PopSugar

Keep it Simple: Portion Sizes

FitSugar — Wed, 16 May 2007 14:30:00 -0700

We all have a hard time deciphering portion sizes, especially when we're eating off a large plate, or even wedge shaped foods. There are some pretty simple ways to measure portion sizes but sometimes even that is too confusing.

One very simple technique for figuring out how much you should eat is using this simple diagram from the Daily Bureau of Canada.

Easy enough, right?

Did you notice half of the plate is dedicated to veggies!!! I didn't think you missed it, but I just wanted to hit that point home.

Fall Pantry Favorite: Cranberry Hazelnut Raincoast Crisps

YumSugar — Thu, 22 Oct 2009 14:00:41 -0700

At a recent happy hour hosted by a friend, I found myself conveniently placed near a certain charismatic snack: rustic crisps studded with slivers of dried cranberries and roasted hazelnuts. Despite my attempts to save my appetite for dinner, I couldn't pull myself away from the crackers, which were just as habit-forming when eaten alone as they were with a slather of good goat cheese.

After a little research, I learned that Lesley Stowe's Raincoast Crisps, as they're called, hail from Canada and come in a multitude of flavors, like Raisin Pecan, Fig and Olive, and Salty Date and Almond, and are sold at many Whole Foods stores. I tried several flavors, but the hazelnut, with its mild nuttiness, paired with the slightly chewy consistency of the cranberries, remains my hands-down favorite combination. I'm keeping some stocked to make a mark at impromptu gatherings this Fall.

Have you ever tried Lesley Stowe's Raincoast Crisps?

Vitamins

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer

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

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

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

Macular Degeneration

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

Osteoporosis

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

Heart Disease

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

Introduction

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following vitamins may have some value for pregnant women:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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


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


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


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


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


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


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


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

Carotenoids

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

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

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

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

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

Phytochemicals

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

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

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

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

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

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

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

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

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

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

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

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

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

Healthy Foods

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


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

Dietary Health Benefits

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

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

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

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

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

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

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

Vitamins and Heart Protection.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

Resources

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

References

Age-Related Eye Disease Study Research Group, SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Arch Ophthalmol. 2007;125(9):1225-1232.

Ambrosini GL, de Klerk NH, Fritschi L, Mackerras D, Musk B. Fruit, vegetable, vitamin A intakes, and prostate cancer risk. Prostate Cancer Prostatic Dis. 2007 May 22; [Epub ahead of print]

Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ. Six months of isoflavone supplement increases fat-free mass in obese-sarcopenic postmenopausal women: a randomized double-blind controlled trial. Eur J Clin Nutr. 2007 Feb 21; [Epub ahead of print]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Riccioni G, Bucciarelli T, Mancini B, Di Ilio C, Della Vecchia R, D'Orazio N. Plasma lycopene and antioxidant vitamins in asthma: the PLAVA study. J Asthma. 2007;44(6):429-432.

Ronnenberg AG, Venners SA, Xu X, Chen C, Wang L, Guang W, Huang A, Wang X. Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss. Am J Epidemiol. 2007;166(3):304-12. Epub 2007 May 2.

Sahin M, Tutuncu NB, Ertugrul D, Tanaci N, Guvener ND. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complications. 2007;21(2):118-123.

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Triantafyllou NI, Kararizou E, Angelopoulos E, Tsounis S, Boufidou F, Evangelopoulos ME, Nikolaou C, Vassilopoulos D. The influence of levodopa and the COMT inhibitor on serum vitamin B12 and folate levels in Parkinson's disease patients. Eur Neurol. 2007;58(2):96-99.

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Wierzbicki AS. Homocysteine and cardiovascular disease: a review of the evidence. Diab Vasc Dis Res. 2007;4(2):143-50.

Zeisel SH. The fetal origins of memory: the role of dietary choline in optimal brain development. J Pediatr. 2006;149(5 Suppl):S131-136.

Ziaei S, Kazemnejad A, Zareai M. The Effect of Vitamin E on Hot Flashes in Menopausal Women. Gynecol Obstet Invest. 2007;64(4):204-207 [Epub ahead of print]

Zollinger PE, Tuinebreijer WE, Breederveld RS, Kreis RW. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study. J Bone Joint Surg Am. 2007;89(7):1424-1431.

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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adam.com

Gastroesophageal reflux disease and heartburn

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Barrett's Esophagus
Diagnosis
Treatment
Prevention
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Research

Obesity and GERD. Increased weight in women is linked to more frequent GERD symptoms, according to the Nurses' Health Study, which included 10,545 female participants. Overweight and obese women were two to three times more likely to have frequent symptoms than women of normal weight. GERD symptoms decreased nearly 40% in women whose body mass index (BMI) dropped by more than 3.5, compared to women whose BMI remained the same.
Proton-Pump Inhibitors and Bone Fracture. Long-term use of PPIs may increase the risk of hip fractures in older adults, according to a study in the Journal of the American Medical Association. People taking high doses of PPIs for more than a year were 2.6 times as likely to fracture a hip as those who were not taking the drug. The authors suggested that the stomach acids blocked by PPIs may be needed to absorb calcium, or the drugs may interfere with the body's natural process of breaking down and rebuilding bones.
PPIs and H2 Blockers in Children. Otherwise healthy children who take PPI inhibitors or H2 blockers may be at increased risk for intestinal and respiratory infections, according to a study of 186 children with GERD. The rate of gastroenteritis and community-acquired pneumonia significantly increased in children who were taking these medications when researchers compared the 4 months before and after enrollment in the study.

New Approval

Proton-Pump Inhibitor Approved for Adolescents. Esomeprazole (Nexium) delayed-release capsules have been approved for use in children ages 12 - 17 for the short-term treatment of GERD. Research shows that this medication reduces heartburn symptoms in adolescents.

Introduction

Gastroesophageal reflux disease (GERD) is a condition in which acids from the stomach move backward into the esophagus (an action called reflux). Reflux occurs if the muscular actions in the esophagus or other protective mechanisms fail.

Click the icon to see an animation about heartburn.

The hallmark symptoms of GERD are:

Heartburn: a burning sensation in the chest and throat.
Regurgitation: a sensation of acid backed up in the esophagus.

Although acid is a primary factor in damage caused by GERD, other products of the digestive tract, including pepsin and bile, can also be harmful.

Heartburn is a condition in which the acidic stomach contents back up into the esophagus, causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. Standing or sitting after a meal can help reduce the reflux that causes heartburn. Continuous irritation of the esophagus lining as in gastroesophageal reflux disease is a risk factor for the development of adenocarcinoma.

The esophagus, commonly called the food pipe, is a narrow muscular tube about nine-and-a-half inches long. It begins below the tongue and ends at the stomach. The esophagus is narrowest at the top and bottom; it also narrows slightly in the middle. The esophagus consists of three basic layers:

An outer layer of fibrous tissue.
A middle layer containing smoother muscle.
An inner membrane, which contains numerous tiny glands.

Click the icon to see an image of the esophagus.

When a person swallows food, the esophagus moves it into the stomach through the action of peristalsis, wave-like muscle contractions. In the stomach, the starch, fat, and protein in food are broken down by acid and various enzymes, notably hydrochloric acid and pepsin. The lining of the stomach has a thin layer of mucous that protects it from these fluids.

If acid and enzymes back up into the esophagus, however, its lining offers only a weak defense. The esophagus is protected using specific muscles and other factors.

The most important structure protecting the esophagus may be the lower esophageal sphincter (LES). The LES is a band of muscle around the bottom of the esophagus where it meets the stomach.

The LES opens after a person swallows to let food enter the stomach and then immediately closes to prevent regurgitation of the stomach contents, including gastric acid.
The LES maintains this pressure barrier until food is swallowed again.

Click the icon to see an image of the stomach.

If the pressure barrier is not sufficient to prevent regurgitation and acid backs-up (reflux), then peristaltic action of the esophagus serves as an additional defense mechanism and pushes the contents back down into the stomach.

Esophagitis. In most people, GERD symptoms are short-lived and occur infrequently. In about 20% of cases, however, the condition becomes chronic. When the acid causes irritation or inflammation, the condition is called esophagitis. If the damage becomes extensive and injures the esophagus, the disorder is known as erosive esophagitis.

Non-Erosive Esophageal Reflux Disease. Symptoms of gastroesophageal reflux disease can occur without any signs of inflammation or injury to the esophagus. This condition is also referred to as non-erosive esophageal reflux disease (NERD). NERD rarely progresses to full-blown GERD. Patients with NERD have no signs of inflammation or erosion in the esophagus, but they experience certain symptoms of GERD, such as burning sensations behind the breastbone for at least 3 months. Researchers suggest that nerves lying near the surface of the lining become exposed to acid that has penetrated the layers. The nerves then trigger prolonged and painful symptoms in response.

Barrett's Esophagus. A small percentage of patients with GERD may eventually develop Barrett's esophagus, a serious complication of GERD that results in precancerous changes in the tissue lining the esophagus.

Eosinophilic Esophagitis. This is a distinct disorder characterized by difficult or painful swallowing. It can occur along with GERD. The lining of the esophagus develops furrows and rings. This condition can be treated with swallowed fluticasone propionate, the active ingredient in some asthma medications.

Causes

Anyone who eats a large amount of acidic foods can have mild and temporary heartburn. This is especially true when lifting, bending over, or taking a nap after eating a large meal high in fatty, acidic foods. Persistent GERD, however, may be due to various conditions, including abnormal biologic or structural factors.

The band of muscle tissue called the LES is responsible for closing and opening the lower end of the esophagus and is essential for maintaining a pressure barrier against contents from the stomach. It is a complex area of smooth muscles and various hormones. If it weakens and loses tone, the LES cannot close up completely after food empties into the stomach. In such cases, acid from the stomach backs up into the esophagus. Dietary substances, drugs, and nervous system factors can weaken the LES and impair its function.

A study showed that more than half of GERD patients had abnormal nerve or muscle function in the stomach. These abnormalities cause impaired motility, which is the inability of muscles to act spontaneously. The stomach muscles do not contract normally, which causes delays in stomach emptying, increasing the risk for acid back-up.

Some studies suggest that most people with atypical GERD symptoms (such as hoarseness, chronic cough, or the feeling of having a lump in the throat) may have specific abnormalities in the esophagus. (In one study, such abnormalities appeared in 73% of patients who had atypical symptoms.)

Motility Abnormalities. Problems in spontaneous muscle action (peristalsis) in the esophagus commonly occur in GERD, although it is not clear if such occurrences are a cause or result of long-term effects of GERD.

Adult-Ringed Esophagus. This condition is characterized by an esophagus with multiple rings and persistent trouble with swallowing (including getting food stuck in the esophagus). It occurs mostly in men.

The hiatus is a small hole in the diaphragm through which the esophagus passes into the stomach. It normally fits very snugly, but it may weaken and enlarge. When this happens, part of the stomach muscles may protrude into it, producing a condition called hiatal hernia. It is very common, occurring in over half of people over 60 years old, and is rarely serious. Until recent years, it was believed that most cases of persistent heartburn were caused by a hiatal hernia. Hiatal hernia may impair LES muscle function. Studies have failed to confirm evidence, however, that it is a common cause of GERD, although its presence may increase GERD symptoms in patients with both conditions.

A hiatal hernia occurs when part of the stomach protrudes up into the chest through the sheet of muscle called the diaphragm. This may result from a weakening of the surrounding tissues and may be aggravated by obesity or smoking.

Studies indicate that 31 - 43% of reflux may be hereditary. An inherited risk exists in many cases of GERD, possibly because of inherited muscular or structural problems in the stomach or esophagus. Genetic factors may play an especially strong role in susceptibility to Barrett's esophagus, a precancerous condition caused by very severe GERD.

At least half of people with asthma also have GERD. Some experts speculate that the coughing and sneezing accompanying asthmatic attacks cause changes in pressure in the chest that can trigger reflux. Certain asthma drugs that dilate the airways may relax the LES and contribute to GERD. On the other hand, GERD has been associated with a number of other upper respiratory problems and may be a cause of asthma, rather than a result.

Crohn's disease is a chronic ailment that causes inflammation and injury in the colon and other parts of the gastrointestinal tract, including the esophagus. Other disorders that may affect areas that can contribute to GERD include diabetes, any gastrointestinal disorder, peptic ulcers, lymphomas, and cancer.

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

Helicobacter Pylori, also called H. pylori, is a bacterium found in the mucous membranes and is now known to be a major cause of peptic ulcers. Antibiotics used to eradicate H. pylori are now accepted treatment for curing ulcers. Of some concern, however, are studies indicating that H. Pylori may actually protect against GERD by reducing stomach acid. Furthermore, curing ulcers by eliminating the bacteria might actually trigger GERD in some people. Studies are mixed, however, on whether patients with cured H. Pylori infections are at risk for GERD. An analysis of 8 studies reported no higher risk for GERD after antibiotic treatments, nor was GERD any worse in patients who already had it. Seven of the 8 studies, however, were conducted only 2 months after antibiotic treatment. Longer follow-up studies are needed to determine long-term consequences, if any.

In any case, the bacteria should be eradicated in infected patients with existing GERD who are taking ongoing acid suppressing agents. There is some evidence that the combination of H. pylori and chronic acid suppression in these patients can lead to atrophic gastritis, a precancerous condition in the stomach.

In some cases, the esophagus appears normal, but GERD symptoms are present. This may indicate an over-reaction of the immune system to irritants that are introduced into the esophagus. In such cases, the immune system reacts with an exaggerated (or hyper-reactive) response, triggering the release of certain factors that end up causing inflammation and possibly injury. (This event is similar to the asthmatic response in the airways.)

NSAIDs. Nonsteroidal anti-inflammatory drugs (NSAIDs), common causes of peptic ulcers, may also cause GERD and increase severity in people who already have GERD. In a 3-year study of 25,000 people, NSAID users were twice as likely to have GERD symptoms as non-users. Symptoms did not become evident until after about 6 months of regular use. There are dozens of NSAIDs, including over-the-counter aspirin, ibuprofen (Motrin, Advil, Nuprin), and naproxen (Aleve), as well as prescription anti-inflammatory medicines. A person with GERD who takes the occasional aspirin or other NSAID will not necessarily experience adverse effects. This is especially true if there are no risk factors or indications of ulcers. Acetaminophen (Tylenol), which is NOT an NSAID, is a good alternative for those who want to relieve mild pain. It does not, however, relieve inflammation.

Other Drugs. Many other drugs can cause GERD, including but not limited to the following: calcium channel blockers (used to treat high blood pressure and angina), anticholinergics (used in drugs that treat urinary tract disorders, allergies, and glaucoma), beta adrenergic agonists (used for asthma and obstructive lung diseases), dopamine (used in Parkinson's disease), bisphosphonates (used to treat osteoporosis), sedatives, antibiotics, potassium, or iron pills.

Weakened peristaltic movement in the esophagus may contribute to GERD. If the mucous membrane is impaired, even a normal amount of acid can harm the esophagus. Pressure on the abdomen caused by obesity and also wearing tight clothing can contribute to acid backing up into the esophagus.

Click the icon to see an image of peristalsis.

Risk Factors

GERD occurs monthly in about half of American adults. People of all ages are susceptible to GERD. Elderly people with GERD tend to have a more serious condition than younger people.

Eating Pattern. Anyone who eats a heavy meal and subsequently lies on the back or bends over from the waist is at risk for an attack of heartburn. Anyone who snacks at bedtime is at high risk for heartburn.

Pregnancy. Pregnant women are particularly vulnerable to heartburn in their third trimester as the growing uterus puts increasing pressure on the stomach. Heartburn in such cases is often resistant to dietary interventions and even antacids.

Obesity. A number of studies suggest that obesity contributes to GERD and may increase the risk for erosive esophagitis in GERD patients. The Nurses' Health Study found that being overweight or obese significantly increased GERD symptoms in women. The higher a woman's body mass index (BMI), the study found, the more frequent were her symptoms. Women who lost weight in the study saw a decrease in their symptoms. Research suggests that the prevalence of GERD symptoms among obese patients has been underreported. Other researchers have reported that increased BMI is associated with a higher risk for cancer of the esophagus (esophageal adenocarcinoma).

Respiratory Diseases. People with asthma are at very high risk for GERD. One study indicated that patients with chronic obstructive pulmonary diseases (e.g., emphysema or chronic bronchitis) were more likely to have GERD.

Chronic obstructive pulmonary disease (COPD) refers to chronic lung disorders that result in blocked air flow in the lungs. The two main COPD disorders are emphysema and chronic bronchitis, the most common causes of respiratory failure. Emphysema occurs when the walls between the lung's air sacs become weakened and the sacs get enlarged and filled with too much air. Damage from COPD is usually permanent and irreversible.

Smoking. Increasing evidence indicates that smoking raises the risk for GERD. Studies suggest that smoking reduces LES muscle function, increases acid secretion, impairs muscle reflexes in the throat, and damages protective mucous membranes. Smoking reduces salivation, which helps neutralize acid. Whether it is the smoke, nicotine, or both that triggers GERD is unknown. Some people who use nicotine patches to quit smoking, for example, experience heartburn, but it is not clear if it's the nicotine or stress that produces acid back-up.

Alcohol Use. Alcohol has mixed effects on GERD. It relaxes the LES muscles and, in high amounts, may irritate the mucous membrane of the esophagus. All alcoholic beverages increase stomach acid levels. A combination of heavy alcohol use and smoking increases the risk for esophageal cancer. (Small amounts of alcohol, however, may actually protect the mucosal layer.)

In general, overweight Caucasian males over 40 are at highest risk for complications, notably Barrett's esophagus. Others at high risk for severe symptoms, inflammation, or both include:

People who use nonsteroidal anti-inflammatory drugs (NSAIDs). Studies suggest that certain NSAID users are at higher risk for GERD, including older adults, women, alcohol and tobacco users, and patients with asthma, hiatal hernia, or obesity. One study reported that NSAIDs put people at risk for ulcers but not for erosive esophagitis or strictures. Interestingly, NSAIDs are being studied for protection against Barrett's esophagus.
People with hiatal hernia

GERD is very common in children of all ages, but it is usually mild. Heartburn has been reported in 1.8% of 3-year-olds and in 5.2% of young people 10 - 17 years old. Children with the following conditions are at higher risk for severe GERD:

Neurologic impairments
Food allergies
Scoliosis
Cyclic vomiting
Cystic fibrosis
Problems in the lungs, ear, nose, or throat
Any medical condition affecting the digestive tract

Symptoms in Children. A physician should examine any child who has the following symptoms as soon as possible, because they may indicate complications such as anemia, failure to gain weight, or respiratory problems. Symptoms of severe GERD in infants and small children may include:

Chronic coughing
Frequent infections
Wheezing
Gasping or frequent cessation in breathing while asleep (called sleep apnea). However, one study found no association between GERD and apneas in premature infants.
Frequent vomiting in infants. About half of all infants up to 3 months old regurgitate milk at least once a day. Some simply spit up; others vomit large amounts after feedings. Vomiting in infants and older children is rarely a sign of GERD. In infants it usually resolves by age one. Severe vomiting -- particularly if it is bilious (green colored) -- always requires a doctor's visit, since it could be a symptom of severe obstruction.
Having to burp babies very frequently during and after feeding.

Babies and children may experience these symptoms without having GERD. An Australian study suggested that many infants who have normal irritability may be treated inappropriately for reflux disorders.

Feeding Problems. Feeding problems may be more severe than previously thought in children with GERD. In one study, children who had GERD and problems swallowing tended to refuse food and were late in eating solids. They also cried more and reacted more negatively in general than non-GERD babies. Such behaviors negatively affected the mothers as well. These findings were supported in an earlier study which reported that children at 1 year who had GERD in infancy were no longer spitting up, but still tended to have negative dining experiences ("too slow," "upsetting"). However, these children were at no greater risk for respiratory illnesses than other 1-year-old children.

Associations with Asthma and Infections in the Upper Airways. In addition to asthma, GERD is associated with other upper airway problems, including ear infections and sinusitis. Some experts argue that the association with common childhood infections and asthma is unfounded, since GERD is normal in most children.

Dental Erosion. GERD can cause irreversible loss of tooth enamel. Based on a 2002 study, some experts suggest checking for GERD in children with dental erosions. In the study, no child without GERD experienced loss of tooth enamel.

Rare Complications in Infants. Although GERD is very common, the following complications are very rare and only occur in certain cases:

Failure to thrive
Feeding problems and severe vomiting may cause anemia
Acid back-up may be inhaled into the airways and cause pneumonia

The infant's life may be in danger if acid reflux causes spasms in the larynx severe enough to block the airways. In fact, some experts believe this action may contribute to sudden infant death syndrome (SIDS). More research is needed to determine whether this association is valid.

Managing GERD in Infancy. Here are some hints on managing GERD in infants:

During and after feeding, infants should be positioned vertically and burped frequently.
If a baby with GERD is fed formula, the mother should ask the doctor how to thicken it in order to prevent splashing up from the stomach.
Parents of infants with GERD should discuss the baby's sleeping position with their pediatrician. Experts strongly recommend that all healthy infants sleep on their backs to help prevent sudden infant death syndrome (SIDS). For babies with GERD, however, lying on the back may obstruct the airways. In one study, infants with gastroesophageal reflux who spent prolonged periods of time in infant seats, including car seats, had more reflux than those who spent waking time on their stomachs. If the physician recommends that babies with GERD sleep on their stomachs, parents should be sure that their infant's mattress is very firm, possibly tilted up at the head, and that there are no pillows. The baby's head should be turned so that the mouth and nose are completely unobstructed.
Because food allergies may trigger GERD in children, parents may want to discuss a dietary plan with their physician that starts the child on formulas using non-allergenic proteins, and then incrementally adds other foods until symptoms are triggered.

Managing GERD in Children. The same drugs used in adults may be tried in children with chronic GERD. While some drugs are available over the counter, they should not be given to children without physician supervision.

Milder medications, such as antacids, are used first.
H2 blockers may be tried next. They are available over the counter and include famotidine (Pepcid AC), cimetidine (Tagamet HB), ranitidine (Zantac 75), and nizatidine (Axid AR). The FDA has issued a warning on Pepcid AC for adults with kidney problems.
Proton-pump inhibitors (PPIs), such as omeprazole (Prilosec) and lansoprazole (Prevacid), are even more powerful agents that suppress the production of stomach acid. Delayed-release esomeprazole (Nexium) capsules have been approved for use in children ages 12 - 17 for the short-term treatment of GERD. One study found that esomeprazole (Nexium) in either a 20 or 40 mg dose once a day significantly reduced heartburn symptoms in adolescents. PPIs appear to be safe and effective even for children as young as 1 year old who fail the less intensive therapies. However, a 2006 study found that otherwise healthy children who were treated with H2 blockers and PPIs had an increased risk of developing respiratory and intestinal infections.

Surgical fundoplication involves wrapping the upper curve of the stomach (fundus) around the esophagus. The goal of this surgical technique is to strengthen the LES. Until recently, surgery was the primary treatment for children with severe complications from GERD because older drug therapies had severe side effects, were ineffective, or had not been designed for children. However, with the introduction of proton-pump inhibitor drugs, some children may be able to avoid surgery. Surgical fundoplication can be performed laparoscopically through small incisions. In one study, of 238 children from 5 months to 16 years of age who underwent laparoscopic fundoplication, all but 9 were symptom free at least 5 years after the surgery. A 2006 study found that children who underwent antireflux surgery before age 4 were less likely to be hospitalized again, or to have reflux-related events such as pneumonia and esophagitis after the surgery.

Symptoms

Heartburn. Heartburn is the primary symptom of GERD. It is a burning sensation that radiates up from the stomach to the chest and throat. Heartburn is most likely to occur in connection with the following activities:

After a heavy meal
Bending over
Lifting
Lying down, particularly on the back

According to one study, nearly three-quarters of patients with frequent GERD symptoms experience them at night. Patients with nighttime GERD also tend to experience more severe pain than those whose symptoms occur at other times. One study found that patients with nighttime pain reported levels of severity that were similar to those reported in angina and heart failure.

The severity of heartburn does not necessarily indicate actual injury in the esophagus. For example, Barrett's esophagus, which causes precancerous changes in the esophagus, may trigger few symptoms, especially in elderly people. On the other hand, people can suffer severe heartburn without the presence of damage to the esophagus.

Dyspepsia. Up to half of GERD patients have dyspepsia, a syndrome consisting of the following:

Pain and discomfort in the upper abdomen
Fullness in the stomach
Nausea after eating

People can have dyspepsia without having GERD.

