination with an antidepressant, may be prescribed. Other types of antidepressants, including tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs), may also be used to treat patients with severe or chronic forms of anxiety disorders.

Drug therapies for anxiety disorders work best in combination with cognitive behavioral therapy.

Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro).

SSRIs can cause agitation, nausea, and diarrhea. Sexual function side effects include low sex drive, inability to have an orgasm, and impotence. Over time, many SSRI-treated patients gain weight, although the degree of weight gain varies depending on the drug. Elderly people taking these drugs should take the lowest effective dose possible, and those with heart problems should be monitored closely.

There have been many concerns about SSRIs and increased risk for suicidal behavior. Both adults and children who are treated with SSRIs should be carefully monitored for any worsening of depressive symptoms or changes in behavior. This is especially important during the first few months of antidepressant treatment.

Paroxetine has been linked to heart-related birth defects when women took this drug during the first trimester of pregnancy. Experts are also advising caution in prescribing other types of SSRIs to pregnant women. While certain SSRIs may carry increased risks for some specific type of rare birth defects, research suggests that the overall risks are minimal. Still, women who are pregnant or who are considering becoming pregnant should discuss the potential risks of these drugs with their doctors.

Serotonin-norepinephrine reuptake inhibitors (SNRIs). SNRIs are known as dual inhibitors because they work on two neurotransmitters -- norepinephrine and serotonin. Venlafaxine (Effexor) is an SNRI that is approved for treatment of generalized anxiety disorder, social anxiety disorder, and panic disorder in adults. (It is not approved for children.) As with many SSRIs, venlafaxine impairs sexual function. Venlafaxine can increase blood pressure and heart rate and should be used with caution in patients with high blood pressure or heart disease. Some patients report severe withdrawal symptoms, including dizziness and nausea. This drug has a serious risk for overdose. Venlafaxine should not be taken during the last trimester of pregnancy because the drug can cause complications in newborn infants.

Duloxetine (Cymbalta) also acts on both serotonin and norepinephrine. In 2007, it was approved for treatment of generalized anxiety disorder. 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.

Mitrazapine (Remeron) is another type of SNRI that is sometimes used for treatment of post-traumatic stress disorder and social anxiety disorder.

Tricyclic Antidepressants. Tricyclics are an older type of antidepressant. Tricyclics used for treatment of anxiety disorder include imipramine (Tofranil, for generalized anxiety disorder, panic disorder), nortriptyline (Pamelor, for panic disorder), desipramine (Norpramin, for panic disorder), and clomipramine (Anafranil, for obsessive compulsive disorder). Clomipramine is approved specifically for OCD, but because of its severe side effects it is usually used only if SSRIs have failed to help.

Side effects of TCAs include sleep disturbance, abrupt reduction in blood pressure upon standing, weight gain, sexual dysfunction, and mental disturbance. Elderly patients and those with a history of seizures, cardiac problems, closed-angle glaucoma, and urinary retention or obstruction should be closely supervised when taking tricyclics.

Monoamine Oxidase Inhibitors. Monoamine oxidase inhibitors (MAOIs) are the oldest type of antidepressant. The MAOI phenelzine (Nardil) is sometimes used to treat social anxiety disorder or post-traumatic stress disorder that has not responded to other treatments.

MAOIs commonly cause weight gain, drowsiness, dizziness, sexual dysfunction, and insomnia. Dietary restrictions are the main problem with these drugs. Severe high blood pressure (hypertension) can be brought on by eating certain foods that have a high tyramine content, including cheese, red wine, and processed meats. High blood pressure can also occur when MAOIs are taken with certain drugs, including some common over-the-counter cough medications and decongestants. MAOIs can cause birth defects and should not be taken by pregnant women.

Most serious, fatal reactions can occur when MAOIs and SSRIs or venlafaxine are taken at the same time. There should be at least a 2- to 5-week break if a patient is changing from one type of antidepressant to the other.

Benzodiazepines are safe and effective medications for most anxiety disorders and have been the standard of treatment for years. However, their on-going use has been associated with a high risk for dependency and abuse. Therefore, they have been supplanted in most cases by SSRIs and other newer antidepressants. For anxiety disorders, benzodiazepines are most often used to treat panic disorder, and are sometimes used for social anxiety disorder and generalized anxiety disorder. These drugs include alprazolam (Xanax), clonazepam (Klonopin), and lorazepam (Ativan).

Benzodiazepines have many side effects, generally associated with chronic use. The most common are daytime drowsiness and a hung-over feeling. In rare cases, they can cause agitation. They may worsen respiratory problems. Benzodiazepines are potentially dangerous when used in combination with alcohol. Overdoses can be serious, although they are very rarely fatal.

The elderly are more susceptible to side effects and should usually start at half the dose prescribed for younger people. These drugs increase the risk of falling, which can increase the risk for hip fracture in older people. Also of concern are studies showing a high risk of automobile accidents in people who take benzodiazepines. Benzodiazepines taken during pregnancy are associated with birth defects, and they should not be used by pregnant women or by nursing mothers.

Loss of Effectiveness and Dependence. Eventually these drugs can lose their effectiveness with continued use at the same dosage. As a result, patients may want to increase their dosage to prevent anxiety. This causes dependency, which can occur after taking these drugs for several weeks.

Withdrawal and its Treatments. Withdrawal symptoms can be very severe, even in people who rapidly discontinue benzodiazepines after taking them for only 4 weeks. Symptoms include sleep disturbance and anxiety, which can develop within hours or days after stopping the medication. Some patients experience stomach distress, sweating, and insomnia, which can last 1 - 3 weeks. The longer the drugs are taken and the higher their dose, the more severe these symptoms can become. Simply tapering off gradually helps about 60% of people stop taking these drugs. Certain medications (anti-seizure drugs, antidepressants, buspirone) may also help with withdrawal.

Azapirones, such as buspirone (BuSpar), act on serotonin receptors called 5-HT(1A). Buspirone appears to work as well as a benzodiazepine for treating generalized anxiety disorder. It usually takes several days to weeks for the drug to be fully effective. It is not useful against panic attacks.

Buspirone does not produce any immediate euphoria or change in sensation, so some people believe, erroneously, that the drug doesn't work. Such qualities result in a very low potential for abuse. In fact, unlike the benzodiazepines, buspirone is not addictive, even with long-term use, so it may be particularly useful for the patient whose anxiety disorder coexists with alcoholism or drug abuse.

Buspirone also seems to have less pronounced side effects than benzodiazepines and no withdrawal effects, even when the drug is discontinued quickly. Common side effects include dizziness, drowsiness, and nausea. Buspirone should not be used with monoamine oxidase inhibitors (MAOIs).

Beta-blockers, including propranolol (Inderal) and atenolol (Tenormin), block the nerves that stimulate the heart to beat faster. They affect only the physiologic symptoms of anxiety (particularly rapid heart rate) and are most helpful for phobias, particularly performance anxiety. They may be taken before entering a situation where anxiety symptoms tend to occur. Beta-blockers are less effective for other forms of anxiety.

Atypical antipsychotics are mostly used for treating schizophrenia, bipolar disorder, and major depressive disorder. Doctors sometimes use the atypical antipsychotic olanzapine (Zyprexa) for treating severe cases of post-traumatic stress disorder. However, olanzapine has severe side effects, including weight gain and increased high blood sugar levels, which can increase the risk for diabetes. [For more information, see In-Depth Report #47: Schizophrenia.]

Pregabalin (Lyrica) and gabapentin (Neurontin) are drugs used to treat seizures and other conditions. Researchers are investigating whether these drugs may be useful for certain anxiety disorders, such as social anxiety disorder and general anxiety disorder. Their exact role in the treatment of anxiety disorders is not clear, however.

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.

Studies indicate that the dietary supplement inositol may have benefits for panic disorder and, possibly, obsessive compulsive disorder. Inositol is part of the vitamin B complex.

Some patients use aromatherapy as a relaxation aid. Aromatherapy is in general safe, but some plant extracts in these formulas have been linked to skin allergies.

There is no evidence supporting the efficacy of valerian, St. John’s wort, or passionflower for treatment of anxiety. The herbal remedy kava has been associated with liver problems and should not be avoided, especially by patients with liver disease or those who use alcohol. Kava can also interact dangerously with medications that are metabolized by the liver.

Other Treatments

The goal of cognitive-behavioral therapy (CBT) is to regain control of reactions to stress and stimuli, thus reducing the feeling of helplessness that often accompanies anxiety disorders. CBT works on the principle that the thoughts that produce and maintain anxiety can be recognized and altered using various techniques that change behavioral responses and eliminate the anxiety reaction. Many studies have shown that a combination of CBT and medication works best for treating anxiety disorders.