Regurgitation. Regurgitation is the feeling of acid backing up in the throat. Sometimes acid regurgitates as far as the mouth and can be experienced as a "wet burp." Uncommonly, it may come out forcefully as vomit.

Many patients with GERD do not experience heartburn or regurgitation. Elderly patients with GERD often have less typical symptoms than do younger people. Instead symptoms may appear in other locations.

Chest Sensations or Pain. Patients may have the sensation that food is trapped behind the breastbone. Chest pain is a common symptom of GERD. It is very important to differentiate it from chest pain caused by heart conditions, such as angina and heart attack.

Symptoms in the Throat. Less commonly, GERD may produce symptoms that occur in the throat:

Acid laryngitis. A condition that includes hoarseness, dry cough, the sensation of having a lump in the throat, and the need to repeatedly clear the throat.
Trouble swallowing (dysphagia). In severe cases, patients may even choke or food may become trapped in the esophagus, causing severe chest pain. This may indicate a temporary spasm that narrows the tube, or it could also be an indication of serious esophageal damage or abnormalities.
Chronic sore throat
Persistent hiccups

Coughing and Respiratory Symptoms. Asthmatic symptoms, such as coughing and wheezing, may occur. In fact, in one study, GERD alone accounted for 41.1% of cases of chronic cough in nonsmoking patients. The incidence was even higher when GERD and asthma were combined.

Chronic Nausea and Vomiting. Nausea that persists for weeks or even months and is not attributable to a common cause of stomach upset may be a symptom of acid reflux. In rare cases, vomiting can occur as often as once a day. All other causes of chronic nausea and vomiting should be ruled out, including ulcers, stomach cancer, obstruction, and pancreas or gallbladder disorders.

Complications

Nearly everyone has an attack of heartburn at some point in their lives. In the vast majority of cases the condition is temporary and mild, causing only transient discomfort. If patients develop persistent gastroesophageal reflux disease with frequent relapses, however, and it remains untreated, serious complications may develop over time. They can include the following:

Erosive esophagitis (severe inflammation in the esophagus)
Severe narrowing (stricture) of the esophagus
Barrett's esophagus
Problems in other areas, including the teeth, throat, and airways leading to the lungs

Older people are at higher risk for complications from persistent GERD. The following conditions also put individuals at risk for recurrent and serious GERD:

The esophagus is very inflamed.
Initial symptoms are severe.
Symptoms persist in spite of treatments that successfully heal the esophagus.
There are severe underlying muscular abnormalities.

Erosive esophagitis develops in chronic GERD patients when acid causes enough irritation and inflammation to produce extensive injuries in the esophagus. Some studies have suggested that overweight Caucasian males with GERD are at highest risk for this condition. In anyone, however, the longer and more severe the GERD condition, the higher the risk for erosive esophagitis.

Bleeding. In one study, bleeding occurred in more than 8% of patients with erosive esophagitis (severe inflammation of the esophagus), which is associated with GERD. In very severe cases, the patient may detect dark-colored, tarry stools (indicating the presence of blood) or may vomit blood, particularly if ulcers have developed in the esophagus. This is a sign of severe damage and requires immediate attention.

Sometimes long-term bleeding can result in iron-deficiency anemia and may even require emergency transfusions. This condition can occur without heartburn or other warning symptoms, or even obvious blood in the stools.

Barrett's Esophagus (BE) and Esophageal Cancer. In some cases, BE develops as an advanced stage of erosive esophagitis. BE results in abnormal cellular changes in the esophagus that, in turn, put a patient at risk for esophageal cancer. There are many issues involved with BE, however, including its prevalence and true severity, that are unresolved.

Of note, GERD itself poses no significant risk for esophageal cancer. One study reported an annual incidence of 6.5 cancer cases per 10,000 people with regular GERD symptoms.

If the esophagus becomes severely injured over time, narrowed regions called strictures can develop, which may impair swallowing (dysphagia). Food may even become blocked in some cases. Stretching procedures or surgery may be required to restore normal swallowing. Paradoxically, strictures may actually prevent other GERD symptoms by helping to keep acid from traveling up the esophagus.

Asthma. Asthma and GERD often occur together. Studies report that reflux disorder coincides with 32 - 80% of asthma cases. Some theories for the causal connection between GERD and asthma are as follows:

Acid leaking from the lower esophagus in GERD stimulates the vagus nerves, which run through the gastrointestinal tract. These stimulated nerves trigger the nearby airways in the lung to constrict, which causes asthma symptoms.
Acid back-up that reaches the mouth may be inhaled into the airways (aspirated). Here, the acid triggers a reaction in the airways that causes asthma symptoms.

There is some evidence that asthma causes GERD. In contrast, some evidence suggests that GERD causes asthma. Some clinical trials report that treating GERD in patients who also have asthma reduces symptoms of both conditions. Not all such patients report improved asthma symptoms with GERD treatments, and these treatments do not appear to have much effect on actual lung function. One study suggested that this approach works in asthmatic individuals who tended to be overweight and to have severe GERD in the lower part of the esophagus.

Other Respiratory and Airway Conditions. Current studies indicate an association between GERD and various upper respiratory problems that occur in the sinuses, ear and nasal passages, and airways of the lung. People with GERD appear to have an above-average risk for chronic bronchitis, chronic sinusitis, emphysema, pulmonary fibrosis (lung scarring), and recurrent pneumonia. If a person inhales fluid from the esophagus (aspirates) into the lungs, serious pneumonia can occur. It is not yet known whether treatment of GERD would also reduce the risk for these respiratory conditions.

Dental erosion (the loss of the tooth's enamel coating) is a very common problem among GERD patients, including children. It results from the acid backing up into the mouth and eroding the enamel.

An estimated 20 - 60% of patients with GERD have atypical symptoms in the throat (hoarseness, sore throat) without any significant heartburn. A failure to diagnose and treat GERD may lead to persistent throat conditions such as chronic laryngitis, hoarseness, difficulty in speaking, sore throat, cough, constant throat clearing, and granulomas (soft, pink bumps) on the vocal cords.

GERD commonly occurs with obstructive sleep apnea, a condition in which breathing stops temporarily but repeatedly during sleep. It is not clear which condition is responsible for the other, but GERD is particularly severe when both conditions occur together. One study reported that spasms in the vocal cords caused by acid reflux may block the flow of air and cause sleep apnea in adults. On the other hand, other research suggests that the disordered breathing in sleep apnea alters pressure in the chest area and causes GERD. Both conditions may also have risk factors in common, such as sleeping on the back. Studies suggest that in such patients GERD can be markedly improved with a continuous positive airway pressure (CPAP) device, which opens the airways and is the standard treatment for severe sleep apnea.

Barrett's Esophagus

Barrett's esophagus (BE) is a serious condition in which changes occur in the cells that line the lower esophagus and cause the cells to become abnormal and precancerous. Barrett's esophagus is categorized as either long-segment or short-segment disease:

Long-segment BE occurs when abnormal cells affect 3 cm or more of the esophagus. This condition occurs in about 3 - 7% of GERD patients. It is associated with a more severe condition.
Short-segment BE affects less than 3 cm of the esophagus and is found in about 10 - 17% of GERD patients.

About 10% of patients with symptomatic GERD have BE. In some cases, BE develops as an advanced stage of erosive esophagitis. Some studies suggest that individuals at highest risk for BE are obese white males over the age of 50 with persistent GERD who drink alcohol. However, a number of studies have reported no relationship between alcohol use or being male and overweight with BE. Such studies have also reported no higher risk in smokers or relatives of BE patients. Only the persistence of symptoms suggested a higher risk. Nevertheless, not all patients with BE have either esophagitis or symptoms of GERD.

The true prevalence of BE, in fact, is not entirely clear, since studies suggest that significantly more than half of people with BE have no GERD symptoms at all. BE, then, is likely to be much more prevalent and probably less harmful than is currently believed. (BE that occurs without symptoms can only be identified in clinical trials or in autopsies, so it is difficult to determine the true extent.) Some evidence suggests that the presence of specific immune factors may be involved in determining the development of BE.

The rate of esophageal cancer has been rising steadily at about 2% a year in white men. The American Cancer Society estimates that there will be 15,560 new cases of esophageal cancer and 13,940 deaths from the disease in 2007. Esophageal cancer is also very difficult to cure. The 5-year survival rate for all stages of esophageal cancer is 17% in white patients, and 12% in African-American patients. Most cases of esophageal cancer start with BE, with less than half of the cases developing with any symptoms. Of note, only a minority of BE patients develop cancer. Some evidence suggests that acid reflux may contribute to the development of cancer in BE. Researchers have speculated that exposure to extra acid in people with Barrett's esophagus produces more of an enzyme called NOX5-S, which may put stress on cells, leading to DNA damage.

Evidence suggests that asymptomatic BE is quite common in the general population, and if true, BE would pose far less of a threat than is now believed. (GERD itself poses no significant risk for esophageal cancer. One study reported an annual incidence of 6.5 cancer cases per 10,000 people with regular GERD symptoms.)

Barrett's esophagus is diagnosed using endoscopy, a procedure that involves inserting a tube down the throat so that the physician can view the esophagus.

Monitoring High-Risk GERD Patients. Some experts recommend a one-time screening test for BE using endoscopy in high-risk patients (such as Caucasian overweight men) with chronic GERD.

Monitoring Patients with Barrett's Esophagus for Cancer. Periodic endoscopy is recommended for detecting early cancer in patients who have been diagnosed with Barrett's esophagus. In an important 2002 study, 5-year survival was 73% in BE patients whose cancer was detected with endoscopy screening and was 0% in patients who were not regularly screened.

To date, no treatments can reverse the cellular damage done after Barrett's esophagus has developed, although some procedures are showing promise.

Medications. Some evidence suggests that a combination of proton-pump inhibitors to suppress acid, coupled with anti-inflammatory COX-2 inhibitors, might be a promising approach.

Proton-Pump Inhibitors. Some experts recommend very aggressive treatments to reduce acid reflux using high-dose proton-pump inhibitors. The standard agent has been omeprazole (Prilosec). Newer oral PPIs include lansoprazole (Prevacid), esomeprazole (Nexium), and rabeprazole (Aciphex). Even when drugs relieve symptoms completely, the condition usually recurs within months after the drugs are discontinued. In chronic cases, drugs may need to be taken throughout a patient's life. These agents provide no protection against Barrett's esophagus. Still, there is some evidence that acid reflux may contribute to the development of cancer in BE, although it is not yet known if acid blockers have any protective effects against cancer in these patients.
COX-2 (cyclooxygenase-2) inhibitors reduce inflammation and pain, as do well-known agents such as aspirin and ibuprofen, but COX-2 inhibitors may pose less of a risk for peptic ulcers and bleeding. Some early evidence suggests they may be protective against cancerous changes in patients with Barrett's esophagus. However, Vioxx and Bextra have been withdrawn from the market due to their association with an increased risk of heart attack. Celebrex remains available, but must be used with caution, especially by patients with cardiovascular risk factors. Also, research is mixed on the benefits of NSAIDs for esophageal cancer. Some studies have found that they may decrease the risk of developing or dying from esophageal cancer. However, a 2007 study indicated that a small dose of Celebrex did not prevent the progression of cancer in Barrett's esophagus patients.

Peptic ulcers may lead to emergency situations. Severe abdominal pain with or without evidence of bleeding may indicate a perforation of the ulcer through the stomach or duodenum. Vomiting of a substance that resembles coffee grounds, or the presence of black tarry stools, may indicate serious bleeding.

Procedures to Remove the Mucous Lining. Various techniques or devices have been developed to remove (ablate) the mucous lining of the esophagus. The intention is to remove early cancerous or precancerous tissue and allow regrowth of new and hopefully healthy tissue in the esophagus. Such techniques include photodynamic therapy (PDT) or laser, electrical, or heat probes.

Studies on the use of these ablation techniques combined with aggressive use of proton-pump inhibitors or surgical treatments are very encouraging. Some of these techniques may eventually even offer potential cures. At this time, they can be very effective in removing harmful tissue, although the benefits do not last in all patients. In one study, an average of 5.6 years after anti-GERD surgery and laser treatment, only a third of patients showed no evidence of renewed precancerous cell growth. These procedures also have complications, such as possible problems swallowing, that patients should discuss with their physician.

Esophagectomy. Esophagectomy is the surgical removal of all or part of the esophagus. Patients with Barrett's esophagus, who are otherwise healthy, are candidates for this procedure if endoscopy shows developing cancer. After esophageal removal, in total or in part, a new conduit for foods and fluids must be established to replace the absent esophagus. Alternatives include the stomach, colon, and part of the small intestine called the jejunum. The stomach is the optimal choice.

Diagnosis

If a patient suffers from chronic heartburn, chances are good the patient also has GERD. (Occasional heartburn does not necessarily indicate the presence of GERD.) The following is the general diagnostic approach:

A physician can usually make an easy diagnosis of GERD if the patient finds relief from persistent heartburn and acid regurgitation after taking antacids for short periods.
If the diagnosis is uncertain but the physician still suspects GERD, a drug trial using a proton-pump inhibitor medication, such as omeprazole (Prilosec) identifies 80 - 90% of people with the conditions. This class of medication blocks stomach acid secretion.

Laboratory or more invasive tests, including endoscopy, may be required if the diagnosis is still uncertain, if atypical symptoms are present, if Barrett's esophagus is suspected, or if complications, such as signs of bleeding or difficulty in swallowing, are present. Some of these tests are described below.

A barium swallow radiograph (x-ray) is useful for identifying structural abnormalities and erosive esophagitis (severe inflammation). When taking this test, the patient drinks a solution containing barium, then x-rays are taken. This test can show stricture, active ulcer craters, hiatal hernia, erosion, or other abnormalities. The test cannot reveal mild irritation.

Upper endoscopy, also called esophagogastroduodenoscopy or panendoscopy, is more accurate than a barium-swallow radiograph. It is also more invasive and expensive. It is widely used in GERD, including for identifying and grading severe esophagitis, for periodic monitoring of patients with Barrett's esophagus or for screening people at high risk, or when other complications are suspected. It is also now employed as part of various surgical techniques.

Endoscopy to Diagnose GERD. Endoscopy may be performed either in a hospital or in a doctor's office:

First, the patient should eat nothing for at least 6 hours before the procedure.
The doctor administers a local anesthetic using an oral spray and an intravenous sedative to suppress the gag reflex and to relax the patient.
Next, the physician places an endoscope (a thin flexible plastic tube containing a tiny camera) into the patient's mouth and down the esophagus. The procedure does not interfere with breathing. It may be slightly uncomfortable for some patients; others are able to sleep through it.
Once the endoscope is in place, the tiny camera allows the physician to see the surface of the esophagus and to search for abnormalities, including hiatal hernia and damage to the mucous lining.
The physician performs a biopsy (the removal and microscopic examination of small tissue sections). The biopsy may detect tissue injury indicative of GERD. It may also be used to detect cancer or other conditions, such as yeast (Candida albicans) or viral infections (e.g., herpes simplex and cytomegalovirus). Such infections are more likely to occur in people with impaired immune systems.
Complications from the procedure are uncommon. If they occur, complications are almost always mild and typically include minor bleeding from the biopsy site or irritation where medications were injected.

If a patient has moderate-to-severe GERD symptoms and the procedure reveals injury in the esophagus, usually no further tests are needed to confirm a diagnosis. The test is not foolproof, however. A visual view misses about half of esophageal abnormalities.

Capsule Endoscopy. Capsule endoscopy was first approved for use in 2001. A new version of this pill-sized camera, renamed PillCam, was approved by the FDA in 2004. PillCam reduces the imaging time previously required by the original capsule endoscopy technique. The PillCam capsule contains tiny video cameras on both ends. After the patient swallows the capsule, a series of 2600 color pictures are transmitted to a recording device where they can be downloaded and interpreted by a doctor. A newer version of the PillCam takes 14 frames per second as opposed to the 4 frames per second of the original device. The newer PillCam is superior in visualizing the entire esophagus and in identifying GERD. The entire procedure takes 20 minutes. The capsule is naturally passed through the digestive system within 24 hours. Capsule endoscopy may provide a more attractive and less invasive alternative for patients than traditional endoscopy. However, while capsule endoscopy is useful as a screening device for diagnosing esophageal conditions such as GERD and Barrett's esophagus, traditional endoscopy is still required for gathering tissue samples or removing polyps.

The (ambulatory) pH monitor examination may be employed to determine acid back-up. It is useful when endoscopy has not detected damage to the mucous lining in the esophagus, but GERD symptoms are present. pH monitoring may be used when patients have not found relief from medicine or surgery. The traditional trans-nasal catheter diagnostic procedure involved inserting a tubular probe through the nose and down to the esophagus. The tube was left in place for 24 hours. This test was irritating to the throat, and uncomfortable and awkward for most patients.

A new method, known as the Bravo pH test, uses a small capsule-sized data transmitter that is temporarily attached to the wall of the esophagus during endoscopy. The capsule records pH levels and transmits these data to a pager-sized receiver worn by the patient. Patients can continue their usual diet and activity schedule during the 24 - 48-hour monitoring period. After a few days, the capsule detaches from the esophagus, passes through the digestive tract, and is eliminated through a bowel movement.

Manometry is a technique that measures muscular pressure. It employs a tube containing various openings, which is placed through the esophagus. As the muscular action of the esophagus exerts pressure on the tube in various locations, a computer connected to the tube measures it. It is useful for the following situations:

To determine if a GERD patient would benefit from surgery by measuring pressure exerted by the lower esophageal sphincter muscles (LES).
To detect impaired stomach motility (an inability of the muscles to contract normally), which cannot be surgically corrected with standard procedures.
To determine if impaired peristalsis or other motor abnormalities are causing chest pain in people with GERD who have these symptoms.

Blood and Stool Tests. Stool tests may show traces of blood that are not visible. Blood tests for anemia should be performed if bleeding is suspected.

Bernstein Test. For patients with chest pain in which the diagnosis is uncertain, a procedure called the Bernstein test may be useful, although it is rarely used. A tube is inserted through the patient's nasal passage. Then solutions of hydrochloric acid and saline are administered separately into the esophagus. If the acid infusion causes symptoms and the saline solution does not, then a diagnosis of GERD is established.

Because many illnesses share similar symptoms, careful analysis and consideration of the patient's history is key to an accurate diagnosis. The following are only a few of the conditions that could accompany or resemble GERD.

Dyspepsia. The most common disorder confused with GERD is dyspepsia, which is defined as pain or discomfort in the upper abdomen without heartburn. Specific symptoms may include a feeling of fullness (particularly early in the meal), bloating, and nausea. Dyspepsia can be a symptom of GERD, but does not always occur with GERD. The drug metoclopramide (Reglan) helps stomach emptying and may be helpful for this condition.

Angina and Chest Pain. About 600,000 people come to emergency rooms each year with chest pains. More than 100,000 of these people are believed to actually have GERD. Chest pain from both GERD and from severe angina can occur after a heavy meal. In general, a heart problem is probably not responsible for the pain if it is worse at night and does not occur after exercise. It should be noted that the two conditions often coexist. In fact, there is some theory that in patients with coronary artery disease, acid reflux may actually trigger angina. In such cases, experts believe that acid in the esophagus may activate nerves that temporarily impair blood flow to the heart.

Asthma. Because asthma and GERD commonly occur together, physicians must be sure that each disorder is diagnosed accurately.

Other Diseases. Many gastrointestinal diseases (e.g., inflammatory bowel disease, ulcers, intestinal cancers) can cause GERD, but they are often easily identified, since they have other symptoms and affect other areas of the intestinal tract.

Treatment

Acid suppression continues to be the mainstay for treating GERD. The aim of drug therapy is to reduce the amount of acid present and improve any abnormalities in muscle function of the lower esophageal sphincter (LES), the esophagus, or the stomach.

Most cases of gastroesophageal reflux are mild and can be managed with lifestyle changes and over-the-counter medications and antacids.

Patients with moderate-to-severe symptoms that do not respond to lifestyle measures, or who are diagnosed at a late stage may be started on more or less potent agents depending on their complications at diagnosis. Experts argue, however, about the best way to initiate drug treatment for GERD in most of these patients. The two major treatment options are known as the step-up and step-down approaches:

Step-up. With a step-up drug approach the patient first tries an H2 blocker drug, which is available over the counter. These drugs include famotidine (Pepcid AC), cimetidine (Tagamet HB), ranitidine (Zantac 75), and nizatidine (Axid AR). If the condition fails to improve, therapy is "stepped up" to the more powerful proton-pump inhibitors, usually omeprazole (Prilosec).
Step-down. A step-down approach first uses a more potent agent, most often a proton-pump inhibitor (PPI), such as omeprazole (Prilosec). When patients have been symptom-free for 2 months or longer, they are then "stepped down" to a half-dose. If symptoms do not recur, the drug is withdrawn. If symptoms recur, the patient is put on high-dose H2 blockers. In one study using this step-down approach, 58% of patients remained symptom-free after a year, with 27% not using any medications at all. Some physicians argue that the step-down approach should be used for most patients with moderate-to-severe GERD.

Recent guidelines indicate that PPIs should be the first drug treatment, and that these drugs should be given once a day for approximately 8 weeks. Even when symptoms are completely relieved by medication, they usually return within a few months after drug treatment has stopped. Long-term maintenance may be necessary.

If neither approach relieves symptoms, the physician should look for other conditions. Endoscopy and other tests might be used to confirm GERD and rule out other disorders. In some cases, bile, not acid, may be responsible for symptoms, so that acid-reducing or blocking agents would not be helpful. (Bile is a fluid that is present in the small intestine and gallbladder.)

Surgery may be indicated under certain circumstances:

If lifestyle changes and drug treatments have failed
In patients with other medical complications
In younger people with chronic GERD, who face a lifetime of expense and inconvenience with maintenance drug treatment

Some physicians are recommending surgery as the treatment of choice for many more patients with chronic GERD, particularly since minimally invasive surgical procedures are becoming more widely available, and since only surgery improves regurgitation. Furthermore, persistent GERD appears to be much more serious than was previously believed, and the long-term safety of acid suppression using medication is still uncertain.

Nevertheless, anti-GERD procedures have many complications and high failure rates (ranging from 30% at 5 years to 63% at 10 years) and, as with medications, current surgical procedures cannot cure GERD. About 15% of patients still require anti-GERD medications after surgery. Furthermore, about 40% of surgical patients are at risk for new symptoms after surgery (e.g., gas, bloating, trouble swallowing), with most occurring more than a year after surgery. Finally, evidence -- notably an important 2002 Swedish study -- now strongly suggests that the procedure does not reduce the risk for esophageal cancer in high-risk patients, such as those with Barrett's esophagus. New procedures may improve current results, but at this time patients should consider surgical options very carefully with both a surgeon and their primary doctor.

Prevention

People with heartburn should first try lifestyle and dietary changes. In one study, 44% of patients who experienced symptoms of gastroesophageal reflux disease (GERD) reported improvement after changing their diet. Some suggestions are the following:

Avoid or reduce consumption of foods and beverages that contain caffeine, chocolate, peppermint, spearmint, and alcohol. Both caffeinated and decaffeinated coffees increase acid secretion.
Avoid all carbonated drinks, because they increase the risk for GERD.
Although physicians often advise patients with GERD to cut down on fatty foods, many studies have found no evidence that a low-fat or high-fat meal makes any difference in symptom exacerbation. One small study, however, found that the frequency of GERD symptoms increased with a high-fat compared to a low-fat diet. Better studies are needed to confirm this. In any case, as a rule, it is always wise to avoid saturated fats (which are from animal products), and cut down on all fats if one is overweight.
Choose low-fat or skim dairy products, poultry, or fish. Increasing protein may help strengthen muscles in the muscle valve.
Consume whole-grain products rich in selenium, which may have some protective role against dangerous cell changes in Barrett's esophagus.
Eat a diet rich in fruits and vegetables, although it's best to avoid acidic vegetables and fruits (e.g., oranges, lemons, grapefruit, pineapple, tomatoes).

Patients who have trouble swallowing should avoid tough meats, vegetables with skins, doughy bread, and pasta.