A number of CBT approaches work well for treating many types of anxiety disorders. Studies suggest that CBT is also helpful for patients who have additional conditions, such as depression, a second anxiety disorder, or alcohol dependency. (It may take longer to achieve a successful outcome in such cases, however.) CBT is often given along with drug treatment. A study in the Journal of the American Medical Association found that children and adolescents with OCD responded better to CBT alone than the antidepressant setraline (Zoloft) alone, but most patients did best when they were treated with a combination of CBT and sertraline.

Both individual and group treatments work well. (However, people with social phobia may do better in individual sessions.) Several recent studies also indicate that telephone-based behavioral therapy works well for people with OCD, generalized anxiety disorder, and panic disorders.

Anxiety disorders are chronic, however, and recurrence is common. Some studies indicate that 30 - 82% of people with panic disorder and phobias have a recurrence of attacks at an average of 9 months, even after successful short-term therapy. Medications, then, are also generally recommended for most patients.

Basic Cognitive Therapy Techniques. Treatment usually takes about 12 - 20 weeks. The essential goal of cognitive therapy is to understand the realities of an anxiety-provoking situation and to respond to reality with new actions based on reasonable expectations.

First, the patient must learn how to recognize anxious reactions and thoughts as they occur. One way of accomplishing this is by keeping a daily diary that reports the occurrences of anxiety attacks and any thoughts and events associated with them. A patient with OCD, for instance, may record repetitive thoughts.
These entrenched and automatic reactions and thoughts must be challenged and understood. Again, using the OCD example, one approach is to record and play back the words of the repetitive thoughts, over exposing the patient to the thoughts and reducing their effect. One effective approach for patients with generalized anxiety disorder targets their intolerance of uncertainty and helps them develop methods to cope with it.
Patients are usually given behavioral homework assignments to help them change their behavior. For example, a person with generalized social phobia may be asked to buy an item and then return it the next day. As the patient performs this action, they observe any unrealistic fears and thoughts triggered by such an event.
As the patient continues with self-observation, they begin to perceive the false assumptions that underlie the anxiety. For example, OCD patients may learn to recognize that their heightened sense of responsibility for preventing harm in non-threatening situations is not necessary or even useful.
At that point, the patient can begin substituting new ways of coping with the feared objects and situations.

Systematic Desensitization. Systematic desensitization is a specific technique that breaks the link between the anxiety-provoking stimulus and the anxiety response. This treatment requires the patient to gradually confront the object of fear. There are three main elements to the process:

Relaxation training
A list composed by the patient that prioritizes anxiety-inducing situations by degree of fear
The desensitization procedure itself, confronting each item on the list, starting with the least stressful

This treatment is especially effective for simple phobias, social phobias, agoraphobia, and post-traumatic stress syndrome.

Exposure and Response Treatment. Exposure treatment purposefully generates anxiety by exposing the patient repeatedly to the feared object or situation, either literally or using imagination and visualization. It uses the most fearful stimulus first. (This differs from the desensitization process because it does not involve relaxation or a gradual approach to the source of anxiety.)

Exposure treatments are usually known as either flooding or graduated exposure:

Flooding exposes the person to the anxiety-producing stimulus for as long as 1 - 2 hours.
Graduated exposure gives the patient a greater degree of control over the length and frequency of exposures.

In both cases, the patient experiences the anxiety over and over until the stimulating event eventually loses its effect. Combining exposure with standard cognitive therapy may be particularly beneficial. This approach has helped certain patients in most anxiety disorder categories, including post-traumatic stress disorder.

Modeling Treatment. Phobias can often be treated successfully with modeling treatment:

The therapy typically uses an actor who approaches an anxiety-producing object or engages in a fear-provoking activity that is similar to the patient's specific problem. Either a live or videotaped situation may be used, although the live model is considered to be more effective.
The patient observes this event and tries to learn how to behave in a comparable manner.

Other forms of psychotherapy, commonly called emotion-based psychotherapy (EBT), psychodynamic therapy, or "talk" therapy, deal more with childhood roots of anxiety and usually, although not always, require longer treatments. They include interpersonal therapy, supportive psychotherapy, attention intervention, and psychoanalysis. All work is done during the sessions. Some research indicates that such therapies might be more useful for generalized anxiety, which may require more sustained work to process and recover from early traumas and fears. Studies suggest that although emotion-based psychotherapies are not as effective as cognitive-behavioral therapy (CBT) in treating panic disorders, patients tend to stay longer in EBT than in CBT. Some doctors suggest adding elements of EBT to the usual CBT and medication treatments.

Anxiety Management Therapy. Anxiety management therapy is sometimes used as an alternative to CBT for generalized anxiety disorder. It involves patient education, relaxation training, and exposure to anxiety-provoking stimuli but does not include exercises in cognitive retraining.