Nearly three-quarters of patients with frequent GERD symptoms have them at night. Patients with nighttime GERD also tend to experience severe pain. It is very important to take preventive measures before going to sleep. Some suggestions for preventing acid reflux at night are as follows:

After meals, take a walk or, at the very least, remain upright.
Avoid bedtime snacks. In general, avoid eating for at least 2 hours prior to bedtime.
When going to bed, try lying on the left side rather than on the right. The stomach is located higher than the esophagus when a person sleeps on the right side, which can put pressure on the lower esophageal sphincter (LES), increasing the risk for fluid back-up.
Sleep in a tilted position to help keep acid in the stomach at night. To do this, raise the bed at an angle using 4- to 6-inch blocks at the head of the bed and use a wedge-support to elevate the top half of the body. (Extra pillows that only raise the head actually increase the risk for reflux.)

A reflux board is prescribed for use in children who have gastroesophageal reflux. A board tilts the child upward while he is lying in bed to prevent the stomach contents from going back into the esophagus and mouth, and possibly into the lungs.

Quitting smoking is essential.
People who are overweight should try to reduce food intake and exercise to lose weight.
People with GERD should avoid tight clothing, particularly around the abdomen.
If possible, GERD patients should avoid nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen (Motrin, Advil), or naproxen (Aleve), among others. Tylenol (acetaminophen) is a good alternative pain reliever.

Although gum chewing is commonly believed to increase the risk for GERD symptoms, one study reported it might be helpful. Because saliva helps neutralize acid and contains a number of other factors that protect the esophagus, chewing gum 30 minutes after a meal has been found to help relieve heartburn and even protect against damage caused by GERD. Chewing on anything at all can help since it stimulates saliva production.

Medications

Antacids neutralize digestive acids and are the primary drugs for mild symptoms. They are best used alone for relief of occasional and unpredictable episodes of heartburn. They all work by neutralizing the acid in the stomach. They may also stimulate the defensive systems in the stomach by increasing bicarbonate and mucous secretion. Many antacids are available without a prescription and are the first drugs recommended to relieve heartburn and mild symptoms. Despite the many brands, they all rely on various combinations of three basic ingredients: magnesium, calcium, or aluminum.

Magnesium. Magnesium salts are available in the form of magnesium carbonate, magnesium trisilicate, and most commonly, magnesium hydroxide (Milk of Magnesia). The major side effect of magnesium salts is diarrhea. Magnesium salts offered in combination products with aluminum (Mylanta and Maalox) balance the side effects of diarrhea and constipation.

Calcium. Calcium carbonate (Tums, Titralac, and Alka-2) is a potent and rapid acting antacid that can cause constipation. These antacids are actually sources of calcium. There have been rare cases of hypercalcemia (elevated levels of calcium in the blood) in people taking calcium carbonate for long periods of time. This can lead to kidney failure and is very dangerous. None of the other antacids has this side effect.

Aluminum. Aluminum salts (Amphogel, Alternagel) are also available. The most common side effect of antacids containing aluminum salts is constipation. People who take large amounts of antacids that contain aluminum may also be at risk for calcium loss, which can lead to osteoporosis.

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 can reduce and even reverse loss of bone density.

It is generally believed that liquid antacids work faster and are more potent than tablets, although evidence suggests that they all work equally well. Antacids can interact with a number of drugs in the intestines by reducing their absorption. These drugs include tetracycline, ciprofloxacin (Cipro), propranolol (Inderal), captopril (Capoten), and H2 blockers. Interactions can be avoided by taking the drugs 1 hour before or 3 hours after taking the antacid. Long-term use of nearly any antacid increases the risk for kidney stones.

H2 blockers impede acid production by blocking or antagonizing the actions of histamine, a chemical found in the body that encourages acid secretion in the stomach. They are available over the counter and provide symptom relief in about half of GERD patients. It takes 30 - 90 minutes for them to work, but the benefits last for hours. The drugs are usually taken at bedtime. Some people may need to take them twice a day.

H2 blockers inhibit acid secretion for 6 - 24 hours and are very useful for people who need persistent acid suppression. They may also prevent heartburn episodes in people who are able to predict its occurrence. In some studies, H2 blockers improved asthmatic symptoms in people who have both conditions. A 2001 study suggested, however, that they rarely provide complete symptom relief for chronic heartburn and dyspepsia and they have done little to reduce office visits to physicians for GERD.

Brands. Four H2 blockers are currently available in the U.S.:

Famotidine (Pepcid AC). Famotidine (Pepcid AC, Pepcid Oral) is the most potent H2 blocker. The most common side effect of famotidine is headache, which occurs in 4.7% of people who take it. Famotidine is virtually free of drug interactions, but the FDA has issued a warning on its use in patients with kidney problems.
Cimetidine (Tagamet, Tagamet HB). Cimetidine (Tagamet) is the oldest H2 blocker. It has few side effects; approximately 1% of people taking it will experience mild temporary diarrhea, dizziness, rash, or headache. Cimetidine interacts with a number of commonly used medications, such as phenytoin, theophylline, and warfarin. Long-term use of excessive doses (more than 3 grams a day) may cause impotence or breast enlargement in men. These problems resolve after the drug is discontinued.
Ranitidine (Zantac, Zantac 75, Zantac Efferdose, Zantac injection, Zantac Syrup). Ranitidine (Zantac) interacts with very few drugs. In a recent study, ranitidine provided more pain relief and healed ulcers more quickly than cimetidine in people less than 60 years old, but there was no difference in older patients. A common side effect associated with ranitidine is headache, which occurs in about 3% of the people who take it.
Nizatidine Capsules (Axid AR, Axid Capsules, Nizatidine Capsules). Nizatidine (Axid) is nearly free of side effects and drug interactions. A controlled-release form is proving to help alleviate nighttime GERD symptoms.

Famotidine is excreted primarily by the kidney. This can pose a danger to people with kidney problems. Physicians are now being advised by the U.S. Food and Drug Administration (FDA) and Health Canada to reduce the dose and increase the time between doses in patients with kidney failure. Use of the drug in those with impaired kidney function can affect the central nervous system and may result in anxiety, depression, insomnia or drowsiness, and mental disturbances.

Drug Combinations.

Over-the-counter antacids and H2 blockers: This combination may be the best approach for many people who experience heartburn after eating. Both classes of drugs are effective in relieving GERD, but have different timing. Antacids work within a few minutes but are short-acting, while H2 blockers take longer but have long-lasting benefits. Pepcid AC combined with an antacid (calcium carbonate and magnesium) is now available as Pepcid Complete.
Proton-pump inhibitors and H2 blockers: Physicians sometimes recommend a nighttime dose of an H2 blocker for people who are taking proton-pump inhibitors twice a day. This is based on the belief that adding the H2 blocker will prevent a rise in acid reflux at night. An important 2002 study, however, reported no additional benefits from the nighttime H2 blocker. Some experts recommended an H2 blocker in patients who are on proton-pump inhibitors only to prevent breakthrough symptoms, such as before a heavy meal.

Long Term Complications. In most cases, these agents have good safety profiles and few side effects. H2 blockers can interact with other drugs, although some less so than others. In all cases, however, the physician should be made aware of any other drugs a patient is taking. More research is needed. Anyone with kidney problems should use famotidine only under the direction of a physician.

Concerns and Limitations. Some experts are concerned that the use of acid-blocking drugs in people with peptic ulcers may mask ulcer symptoms and increase the risk for serious complications.

These agents provide no protection against Barrett's esophagus. In fact, of concern are reports that long-term acid suppression with these drugs may cause cancerous changes in the stomach in patients who are infected with H. pylori. Research on this question is still ongoing.

Proton-pump inhibitors (PPIs) suppress the production of stomach acid and work by inhibiting the molecule in the stomach glands that is responsible for acid secretion, which is called the gastric acid pump. According to recent guidelines, initial drug treatment should be with PPIs once daily for about 8 weeks.

The standard agent has been omeprazole (Prilosec), which is now available over the counter without a prescription. Newer prescription oral PPIs include esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprazole (Protonix).

Studies report significant relief from PPIs in most patients with heartburn. PPIs are effective for healing erosive esophagitis and may also be helpful in patients with chronic laryngitis that is suspected to be caused by GERD. The newer agents provide quicker symptom relief compared to omeprazole. However, a comparison study suggested that, to date, esomeprazole (Nexium) is the only newer oral PPI to show any significant advantage over omeprazole (Prilosec). All PPIs are more effective than the H2 blockers.

In addition to relieving most common symptoms, including heartburn, proton-pump inhibitors also have the following advantages:

They are effective in relieving chest pain and laryngitis caused by GERD.
They may also reduce acid reflux that typically occurs during strenuous exercise.

Patients with impaired esophageal muscular action are still likely to experience acid breakthrough and reflux at night. Proton-pump inhibitors also may have little or no effect on regurgitation or asthmatic symptoms. Some experts believe, however, that they should be the first drugs of choice, even for patients with milder symptoms. At this time, these drugs are recommended for the following patients:

Those with moderate symptoms that do not respond to H2 blockers
Those with severe symptoms
Those who have respiratory complications
Those who have persistent nausea
Those who have esophageal injury

These agents have no affect against non-acid reflux, such as bile back-up.

Adverse Effects. Proton-pump inhibitors may pose the following concerns:

Side effects are uncommon but may include headache, diarrhea, constipation, nausea, and itching.
Proton-pump inhibitors should be avoided by pregnant women and nursing mothers, although recent studies suggest that they do not pose an increased risk of birth defects.
They may interact with certain drugs, such as anti-seizure agents (such as phenytoin), anti-anxiety drugs (such as diazepam), and blood thinners (such as warfarin).
Long-term use of high-dose PPIs may produce vitamin B12 deficiencies, but studies are needed to confirm whether there is any significant risk. High-dose PPIs used over the long-term also may increase the risk of hip fracture in older adults, according to one study.

There is some evidence that acid reflux may contribute to the higher risk of cancer in BE, but it is not yet confirmed whether acid-blockers have any protective effects against cancer in these patients. In fact, the long-term use of proton-pump inhibitors by people with H. pylori may, in theory at least, reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach). This condition is a risk factor for stomach cancer. To compound concerns, long-term use of PPIs may mask symptoms of stomach cancer and so delay a diagnosis. To date, however, there have been no reports of an increased risk of stomach cancer with the long-term use of these drugs.

Sucralfate (Carafate) protects the mucous lining in the gastrointestinal tract. It seems to work by sticking to an ulcer crater and protecting it from damage due to stomach acid and pepsin. It may be helpful for maintenance therapy in people with mild-to-moderate GERD. Other than constipation, which occurs in 2.2% of patients, the drug has few side effects. Sucralfate interacts with a wide variety of drugs, however, including warfarin, phenytoin, and tetracycline.

Most drugs used for GERD have no effect on non-acid reflux, such as back-up of bile. Baclofen, known as a gamma-amino butyric acid agonist, is commonly used to reduce muscle spasms. Investigators are now showing that it can reduce both acid and non-acid reflux episodes (as much as 70% in one study) and increase LES pressure, an important factor for preventing back-up.

Surgery

The standard surgical treatment for GERD is fundoplication. The goal of this procedure is twofold:

To increase LES pressure and, therefore, prevent acid back-up (reflux)
To repair any present hiatal hernia

There are two primary approaches:

Open Nissen fundoplication (the more invasive technique)
Laparoscopic fundoplication

In general, the overall long-term benefits of these procedures are similar. Some studies report that more than 90% of patients are free of heartburn after the operation and satisfied with their choice, even after 5 years. Fundoplication relieves GERD-induced coughs and some other respiratory symptoms in up to 85% of patients. (Its effect on asthma associated with GERD, however, is unclear.) It may enhance stomach emptying and improve peristalsis in about half of patients. (It may actually cause abnormal peristalsis in about 14% of patients, although in such cases the problem does not appear to be very significant.)

Still, it has other significant limitations and postoperative problems. For example, the results of one 2003 survey suggested that 18% of surgical patients still required anti-GERD medications and 38% had new symptoms (e.g., gas, bloating, trouble swallowing), with most occurring more than a year after surgery. Other studies have reported similar results. Also, fundoplication does not cure GERD. Finally, evidence from a 2002 Swedish study strongly suggests that the procedure does not reduce the risk for esophageal cancer in high-risk patients, such as those with Barrett's esophagus.

Candidates. Fundoplication is recommended for patients whose condition includes one or more of the following:

Esophagitis (inflamed esophagus)
Symptoms that persist or are recurrent in spite of anti-reflux drug treatment
Strictures
Failure to gain or maintain weight (children)

Fundoplication has little benefit for patients with impaired stomach motility (an inability of the muscles to move spontaneously).

The Open Nissen Fundoplication Procedure. Until recently, most fundoplication procedures for GERD have been the 360° Nissen fundoplication. This is called an open procedure because it requires wide surgical incisions.

With this procedure, the physician wraps the upper part of the stomach (fundus) completely around the esophagus to form a collar-like structure.
The collar places pressure on the LES and prevents stomach fluids from backing up into the esophagus.
Open fundoplication requires a 6- to 10-day hospital stay.

Click the icon to see an illustrated series detailing gastroesophageal reflux surgery.

Laparoscopic Fundoplication. The standard invasive fundoplication procedure has been replaced in many cases by a less invasive fundoplication procedure that uses laparoscopy. In the operation:

Tiny incisions are made in the abdomen.
Small instruments and a tiny camera are inserted into tubes, through which the surgeon can view the region.
The surgeon creates a collar using the fundus, although the area is smaller to work with.

When performed by experienced surgeons, the procedure shows results that are equal to those of standard open fundoplication, but with faster recovery time.

Overall, laparoscopic fundoplication appears to be safe and effective in people of all ages, even babies. Laparoscopy is more difficult to perform in certain patients, including those who are obese, who have a short esophagus, or who have a history of previous surgery in the upper abdominal area. It may also be less successful in relieving atypical symptoms of GERD, including cough, abnormal chest pain, and choking. In about 8% of laparoscopies, it is necessary to convert to open surgery during the procedure because of unforeseen complications.

Other Variations. There are now a number of variants of fundoplication procedures. Examples include the following:

Toupet fundoplication employs only a partial wrap, as does a Thal fundoplication. Partial fundoplication procedures may be more effective in patients with poor or no esophageal motility (spontaneous muscle contraction). Those with normal motility may do better with the full-circle wrap.
Others use a very short and "floppy" Nissen full wrap.

Many surgeons report that such limited fundoplications result in earlier feeding and discharge from the hospital and a lower incidence of complications (trouble swallowing, gas bloating, gagging) than the full Nissan fundoplication. A British study, however, reported no significant differences in swallowing problems.

Postoperative Problems and Complications after Fundoplication. Postoperative problems can include a delay in intestinal functioning causing bloating, gagging, and vomiting. These side effects usually resolve in a few weeks. A 2003 study suggested, however, that 38% of patients develop such symptoms, and most occur more than a year after the procedures. If symptoms persist or if they start weeks or months after surgery, particularly if vomiting is present, then surgical complications are likely. Complications include the following:

An excessively wrapped fundus. This is fairly common and can cause difficulty swallowing (dysphagia), as well as gagging, gas, bloating, or an inability to burp. (A follow-up procedure that dilates the esophagus using an inflated balloon may help correct dysphagia, although it cannot treat other symptoms.)
Bowel obstruction
Wound infection
Injury to nearby organs
Respiratory complications, such as a collapsed lung. These are uncommon, particularly with laparoscopic fundoplication.
Muscle spasms after swallowing food. This can cause intense pain, and patients may require a liquid diet, sometimes for weeks. This is a rare complication in most patients, but it can be very high in children with neurologic abnormalities. Such children are already at very high risk for GERD.

Reasons for Treatment Failure. Long-term failure rates after fundoplication are 30% after 5 years and 63% after 10 years. Hiatal herniation is the most common reason for surgical failure and the need for a repeat fundoplication. Other common reasons for reoperation include breakdown, slippage, and excessive tightness of the wrap. Surgeon experience can lessen complication risks. Some studies have reported that repeat operations after open procedures occur in 9 - 30% of cases and 13% after laparoscopy. (Repeat surgery usually has good results.)

A number of treatments that make use of endoscopy are being used or investigated for increasing LES pressure and preventing reflux, as well as for treating severe GERD and its complications.

Transoral Flexible Endoscopic Suturing. Transoral flexible endoscopic suturing (sometimes referred to as Bard's procedure) uses a tiny device at the end of the endoscope that acts like a miniature sewing machine. It places stitches in two locations near the LES, which are then tied to tighten the valve and increase pressure. There is no incision and no need for general anesthesia.

Radiofrequency. Radiofrequency energy generated from the tip of a needle (sometimes called the Stretta procedure) heats and destroys tissue in the problem spots in the LES. Either the resulting scar tissue strengthens the muscle, or the heat kills the nerves that caused the malfunction. Patients may experience some chest or stomach pain afterwards. Few serious side effects have been reported, although there have been reports of perforation, hemorrhage, and even death. A recent study reported that 81% of patients remained symptom-free for up to 3 years following the Stretta procedure.

Implants. In 2003, the FDA approved the Enteryx procedure as a treatment option for people who have persistent symptoms of GERD and who regularly take and respond to PPIs. In 2005, however, the manufacturer of Enteryx (Boston Scientific), voluntarily removed Enteryx from clinical use due to problems related to the difficult injection technique.

Techniques to Stop Bleeding. Endoscopic ablation treatment of bleeding involves using a probe passed through the endoscopic tube, which applies electricity or heat to coagulate blood and stop the bleeding.

Dilation Procedures. Strictures (abnormally narrowed regions) may need to be dilated (opened) with endoscopy. Dilation may be performed by inflating a balloon in the passageway. About 30% of patients who need this procedure require a series of dilation treatments over a long duration in order to fully open the passageway. Long-term use of proton-pump inhibitors may reduce the duration of treatments.

One study also suggested that dilation may help correct swallowing problems that can occur after fundoplication. In the study dilation improved dysphagia in 67% of the surgical patients who had experienced it.

A recent advance is the development of small-caliber upper endoscopy, which does not require sedation and can be performed in the physician's office.

Resources

http://digestive.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www.asge.org -- American Society for Gastrointestinal Endoscopy
www.ssat.com -- Society for Surgery of the Alimentary Tract
www.naspgn.org -- North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
www.reflux.org -- Pediatric/Adolescent Gastroesophageal Reflux Association
www.iffgd.org -- International Foundation for Functional Gastrointestinal Disorders

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Rudolph CD, Mazur LJ, Liptak GS, Baker RD, Boyle JT, Colletti RB, et al. Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr. 2001;32 Suppl 2: S1-S31.

Review Date:
5/22/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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adam.com

Birth control options for women

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

In This Report

Highlights

Introduction

Oral Contraception

Implant Contraception

Injected Contraception

Intrauterine Devices (IUDs)...

Spermicidal and Barrier Con...

Natural Family Planning Met...

Emergency Contraception

Female Sterilization

Resources

References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

First "No-Period" Birth Control Pill Approved

In May 2007, the Food and Drug Administration approved Lybrel, the first birth control pill that completely eliminates monthly menstrual periods. Lybrel contains low doses of the estrogen estradiol and the progestin levonorgestrol. The active pills are taken 365 days a year with no inactive pill breaks. In clinical trials, 59% of women who took Lybrel completely stopped having menstrual periods by the end of the first year. Some women, however, continued to experience occasional unscheduled bleeding or spotting during the first 3 - 6 months of use.

Third-Generation Progestins Controversy

In February 2007, the consumer advocacy organization Public Citizen petitioned the Food and Drug Administration to ban the use of desogestrel in oral contraceptives. According to some studies, desogestrel has nearly double the risk for blood clots compared to older, second-generation progestins like levonorgestrel. (However, other studies have not found an increased risk.) Desogestrel is contained in birth control pills such as Mircette.

Oral Contraceptives and Heart Attack Risks

Low-dose oral contraceptives do not increase the risk of heart attack for women in their 30s and 40s, indicates a 2007 study in Fertility and Sterility.

Oral Contraceptives and Cancer Risks

Combination oral contraceptives may reduce the risk for uterine, ovarian, and colorectal cancer, but women who use them for more than 8 years have an increased risk for cervical, breast, and central nervous system cancers, according to a 2007 study in the British Medical Journal.

Birth Control Patch and Blood Clot Risk

Women who use the birth control patch (Ortho Evra) have double the risk for blood clots as women who use oral contraceptives, suggests a 2007 study in Obstetrics & Gynecology. Other studies have reported few differences in risks between the two types of contraceptives. Some experts are concerned that prolonged estrogen exposure with the birth control patch (and ring) increases the risks for blood clots.

Introduction

Contraceptives are devices or methods for preventing pregnancy, either by preventing the fertilization of the female egg by the male sperm or by preventing implantation of the fertilized egg. Contraceptives are not modern inventions. The first prescription for a contraceptive device described a tampon barrier device and was written on papyrus in 1550 BC.

Choosing the appropriate contraceptive varies from individual to individual. Contraceptive options include:

Hormonal contraceptives (oral contraceptives, skin patch, vaginal ring, implant, injection)

Intrauterine devices (IUDs), which contain either a hormone or copper

Barrier devices with or without spermicides (diaphragm, cervical cap, sponge, condom)

Natural family planning methods (basal body temperature, cervical mucus, symptothermal)

Female sterilization (tubal ligation, Essure)

The pill works in several ways to prevent pregnancy. The pill suppresses ovulation so that an egg is not released from the ovaries, and changes the cervical mucus, causing it to become thicker and making it more difficult for sperm to swim into the womb. The pill also does not allow the lining of the womb to develop enough to receive and nurture a fertilized egg. This method of birth control offers no protection against sexually-transmitted diseases.

Contraceptive effectiveness is characterized by "typical use" and "perfect use":

Typical use refers to real-life conditions, in which mistakes (such as forgetting to take a birth control pill at the right time) sometimes happen.

Perfect use refers to contraceptives that are used correctly each time intercourse occurs.

Research has shown that the four most effective standard female contraceptives are surgical sterilization, the intrauterine device (IUD), implants, and injections. They all have an estimated failure rate of less than 1% during the first year of normal (typical) use. Vasectomy (male surgical sterilization) is the only male contraceptive that is equally effective. By comparison, the estimated failure rate of the male latex condom used without spermicide is 14% with typical use and 3% with perfect use. To put these rates into perspective, a sexually active woman of reproductive age who does not use contraception faces an 85% likelihood of becoming pregnant in the course of a year.

Birth control is a controversial subject. In recent years, there has been a growing movement in the United States to restrict a woman's access to contraceptives. In addition to the political battles over non-prescription access to emergency contraception (Plan B), 18 states (as of 2006) are considering legislation that would allow pharmacists to refuse to dispense medications due to moral or religious objections. There have been hundreds of reports of pharmacists refusing to fill birth control prescriptions. In response to this trend, several members of Congress introduced in April 2005 the Access to Legal Pharmaceuticals Act, which would override any state legislation. The bill would require that pharmacies fill birth control prescriptions and would protect women’s legal right to purchase such products.

Oral Contraception

Oral contraceptives are available only by prescription and come in either a combination of estrogen and progestin or progestin alone. Many brands of each form are available. Although both are equally effective with typical use, the combined pill is more effective with perfect use, and most women choose this form.

Some women, however, experience severe headaches or high blood pressure from the estrogen in the combined pill and must take the progestin-only pill. Not all combined pills or progestin-only pills are alike, and brands differ in the amount of estrogen or progestin they contain. Many oral contraceptive combined brands now use lower estrogen doses than previous brands and are proving to be safe and effective while providing a better quality of life than earlier oral contraceptives.

For all oral contraceptive users, a check-up at least once a year is essential. It is also important for women to have their blood pressure checked 3 months after beginning the pill. Former pill users who want to bear children usually regain fertility in 3 - 6 months, but they may regain it even sooner.

Estrogen (Estradiol)

Estrogen is the major female hormone and is responsible for female characteristics. The estrogen compound used in most oral contraceptives is estradiol and is always used with a progestin.

Effects on Reproduction. When used throughout a menstrual cycle with progesterone, estrogen suppresses the actions of other reproductive hormones (luteinizing hormone, or LH, and follicle stimulating hormone, or FSH) and prevents ovulation. Estrogen also changes the cellular structure of the lining of the uterus (the endometrium) and hinders implantation of a fertilized egg.

Side Effects of Estrogen. During the first 2 - 3 months of use of oral contraceptives, side effects from estrogen in the combined pill include:

Nausea and vomiting (can often be controlled by taking the pill during a meal or at bedtime)

Headaches (in women with a history of migraines, they may worsen)

Dizziness

Breast tenderness and enlargement

Progesterone (Progestin)

When used in contraception, progesterone is referred to by one of several names:

Progesterone is the name for the natural hormone.

Progestogen is a synthetic form.

Progestin is the term for any hormone, natural or synthetic, that causes progesterone effects; it is used as the general term in this report.

Progestins may be used alone or with estrogen in oral contraceptives. In addition, certain specific progestins are used in other kinds of contraceptives, such as etonogestrel in the Implanon implant and depo-medroxyprogesterone acetate in the injectable contraceptive Depo-Provera.

Progesterone can prevent pregnancy by itself in several ways:

Blocking luteinizing hormone (LH), one of the reproductive hormones important in ovulation

Maintaining a powerful barrier against the entry of sperm into the uterus by keeping the cervical mucus thick and sticky

Changing the lining of the uterus, making it more difficult for the fertilized egg to implant

Progestins used in contraceptives are referred to as:

Second generation (levonorgestrel, norethisterone).

Third generation (desogestrel, gestodene, norgestimate, drospirenone). The third-generation progestins tend to have fewer male-like side effects. Some studies suggest, however, they may pose a slightly higher risk for blood clots than the older progestins, although the risk is still small.

In 2007, the consumer advocacy group Public Citizen petitioned the Food and Drug Administration (FDA) to ban desogestrel-containing contraceptives, citing studies that indicated a nearly 2-fold increased risk for blood clots compared to second-generation oral contraceptives. Some experts, however, have criticized Public Citizen’s report for relying on older studies. The FDA has said that it will review Public Citizen’s petition.

Side Effects of Progestins. Side effects of progestin occur in both the combination oral contraceptives and any contraceptive that uses only progestin. Side effects may be less or more severe depending on the form and dosage of the contraceptive. Side effects may include:

Changes in uterine bleeding such as higher amounts during periods, spotting and bleeding between periods (called break-through bleeding), or absence of periods

Unexpected flow of breast milk (check with your doctor if this occurs to be sure other conditions are not causing it)

Abdominal pain or cramps

Diarrhea

Fatigue, unusual tiredness, weakness

Hot flashes

Decreased sex drive

Nausea

Trouble sleeping

Acne or skin rash (not all oral contraceptives have this side effect; low-dose oral contraceptives actually improve acne)

Depression, irritability, or other mood changes (although some oral contraceptives are helpful for women with premenstrual dysphoric syndrome)

Swelling in the face, ankles, or feet

Weight gain

Newer formulations of combination pills that use low-dose estrogen, and newer progestins, may reduce and even lower the risk of many of these side effects, including weight gain. Low-dose progestins used in non-oral contraceptives, such as the LNG-IUS IUD, also may not pose as high a risk for these side effects. If side effects continue or are severe, talk to your doctor. For many of those who do have side effects, their bodies eventually adjust.

Click the icon to see an image of a blood clot.

Oral contraceptives that contain both estrogen and progestin are the more common type of oral contraceptive. At least 10 million American women and 100 million women worldwide use combination oral contraceptives. When they were first marketed in the early 1960s, oral contraceptivescontained as much as 5 times the amount of estrogen and up to 10 times the amount of progestins currently used. After reports of severe complications (stroke, heart attack, and pulmonary embolisms) in young women, the hormone amounts were significantly reduced.

The estrogen compound used in most oral contraceptives is ethinyl estradiol (also called estradiol, or EE). Fifty micrograms of estradiol is considered high dose, 30 - 35 micrograms are considered average dose, and 20 micrograms or fewer is low-dose. (The high doses found in current oral contraceptives are still much lower than earlier forms of the pill.) Doctors recommend using the lowest possible progestin and estrogen doses. Estrogen doses should not exceed 50 micrograms, as higher doses increase the risk for complications.

Many different types of progestins are used in combination with estradiol. Some common types of progestin, and popular combination oral contraceptive brands, include:

Desogestrel is the progestrin used in Mircette. Approved in 1998, Mircette was the first oral contraceptive to offer a low estrogen dose and a new type of dosing regimen. Some studies suggest an increased risk for blood clots with desogesterel (see "Hormones Used in Contraceptives").

Drospirenone is used in Yasmin and Yaz. (Yaz contains a lower dose of estrogen than Yasmin.) Because drospirenone increases blood levels of potassium, women should not use Yasmin or Yaz if they have kidney, liver, or adrenal diseases.

Levonorgestrel is used in Seasonale and Seasonique, as well as many other oral and non-oral contraceptives.

Norethindrone is used in Loestrin and Loestrin 24 Fe (which adds iron supplements to the placebo pills).

Norgestrel is used in various generic and brand contraceptives.

Many types of medications and supplements (Tylenol, anti-seizure drugs, antibiotics, vitamin C, St. John's wort) can interact with progestin and reduce its effectiveness. Make sure your doctor is aware of any drugs, vitamins, and herbal supplements that you take.

Types of Regimens. Combination pills are sold in 21-day or 28-day packs:

Each pill in a 21-day pack contains estrogen and progestin. Women take 1 pill a day for 21 days, and then wait 7 days before starting a new 21-day pack.

28-day packs typically start with 21 hormone pills and add 7 placebo pills that do not contain hormones. After taking hormone pills for 21 days, a woman takes the inactive pills for 7 days. Some newer brands, like Yaz, use 24 days of active pills and 4 days of inactive pills. Mircette uses 21 days of low-dose progestin and estrogen, followed by 2 placebo days, and then 5 days of very low-dose estrogen. Loestrin 24 Fe uses 24 days of active pills followed by 4 days of iron-containing placebo pills.

Oral contraceptives may be taken in cycles that include pills of the same or different strengths. These are categorized as monophasic (one-phase), biphasic (two-phase), or triphasic (three-phase). Monophasic pills contain the same amount of hormones in each dose. Biphasic and triphasic pills contain different dosages of hormones within the pill packs. Because monophasic pills have a consistent amount of hormones, they tend to cause fewer hormone-fluctuating side effects than biphasic or triphasic pills. Several 2006 reviews found little difference in effectiveness between these three types of oral contraceptives. Many experts recommend monophasic pills as the best first-choice for birth control pills.

Taking the Pills. A woman usually takes the first pill either on the Sunday after her period starts or during the first 24 hours of her period. (The first pill can be started at any time during the menstrual cycle without affecting the bleeding patterns. Ovulation can occur that month, however.) The remaining pills are taken once a day, ideally at the same time of day, until the pack is used up. If a woman has a 21-day pack, she waits 7 days before starting a new pack. If she is on the 28-day pack, she takes the 7 inactive pills.

If you skip one or more pills, take the following precautions:

Missing the first pill in a new cycle. Take a tablet as soon as you remember and the next one at the usual time. Two tablets can be taken in one day. Use barrier contraception for 7 days after the missed dose. [See "Spermicidal and Barrier Contraception."]

Missing a pill 2 days in a row. Take 2 pills as soon as you remember and then 2 more the following day. Also use back-up barrier contraception until the next pill cycle.

Missing more than 2 days. Discard the pack, use a back-up birth control method, and begin a new cycle on the following Sunday, even if you have started bleeding.

Standard oral contraceptives come in a 28-pill pack that contains 21 active pills and 7 inactive pills. Newer "continuous-dosing" (also called "continuous-use") oral contraceptives aim to reduce -- or even eliminate -- monthly periods and thereby prevent the pain and discomfort that often accompanies menstruation. These oral contraceptives contain a combination of estradiol and the progesterone levonorgestrel, but use extending dosing of active pills.

Seasonale, the first continuous-dosing contraceptive, was approved in 2003. It contains 81 days of active pills followed by 7 days of inactive pills. Women who take Seasonale have on average a period every 3 months. Seasonique, a follow-up to Seasonale, was approved in 2006. As with Seasonale, it produces about 4 periods a year. With Seasonique, a women takes 84 days of levonorgestrol-estradiol pills followed by 7 days of pills that contain only low-dose estradiol.

In 2007, the Food and Drug Administration approved Lybrel, which supplies a daily low dose of levonorgestrol and estradiol with no inactive pills. Because Lybrel contains only active pills, which are taken 365 days a year, it completely eliminates monthly menstrual periods. In clinical trials, 59% of women who took Lybrel completely stopped menstrual periods by the end of the first year. Some women, however, experienced occasional unscheduled bleeding or spotting during the first 3 - 6 months. In clinical trials, women who took Lybrel experienced relief of premenstrual syndrome symptoms within a month of starting the drug.

Progestin-only pill brands include:

Levonorgestrel (Plan B)

Norethindrone (Micronor, Avgestin, Norlutin, Nor-QD). (This progestin is made from male hormones, so may cause more male side effects than others.)

Norgestrel (Ovrette)

Progestin-only pills, which only contain progestins, are always sold in 28-day packs and all the pills are active. (An exception is Plan B, which is emergency contraception.) Progestin-only pills must be taken at precisely the same time each day to maintain top effectiveness. If a woman deviates from her pill schedule by even 3 hours, she should call her doctor about using back-up contraception for the next 2 days. Progestin-only pill users will experience even lighter periods than those taking combination pills. Some may not have periods at all. These hormones should not be used by premenopausal women in their 40s, since they pose a higher risk for adverse effects in this group.

Oral contraceptives are the choice of most American women who use birth control, making them the most popular reversible contraceptives in the U.S. Oral contraceptives are among the most effective contraceptives. Failure rates are very low and are usually due to noncompliance. Some studies have suggested that women who are overweight may have a higher risk for failure. The risk for these women is also still very low, however.

Oral contraceptives also have the following advantages:

More sexual freedom. oral contraceptives do not interfere with intercourse, and in fact, many women report that sex is more pleasurable because they no longer have to worry about pregnancy.

Reduce menorrhagia (heavy bleeding) and, therefore, reduce the risk for anemia.

Reduction in dysmenorrhea (severe pain). High-dose oral contraceptives have been especially helpful, but they carry risks. Specific newer low-dose oral contraceptives that contain certain progestins, such as Yasmin (with drospirenone) and Mircette (with desogestrel), may reduce menstrual pain.

Possible reduction in premenstrual syndrome with specific oral contraceptives, notably Yaz (which was approved for treating premenstrual dysphoric disorder -- premenstrual depression -- in 2006.) Some oral contraceptives, however, are associated with worse emotional changes. Monophasic oral contraceptives may have a more beneficial effect on mood than triphasic oral contraceptives.

Reduction in endometriosis.

Endometriosis is the condition in which the tissue that normally lines the uterus (endometrium) grows on other areas of the body causing pain and irregular bleeding.

Possible protection against multiple sclerosis. Some studies have suggested that women who take oral contraceptives may be less likely to develop multiple sclerosis

Acne improvement with low-dose oral contraceptives. (Some low-dose contraceptives, such as Ortho Tri-Cyclen, have been specifically approved for acne reduction, although most low-dose oral contraceptives reduce testosterone levels and so help reduce acne.)

Possible protection against bone loss with low-dose oral contraceptives. The effect of contraceptives on bone density is unclear and may depend on the specific formulas and types of progestins used.

Common Side Effects. Estrogen and progesterone have different side effects. Women on the combined pill may experience different effects from those on the progestin-only pill. Symptoms of serious problems include severe abdominal pain, chest pain, unusual headaches, visual disturbances, or severe pain or swelling in the legs. In spite of some concerns, combination oral contraceptives do not generally cause weight gain.

[For specific side effects of estrogen and progestin, see "Hormones Used in Contraception."]

Serious Effects on Heart and Circulation. Combination birth control pills contain estrogen, which can increase the risk for stroke, heart attack, and blood clots in some women. The risk is highest for women who smoke or have a history of heart disease risk factors (such as high blood pressure) or cardiac events. Women who have certain metabolic disorders, such as polycystic ovary syndrome (PCOS), are also at higher risk for heart-related complications associated with these pills.

When birth control pills were first introduced, heart and circulatory risks were higher than they are now. Current brands of combination oral contraceptives contain much lower dosages of estrogen and are safer than those earlier pills. Some studies, however, including a 2005 review, suggest that even low-dose combination birth control pills have some cardiovascular risks. Other research, such as a 2007 study of older women ages 30 - 49, indicate that low-dose oral contraceptives do not increase heart attack risk.

All combination estrogen/progestin birth control products carry an increased risk for blood clots in the veins (venous thromboembolism). The risk is lower for oral contraceptives than for the birth control patch (Ortho Evra) or the ring (NuvaRing), which expose women to higher levels of estrogen than birth control pills. Women who smoke or who have other heart disease risk factors may want to consider using alternatives to combination oral contraceptives, such as progestin-only oral contraceptives ("mini-pills"), intrauterine devices, or barrier contraceptive methods. Discuss your lifestyle and health history with your doctor to determine if combination birth control pills are safe for you.

Click the icon to see an image of stroke.

Overall Cancer Risks. Combination oral contraceptives appear to increase the risk for some types of cancers (cervical) and reduce the risks for others (ovarian and uterine). For other types of cancer, such as breast cancer, the evidence is less clear. According to a 2007 study in the British Medical Journal, current users of high-dose (50 micrograms/day) combination oral contraceptives have a reduced risk for uterine, ovarian, and possibly colorectal cancer. However, women who use estrogen-containing oral contraceptives for more than 8 years have an increased risk for cervical, breast, and central nervous system cancers. Researchers found that once women stopped taking birth control pills, the risks for breast and cervical cancer returned to those of non-users within 10 years.

Breast Cancer. Studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer, and if it does, which women are at risk. Some studies indicate that the risk may be higher for premenopausal breast cancer when women use oral contraceptives before their first pregnancy. The most definitive study to date -- the 2002 Women’s Contraceptive and Reproductive Experiences (CARE) study -- evaluated oral contraceptive use and breast cancer among women ages 35 - 64. The CARE study found that current or former oral contraceptive use did not increase the risk for breast cancer.

Cervical Cancer. Several studies have reported a strong association between cervical cancer and long-term use of oral contraception. Women who have taken oral contraceptives for more than 10 years have a much higher risk of human papilloma virus (HPV) infection (up to four times higher) than those who do not use oral contraceptives. Women taking oral contraceptives for less than 5 years have no significantly higher risk. The reasons for this risk from oral contraceptive use are not entirely clear. Women who use oral contraceptives may be less likely to use a diaphragm, condoms, or other methods that offer some protection against sexual transmitted diseases, including HPV. Some experts also suggest that the hormones in oral contraceptives might facilitate entry of the HPV virus in the genetic material of cervical cells. HPV is the main cause of cervical cancer, as well as genital warts.

Ovarian and Uterine Cancers. Evidence clearly indicates that oral contraceptives reduce the risk of ovarian cancer. The risk decreases by 10 - 12% after 1 year of use and by 50% after 5 years of use. Contraceptives with high levels of progestins may reduce ovarian cancer risk more than contraceptives with low levels of progestins. Oral contraceptives also reduce the risk of uterine (endometrial) cancer. The protective effect of oral contraceptives continues for many years after a woman stops taking the pills.

Click the icon to see an image of cervical cancer.

Other Complications. Other complications have been associated with the use of oral contraceptives:

Taking oral contraceptives containing certain progestins (desogestrel in one study) may increase the risk for periodontal disease. Other types of progestins do not pose a risk for gum disease.

There has been some debate over whether the progestin-only pill increases the risk for permanent type 2 diabetes in women who develop a temporary form of diabetes during pregnancy (called gestational diabetes). In any case, the low-dose combination pill does not appear to pose such a risk. Women with a history of gestational diabetes should discuss this controversy with their doctor.

Some evidence suggests that oral contraceptives may reduce lung capacity during exercise. There have been a few reports of worsening asthma symptoms with oral contraceptives, but this is not common.

The pill can affect the liver and, rarely, has been associated with liver tumors, gallstones, or jaundice. Women with a history of liver disease, such as hepatitis, should consider other contraceptive options.

Interactions with Other Medications. Oral contraceptives can interact with many other medications and herbal supplements.

New methods of administering the combination of progestin and estrogen are now available. Failure rates with perfect use (0.1 - 0.6%) are similar to those with combined oral contraceptives. The recommendations and side effects are the same as those for oral contraceptives. None of these methods protect against sexually transmitted diseases.

Skin Patches. Ortho Evra was approved in 2002 as the first birth control skin patch. It contains a progestin (norelgestromin) and estrogen. The patch is placed on the lower abdomen, buttocks, or upper body (but not on the breasts). Each patch is worn continuously for a week and reapplied on the same day of each week. After three weekly patches, the fourth week is patch-free, which allows menstruation. (The patch remains effective for 9 days, so being slightly late in changing it should not increase the risk for pregnancy.)

In 2005, the Food and Drug Administration warned that the Ortho patch exposes women to higher levels of estrogen than most birth control pills, and therefore may increase the risk for blood clots and other serious side effects. A 2007 study reported that women who use the patch have twice the risk of blood clots as women who use estrogen/norelgestromin oral contraceptives. In contrast, other studies in 2006 and 2007 suggested that the patch and oral contraceptives carry similar blood clot risks. Older women (over age 40) and women with risk factors for blood clots (such as cigarette smoking) may find other birth control products to be a safer choice. Discuss with your doctor whether the patch is appropriate for you.

Vaginal Ring. NuvaRing is a 2-inch flexible ring that contains both estrogen and progestin (etonogestrel). It is inserted into the vagina. Women can insert the ring by themselves once a month and take it out at the end of the third week to allow menstruation. It works well and may cause less irregular bleeding than oral contraceptives. Some women find it uncomfortable, and a few have reported vaginal irritation and discharge, but such problems rarely cause a woman to discontinue use. As with the patch, NuvaRing may put women who take it at higher risk for blood clots than oral contraceptives.

Implant Contraception

Implant contraception involves inserting a rod under the skin. The rod releases into the bloodstream tiny amounts of the hormone progestin.

The first implant was the Norplant system, which used six rods that contained levonorgestrel. Due in part to serious complications, Norplant was withdrawn from the U.S. market in 2002. The main complication was difficulty inserting and, in particular, removing the rods. (Many women experienced scarring.) In addition, some women who used Norplant experienced heavy irregular bleeding. A two-rod implant called Jadelle is sold in other countries, but not the United States.

In 2006, the Food and Drug Administration approved Implanon, a new implant contraceptive. In contrast to Norplant:

Implanon uses one rod, not six.

It is not inserted as deeply into the skin.

It uses etonogestrel, a different type of progestin than the levonorgestrel used in Norplant.

Only specially trained health care providers are allowed to insert and remove Implanon.

Implanon insertion takes about a minute and is performed with a local anesthetic in a doctor’s office. The rod remains in place for 3 years, although it can be removed at any time. (The removal procedure takes a few minutes longer than insertion.) After the rod is removed, a new one can be inserted.

Studies indicate that Implanon is safe. Irregular bleeding is the main side effect. However, some doctors are concerned that Implanon may have some of the same risks as Norplant.

Injected Contraception

Injected contraceptives are given once every 3 months. Most injectables are progestin-only. In the United States, depo-medroxyprogesterone acetate (Depo-Provera) is the only approved injected contraceptive. Depo-Provera (also called Depo, or DMPA) uses a progestin called medroxyprogesterone. Like other progestin contraceptives, Depo-Provera prevents pregnancy by halting ovulation, thickening the cervical mucus, and stopping the implantation of fertilized eggs in the uterine lining.

Depo-Provera is very effective in preventing pregnancies. About 3 in 100 women who use it become pregnant. However, Depo also carries the risk for many mild and serious side effects. The most serious side effect is loss of bone density (see "Disadvantages"). Because of this complication, Depo-Provera should not be used for more than 2 years.

Administering Injections:

A physical examination is necessary before beginning the injections.

Depo is injected into a muscle in the patient's arm or buttock. During months between injections, the hormone slowly diffuses out of the muscle into the bloodstream.

Depo requires an injection by the doctor once every 3 months.

If more than 2 weeks pass beyond the regular injection schedules, the woman should have a pregnancy test before receiving the next injection.

Because Depo-Provera does not contain estrogen, it is safe for many women who are not candidates for combination oral contraceptives, such as women smokers over age 35.

Depo-Provera should not be given to women who have a history of:

Current or past breast cancer

Stroke or blood clots

Liver disease

Epilepsy, migraine, asthma, heart failure, or kidney disease (due to the fact that the drug causes fluid retention)

Unexplained vaginal bleeding

Risk for osteoporosis

Because of the long lag time between ending treatments and restoration of fertility, Depo-Provera is not recommended for women who are thinking of becoming pregnant within 2 years.

Provides highly effective reversible protection against pregnancy without placing heavy demands on the user's time or memory.

Does not increase risk for breast, ovarian, or cervical cancer. May protect against endometrial cancer.

May be useful for women with painful periods, heavy bleeding (including heavy bleeding caused by fibroids), premenstrual syndrome, and endometriosis.

Weight gain. Most women gain an average of 5 - 8 pounds.

Other common side effects include menstrual irregularities (bleeding or cessation of periods), abdominal pain and discomfort, dizziness, headache, fatigue, nervousness.

Most users of Depo-Provera stop menstruating altogether after a year. Depo can cause persistent infertility for up to 22 months after the last injection, although the average is 10 months.

Long-term (more than 2 years) use of Depo-Provera can cause loss of bone density. In November 2004, the Food and Drug Administration (FDA) added a “black box” warning to the Depo-Provera label advising of this risk. The warning notes that the decline in bone density increases with duration of use and may not be completely reversible even after the drug is discontinued. Based on this information, the FDA recommends that Depo-Provera should not be used for longer than 2 years unless other birth control methods are inadequate. A 2005 study of young women (age 14 - 18 years) found that adolescents who stop taking Depo-Provera do regain bone density.

The injections do not provide protection against sexually transmitted diseases. According to a 2004 study, women who take Depo-Provera have three times the risk of acquiring chlamydia and gonorrhea as women who do not use a hormonal contraceptive. The reason for this increased risk is unclear. The same study found that oral contraceptive use, in comparison to non-hormonal contraceptives, was not associated with increased risk.

Intrauterine Devices (IUDs)

The intrauterine device (IUD) is a small plastic T-shaped device that is inserted into the uterus. An IUD's contraceptive action begins as soon as the device is placed in the uterus and stops as soon as it is removed. IUDs have an effectiveness rate of close to 100%. They are also a reversible form of contraception. Once the device is removed, a woman regains her fertility.

The intrauterine device (IUD) is one of the safest, least expensive, and most effective contraceptive devices available. In spite of its clear advantages and current safety record, only 1% of American women currently use the IUD. (Over 10% of European women have chosen the IUD.) This low use in America is mainly due to persisting and now unwarranted fears of serious infection and other complications. However, the evidence available today should reassure providers and patients about the following concerns:

Pelvic infections. What was thought to be an increased risk of pelvic inflammatory disease has proven not to be true. Large groups of patients have been evaluated, and their risk does not seem to be any greater than the risk in the general population The risk for infection may be increased around the time of insertion of the IUD, but routine screening before insertion is generally not recommended There is also no evidence that IUD usage increases the risk of HIV infection.

Infertility. IUDs were thought to cause infertility, mostly because of concerns about infections. However, studies have shown that women with a history of using an IUD are no more likely to be diagnosed with infertility than those who have not used IUDs. This seems to be true for women who have never been pregnant or women who have been pregnant previously.

Ectopic pregnancy. Another concern was a presumed increased risk for an ectopic pregnancy. In reality, women using IUDs have a significantly lower rate of ectopic pregnancies than women using no contraception at all. Even for women who have a history of ectopic pregnancies when not using contraception, the IUD is considered safe and may even lower their risk for another one.

The intrauterine device (IUD) shown uses copper as the active contraceptive, others use progesterone in a plastic device. IUDs are very effective at preventing pregnancy (less than 2% chance per year for the progesterone IUD, less than 1% chance per year for the copper IUD). IUDs come with increased risk of ectopic pregnancy and perforation of the uterus and do not protect against sexually transmitted disease. IUDs are prescribed and placed by health care providers.

Two types of intrauterine devices (IUDs) are available in the United States:

Copper-Releasing (ParaGard). This type of IUD can remain in the uterus for up to 10 years. Cooper ions released by the IUD are toxic to sperm, thus preventing fertilization.

Progestin-Releasing (Mirena). This type of IUD can remain in the uterus for up to 5 years. Mirena is also known as a levonorgestrel-releasing intrauterine system, or LNG-IUS. Levonorgestrel impairs sperm motility and viability, thus preventing fertilization. LNG-IUS is long-acting, safe, very effective in preventing heavy bleeding, and helps reduce cramps. In fact, some experts describe it as a nearly ideal contraceptive. This device is also proving beneficial for women with menstrual disorders, particularly heavy bleeding.