Relaxation Training. Relaxation techniques use muscle relaxation and mental visualization to help focus attention towards a calming feeling. Some people find meditation helpful.

Breathing Retraining. Breathing retraining techniques may help reduce the physical effects of anxiety. For example, hyperventilation is one of the primary physical manifestations of panic disorders. This involves rapid, tense breathing, resulting in chest pain, dizziness, tingling of the mouth and fingers, muscle cramps, and even fainting. By practicing measured, controlled breathing at the onset of a panic attack, patients may be able to prevent full attacks.

Biofeedback. Biofeedback uses special sensors that allow patients to recognize anxiety states by changes in specific physical functions, such as changes in pulse rate, skin temperatures, and muscle tone. Eventually they learn to modify these changes, which in turn helps relieve anxiety. While commonly used, there are not many rigorous studies showing that biofeedback helps patients reduce or eliminate their symptoms over the long term.

Several types of psychological treatments have been designed specifically for treating patients with PTSD. These approaches include a special type of CBT known as trauma-focused cognitive behavioral therapy (TFCBT), and a psychotherapy treatment called eye movement desensitization and reprocessing (EMDR).

With TFCBT, patients are taught stress management skills. The therapist helps the patient develop a narrative (verbal, written, or artistic) about the traumatic event. Patients may be exposed to reminders about the trauma and are taught how to cope with future reminders. Through the process, the patient learns how to reprocess their thoughts, feelings, and behaviors.

With EMDR, the patient focuses on remembering the traumatic experience while visually following the rhythmic movement of the therapist’s fingers. The patient recounts to the therapist what memories have been provoked during the exercise. EMDR may help patients recall details and sensations that they had blocked out. Through this breakthrough, patients learn how to regain emotional control.

Transcranial magnetic stimulation (TMS) uses high frequency magnetic pulses to target and stimulate specific areas of the brain. Research has particularly focused on possible benefits for obsessive-compulsive behavior. Some studies have found some improvement in mood, but more research is needed to determine its value for reducing anxiety and obsessions.

In 2006, the U.S. National Institutes of Health funded a large study to examine whether deep brain stimulation (DBS) can help patients with OCD. DBS involves implanting tiny stimulators into the brain to block abnormal nerve signals that cause obsessive symptoms. These “brain pacemakers” are approved to treat epilepsy and Parkinson’s disease. Researchers hope that DBS may eventually provide a new treatment option for patients with severe OCD.

A surgical technique called cingulotomy involves interrupting the cingulate gyrus, a bundle of nerve fibers in the front of the brain. It is sometimes used as a last resort for patients with severe OCD. A variation of this procedure using magnetic resonance imaging (MRI) to guide the surgeon has resulted in long-term improvement in about 25 - 33% of OCD patients in whom it is performed. The procedure is generally safe with few serious complications and does not affect intellect or memory.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.adaa.org -- Anxiety Disorders Association of America
www.nami.org -- National Alliance on Mental Illness
www.psych.org -- The American Psychiatric Association
www.apa.org -- The American Psychological Association
www.istss.org -- International Society for Traumatic Stress Studies
www.ncvc.org -- National Center for Victims of Crime
www.ncptsd.va.gov -- National Center for Post-Traumatic Stress Disorders
www.rainn.org -- Rape, Abuse, and Incest National Network
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.ocfoundation.org -- Obsessive Compulsive Foundation

References

Bisson J, Andrew M. Psychological treatment of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2007 Jul 18;(3):CD003388.

Bisson JI. Post-traumatic stress disorder. BMJ. 2007 Apr 14;334(7597):789-93.

Bridge JA, Iyengar S, Salary CB, et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007 Apr 18;297(15):1683-96.

Connolly SD, Bernstein GA; Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with anxiety disorders. J Am Acad Child Adolesc Psychiatry. 2007 Feb;46(2):267-83.

Gale C, Davidson O. Generalised anxiety disorder. BMJ. 2007 Mar 17;334(7593):579-81.

Heyman I, Mataix-Cols D, Fineberg NA. Obsessive-compulsive disorder. BMJ. 2006 Aug 26;333(7565):424-9.

Hunot V, Churchill R, Silva de Lima M, Teixeira V. Psychological therapies for generalised anxiety disorder. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001848.

Ipser JC, Carey P, Dhansay Y, Fakier N, Seedat S, Stein DJ. Pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD005473.

Katon WJ. Clinical practice. Panic disorder. N Engl J Med. 2006 Jun 1;354(22):2360-7.

Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB; American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007 Jul;164(7 Suppl):5-53.

Kroenke K, Spitzer RL, Williams JB, Monahan PO, Löwe B. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med. 2007 Mar 6;146(5):317-25.

Saeed SA, Bloch RM, Antonacci DJ. Herbal and dietary supplements for treatment of anxiety disorders. Am Fam Physician. 2007 Aug 15;76(4):549-56.

Schneier FR. Clinical practice. Social anxiety disorder. N Engl J Med. 2006 Sep 7;355(10):1029-36.

Smoller JW, Pollack MH, Wassertheil-Smoller S, et al. Panic attacks and risk of incident cardiovascular events among postmenopausal women in the Women's Health Initiative Observational Study. Arch Gen Psychiatry. 2007 Oct;64(10):1153-60.

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

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

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

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

References

Allen JJ, Schnyer RN, Chambers AS, Hitt SK, Moreno FA, Manber R. Acupuncture for depression: a randomized controlled trial. J Clin Psychiatry. 2006 Nov;67(11):1665-73.

Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM; National Birth Defects Prevention Study. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med. 2007 Jun 28;356(26):2684-92.

Cheung AH, Zuckerbrot RA, Jensen PS, Ghalib K, Laraque D, Stein RE; GLAD-PC Steering Group. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): II. Treatment and ongoing management. Pediatrics. 2007 Nov;120(5):e1313-26.

Diem SJ, Blackwell TL, Stone KL, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007 Jun 25;167(12):1240-5.

Eranti S, Mogg A, Pluck G, et al. A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression. Am J Psychiatry. 2007 Jan;164(1):73-81.

Frederikse M, Petrides G, Kellner C. Continuation and maintenance electroconvulsive therapy for the treatment of depressive illness: a response to the National Institute for Clinical Excellence report. J ECT. 2006 Mar;22(1):13-7.

George MS, Nahas Z, Borckardt JJ, et al. Brain stimulation for the treatment of psychiatric disorders. Curr Opin Psychiatry. 2007 May;20(3):250-4; discussion 247-9.

Gross M, Nakamura L, Pascual-Leone A, Fregni F. Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies. Acta Psychiatr Scand. 2007 Sep;116(3):165-73.

Hetrick S, Merry S, McKenzie J, Sindahl P, Proctor M. Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004851.

Institute for Clinical Systems Improvement. Health Care Guideline: Major Depression in Adults in Primary Care. Tenth addition. May 2007.

Jarema M. Atypical antipsychotics in the treatment of mood disorders. Curr Opin Psychiatry. 2007 Jan;20(1):23-9.

Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M. Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial. BMC Med. 2006 Jun 23;4:14.

Kellner CH, Knapp RG, Petrides G, et al. Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry. 2006 Dec;63(12):1337-44.

Krishnan KR. Revisiting monoamine oxidase inhibitors. J Clin Psychiatry. 2007;68 Suppl 8:35-41.

Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry. 2007 Jul;68(7):1056-61.

Louik C, Lin AE, Werler MM, Hernández-Díaz S, Mitchell AA. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med. 2007 Jun 28;356(26):2675-83.

Mahmoud RA, Pandina GJ, Turkoz I, et al. Risperidone for treatment-refractory major depressive disorder: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):593-602.

Papakostas GI, Shelton RC, Smith J, Fava M. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry. 2007 Jun;68(6):826-31.

Rapaport MH. Dietary restrictions and drug interactions with monoamine oxidase inhibitors: the state of the art. J Clin Psychiatry. 2007;68 Suppl 8:42-6.

Rohan KJ, Roecklein KA, Tierney Lindsey K, et al. A randomized controlled trial of cognitive-behavioral therapy, light therapy, and their combination for seasonal affective disorder. J Consult Clin Psychol. 2007 Jun;75(3):489-500.

Ruhé HG, Huyser J, Swinkels JA, Schene AH. Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry. 2006 Dec;67(12):1836-55.

Stewart JW. Treating depression with atypical features. J Clin Psychiatry. 2007;68 Suppl 3:25-9.

Thachil AF, Mohan R, Bhugra D. The evidence base of complementary and alternative therapies in depression. J Affect Disord. 2007 Jan;97(1-3):23-35. Epub 2006 Aug 22.

Zuckerbrot RA, Cheung AH, Jensen PS, Stein RE, Laraque D; GLAD-PC Steering Group. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): I. Identification, assessment, and initial management. Pediatrics. 2007 Nov;120(5):e1299-312.

A.D.A.M. Copyright

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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

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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.

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