With some exceptions, an intrauterine device (IUD) can be inserted at any time, except during pregnancy or when an infection is present. It may be inserted immediately postpartum or after elective or spontaneous miscarriage. It is typically inserted in the following manner by a trained health professional:

A plastic tube containing the IUD (the inserter) is slid through the cervical canal into the uterus.

A plunger in the tube pushes the IUD into the uterus.

Attached to the base of the IUD are two thin but strong plastic strings. After the instruments are removed, the health care provider cuts the strings so that about an inch of each dangles outside the cervix within the vagina.

The strings have two purposes:

They enable the user or health care provider to check that the IUD is properly positioned. (Because the IUD has a higher rate of expulsion during menstruation, the woman should also check for the strings after each period, especially if she has heavy cramps.)

They are used for pulling the IUD out of the uterus when removal is warranted.

The insertion procedure can be painful and sometimes causes cramps, but for many women it is painless or only slightly uncomfortable. Patients are often advised to take an over-the-counter painkiller ahead of time. They can also ask for a local anesthetic to be applied to the cervix if they are sensitive to pain in that area. Occasionally a woman will feel dizzy or light-headed during insertion. Some women may have cramps and backaches for 1 - 2 days after insertion, and others may suffer cramps and backaches for weeks or months. Over-the-counter painkillers can usually moderate this discomfort.

Intrauterine devices are an excellent choice of contraception for women who are seeking a long-term and effective birth control method, particularly those wishing to avoid risks and side effects of contraceptive hormones. The LNG-IUS may be better suited for women with heavy or regular menstrual flow.

Around the time of insertion and shortly afterwards, women should be considered at low risk for sexually transmitted disease (mutually monogamous relationship, using condoms, or not sexually active).

Women with risk factors that preclude hormonal contraceptives should probably avoid progestin-releasing IUDs, although the progestin doses are much lower with LNG-IUS and probably do not pose the same risks.

Women with the following history or conditions may be poor candidates for IUDs:

Current or recent history of pelvic infection

History of menstrual disorders -- mostly for the copper-releasing IUDs, however

Current pregnancy

Abnormal Pap tests

Cervical or uterine cancer

A very large or very small uterus

IUDs have the following advantages:

The IUD is more effective than oral contraceptives at preventing pregnancy, and it is reversible. Once it is removed, fertility returns. (In spite of outdated concerns, studies have found no adverse effects on fertility with the current IUDs.)

Unlike the pill, there is no daily routine to follow.

Unlike the barrier methods (spermicides, diaphragm, cervical cap, and the male or female condom), there is no insertion procedure to cope with before or during sex.

Intercourse can resume at any time, and, as long as the IUD is properly positioned, neither the user nor her partner typically feels the IUD or its strings during sexual activity.

It is the least expensive form of contraception over the long term.

Additional advantages, depending on the specific IUD, include:

The progestin-releasing LNG-IUS (Mirena) is now considered to be one of the best options for treating menorrhagia (heavy menstrual bleeding). (However, irregular breakthrough bleeding can occur during the first 6 months.) It may even be appropriate and protective for women with uterine fibroids.

The copper-releasing IUDs do not have hormonal side effects and may help protect against endometrial (uterine) cancer.

Menstrual Bleeding. Both intrauterine device (IUD) forms have effects on menstruation, although they differ significantly by type:

Copper releasing IUDs can cause cramps, longer and heavier menstrual periods, and spotting between periods. Prescription medications are available to control the bleeding and pain, which, in any event, usually subside after a few months.

Progestin-releasing IUDs produce irregular bleeding and spotting during the first few months. Bleeding may disappear altogether. (This characteristic is a major advantage for women who suffer from heavy menstrual bleeding but may be perceived as a problem for others.)

Menstrual difficulties can be so troublesome with either IUD that, according to one study, they were responsible for a removal rate of 5 - 15% within a year of insertion.

Ovarian Cysts. The LNG-IUS may increase the risk for ovarian cysts, but such cysts usually do not cause symptoms and resolve on their own.

Expulsion. An estimated 2 - 8% of IUDs are expelled from the uterus within the first year. Expulsion is most likely to occur during the first 3 months after insertion. Expulsion rates may be higher than average if the IUD is inserted immediately after delivery of a child. In 1 in 5 cases, the woman fails to notice that the device is gone, and thus faces the risk of unintended pregnancy. The risk for expulsion is highest during menstruation, so women should be sure to check the strings to make sure the IUD is in place.

Effects on Pregnancy. None of the current IUDs increase the risk for infertility. In the very unlikely event that a woman conceives with an IUD in place, however, there is a higher risk of an ectopic pregnancy or miscarriage.

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

If the IUD is removed right after conception, the risk for miscarriage is close to average (about 20%). There is no evidence that the IUD in a pregnant woman increases the risk for birth defects in the infant.

Perforation. A potentially serious complication of the IUD is the accidental perforation of the uterus during insertion or later perforation if the IUD shifts position. Such an occurrence is very rare, and the risk is higher or lower depending on the skill of the doctor.

Spermicidal and Barrier Contraception

Barrier contraceptives are devices that provide a physical barrier between the sperm and the egg. Examples of barrier contraceptives include the male condom, female condom, diaphragm, cervical cap, and sponge. [For a description of the male condom, see "Male Condom."] Barrier devices are the only contraceptive methods that can help prevent sexually transmitted diseases (STDs).

Spermicides are sperm-killing substances available as foams, creams, or gels, and are often used in female contraception with barrier and other devices. Spermicides are usually available without a prescription or medical examination.

The active ingredient in U.S.-made spermicides is usually nonoxynol-9, which attacks the surface of the sperm cell. Nonoxynol-9, however, does not provide any additional protection against sexually-transmitted diseases. Research indicates that frequent use can cause vaginal irritation and abrasions and actually increase the risk for HIV transmission in women. In addition, use of a spermicide with a barrier device doubles or triples the risk for a urinary tract infection in women, regardless of whether the device is a condom or diaphragm. Spermicides are no longer recommended with male condoms. (Non-spermicidal lubricated condoms are safe to use.) Some experts think they are not necessary for use with diaphragms, but this issue is still under debate.

In general, spermicides may be an appropriate choice for women who have intercourse only once in a while, or need backup protection against pregnancy (for instance, if they forget to take their birth control pills). Spermicides should not be used alone as the primary method of birth control. Nor should they be used to prevent sexually transmitted diseases.

The diaphragm, which is generally used with a spermicidal cream, foam, or gel, is a small dome-shaped latex cup with a flexible ring that fits over the cervix. The cup acts as a physical barrier against the entry of sperm into the uterus. The spermicide provides added chemical protection but, as stated above, some doctors think they are not necessary for use with diaphragms.

The diaphragm is a flexible rubber cup that is filled with spermicide and self-inserted over the cervix prior to intercourse. The device is left in place several hours after intercourse. The diaphragm is a prescribed device fitted by a health care professional and is more expensive than other barrier methods, such as condoms.

There are three basic rim designs:

The Arcing Spring diaphragm applies strong pressure and easily flips into place. It is useful for women with weak vaginal muscles and for new users who are worried about incorrect placement.

The Coil Spring Rim is useful for women with strong vaginal muscles.

The Flat Spring Rim has a delicate rim and a gentle spring, and may be appropriate for women who have not had children.

Diaphragms come in different sizes and require a fitting by a trained health care provider. The health care provider also advises and prescribes the correct size of diaphragm for the user. Some women will need to be refitted with a different-sized diaphragm after pregnancy, abdominal or pelvic surgery, or weight loss or gain of 10 pounds or more. As a general rule, diaphragms should be replaced every 1 - 2 years.

Although the diaphragm has a relatively high failure rate, even with perfect use, it is considered a good choice for women whose health or lifestyle prevents them from using more effective hormonal contraceptives. Certain conditions of the vagina and uterus, a history of toxic shock syndrome, or a history of recurrent urinary tract infections, may disqualify a woman from using the device. The diaphragm should not be used if either partner is allergic to latex or spermicides.

Using and Inserting the Diaphragm. The diaphragm can be placed in the vagina up to 1 hour before intercourse and can be used even when a woman is menstruating. The following are general guidelines for insertion:

Before or after each use, the woman should hold the diaphragm up to the light and fill it with water to check for holes, tears, or leaks.

A small amount of spermicide (about 1 tablespoon) is usually placed inside the cup, and some is smeared around the lip of the cup.

The device is then folded in half and inserted into the vagina by hand or with the assistance of a plastic inserter.

The diaphragm should fit over the cervix, blocking entry to the womb.

If more than 6 hours pass before repeat intercourse occurs, the diaphragm is left in place and extra spermicide is inserted into the vagina using an applicator.

The diaphragm must remain in the vagina for 6 - 8 hours after the final act of intercourse, and can safely stay there up to 24 hours after insertion.

The diaphragm should be washed with soap and warm water after each use and then dried and stored in its original container, which should be kept in a cool dry place.

Advantages of the Diaphragm. The diaphragm can be carried in a purse, can be inserted up to an hour before intercourse begins, and usually cannot be felt by either partner. It may protect against cervical gonorrhea, Chlamydia, and trichomoniasis, although more research is needed to confirm this. It does not provide protection against sexually-transmitted infections in areas other than the cervix.

Disadvantages and Complications of the Diaphragm. Some disadvantages or complications are as follows:

Failure rates are high, about 20% with typical use.

Some women dislike having to insert the device every time intercourse occurs or have trouble mastering the insertion and removal process.

Frequent urinary tract infections are a problem for some women. This difficulty can sometimes be resolved by a refitting, by urinating before inserting the device, or by urinating after intercourse.

Cases of toxic shock syndrome have been reported among diaphragm users, but it is very rare. To be safe, the diaphragm should not stay in place for more than 24 hours. (It is still important for pregnancy protection, however, to retain the diaphragm for 6 - 8 hours after intercourse.)

It provides protection against sexually transmitted disease only in the cervix, and women should not rely on it for protection against HIV.

The cervical cap (Prentif, FemCap) is a thimble-shaped latex cup that fits over the cervix. It is always used with a spermicidal cream or gel. It is similar to a diaphragm, but smaller, and is available in only four sizes. The cap is sold by prescription and requires a pelvic examination, Pap test, and fitting by a health care provider.

Insertion and Use of the Cervical Cap. After a small amount of spermicide is placed in the cap, the device is inserted by hand. As in diaphragm use, instruction and practice is required. The cap must be kept in the vagina for 8 hours after the final act of intercourse. Caps wear out and should be replaced every 1 - 2 years. A refitting may also be needed when a woman experiences certain changes in her health or physical status.

Click the icon to see an image of a cervical cap.

Candidacy for the Cervical Cap. Because of the restricted range of available sizes, about 1 in 5 woman will not be able to be fitted for the cap. The cap is not widely used, and some women, particularly those who live in sparsely populated areas, may not have access to health care professionals who are trained in fitting this device. Other conditions that can preclude cap use include:

An abnormal Pap test

A history of toxic shock syndrome

A sexually transmitted or reproductive tract infection

Inflammation of the cervix

The cap has little value for women who have had children, because the stretching of the vagina and cervix makes a proper fit more difficult and failure rates are high.

Advantages of the Cervical Cap. Among women who have never given birth, the cap's failure rate, at least with Prentif cervical cap, is similar to that of the diaphragm. (The FemCap appears to have a higher failure rate.) The cap in general is also similar to the diaphragm in terms of cost, ease of use, protection against sexually transmitted diseases (STDs), and also the potential for latex or spermicidal allergies. But unlike the diaphragm, the cap can safely remain in the vagina for up to 48 hours (twice the time limit for a diaphragm), so it can be inserted well in advance of intercourse. The cap is rarely associated with urinary tract infections, and no documented cases of toxic shock syndrome have been reported.

Disadvantages of the Cervical Cap. The following are disadvantages of the cervical cap:

Failure rate with any cap is high in women who have given birth (40%). In general, the FemCap has a higher risk for failure than either the diaphragm or the Prentif cap.

Unlike the diaphragm, the cap cannot be used during menstruation.

Use of the cervical cap (particularly the Prentif cap) poses a higher risk for abnormal cervical cell growth than with the diaphragm.

The female condom (Reality, Femidom) is a lubricated, loose-fitting pouch that lines the vagina. It is designed to create a physical barrier against sperm and sexually transmitted diseases by surrounding the penis during intercourse. The failure rate for the female condom is about the same as for the diaphragm and cervical cap. It is available without a prescription but may be hard to find.

Use and Insertion of the Female Condom. The female condom is about 3 inches wide and 6 - 7 inches long (larger than a male condom), with a flexible ring at both ends. Current products are made of polyurethane.

The ring at the closed end is used to insert the device into the vagina and hold it in place over the cervix.

The ring at the open end remains outside the vagina and partly covers the labia (lips).

The insertion process may seem difficult at first but becomes much easier with practice:

The female condom is inserted by hand into the vagina up to 8 hours before intercourse. (It should never be used in combination with a male condom.)

Although the female condom is prelubricated, extra lubricant is sometimes needed while inserting the device or during intercourse. (It is not made of latex, so oil lubricants will not harm it.)

During intercourse, the woman checks to be sure that the outer ring is lying flat against her labia and then guides her partner's penis into the ring.

The female condom should be removed in the following circumstances:

If it tears during insertion or use

If the outer ring is pushed inside

If it bunches up inside the vagina

The female condom may be the best option for women at risk for sexually transmitted diseases and who are not certain that their male partner will use a condom. There are virtually no obstacles against its use except a negative psychological perception. It is not completely fail-proof against pregnancy or sexually transmitted diseases.

Advantages of the Female Condom. In one study, 75% of the women preferred the female to the male condom. Many men also find it more appealing than the latex male condom. The female condom has a number of advantages over the male condom:

The female condom is an effective barrier to viruses, including HIV, and other sexually transmitted organism, particularly since it covers a large area, including external genitals. However, there are not enough clinical studies at this time to determine its protection against sexually transmitted diseases. No contraceptive device is foolproof.

The standard female condom is made of polyurethane, which is thin and soft but at the same time 40% stronger than the latex male condoms. Polyurethane is not damaged by lubricating oils, as latex is and is also less likely to cause an allergic reaction. It transmits body heat better than latex, providing a more "natural" sensation, and possibly enhancing the pleasure of the sexual act.

The man does not have to withdraw his penis immediately after ejaculation, as is the case with the male condom, but can, if he wishes, withdraw after he has lost his erection.

Disadvantages and Complications of the Female Condom. Compliance rates are low for many reasons. About 25% of women have difficulty on the first attempt at self-insertion. Some women are distressed by self-insertion. The inner ring may be uncomfortable for some women (in which case it can be removed). Some couples complain that the female condom is unpleasant to look at and can be noisy during intercourse. Without sufficient lubrication, it can also be pushed out of place by the penis. Using more lubricant can help keep the female condom in place and reduce the noise. Female condoms are also expensive, and some women wash them out and reuse them to save money. (In such cases, they should be disinfected first and then washed carefully.) Repeated washings can increase the risk for damage and holes. It is not known how many rewashings are safe.

The sponge (Today, Protectaid) is a disposable form of barrier contraception. It is made of soft polyurethane, is round in shape, and fits over the cervix like a diaphragm, but is smaller and easily portable. In 1994, the popular over-the-counter contraceptive was taken off the U.S. market because of problems at the company's manufacturing facility. A new company has since acquired the rights to manufacture the sponge, and has been selling it in Canada and online since 2003. In April 2005, the Food and Drug Administration granted re-approval for the Today sponge to return to the U.S. market.

Use and Insertion. To use the sponge, the woman first wets it with water, then inserts it into the vagina with a finger, using a cord loop attachment. It can be inserted up to 6 hours before intercourse and should be left in place for at least 6 hours following intercourse. The sponge provides protection for up to 12 hours. It should not be left in for more than 30 hours from time of insertion.

The sponge should not be used during menstruation, after childbirth, miscarriage, or termination of pregnancy, or by women with a history of toxic shock syndrome.

Advantages. Because the sponge is not felt during intercourse and can be inserted up to 6 hours before intercourse, it encourages spontaneity. It appears to protect against cervical gonorrhea and Chlamydia.

Disadvantages. Failure rates (about 10%) are higher than with the diaphragm. There is a very small risk for toxic shock using the sponge, as there is for other barrier methods of contraception. The sponge may increase the risk for candidiasis (yeast infection). People who are allergic to spermicides should not use the sponge. The sponge does not protect against HIV or sexually transmitted diseases outside the cervix. The Today sponge contains 10 times the amount of the spermicide nonoxynol-9 than other products, and there is some evidence that this spermicide may increase the risk for HIV. The Protectaid sponge, available in Canada, contains a mix of three spermicides (nonoxynol-9, sodium cholate and benzal konium chloride).

The Lea shield is made of silicone, and its cup-shaped bowl completely surrounds the cervix without resting on it. The shield does not need to be fitted, and is as effective as the diaphragm and cap when used with spermicide. Its advantages are:

One size fits all

Can be left for 48 hours after intercourse

Reusable for 6 months

The condom is still the only reversible form of male contraception currently available.

Pregnancy Protection. The condom should be put on before intercourse when the penis is erect, long before ejaculation, since the male can discharge sufficient semen to cause pregnancy before ejaculation occurs. The average rate of pregnancy for couples that rely only on condoms for protection is high -- about 12%. In adolescents the risk of pregnancy with condoms is even higher, 18%. Even for those who use a good-quality condom correctly, the annual risk for pregnancy is 3%.

Prevention of Sexually Transmitted Diseases. Condoms are important in the prevention of sexually transmitted disease in both male and female partners, but they have limitations. They are more protective in men against fluid-transmitted infections (gonorrhea, Chlamydia, trichomoniasis, and HIV) than in preventing infections transmitted by skin-to-skin contact (herpes simplex virus, human papilloma virus, syphilis, and chancroid). Male condoms, in fact, offer better protection against herpes for women than they do for men. (Men often shed the virus from the skin of the penis, which is covered by the condom. In women the virus is often shed from areas around their genitals, which can contact male skin outside the condom.)

Some condoms come pre-lubricated with the spermicide nonoxynol-9, which is no longer recommended with condoms because of a higher risk for HIV infection. Its use in male condoms also promotes yeast and urinary tract infections in women. Other condoms come pre-lubricated without spermicide. Lubricants can also be purchased and applied separately. Only water-based lubricants (K-Y Jelly, Astroglide, AquaLube, glycerin) should be used with latex condoms. Do not use petroleum jelly or other oil-based lubricant products as these can damage the condom. In general, it's best to use a pre-lubricated condom or to apply a water-based lubricant. Unlubricated condoms may injure vaginal tissue and make it vulnerable to infections.

Condom Materials.

Latex. Condoms made of latex rubber are the most common types. They are less likely to slip or break than those made of polyurethane, and they are contoured for a better fit that can provide fairly effective protection. Some people are allergic to latex, however, and in some cases the reaction can be very dangerous. The latex smell may also be unpleasant for some people.

Polyurethane. Polyurethane condoms (Avanti, eZ-on) are also available. It is hoped that eventually they will prove to be superior to latex in a number of ways, including strength, sensitivity, and durability. At this point, they have good acceptance by couples but have a higher breakage rate (6 - 7.2%) compared to the latex condom (1.1 - 2%). Other synthetic materials are under investigation.

Animal Membranes. Condoms made from animal membrane (such as lambskin) can prevent pregnancy, but they are permeable and do not protect against sexually transmitted infections.

Natural Family Planning Methods

Natural family planning contraceptive methods do not use medication, physical devices, or surgery to prevent pregnancy. Instead, these cycle-based fertility awareness methods rely on tracking the changes in the body that signal fertility. A woman is only fertile during part of her menstrual cycle. By monitoring certain changes in her body, a woman can more or less predict the fertile phase and abstain from sexual intercourse during that time. She can also use barrier methods if they are not prohibited by religious beliefs. The Roman Catholic Church, for example, generally approves of most natural family planning methods.

Natural family planning methods include:

Basal body temperature

Cervical mucus

Symptothermal

Lactational amenorrhea

Calendar

Basal Body Temperature Method. To determine the most likely time of ovulation and therefore the time of fertility, a woman is instructed to take her body temperature, called her basal body temperature. This is the body's temperature as it rises and falls in accord with hormonal fluctuations.

Each morning before rising, the woman takes her temperature with a specialized basal body thermometer and marks the result on a graph-paper chart.

She also notes the days of menstruation and sexual activity.

The so-called "fertile window" is 6 days long. It starts 5 days before ovulation and ends the day of ovulation.

The chances for fertility are considered to be highest between days 10 - 17 in the menstrual cycle (with day 1 being the first day of the period and ovulation occurring about 2 weeks later). However, one study reported that only 30% of women were fertile within that period of time. In the study, women had a 10% chance of ovulating on each day between day 6 and 21. The researchers suggested that each woman track the length of her cycle, which in the general population of women actually runs 19 - 60 days. A long cycle, for example, suggests a delayed ovulation date.

Immediately after ovulation, the body temperature increases sharply in about 80% of cases. (Some women can be ovulating normally yet not show this temperature pattern.)

By studying the temperature patterns over a few months, couples can begin to anticipate ovulation and plan their sexual activity accordingly. To avoid losing spontaneity, couples should try to avoid becoming fixated on the chart in scheduling their sexual activity.

Cervical Mucus Method. The cervical mucus method (also called the ovulation method) requires a woman to take a sample (by hand) of her cervical mucus every day for a least a month and to record its quantity, appearance, feel, and to note other physical signs connected with the reproductive system. Cervical mucus changes in predictable ways over the course of each menstrual cycle:

Six days before ovulation, mucus is affected by estrogen and becomes clear and elastic. Ovulation is likely to occur the last day that mucus has these properties.

Right after ovulation, mucus is affected by progesterone and is thick, sticky, and opaque.

Once a woman's individual pattern is understood, analyzing cervical mucus can provide a highly accurate guide to fertility.

Symptothermal Method. This method uses both the basal body temperature and cervical mucus methods. In addition, the woman tracks symptoms that may identify her fertile period. These symptoms include changes in the shape of the cervix, breast tenderness, and cramping pain.

Prolonged Breast-feeding (The Lactational Amenorrhea Method). Breast-feeding often delays the onset of ovulation and menstruation for about 6 months. A technique called the Lactational Amenorrhea Method (LAM) allows women to rely on breastfeeding for natural family planning. New mothers are candidates for LAM if their periods have not returned after delivery. They must be breastf-eeding the baby on demand, day and night, without regularly substituting other liquids or foods in the baby's diet.

The risk for pregnancy with this method is less than 2% in the early months, although by 6 months after birth it increases to over 5%. The return of menstruation indicates the return of fertility. Bleeding or spotting during the first 56 days is not considered menstruation. After that, 2 or more consecutive days of bleeding are usually an indicator that periods have returned. Ovulation can occur before menstruation resumes, although it is less likely within 6 months of delivery (particularly if the mother is intensively breast-feeding).

Calendar Method. The calendar (rhythm method) is considered the least reliable of natural family planning methods, with an effectiveness rate of about 87%. Women who have very irregular periods may have even less success with this method. In the calendar method, the woman first keeps a record of her menstrual periods for about 6 - 12 months. She then subtracts 18 days from the shortest and 11 days from the longest of the previous menstrual cycles. For example, if a woman's shortest cycle was 26 days and her longest cycle was 30 days, she must abstain from intercourse from day 8 through day 19 of each cycle.

Because of the high risk for pregnancy, natural family planning methods are recommended only for those whose strong religious beliefs prohibit standard contraceptive methods. Couples who are not guided by religious authority, but who simply want a more natural sexual life, should use a barrier contraceptive during the fertile phase and no contraception during the rest of the cycle. To be effective against pregnancy, cycle-based methods require not only training, commitment, discipline, and perseverance, but also the cooperation of the male partner. Cycle-based methods are not recommended for women unless they are in a stable, monogamous relationship, and can count on their partner's willing participation.

Many couples, especially older ones, who have used these methods for a while and are strongly motivated, are able to successfully incorporate fertility awareness into their lives. For those with strong religious beliefs, natural family planning allows them to have a fulfilling sexual life yet still adhere to the rules of their church.

Couples who adopt a cycle-based approach to pregnancy avoidance must often abstain from sex or substitute other kinds of sexual intimacy for vaginal intercourse. Some couples find this self-denial and the need for vigilant tracking of the cycle difficult and stressful for the relationship. Failure rates are high with natural family planning. The risk for sexually transmitted diseases is also of particular concern, because such methods offer no protection against infection and religious beliefs usually preclude barrier protection.

Emergency Contraception

Emergency contraception is available to prevent pregnancy:

After sexual assault

After consensual intercourse in which contraception is not used

When contraception is used but fails (for instance, when a condom breaks or a diaphragm dislodges)

Emergency contraception, also called the “morning after pill,” uses the hormones found in birth control pills to prevent either fertilization or the implantation of a fertilized egg in the uterine lining. The pill known as Plan B contains progestin. Emergency contraception is usually given as hormone pills within 72 hours of unprotected sex. It is not the same thing as the "abortion pill" [See "mifepristone," below]. Emergency contraception is also sometimes prescribed as an intrauterine device (IUD), which is inserted within 5 days of unprotected sex.

In 2006, the Food and Drug Administration approved the Plan B brand as the first over-the-counter emergency contraception. It is available without a prescription at pharmacies and health clinics for women over age 18. Women will need to present proof of age to purchase it. Girls younger than age 18 will still need a prescription from their doctors.

Emergency Oral Contraception. There is one form of emergency oral contraception:

Plan B uses two doses of the progestin levonorgestrel. In one large study, levonorgestrel prevented pregnancy in 85% of women requiring emergency contraception.

The woman takes her first pill or pills within 72 hours of intercourse and a second dose 12 hours later. The sooner the drug is taken, the more effective it is in preventing pregnancy. Some evidence suggests the pills may be effective up to 5 days after sex, although effectiveness is greater if used within 72 hours. Although these regimens are popularly called morning-after pills, they are actually the same oral contraceptives that users of oral contraceptives take regularly.

Side effects of emergency oral contraception include:

Nausea and vomiting

Fatigue

Headaches

Dizziness

Diarrhea

Breast tenderness

Fluid retention

Changes in the timing or flow of the woman's next menstrual period. A 2006 study found that emergency contraceptive pills (such as Plan B) that contain levonorgestrel may alter the menstrual cycle and the length of periods.

Immediate side effects typically subside within 1 - 2 days of taking the second dose. Family planning experts warn that emergency pill use should not be treated as a substitute for regular contraception.

Copper-Releasing Intrauterine Device. An alternative emergency contraception relies on insertion of a copper-releasing intrauterine device (IUD) within 6 days of intercourse. It can be removed after the woman's next period, or left in place to provide ongoing contraception. The copper IUD reduces the risk of pregnancy by 99.9%.

Female Sterilization

Female surgical sterilization (also called tubal sterilization, tubal ligation, and tubal occlusion) is a low-risk, highly effective one-time procedure that offers lifelong protection against pregnancy. About 700,000 women undergo this procedure each year in the United States.

Female surgical sterilization procedures block the fallopian tubes and thereby prevents sperm from reaching and fertilizing the eggs. The ovaries continue to function normally, but the eggs they release break up and are harmlessly absorbed by the body. Tubal sterilization is performed in a hospital or outpatient clinic under local or general anesthesia.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Sterilization does not cause menopause. Menstruation continues as before, with usually very little difference in length, regularity, flow, or cramping. (One study suggested that women with a history of Cesarean section may experience slightly heavier bleeding.) Sterilization does not offer protection against sexually transmitted diseases.

Click the icon to see an image of tubal ligation.

Laparoscopy. Laparoscopy is the most common surgical approach for tubal sterilization:

The procedure begins with a tiny incision in the abdomen in or near the navel. The surgeon inserts a narrow viewing scope called a laparoscope through the incision.

A second small incision is made just above the pubic hairline, and a probe is inserted.

Once the tubes are found, the surgeon closes them using different methods: clips, tubal rings, or electrocoagulation (using an electric current to cauterize and destroy a portion of the tube).

Laparoscopy usually takes 20 - 30 minutes and causes minimal scarring. The patient is often able to go home the same day and can resume intercourse as soon as she feels ready.

Click the icon to see an illustrated series detailing tubal ligation.

Minilaparotomy. Minilaparotomy does not use a viewing instrument and requires an abdominal incision, but it is small -- about 2 inches long. The tubes are tied and cut. Generally speaking, minilaparotomy is preferred for women who choose to be sterilized right after childbirth, while laparoscopy is preferred at other times. Minilaparotomy usually takes approximately 30 minutes to perform. Women who undergo minilaparotomy typically need a few days to recover and can resume intercourse after consulting their doctor.

Laparotomy. Laparotomy, a less common approach, requires an extensive 2- to 5-inch incision in the abdomen. It is considered major surgery and can require a hospital stay of a few days followed by recovery at home for several weeks. Resumption of intercourse depends on how quickly one is able to recover.

Culdoscopy. Culdoscopy involves inserting a scope through the vagina and into the pelvic cavity. Although it is less invasive than laparoscopy, a major 2002 analysis reported that it has a higher complication rate than either laparoscopy or minilaparotomy.

Essure. Approved in 2002, the Essure method uses a small spiral-like device to block the fallopian tube. Unlike tubal ligation, the Essure procedure does not require incisions or general anesthesia. It can be performed in a doctor’s office and takes about 45 minutes. A specially trained doctor uses a viewing instrument called a hysteroscope to insert the device through the vagina and into the uterus, and then up into the fallopian tube. Once the device is in place, it expands inside the fallopian tubes. During the next 3 months, scar tissue forms around the device and blocks the tubes. This results in permanent sterilization.

Before undergoing sterilization, a woman must be sure that she no longer wants to bear children and will not want to bear children in the future, even if the circumstances of her life change drastically. She must also be aware of the many effective contraceptive choices available. Possible reasons for choosing female sterilization procedures over reversible forms of contraception include:

Not wanting children and being unable to use other methods of contraception

Health problems that make pregnancy unsafe

Genetic disorders

If married, both partners should completely agree that they no longer want to have children and should also have ruled out vasectomy for the man. Vasectomy is a simple procedure that has a lower failure rate than female surgical sterilization, carries fewer risks, and is less expensive. [See In-Depth Report #37: Vasectomy.]

Even if all these factors are present, a woman must consider her options carefully before proceeding. Studies report that over time, 14 - 25% of women eventually regret this choice. Women at highest risk for regretting sterilization include:

Women who are younger at the time of sterilization. In one long-term study, over 40% of women who had had tubal ligation between the ages of 18 - 24 regretted their choice. (Only about 4% of women over 35 had these regrets.)

Women who had the procedure immediately after a vaginal delivery.

Women who had the procedure within 7 years of having their youngest child.

Women in lower income groups.

If a woman changes her mind and wants to become pregnant, a reversal procedure is available, but it is very difficult to perform and requires an experienced surgeon. Subsequent pregnancy rates after reversal are between 20 - 84%, depending on the surgical skill, the age of the woman, and, to a lesser degree, her weight and the length of time between the tubal ligation and the reversal procedure. Not all insurance carriers cover the cost of reversal.

Women who choose sterilization no longer need to worry about pregnancy or cope with the distractions and possible side effects of contraceptives. Sterilization does not impair sexual desire or pleasure, and many people say that it actually enhances sex by removing the fear of unwanted pregnancy. There is some evidence it may help reduce the risk for ovarian cancer.

Failure is rare, but about 1 in 200 women become pregnant during the first year after sterilization, and failure rate can rise to 5% after 10 years. About a third of these pregnancies are ectopic, which require surgical treatment.

After any of the procedures, a woman may feel tired, dizzy, nauseous, bloated, or gassy, and may have minor abdominal and shoulder pain. In general, there is more postoperative pain with the tubal ring than with electrocoagulation.

Serious complications from female surgical sterilization are rare and are most likely to occur with abdominal procedures. They include bleeding, infection, or reaction to the anesthetic. On rare occasions the bowels or blood vessels are injured and require major surgical repair. The use of electrocoagulation poses a risk for burns in the small intestine and may increase the risk for menstrual disorders afterward.

Resources

www.nichd.nih.gov -- National Institute of Child Health and Human Development

www.plannedparenthood.org -- Planned Parenthood

www.engenderhealth.org -- EngenderHealth

http://ec.princeton.edu -- Emergency Contraception Website

www.acog.org -- American College of Obstetricians and Gynecologists

www.guttmacher.org -- The Alan Guttmacher Institute

References

Archer DF, Jensen JT, Johnson JV, Borisute H, Grubb GS, Constantine GD. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006 Dec;74(6):439-45. Epub 2006 Sep 18.

Cole JA, Norman H, Doherty M, Walker AM. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users. Obstet Gynecol. 2007 Feb;109(2 Pt 1):339-46.

Hannaford PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ. Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner's oral contraception study. BMJ. 2007 Sep 11; [Epub ahead of print]

Jick S, Kaye JA, Li L, Jick H. Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception. 2007 Jul;76(1):4-7. Epub 2007 May 11.

Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception. 2006 Mar;73(3):223-8. Epub 2006 Jan 26.

Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism with oral contraceptives containing norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel. Contraception. 2006 Jun;73(6):566-70. Epub 2006 Mar 29.

Kahlenborn C, Modugno F, Potter DM, Severs WB. Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis. Mayo Clin Proc. 2006 Oct;81(10):1290-302.

MacIsaac L. Intrauterine contraception: the pendulum swings back. Obstet Gynecol Clin North Am. 2007 March;34(1):91-111, ix.

Margolis KL, Adami HO, Luo J, Ye W, Weiderpass E. A prospective study of oral contraceptive use and risk of myocardial infarction among Swedish women. Fertil Steril. 2007 Aug;88(2):310-6. Epub 2007 Jul 10.

Martinez F, Avecilla A. Combined hormonal contraception and venous thromboembolism. Eur J Contracept Reprod Health Care. 2007 Jun;12(2):97-106.

van Vliet HA, Grimes DA, Helmerhorst FM, Schulz KF. Biphasic versus monophasic oral contraceptives for contraception. Cochrane Database Syst Rev. 2006 Jul 19;3:CD002032.

van Vliet HA, Grimes DA, Lopez LM, Schulz KF, Helmerhorst FM. Triphasic versus monophasic oral contraceptives for contraception. Cochrane Database Syst Rev. 2006 Jul 19;3:CD003553.

Review Date:
3/11/2008
Reviewed By:
A.D.A.M. Editorial Team: David Zieve, MD, MHA, Greg Juhn, MTPW, David R. Eltz, Kelli A. Stacy, ELS. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (10/29/2007).

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).

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Alzheimer's disease

FitSugar — Wed, 08 Oct 2008 17:35:13 -0700

In This Report

Highlights

Introduction

Causes

Risk Factors

Prevention

Symptoms

Diagnosis

Medications

Stages

Resources

References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Alzheimer’s Disease Toll Increasing

More than 5 million Americans now have Alzheimer’s disease, and the number could increase to 16 million by mid-century, according to a 2007 report from the Alzheimer’s Association.

New Drug Indication

In 2006, the FDA expanded the use of donepezil (Aricept) to include treatment of people with severe dementia associated with Alzheimer’s disease. Donepezil was previously approved only for people with mild-to-moderate dementia.

Managing Psychotic and Behavioral Symptoms

Newer antipsychotic drugs are no better than placebo for controlling psychosis, aggression, and agitation in patients with Alzheimer’s disease, indicates an important study in the New England Journal of Medicine. In addition, these drugs can cause severe side effects and have been associated with increased death rate.

Non-drug approaches, such as behavioral techniques and bright light boxes, may be helpful for these patients, suggests an Archives of Internal Medicine study.

Brain Exercises Prevent Mental Decline

Cognitive training exercises that help boost memory, reasoning, and processing speed may help slow mental decline and improve functional abilities in older adults, indicates a Journal of the American Medical Association study.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Do Not Prevent Alzheimer’s

The NSAIDs naproxen (Aleve) and celecoxib (Celebrex) do not protect against Alzheimer’s disease, indicates a data analysis from a large-scale U.S. National Institutes of Health (NIH) clinical trial.

Docosahexaenoic Acid (DHA) for Alzheimer’s Prevention

DHA, an omega-3 fatty acid found in some types of fish, may lower the risk for dementia and Alzheimer’s disease as well as delay its progression. However, researchers are uncertain whether DHA dietary supplements provide the same benefits as food sources (salmon, mackerel, and other types of fatty fish). In 2007, the NIH announced the launch of a national clinical trial to evaluate whether DHA can slow cognitive and functional decline in people with mild-to-moderate Alzheimer’s disease.

Support for Caregivers

Intensive programs that combine counseling, support groups, and problem-solving techniques can dramatically improve caregivers’ quality of life and may help delay patients’ transfers to nursing homes, several recent studies suggest.

Introduction

Alzheimer's disease (AD) is a degenerative disease of the brain from which there is no recovery. The disease slowly attacks nerve cells in all parts of the cortex of the brain and some surrounding structures, thereby impairing a person's abilities to govern emotions, recognize errors and patterns, coordinate movement, and remember. Ultimately, a person with AD loses all memory and mental functioning.

The major areas of the brain have one or more specific functions.

Causes

Researchers are finding specific biologic factors involved with Alzheimer's disease. Various environmental and genetic players appear to contribute to or trigger the process by which these factors destroy nerve cells leading to this disease.

Imaging techniques in patients with Alzheimer's disease have found significant loss of cells and volume in the regions of the brain devoted to memory and higher mental functioning. Important abnormalities have specifically been observed during biopsies:

Twisted nerve cell fibers, known as neurofibrillary tangles

A sticky protein, beta amyloid

Other factors also play a role.

Click the icon to see an animation about Alzheimer's disease.

The Effects of Neurofibrillary Tangles and Beta Amyloid in Alzheimer's Disease. These biologic factors appear to be involved in the development Alzheimer's disease in the following ways:

Neurofibrillary tangles are the damaged remains of microtubules, the support structure that allows the flow of nutrients through the neurons (nerve cells). A key component in these tangled fibers is an abnormal form of the tau protein, which in its healthy version helps in the assembly of the microtubule structure. The defective tau, however, appears to block the actions of the normal version.

Beta Amyloid (also called A beta) is the second significant finding. This insoluble protein accumulates and forms sticky patches called neuritic plaque, which are found surrounded by the debris of dying nerve cells in the brains of Alzheimer's victims.

Amyloid precursor protein (APP) is a large nerve-protecting protein that is the source of beta amyloid. In Alzheimer's certain enzymes, particularly those called gamma-secretases, snip APP into beta amyloid pieces. This process is controlled by factors called presenilin proteins. (Genetic abnormalities that affect either APP or presenilin proteins occur in some inherited cases of early-onset Alzheimer's.)

High levels of beta amyloid are associated with reduced levels of the neurotransmitter acetylcholine. (Neurotransmitters are chemical messengers in the brain.) Acetylcholine is part of the cholinergic system, which is essential for memory and learning and is progressively destroyed in Alzheimer's disease.

Beta amyloid may also disrupt channels that carry sodium, potassium, and calcium. These elements serve the brain as ions, producing electric charges that must fire regularly in order for signals to pass from one nerve cell to another. If the channels that carry ions are damaged, an imbalance can interfere with nerve function and signal transmission.

Click the icon to see an image of amyloidosis.

Other Proteins. Researchers have now identified other important proteins in the areas of the brain affected by Alzheimer's disease.

ERAB (endoplasmic-reticulum associated binding protein) appears to combine with beta amyloid, which in turn attracts new beta amyloid from outside the cells. High amounts of ERAB may also enhance the nerve-destructive power of beta amyloid.

AMY plaques resemble beta amyloid so closely that researchers were able to detect them only with the use of highly sophisticated techniques.

Elevated levels of a protein called prostate apoptosis response-4 (Par-4) may cause nerve cells to self-destruct.

Researchers are also attempting to discover why beta amyloid is so toxic to nerve cells. Some researchers are focusing on two processes in the body that may be involved with Alzheimer's disease: oxidation and the inflammatory process. There is some evidence that such events can begin decades before Alzheimer's disease actually develops. One scenario for their role in Alzheimer's is as follows:

The Role of Oxidation.

As beta amyloid breaks down it releases unstable chemicals called oxygen-free radicals. Once released, oxygen-free radicals bind to other molecules through a process called oxidation.

Oxidation is the result of many common chemical processes in the body, but when oxidants are overproduced, they can cause severe damage in cells and tissue, including even affecting genetic material in cells (its DNA). Oxidation is known to play a role in many serious diseases, including coronary artery disease and cancers, and experts believe it may also contribute to Alzheimer's.

The Inflammatory Response.

One result of oxidation is the marshaling of immune factors to repair the cellular injuries it produces. Overproduction of some of these factors, however, produces the so-called inflammatory response, in which the immune process itself can actually damage the body's own cells themselves.

Principle immune cells in the brain are called macrophage/microglia (M phi). In the healthy brain, they play an important protective role against invading organisms. However, when they are activated by beta amyloid oxidation, they release toxic molecules called cytokines, which are known to cause harm. For example, significantly high levels of interleukin-6, a specific cytokine, have been detected in people with Alzheimer's.

Other inflammatory factors of specific interest in Alzheimer's research are the enzyme cyclooxygenase (COX) and its products called prostaglandins. Excess amounts of these factors may increase levels of glutamate. Glutamate is an amino acid that excites nerves and, when overproduced, is a powerful nerve-cell killer.

The inflammatory process has also been associated with the release of soluble toxins called amyloid beta-derived diffusible ligands, which some investigators believe may prove to key players in the destructive process.

Major research targets in Alzheimer's disease are the factors responsible for beta amyloid build-up and concentration in certain people and not in others. Genetic factors are believed to play a role in many cases. In 2003, the National Institute on Aging (NIA) launched the ambitious AD Genetics Initiative, a 3-year national project to bank genetic material from families who have at least two members with late-onset Alzheimer's.

The ApoE Gene and Late-Onset Alzheimer's. The major target in genetic research on late-onset Alzheimer's disease (called LOAD) has been apolipoprotein E (ApoE), which plays a role in the movement and distribution of cholesterol for repairing nerve cells during development and after injury.

The gene for ApoE comes in three major types:

ApoE4. Studies have reported the greatest deposits of beta amyloid in people with ApoE4, which is now believed to be a major risk factor for late-onset Alzheimer's. Some evidence suggests that the ApoE protein removes beta amyloid but the ApoE4 variant does so less efficiently than other ApoE types. (ApoE4 has also been studied for years as a risk factor for heart disease.)

ApoE3 and ApoE2. Fewer beta amyloid deposits have been observed in people with the ApoE3, and the fewest deposits have been observed in people with ApoE2, which may actually be protective.

People inherit a copy of one type from each parent, but Alzheimer's disease is not inevitable even in people with two copies of the ApoE4 gene. Reports vary widely in estimating the extent of risk:

People without ApoE4 have an estimated risk of between 9 - 20% for developing Alzheimer's by age 85.

In people with one copy of the gene, the risk is between 25 - 60%.

In people with two copies, the risk ranges from 50 - 90%. (Only 2% of the population carries two copies of the ApoE4 gene.)

Some researchers suspect that some specific variation of the ApoE4 gene or combinations with other genes are critical for the disease, since many people who carry the ApoE4 exhibit no signs of Alzheimer's. For example, evidence suggests that genetic factors play a role in a common subtype of late-onset Alzheimer's disease that also includes psychosis. An important 2002 genetic study has identified certain genetic linkages associated with ApoE4 that appear to play a strong role in this subtype.

Other Genetic Factors in Late-Onset Alzheimer's. Most people with late-onset Alzheimer's disease do not carry the ApoE4 gene. Increasingly, researchers believe that many cases of late-onset Alzheimer's result from a combination of genetic factors that participate in the process of producing or degrading beta amyloid. Some under investigation include:

Researchers are targeting chromosomes 9, 10, and 12 as possible locations for genetic factors involved with Alzheimer's disease. (The ApoE4 gene is on chromosome 19.) In 2005, researchers announced that mutations linked to the ubiquilin 1 (UBQLN1) gene, located on chromosome 9, might be associated with increased risk for late-onset Alzheimer's disease.

Researchers have detected mutations in the proteins amyloid precursor protein (APP) and ubiquitin-B (Ubi-B), which may account for some cases of late- and early-onset Alzheimer's. Such mutations are not inherited, however, but appear to be genetic mistakes that occur during transcription, the coding process in which DNA establishes the pattern for the production of its proteins and other molecules.

In 2007, researchers identified mutations in the SORL1 gene as a possible factor in late-onset Alzheimer’s disease. Researchers think that variations in this gene may contribute to amyloid plaque formation in Alzheimer’s disease.

Genetic Factors for Early-Onset Alzheimer's. Scientists are coming closer to identifying defective genes responsible for early-onset Alzheimer's, an uncommon, but extremely aggressive form of the disease.

Mutations in genes known as presenilin-1 (PS1) and presenilin-2 (PS2) account for most cases of early-onset inherited Alzheimer's disease. The defective genes appear to accelerate beta amyloid plaque formation and apoptosis, a natural process by which cells self-destruct.

Genetic mutations in the genes that control amyloid precursor protein (APP) are also being targeted as causes of early-onset Alzheimer's. The genetic disease Down syndrome, for example, overproduces beta-amyloid precursor protein (APP), the source of beta amyloid, and almost always leads to early Alzheimer's. Other APP mutations are being identified.

Researchers are also investigating environmental factors (infections, metals, industrial and other toxins) that may trigger oxidation, inflammation, and the disease process, particularly in people with a genetic susceptibility to Alzheimer's.

Infectious Organisms. Slow, infectious viruses cause a number of other degenerative neurologic diseases, such as kuru and Creutzfeldt-Jakob disease.

Click the icon to see an image of Creutzfeldt-Jakob disease.

Although no specific virus has been linked to Alzheimer's, some researchers theorize that people with a genetic susceptibility to Alzheimer's may be vulnerable to the actions of certain viruses, particularly under circumstances when the immune system may be weakened.

Metals. Some laboratory studies have reported excessive amounts of metal ions such as zinc, copper in the brain of people with Alzheimer's disease. Such ions may possibly change the chemical architecture of normal beta amyloid, making it more harmful. A mildly acidic environment appears to be important in the process that binds these metals to beta amyloid. Experts observe that such conditions (acidic environment and higher levels of zinc and copper) commonly occur as part of the inflammatory response to local injury.

Electromagnetic Fields. Some studies on people exposed to intense electromagnetic fields (EMF) have reported a higher incidence of Alzheimer's. However, the association between EMF and Alzheimer's is very weak.

Risk Factors

Alzheimer's disease is the seventh leading cause of death in American adults. It affects about 5 million Americans and 8 million more people worldwide. According to the U.S. Alzheimer’s Association, 1 in 8 people age 65 and older, and nearly 1 in 2 people over age 85, have Alzheimer’s disease.

Age is the greatest risk factor for Alzheimer's disease. The number of cases of Alzheimer's disease doubles every 5 years in people over 65. By age 85, almost half of all people are afflicted. People with the disease survive, on average, half as long as similarly aged adults without the disease.

With the increasing numbers of aging adults, unless effective methods for prevention and treatment are developed, Alzheimer's disease will reach epidemic proportions, afflicting about 16 million Americans within 50 years. Evidence points to older age, high blood pressure, cholesterol levels, and a family history of the disease as the most important risk factors for Alzheimer's disease.

Several studies have reported that women have a much higher risk for Alzheimer's disease than men. If there is a gender difference, it is likely to be due estrogen, the primary female hormone, which appears to have properties that protect against the memory loss and lower mental functioning associated with normal aging. Such actions include blocking production of beta amyloid, offering antioxidant protection, and regulating blood sugar (glucose) levels in the brain. The drop in estrogen levels after menopause may explain a higher risk for Alzheimer's disease in older women than in men. (Testosterone, the male hormone, converts to estrogen, which may help protect men.) Studies have been mixed, however, on the association between the decline in natural estrogen levels and mental functioning in older women.

People with a family history of the disease are at higher than average risk for Alzheimer's disease. Researchers are identifying important genetic factors, notably the ApoE4 gene, that may be responsible for late- and early-onset cases.

Dietary and other cultural factors that increase the risk for hypertension and unhealthy cholesterol levels may also play a role. For example, a study of Japanese men showed that their risk increased if they emigrated to America. And the disease is much less common in West Africa than in African-Americans, who share the same or higher risk with Caucasians in America.

High blood pressure and unhealthy cholesterol levels -- the same important risk factors for heart disease and stroke -- may also be risk factors for Alzheimer's disease. In fact, they appear to be more important than ApoE4, the genetic factor most commonly associated with Alzheimer's disease.

Blood pressure is the force applied against the walls of the arteries as the heart pumps blood through the body. The pressure is determined by the force and amount of blood pumped and the size and flexibility of the arteries.

High Blood Pressure. Studies have reported an association between Alzheimer's disease and systolic hypertension (the higher and first number in blood pressure measurement). High blood pressure can cause problems with the vascular system, which is responsible for delivering blood to the brain. Recent research suggests that some types of blood pressure medication may lower Alzheimer's risk.

High Cholesterol Levels. Research indicates an association between high cholesterol levels and Alzheimer's disease in some people. One theory is that cholesterol regulates the processing and accumulation of amyloid beta-protein.

Click the icon to see an image of cholesterol.

Stroke. High blood pressure and heart disease can increase the risk for stroke. For people who have Alzheimer’s disease or mild cognitive impairment, stroke can increase the decline of cognitive function and accelerate dementia.

Diabetes. Patients with diabetes often have high blood pressure, lipid imbalances, and circulatory disorders that affect the heart and vascular system, which in turn increases the risk for Alzheimer’s. In patients who do not have other risk factors for Alzheimer’s, diabetes itself may increase risk. Research also suggests that diabetes can increase the risk for mild cognitive impairment, a condition that often precedes Alzheimer’s disease.

High Homocysteine Levels. Homocysteine is an amino acid that has been identified as a modest risk factor in heart disease. It has also been associated with a higher risk for Alzheimer's disease. High levels are general due to deficiencies of the B vitamins B6, B12, and folate. Such vitamins are also related to nerve protection. Researchers theorize that homocysteine impairs the ability of DNA to repair nerve cells. The weakened cells are then more vulnerable to the harmful effects of oxidized beta amyloid.

Nearly all patients who inherit Down syndrome develop changes in the brain that resemble Alzheimer's if they live into their 40s, although onset varies and can occur as late as age 70. Women under the age of 35, but not older mothers, who give birth to children with Down syndrome are also at much higher risk for Alzheimer's.

Lower Education and Economic Groups. A number of studies have reported either a higher risk for Alzheimer's disease in people with less education or a lower risk for Alzheimer's disease in those who remain mentally active. Some experts speculate that learning itself may stimulate more neurons to grow and thus create a larger reserve in the brain so that it takes longer for brain cells to be destroyed. Some evidence suggests that early malnutrition, which is more likely to occur in lower income and educational groups, has been associated with smaller brains and with Alzheimer's disease in old age. Low-birth weight can cause problems in growth factors that could affect both mental and physical health later on in adulthood.

Small Head Size. The size of the skull is fixed by age 7. Brain size approximates the head size until old age, when it begins to shrink. Some evidence has reported an association between small head size (and therefore less brain volume) and Alzheimer's disease, possibly because people who start with larger brains can sustain more injury over time. For example, a 2002 study indicated that it was reduction in overall brain volume, not specific regions, that contributed to mental impairment in older healthy adults. Another study reported that people who had small heads plus the ApoE4 gene had 14 times the risk for Alzheimer's disease than those without this combination. Nevertheless, other studies have found no association between a small head size and Alzheimer's disease.

Some experts suggest that the relationship observed in other research may simply be due to social and economic factors, such as malnutrition or low birth weight, which have been associated with both Alzheimer's disease and small head size. Small head size independent of other factors, they argue, does not pose a higher risk for either Alzheimer's disease or low intelligence

Depression. There is a significant overlap between depression and dementia in the elderly. In fact depression itself is often an early symptom of Alzheimer's disease. In a 2002 study of Catholic nuns, for each of four depressive symptoms, the risk for developing Alzheimer's disease increased by an additional 19%. For example, for a woman with four depressive symptoms the risk increased by 76%. Some evidence suggests that there may even be common genetic factors in people who have both early depression and Alzheimer's disease.

Head Injury. Some studies have found an association between serious head injuries in early adulthood and the development of Alzheimer's. It is not yet known if such injuries directly cause Alzheimer's or simply accelerate the disease in people who are already susceptible to it.

Prevention

Although there is no strong evidence that any lifestyle change can prevent Alzheimer's disease, studies suggest that certain behaviors may help protect against mental decline. In particular, medications and lifestyle choices that protect the heart may be of specific importance. Various preventive drugs are under investigation, including antioxidant and anti-inflammatory therapies.

In 2004, the National Institutes of Health (NIH) halted a large clinical trial that was investigating the use of anti-inflammatory drugs in preventing Alzheimer's disease. While prior data had confirmed that NSAIDs were not effective in treating AD, research continued to explore these drugs' potential preventive benefits.

The Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT) was launched in 2001 to investigate whether long-term use of naproxen (Aleve) or celecoxib (Celebrex) could decrease the risk of developing AD. The trial was based on the premise that because inflammation is known to be involved in the process of Alzheimer’s disease, anti-inflammatory drugs may help to prevent it. The NIH suspended this trial due to evidence that the NSAID naproxen was associated with increased incidence of cardiovascular and cerebrovascular events among participants. No adverse effects appeared during this trial for the COX-2 inhibitor celecoxib. However, heart safety concerns about this drug had been raised in other trials, and investigators did not believe that celecoxib's potential benefits outweighed its risks.

Since 2004, the ADAPT investigators have continued to monitor the trial’s participants to see if these treatments had any effect in changing their risk for Alzheimer’s. In an update analysis of ADAPT data published in 2007, the researchers announced that neither naproxen nor celecoxib appear to reduce the risk for Alzheimer’s.

The same lifestyle and medical choices that reduce risk factors for heart disease and diabetes are important for reducing the risk for Alzheimer's disease. And, experts believe that treating high blood pressure and diabetes may help slow the progression of Alzheimer’s disease. The following are some heart-protective medications that may also protect the brain.

Blood Pressure Drugs. Because high blood pressure is associated with increased risk of Alzheimer’s, researchers have been studying whether blood pressure medication can reduce this risk. In a 2006 study of patients who took high blood pressure drugs, researchers found that potassium-sparing diuretics reduced the risk of developing Alzheimer’s by 70%. Beta-blockers and certain calcium channel blockers also helped to a lesser extent. ACE inhibitors appeared to offer no protection.

Statins. Statins are common drugs used to lower cholesterol levels. In past years, a number of studies reported a significantly lower risk for Alzheimer's disease in patients who took statins. However, newer studies have failed to prove that statins can help prevent Alzheimer's disease. In these recent studies, large numbers of elderly people had their dementia evaluated at baseline and then monitored over several years. The results indicated that statin use did not predict onset of AD. In the meantime, the NIH is conducting a clinical trial to investigate whether simvastatin can slow the progression of AD.

Hormone Replacement Therapy. Hormone replacement therapy (HRT) has been studied for years for health effects after menopause, including its effect on mental decline. A number of studies, including a major 2003 analysis, have found no differences in mental performance and no protection from Alzheimer's disease in women taking HRT compared to non-users. The 2003 trial, called the Women's Health Initiative Memory Study (WHIMS), enrolled 4,500 women over 65 years of age. The WHIMS study showed that older postmenopausal women who took combination HRT (estrogen plus progestin) had twice the risk of developing dementia than similarly aged women who received placebo pills. In addition to increasing the risk for dementia (including Alzheimer's disease), combination HRT failed to prevent the development of mild cognitive impairment. Based on these results, the researchers from the National Institute on Aging (NIA) recommended against prescribing combination hormone therapy to older women for maintaining or improving cognitive function. The NIA continued to research whether estrogen-only therapy could prevent or delay the onset of Alzheimer's disease. Results released in 2004 indicated that women ages 65 years and older who took estrogen-only HRT had a slightly increased risk of developing dementia.

Testosterone. Some testosterone converts to estrogen, which may be why older men appear to have a lower risk for Alzheimer's disease than older women. Animal studies have suggested that testosterone may help reduce levels of beta amyloid. There is also some evidence that low testosterone levels may be a particular risk factor in men with the ApoE4 gene. Some experts believe that giving testosterone to elderly men, and combinations of testosterone and estrogen to older women, may prove to be protective. Side effects of testosterone in women include increased body hair, acne, fluid retention, anxiety, and depression. Long term benefits or serious adverse effects are unknown.

DHEA. Dehydroepiandrosterone (DHEA) is a male-like hormone in the body that declines with age. Some evidence suggests that it may help reduce mental decline in older women, but not in older men. Studies are under way. The hormone may, however, reduce HDL (the so-called good cholesterol) when taken in higher doses. While its effect on cancer-cell growth is unknown, some evidence indicates that high levels may increase cancer risk. In any case, DHEA is not regulated, and brands vary widely in their content.

Because Alzheimer's disease rates vary among different populations, investigators are researching how diet can help in prevention. Caloric intake itself may play a role in brain health. In one study on animals, restricting calories below normal (but above starvation levels) helped prevent age-related nerve degeneration. However, in patients with existing Alzheimer's, weight loss is a strong indicator of mental decline.

Fats and Oils. Some studies suggest an association between fat and Alzheimer's disease:

In China and Nigeria, where fat intake is low, the risk of developing Alzheimer's is 1% at age of 65 compared to 5% in the U.S.

A study in the Netherlands reported an association between dementia and diets high in total fat, saturated fat, and cholesterol.

A number of studies suggest that a high-fat high-calorie diet in people who carry the ApoE4 gene may confer a particularly high risk. For example, in one study, adults who carried the ApoE4 gene and whose diet consisted of 40% fat calories had 29 times the risk for Alzheimer's compared to non-ApoE4 carriers on the same high-fat diet.

The recommended dietary goal is to limit total fat intake to 25 - 35% of total daily calories. But not all fats are alike. Unhealthy fats include saturated fats (contained in animal products such as meat) and trans-fatty acids (contained in fast foods and commercially baked products). The American Heart Association recommends limiting saturated fat intake to less than 7% of total daily calories and trans-fatty acid intake to less than 1% of total daily calories.

It is best to replace saturated fats and trans-fatty acids with unsaturated fats from plant and fish oils. Omega-3 fatty acids are excellent sources of unsaturated fats. Plant sources of omega-3 fatty acids include canola oil, soybeans, flaxseed, and certain types of nuts such as walnuts. For fish sources, salmon, mackerel, sardines, lake trout, herring, and albacore tuna are especially high in marine omega-3 fatty acids. For heart health, and possibly brain health, experts recommend eating these types of fish at least twice a week.

Two types of omega-3 fatty acids are found in fish oils: Docosahexaenoic acid (DHA) and eicosapentaneoic acid (EPA). Researchers are particularly interested in the role that DHA may play in Alzheimer’s disease prevention. DHA has been linked to many brain cell functions, and appears to have particular importance for aging brains. Studies indicate that people who have higher blood levels of DHA have a much lower risk of developing dementia and Alzheimer’s disease.

Although evidence suggests that consuming DHA-rich foods later in life helps to increase DHA levels in the brain, it is unclear whether dietary supplements can provide similar benefits. A 2007 study indicated that omega-3 fatty acid supplements may help slow cognitive decline in some patients with very mild Alzheimer’s disease, but that the supplements have little effect for advanced stages of the disease. In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to evaluate whether DHA supplements can slow the progression of cognitive and functional decline in people with mild-to-moderate Alzheimer’s disease.

Mediterranean diet is an eating plan that has specific heart-health benefits. It is rich in fiber and nutrients, including omega-3 fatty acids and antioxidant vitamins. The diet emphasizes fish, fruits, vegetables, and monounsaturated (“good”) fats, particularly olive and canola oils. A 2006 study suggested that the Mediterranean diet may also be good for the brain. In the study, patients who strictly followed the diet had a 40% lower risk of developing Alzheimer’s disease than patients who ate a conventional American diet. Other studies also indicate the Mediterranean diet is associated with a lower risk for Alzheimer’s.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with IBD (inflammatory bowel disease).

Fruits and Vegetables. According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. Blueberries, which are very rich in antioxidants, are of particular interest. A 2006 study of over 3,000 elderly adults found that consumption of vegetables (especially green leafy vegetables) helped reduce the rate of cognitive decline, but fruit intake had no effect.

Alcohol. Some studies have suggested that moderate intake of alcohol (one or two drinks a day) may protect the aging brain, possibly by releasing acetylcholine, the chemical in the brain that is deficient in Alzheimer's disease. Not all studies have been positive. In any case, heavy alcohol consumption offers no protection and is dangerous.

Folate and Vitamin B12. Some studies suggest that deficiencies of vitamins B6, B12, and folate (folic acid) may be a risk factor for Alzheimer' diseases. Deficiencies in these vitamins can increase homocysteine levels, which some research associates with a higher risk for Alzheimer's disease. Foods containing folate include avocados, bananas, oranges, asparagus, green leafy vegetables, and dried beans. In the United States and some other countries, grain and cereal products are fortified with folate. B12 is found only in animal, dairy, and fish products. B6 is found in a variety of foods, including fortified cereals, beans, meat, fish, and some fruits and vegetables.

Click the icon to see an image of vitamin B12 sources.

Click the icon to see an image of folate sources.

Research is still inconclusive and conflicting about whether increased consumption of folate, through food or dietary supplements, can help prevent Alzheimer’s disease or slow its progression. A small 2006 study of healthy older adults, published in the New England Journal of Medicine, found that supplements containing folate, vitamin B12, and vitamin B6 did not help improve cognitive performance. A 2007 Lancet study indicated that folic acid supplements may help slow cognitive decline. People in the Lancet study took 800 mcg of folic acid daily, which is twice the recommended daily allowance of 400 mcg. However, this study was conducted in the Netherlands, where people tend to get less folate in their daily diets than in the United States.

Another 2007 study found that elderly people who consumed folate from both diet and supplement sources had a reduced risk for Alzheimer’s disease. Neither diet alone nor supplements alone affected Alzheimer’s risk; only the combination of the two produced an effect. The study also indicated that vitamins B6 and B12 do not affect Alzheimer’s risk.

Antioxidant Supplements. Much research on Alzheimer's disease has indicated that oxidation (release of damaging unstable particles) may play an important role in the disease process. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. Other studies suggest that vitamin E protects only those who carried the ApoE4 gene. Most of the evidence finding any benefits from other antioxidants comes from using a combination of antioxidant vitamins, such as vitamins C and E, but not from using them separately. However, there is no strong evidence of protection to date from using antioxidant supplements.

Physical Exercise. Studies indicate that exercise may help prevent the development of Alzheimer’s disease and other forms of dementia. A 2006 study found that older adults (65 years and older) who exercised three times a week reduced their risk for Alzheimer’s by about 40%. Exercise in the study included walking, hiking, aerobics, calisthenics, swimming, water aerobics, weight training, and stretching.

Mental Exercise. Cognitive training that includes exercises to stimulate memory, reasoning, and mental processing speed may help improve both mental ability and daily functioning. In an important 2006 study in the Journal of the American Mental Association, older community-dwelling adults who received cognitive training showed reductions in cognitive decline. In addition, they were better able to handle daily living tasks -- such as performing housework, managing money, and preparing meals -- than people who did not receive the training. The benefits of cognitive training lasted for up to 5 years afterwards. Other studies indicate that participating in intellectually engaging activity -- such as doing crossword puzzles or learning a new language -- may help reduce the risk of Alzheimer’s disease.

Social Interaction. Social interaction is also important for maintaining emotional health as well as keeping the mind active and energized. A 2007 study indicated that adults who are lonely have twice the risk of developing Alzheimer’s dementia as those who are not socially isolated.

Symptoms

The early symptoms of Alzheimer's disease (AD) may be overlooked because they resemble signs of natural aging. Older adults who begin to notice a persistent mild memory loss of recent events may have a condition called mild cognitive impairment (MCI). MCI is now believed to be a significant sign of early-stage Alzheimer's in older people. Studies now suggest that older individuals who experience such mild memory abnormalities can later develop Alzheimer's disease.

Early symptoms of Alzheimer's disease may include:

Forgetfulness (particularly of recent events or information)

Loss of concentration (having trouble planning or completing familiar tasks, difficulty with abstract thinking such as simple arithmetic problems)

Language problems (forgetting the names of objects, mixing up words, difficulty completing sentences)

Confusion about time and place (difficulty recognizing familiar neighborhoods or remembering how you arrived at a location, confusion about months or seasons )

Impaired judgment (dressing inappropriately or making poor financial decisions)

Impaired movement and coordination (slowing of movements, halting gait, reduced sense of balance)

Mood and behavior changes (rapid mood swings, emotional outbursts, personality changes, increased fear or suspicion)

Apathy and depression (loss of interest in activities, increased sleeping, sitting in front of the television for long periods of time)

Diagnosis

A definitive test to diagnose Alzheimer's disease, even in patients showing signs of dementia, has not yet been developed. A number of expert groups have developed criteria to help diagnose Alzheimer's disease and rule out other disorders. A diagnosis often involves answering questions about the patient:

Do psychological tests indicate dementia?

Does the patient have deficits in two or more areas of mental functioning (such as language, motor skills, and perceptions)?

Has memory and mental functions gotten progressively worse?

Is consciousness disturbed? (It is not in Alzheimer's disease.)

Is the patient over age 40?

Are other medical or physical conditions present that could account for the same symptoms?

Are daily activity impaired or has the behavior changed?

Is there a family history of Alzheimer's disease?

Are there other symptoms, such as depression, insomnia, incontinence, delusions, hallucinations, dramatic verbal, emotional or physical outbursts, sexual disorders, and weight loss?

Other steps involved in making a decision include laboratory tests (EEG and possibly tests to rule out other diseases) and psychological testing to determine the presence of dementia.

Although some memory impairment occurs in many people as they age, only some of these people develop Alzheimer's disease. Many similar symptoms can occur in healthy older individuals from other conditions associated with aging:

Fatigue

Grief or depression

Illness

Vision or hearing loss

The use of alcohol or certain medications

Simply the burden of too many details to remember at once

The first step in diagnosing Alzheimer's disease is to rule out other conditions that might cause memory loss or dementia. There are a number of causes for dementia in the elderly besides Alzheimer's disease:

Vascular dementia (abnormalities in the vessels that carry blood to the brain)

Lewy bodies variant (LBV), also called dementia with Lewy bodies

Parkinson's disease

Frontotemporal dementia

Experts believe that 60% of cases of dementia are due to Alzheimer's, 15% to vascular injuries, and the rest are a mixture of the two or caused by other factors.

Vascular Dementia. Vascular dementia is primarily caused by either multi-infarct dementia (multiple small strokes) or Binswanger's disease (which affects tiny arteries in the midbrain). One major analysis suggested that patients with vascular dementia have better long-term verbal memory than patients with Alzheimer's disease, but poorer executive function (less ability to integrate and organize).

Lewy Bodies Variant. Lewy bodies are abnormalities found in the brains of patients with both Parkinson's disease and Alzheimer's. They can also be present in the absence of either disease; in such cases, the condition is called Lewy bodies variant (LBV). In all cases, the presence of Lewy bodies is highly associated with dementia. LBV was defined in 1997, and some experts believe it may be responsible for about 20% of people who have been diagnosed with Alzheimer's. They can be difficult to distinguish. Compared to Alzheimer's disease patients, those with LBV may be more likely to have hallucinations and delusions early on, to walk with a stoop (similar to Parkinson's disease), to have more fluctuating attention problems, and to perform better than Alzheimer's disease patients on verbal recall but less well with organizing objects.

Parkinson's Disease. Dementia is about six times more common in the elderly Parkinson patient than in the average older adult. It is most likely to occur in older patients who have had major depression. Unlike in Alzheimer's, language is not usually affected in Parkinson's related dementia. Visual hallucinations occur in about a third of people on long-term medications.

Parkinson's disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination.

Frontotemporal Dementia (FTD). Once considered rare, FTD is now considered to be the second most common cause of early-onset dementia. People who develop this condition tend to be in their mid-fifties although it can develop later on. It results in greater behavioral impairment (apathy, reduced empathy, poor self-care, unrestrained behavior) than with Alzheimer's disease. It may also be marked by speech problems and early incontinence. Brain imaging scans can help diagnose this problem.

Other Conditions that Cause Similar Symptoms. Some elderly people have a condition called mild cognitive impairment, which involves more severe memory loss than normal but no other symptoms of Alzheimer's. A number of conditions, including many medications, can produce symptoms similar to Alzheimer's:

Severe depression

Drug abuse

Thyroid disease

Severe vitamin B12 deficiency

Blood clots

Hydrocephalus (excessive accumulation of spinal fluid in the brain)

Syphilis

Huntington's disease

Creutzfeldt-Jakob disease

Brain tumors

It is important that the doctor recognize any treatable conditions that might be causing symptoms or worsening existing dementia caused by Alzheimer's or vascular abnormalities.

A number of psychological tests are used or being developed to assess difficulties in attention, perception, and memory and problem-solving, social, and language skills. Experts are researching specific tests that may help identify early on people with mild memory impairment who are at high risk for Alzheimer's disease.

Two commonly used tests that are very useful in identifying individuals who may be at risk for Alzheimer's are the Mini-Mental State Exam (MMSE) and the Mattis Dementia Rating Scale. Still, these tests have limitations.

A clock drawing test is also a good test for Alzheimer's disease. The patient is given a piece of paper with a circle on it and is first asked to write the numbers in the face of a clock and then to show "10 minutes after 11." The score is based on spacing between the numbers and the positions of the hands.

Electroencephalography (EEG) traces brain-wave activity; in some patients with Alzheimer's disease this test reveals "slow waves." EEG data helps distinguish a potential patient with Alzheimer's disease from a patient with severe depression, whose brain waves are normal.

Imaging tests include magnetic resonance imaging (MRI), positron-emission tomography (PET), and single photon emission computed tomography (SPECT). These tests are sometimes used to rule out other disorders, such as multi-infarct dementia, stroke, blood clots, and tumors. Research is being conducted to determine if these tests can help to confirm a diagnosis of Alzheimer's disease and improve understanding of disease progression. Researchers hope that imaging tests may also be able to provide diagnoses of Alzheimer’s disease while it is still in its early stages.

In 2006, scientists developed a new imaging molecule called FDDNP that they hope will enable earlier detection of Alzheimer’s disease. Research also continues on Pittsburgh compound B, a tracer molecule used in PET brain scans to highlight beta-amyloid protein deposits. Results from all this research may help to define potential drug targets and aid in the development of new Alzheimer's drugs.

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

In 2005, the National Institute of Aging, in collaboration with industry partners, launched the $60 million Alzheimer's Disease Neuroimaging Initiative (ADNI). This landmark 5-year clinical trial, which will be conducted at 50 sites throughout the United States and Canada, will investigate whether neuroimaging techniques, such as MRI and PET scans, can be combined with biomarkers and neuropsychological tests to measure the progression of AD and mild cognitive impairment. In 2004, the U.S. Medicare system expanded insurance coverage of PET scans for eligible beneficiaries who meet specific diagnostic criteria for both Alzheimer's disease and fronto-temporal dementia. Medicare also covers the costs for patients enrolled in its agency-approved imaging clinical trials.

Blood Tests. Blood tests are currently used to check for anemia and other disorders that can produce dementia symptoms. Investigators are researching serum biomarkers, such as the iron transport protein p97, that might help detect the presence of Alzheimer's disease.

Cerebrospinal Fluid Test. Scientists are developing new nanotechnology screening methods that may eventually be used to identify Alzheimer's disease while it is still in its earliest stages and before plaque deposits accumulate. In 2005, a research team announced it had used a bio-barcode assay to detect tiny amounts of a protein called amyloid-beta-derived diffusable ligand (ADDL) in cerebrospinal fluid. ADDLs may be involved in cognitive decline and are a potential biomarker for early stage Alzheimer's disease. Tests for other proteins are also being developed.

Odor Test. Investigators are also using the impairment of smell in Alzheimer's disease to develop tests that require patients to distinguish between odors.

Once a diagnosis has been made, some experts observe that certain factors at the time of diagnosis indicate a higher risk for a more rapid decline:

Older age

Being male

The presence of high blood pressure

Signs of loss of motor control and coordination

Tremor

Social withdrawal

Loss of appetite and severe weight loss

Accompanying sensory problems, such as hearing loss and a decline in reading ability

General physical debility

Medications

Most drugs used to treat Alzheimer's, and those under investigation, are aimed at slowing progression. There are no cures to date. In addition, the improvements from some of these drugs may be so modest that even the patients and their families are not aware of them. Even in these cases, however, the drugs may delay the need for admission to nursing homes.

There are currently two drug classes that have been approved by the U.S. Food and Drug Administration (FDA) to treat the cognitive symptoms of Alzheimer's disease:

Cholinesterase inhibitors (generally used to treat mild-to-moderate Alzheimer's; donepezil is also approved for treatment of severe dementia )

N-methyl-D-aspartate (NMDA) receptor antagonists (used to treat moderate-to-severe Alzheimer's)

Cholinesterase inhibitors are designed to protect the cholinergic system, which is essential for memory and learning and is progressively destroyed in Alzheimer's. These drugs work by preventing the breakdown of the brain chemical acetylcholine and are recommended for the treatment of mild-to-moderate Alzheimer's. The first cholinesterase inhibitor, tacrine, was approved in 1993 but is rarely prescribed today due to safety concerns. The three most commonly prescribed cholinesterase inhibitors are donepezil (approved in 1996), rivastigmine (approved in 2000), and galantamine (approved in 2001).

Cholinesterase inhibitors may increase the risk for gastrointestinal bleeding or ulcers, and patients should be cautious about using these medicines with NSAIDs (which can also cause gastric irritation). Common side effects of cholinesterase inhibitors, especially when taken at higher doses, may include nausea, vomiting, diarrhea, and upset stomach.

Donepezil. Donepezil (Aricept) is the only Alzheimer’s drug approved for all stages of dementia, from mild to severe. It is taken once a day and has only modest benefits, but it does help slow loss of function and reduce caregiver burden. It works equally in patients with or without the ApoE4 gene. Several trials, including an important 2005 New England Journal of Medicine (NEJM) study, have found that donepezil may have short-term benefits for patients with mild cognitive impairment by delaying progression to AD. In the NEJM study, donepezil slowed progression during the first year of therapy, but demonstrated no benefits by the conclusion of the 3-year trial. Studies also suggest that donepezil may help improve behavior and memory in patients with moderate-to-severe Alzheimer’s when it is given in combination with memantine (Namenda).

Rivastigmine. Rivastigmine (Exelon) targets two enzymes: Acetylcholinesterase and butyrylcholinesterase. It is taken as a pill twice a day. (The FDA approved a skin patch version of the drug in 2007.) Rivastigmine may be particularly helpful for patients with rapidly progressing disease. It has slowed or slightly improved disease status even in patients with advanced disease. Rivastigmine may cause significantly more side effects than donepezil, including nausea, vomiting, and headache.

Galantamine (Razadyne). Galantamine not only protects the cholinergic system but also acts on nicotine receptors, which are also depleted during Alzheimer's. Studies report that it improves daily living, behavior, and mental functioning, including in patients with mild to advanced-moderate Alzheimer's disease and those with a mix of Alzheimer's disease and vascular dementia. Some studies have suggested that the effects of galantamine may persist for a year or longer and even strengthen over time. In 2005, the name of galantamine was changed from Reminyl to Razadyne.

Tacrine. Tacrine (Cognex) was the first cholinergic protective drug. It needs to be taken four times a day, has only modest benefits, and has no benefits for patients who carry the ApoE4 gene. In high doses, it can also injure the liver. In general, newer cholinergic protective drugs that do not pose as great a risk for the liver are now used for Alzheimer's.

About half of patients with mild-to-moderate disease show slight improvement with these drugs. Comparative studies have reported little differences in effectiveness among them. All drugs have gastrointestinal side effects, including nausea. Of note, some of the drugs often used in elderly Alzheimer's disease patients are known as anticholinergics and may offset the effects of the Alzheimer's disease pro-cholinergic drugs. Such drugs include antihistamines, antipsychotic drugs, and some anti-incontinence drugs.

In any case, the benefits of these drugs are far from dramatic. In fact, many experts have reservations about developing any additional drugs that affect the cholinergic system since, at best, they only slow progression and do not appear to affect the basic destructive disease process. When patients go off the drugs, the deterioration continues. In 2005, the United Kingdom’s National Institute for Clinical Excellence (NICE) recommended against the use of donepezil, rivastigmine, galantamine, and memantine for Alzheimer’s disease treatment. The agency contended that the costs of these drugs outweigh their modest benefits.

Memantine (Namenda) is approved for treatment of moderate-to-severe Alzheimer’s disease. (Most cholinesterase inhibitors are used to treat mild-to-moderate stages of the disease.) By blocking NDMA receptors, memantine protects against the overstimulation of glutamate, an amino acid that excites nerves and, in excess, is a powerful nerve-cell killer.

Memantine is prescribed either alone or in combination with donepezil. Studies indicate that memantine may help improve cognitive function and delay the progression of Alzheimer’s disease for up to 1 year. Side effects are generally mild but may include dizziness, drowsiness, or fainting.

In one study of effects on moderate-to-severe Alzheimer's, patients who received memantine showed a small but statistically significant benefit in cognitive function and performance of daily abilities compared with those patients who were given placebo. In a 2004 study, memantine was added to the drug regimen of patients with moderate-to-severe Alzheimer's who had taken donepezil for at least 6 months. In comparison to patients who took only donepezil, patients who received the combination donepezil-memantine therapy showed a greater improvement in measures of cognitive function, activities of daily living, and behavior parameters. A 2006 study indicated that memantine combined with donepezil may help reduce behavior problems -- such as agitation, aggression, and irritability -- and improve disturbances in appetite and eating.

Although cholinesterase inhibitors and memantine are the best available medications for Alzheimer's, their benefits are, unfortunately, quite modest. More effective methods of prevention and treatment are urgently needed.

There has been considerable controversy over whether NSAIDs may help in the treatment of Alzheimer's disease. As inflammation is involved in the destruction of brain cells, it has been suggested that anti-inflammatory drugs might be able to halt this process and thus slow the progression of the disease. In a rigorous 2003 study, patients with mild-to-moderate Alzheimer's were randomized to receive either naproxen (Aleve) or rofecoxib (Vioxx) or placebo. After 12 months of treatment, patients in the anti-inflammatory groups did not show any difference in cognitive improvement compared to those patients who received placebo.

Results from another large study, published in 2004, also failed to demonstrate improvement in cognitive function for patients with mild-to-moderate Alzheimer's who were treated with rofecoxib. Since the completion of these studies, rofecoxib was withdrawn from the market, and the NIH suspended a clinical study assessing naproxen’s preventive benefits (see Nonsteroidal Anti-Inflammatory Drugs as Prevention). As mentioned earlier, patients should be cautious about taking NSAIDs in combination with cholinesterase inhibitors as they may increase the risk of gastrointestinal bleeding.

Nicotine enhances the actions of the cholinergic system (which is depleted in Alzheimer's disease) and is known to improve concentration and memory in the short term. Some studies have suggested that nicotine may protect nerve cells and help prevent the formation of beta amyloid. One study indicated that nicotine might help protect against Alzheimer's disease in carriers, but not noncarriers, of the ApoE4 gene. Another reported improvement in verbal recall and word retrieval in healthy relatives of Alzheimer's disease patients who wore a low-dose nicotine patch. Research to date, however, has found no strong evidence of improvement in Alzheimer's disease patients with nicotine replacement methods. No one should smoke to prevent or treat Alzheimer's disease.

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. Always check with your doctor before using any herbal remedy or dietary supplement.

Ginkgo Biloba. Ginkgo biloba is a common herb that has antioxidant properties and appears to increase blood flow to the brain. A 2002 study of healthy people who took over-the-counter ginkgo for 6 weeks reported no improvements in memory or mental function. Studies are reporting that a ginkgo biloba extract, called Egb 761, may slightly improve the memory of patients with mild to moderate Alzheimer's disease. The herb poses a small increased risk for bleeding, which may be hazardous in combination with other blood-thinning medications, such as warfarin or high-doses of vitamin E.

Turmeric. Studies suggest that circumin, a compound found in the spice turmeric, has properties that may protect against the Alzheimer's disease process.

Melatonin. Melatonin, a natural hormone involved in sleep regulation, is of interest to researchers. It is an antioxidant, may break down beta amyloid, and is able to pass through the blood-brain barrier. Deficiencies have been observed in patients with Alzheimer's disease. A number of studies (but not all) report that melatonin may improve sleep habits in these patients. Some studies reported slower progression of mental impairment.

A number of drugs are being investigated for treatment and prevention of Alzheimer's disease. Intense areas of research are focusing on drugs that prevent beta amyloid build-up, its toxic effects on nerve cells, or other mechanisms of the disease process. Promising research in late-stage clinical trials include.

Tramiprosate (Alzhemed) is an experimental drug designed to prevent beta-amyloid accumulation in the brain.

Flurizan (MPC-7869) may help reduce amyloid plaque development. It is currently being studied in Phase III trials for adults with mild Alzheimer’s disease.

Rosiglitazone XR (Avandia) is an extended-release formulation of a drug used to treat type 2 diabetes. Its anti-inflammatory properties are being studied as a treatment for patients with mild-to-moderate Alzheimer’s who do not carry the APOE-e4 gene. Phase III results have been promising, but this drug has been linked to increased risk for heart attack deaths in patients with diabetes. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Patients or caregivers of patients who take rosiglitazone, especially those who have heart disease or who are at high risk for heart attack, should discuss their treatment options with their doctors.

Dimebon is an antihistamine, which researchers think may help prevent brain cell death. The drug is currently in Phase II trials.

Antioxidants such as vitamin E and selenium are being investigated for their preventive effects. Antioxidant treatment trials include curcumin (the yellow pigment found in turmeric spice) and a combination trial with fish oil and alpha-lipoic acid.

Depression. Major depression with dementia that occurs in elderly people may be an early sign of Alzheimer's. In such cases, it precedes Alzheimer's by 2 years or less. (It is, in fact, sometimes difficult to differentiate major depression from early-stage Alzheimer's disease.) Antidepressants known as selective serotonin reuptake inhibitors (SSRIs), including fluoxetine (Prozac) and sertraline (Zoloft), may be effective in relieving depression, irritability, and restlessness associated with Alzheimer's in some patients.

Apathy. Depression is often confused with apathy. An apathetic patient lacks emotions, motivation, interest, and enthusiasm while a depressed patient is generally very sad, tearful, and hopeless. According to one study, apathy is more common than depression in patients with Alzheimer's disease. It responds to stimulants, such as methylphenidate (Ritalin), rather than antidepressants.

Psychosis. Antipsychotic drugs are used to treat verbally or physically aggressive behavior and hallucinations. Because older antipsychotic drugs, such as haloperidol (Haldol), have severe side effects, most doctors now prescribe newer atypical antipsychotics, such as risperidone (Risperdal) or olanzapine (Zyprexa).

However, these newer antipsychotic drugs still can cause serious side effects, including confusion, sleepiness, and Parkinsonian-like symptoms. In addition, studies indicate that their safety risks may outweigh any possible benefits. A 2005 study showed that these drugs produce a slightly increased rate of death in patients with Alzheimer’s disease or dementia. In addition, several studies from 2006 and 2007 published in the New England Journal of Medicine suggested that atypical antipsychotics work no better than placebo in controlling psychosis, aggression, and agitation in patients with Alzheimer’s.

Most experts now recommend that doctors delay prescribing antipsychotic medication unless absolutely necessary. They recommend first trying behavioral treatments and controlling changes in the patient’s environment and routine. Anti-seizure drugs, such as carbamazepine (Tegretol) or valproate (Depakote), can also sometimes treat agitation and other psychotic symptoms. Non-drug treatments, such as bright light boxes, are also showing promise for managing psychotic and behavioral symptoms.

Disturbed Sleep. Patients with Alzheimer's disease commonly experience disturbances in their sleep/wake cycles. Moderately short-acting sleeping drugs, such as temazepam (Restoril), zolpidem (Ambien), or zaleplon (Sonata), or sedating antidepressants, such as trazodone (Desyrel, Molipaxin), may be useful in managing insomnia. Some research suggests that exposure to brighter-than-normal artificial light during the day for patients with normal vision may help reset wake/sleep cycles and prevent nighttime wandering and sleeplessness. Trials on melatonin, a natural hormone that helps trigger sleep at night, are in progress.

Stages

The lifespan of patients with Alzheimer's is generally reduced, although a patient may live anywhere from 3 - 20 years after diagnosis. The final phase of the disease may last from a few months to several years, during which time the patient becomes increasingly immobile and dysfunctional. Caregivers should understand the phases of this illness in order to help determine their own capacities for dealing with this painfully sad disease.

Telling the Patient. Often doctors will not tell patients that they have Alzheimer's. If a patient expresses a need to know the truth, it should be disclosed. Both the caregiver and the patient can then begin to address issues that can be controlled, such as access to support groups and drug research.

Mood and Emotional Behavior. Patients display abrupt mood swings, and many become aggressive and angry. Some of this erratic behavior is caused by chemical changes in the brain. But it may also be due to the experience of losing knowledge and understanding of one's surroundings, causing fear and frustration that patients can no longer express verbally.

The following recommendations for caregivers may help soothe patients and avoid agitation:

Keep environmental distractions and noise at a minimum if possible. (Even normal noises, such as people talking outside a room, may seem threatening and trigger agitation or aggression.)

Speak clearly. Most experts recommend speaking slowly to a patient with Alzheimer's disease, but some caregivers report that patients respond better to clear, quickly spoken, short sentences that they can more easily remember.

Use a combination of facial expressions, voice tones, and words for communicating emotions. (One study suggested that patients may have difficulty in recognizing the meaning of facial expressions, particularly those signaling sadness, surprise, and disgust.)

Limit choices (such as clothing selection).

Offer diversions, such as a snack or car ride, if the patient starts shouting or exhibiting other disruptive behavior.

Simply touching and talking may also help.

Maintain as natural an attitude as possible. Patients with Alzheimer's disease can be highly sensitive to the caregiver's underlying emotions and react negatively to patronization or signals of anger and frustration.

Showing movies or videos of family members and events from the patient's past may be comforting.

Although much attention is given to the negative emotions of patients with Alzheimer's disease, some patients become extremely gentle, retaining an ability to laugh at themselves or appreciate simple visual jokes even after their verbal abilities have disappeared. Some patients may seem to be in a drug-like or "mystical" state, focusing on the present experience as their past and future slip away. Encouraging and even enjoying such states may bring some comfort to a caregiver.

There is no single Alzheimer's personality, just as there is no single human personality. All patients must be treated as the individuals they continue to be, even after their social self has vanished.

Appearance and Cleanliness. For the caregiver, grooming the patient may be an alienating experience. For one thing, many patients resist bathing or taking a shower. Some spouses find that showering with their afflicted mate can solve the problem for a while. Often patients with Alzheimer's disease lose their sense of color and design and will put on odd or mismatched clothing. It is important to maintain a sense of humor and perspective and to learn which battles are worth fighting and which ones are best abandoned.

Driving. As soon as Alzheimer's is diagnosed, the patient should be prevented from driving. One study found that more than half of elderly people involved in fatal accidents had some degree of neurologic damage.

Wandering. A potentially dangerous trait is the patient's tendency to wander. At the point the patient develops this tendency, many caregivers feel it is time to seek out nursing homes or other protective institutions for their loved ones. For those who remain at home, the following precautions are recommended:

Locks should be installed outside the door, which the caregiver can open, but the patient cannot.

Alarms may be installed at exits.

A daily exercise program should be implemented, which may help tire the patient. One study showed that walking 30 minutes, three times a day, also improved communication.

The caregiver should contact organizations, such as Alzheimer's Association or Medic Alert, for identification supplies and procedures that help locate patients who wander away from home and become lost.

Some experts are discussing the benefits versus the ethics of electronic tagging, which would emit a radio signal or alarm that allows the patient to be tracked using a detector.

Speech Problems. Some evidence suggests that speech therapy combined with Alzheimer's disease medications may be helpful for maintaining verbal skills patients with mild symptoms.

Sexuality. In many cases, the patient becomes uninhibited sexually. At the same time, the patient's physical deterioration and receding capacity to recognize the spouse as a known and loved individual can make sexual activity unattractive for the caregiving spouse. Other patients may lose interest in sex. If sexual issues are a problem, they should be discussed openly with the doctor. Ways should be found to maintain non-sexual physical affection that can bring comfort to both the patient and the spouse.

Patients with Alzheimer's disease need 24-hour a day attention. Even if the caregiver has the resources to keep the patient at home during later stages of the disease, outside help is still essential. If available, home visits by a health profession can have a favorable impact on survival and delay the need for a nursing home. Medicare now covers many Alzheimer's services, and patients should be able to stay at home longer than previously.

Incontinence. A patient's incontinence is generally devastating to the caregiver and a primary reason why many caregivers decide to seek nursing home placement when the patient reaches this stage. When the patient first shows signs of incontinence, the doctor should make sure that it is not caused by an infection. Urinary incontinence may be controlled for some time by trying to monitor times of liquid intake, feeding, and urinating. Once a schedule has been established, the caregiver may be able to anticipate incontinent episodes and get the patient to the toilet before they occur.

Immobility and Pain. As the disease progresses, patients become immobile, literally forgetting how to move. Eventually, they become almost entirely wheelchair-bound or bedridden. Bedsores can be a major problem. Sheets must be kept clean, dry, and free of food. The patient's skin should be washed frequently, gently blotted thoroughly dry, and moisturizers applied. The patient should be moved every 2 hours and the feet kept raised with pillows or pads. Exercises should be administered to the legs and arms to keep them flexible.

Dehydration. Dehydration can become a problem. It is essential to encourage fluid intake equal to 8 glasses of water daily. Coffee and tea are diuretics and will deplete fluid.

Eating Problems. Weight loss and the gradual inability to swallow are two major related problems in late-stage Alzheimer's and are associated with an increased risk of death. Weight gain, however, is linked to a lower risk of dying. The patient can be fed through a feeding syringe, or the caregiver can encourage chewing action by pushing gently on the bottom of the patient's chin and on the lips. The caregiver should offer the patient foods of different consistency and flavor. Because choking is a danger, the caregiver should learn to administer the Heimlich maneuver, which may be taught by the local Red Cross. In very late stages, some caregivers choose feeding tubes for the patient. They should be aware that feeding tubes have no measurable impact on survival.

About 80% of patients with Alzheimer's disease are cared for by family members, who often lack adequate support, finances, or training for this difficult job. Few diseases disrupt patients and their families so completely or for so long a period of time as Alzheimer's. The patient's family endures two separate losses and grieves twice:

First, they must grieve for the ongoing disappearance of the personality they recognize. Dealing with the patient throughout the course of the disease is like Alice's fall down the rabbit hole into Wonderland. No sooner has the caregiver grappled with one set of problems, when the patient's further deterioration creates new and more intractable ones.

Finally, the caregiver must grieve the actual death of the person.

Often, caregivers themselves begin to show signs of mental disorder or ill health. Depression, empathy, exhaustion, guilt, and anger can play havoc with even a healthy individual faced with the care of a loved one suffering from Alzheimer's.

Fortunately, research shows that intensive support services can greatly improve caretakers’ quality of life and make it easier for them to continue caring for patients in their homes. In a 2006 study, caregivers who received individual and family counseling, telephone counseling, support groups, and stress management and problem-solving techniques reported reduced rates of depression and improved self-confidence compared with those who received only written educational materials. Another 2006 study indicated that improving caregivers’ access to counseling and support services can help delay nursing home placement of patients. National and local Alzheimer's associations can provide important support and other services.

A point comes when the most devoted caregiver will probably need to institutionalize the patient. That point is determined not only by the caregiver's emotional endurance, but also by their physical strength and stamina, as a patient typically takes on the random, undisciplined behavior of a very young child. Financial considerations in finding a nursing home are often paramount, but the kind of care is equally important. Although fully half of all nursing home patients suffer from Alzheimer's, not all nursing homes have programs specifically designed for them. Some institutions may claim that they do, but often they simply group patients together without offering any special programs. If a caregiver manages to find a facility that offers good services, it may be located far from home, making visits difficult. The caregiver must then decide whether superior care at a distant institution is worth seeing the patient less frequently. When the patient's illness becomes terminal, a hospice program may be another option.

1. Although I cannot control the disease process, I need to remember I can control many aspects of how it affects my relative.

2. I need to take care of myself so that I can continue doing the things that are most important.

3. I need to simplify my lifestyle so that my time and energy are available for things that are really important at this time.

4. I need to cultivate the gift of allowing others to help me, because caring for my relative is too big a job to be done by one person.

5. I need to take one day at a time rather than worry about what may or may not happen in the future.

6. I need to structure my day because a consistent schedule makes life easier for me and my relative.

7. I need to have a sense of humor because laughter helps to put things in a more positive perspective.

8. I need to remember that my relative is not being difficult on purpose; rather their behavior and emotions are distorted by the illness.

9. I need to focus on and enjoy what my relative can still do rather than constantly lament over what is gone.

10. I need to increasingly depend upon other relationships for love and support.

11. I need to frequently remind myself that I am doing the best that I can at this very moment.

12. I need to draw upon the Higher Power, which I believe is available to me.

Source: The American Journal of Alzheimer's Care and Related Disorders & Research, Nov/Dec 1989

Resources

www.alzheimers.org -- Alzheimer's Disease Education and Referral Center

www.alz.org -- Alzheimer's Association

www.alzforum.org -- Alzheimer's Research Forum

www.alzfdn.org -- Alzheimer's Foundation of America

www.alz.co.uk -- Alzheimer's Disease International

www.nia.nih.gov -- National Institute on Aging

www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke

www.aan.com -- American Academy of Neurology

www.medicalert.org -- Medic Alert

www.ahaf.org -- American Health Assistance Foundation

www.clinicaltrials.gov -- Find clinical trials

www.medicare.gov/NHCompare/Home.asp -- Find a nursing home

References

ADAPT Research Group, Lyketsos CG, Breitner JC, Green RC, Martin BK, Meinert C, et al. Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology. 2007 May 22;68(21):1800-8. Epub 2007 Apr 25.

Akomolafe A, Beiser A, Meigs JB, Au R, Green RC, Farrer LA, et al. Diabetes mellitus and risk of developing Alzheimer disease: results from the Framingham Study. Arch Neurol. 2006 Nov;63(11):1551-5.

Ayalon L, Gum AM, Feliciano L, Arean PA. Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Arch Intern Med. 2006 Nov 13;166(20):2182-8.

Belle SH, Burgio L, Burns R, Coon D, Czaja SJ, Gallagher-Thompson D, et al. Enhancing the quality of life of dementia caregivers from different ethnic or racial groups: a randomized, controlled trial. Ann Intern Med. 2006 Nov 21;145(10):727-38.

Cummings JL, Schneider E, Tariot PN, Graham SM; Memantine MEM-MD-02 Study Group. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology. 2006 Jul 11;67(1):57-63.

Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007 Jan 20;369(9557):208-16.

Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006 Oct;63(10):1402-8.

Gamaldo A, Moghekar A, Kilada S, Resnick SM, Zonderman AB, O'Brien R. Effect of a clinical stroke on the risk of dementia in a prospective cohort. Neurology. 2006 Oct 24;67(:1363-9.

Luchsinger JA, Reitz C, Patel B, Tang MX, Manly JJ, Mayeux R. Relation of diabetes to mild cognitive impairment. Arch Neurol. 2007 Apr;64(4):570-5.

Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol. 2007 Jan;64(1):86-92.

McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006 Jun 29;354(26):2764-72.

Mittelman MS, Haley WE, Clay OJ, Roth DL. Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease. Neurology. 2006 Nov 14;67(9):1592-9.

Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Associations of vegetable and fruit consumption with age-related cognitive change. Neurology. 2006 Oct 24;67(:1370-6.

Regan C, Katona C, Walker Z, Hooper J, Donovan J, Livingston G. Relationship of vascular risk to the progression of Alzheimer disease. Neurology. 2006 Oct 24;67(:1357-62.

Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet. 2007 Feb;39(2):168-77. Epub 2007 Jan 14.

Scarmeas N, Stern Y, Mayeux R, Luchsinger JA. Mediterranean diet, Alzheimer disease, and vascular mediation. Arch Neurol. 2006 Dec;63(12):1709-17. Epub 2006 Oct 9.

Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol. 2006 Nov;63(11):1545-50.

Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007 Jun 13; [Epub ahead of print]

Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12;355(15):1525-38.

Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, et al. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006 Dec 21;355(25):2652-63.

Willis SL, Tennstedt SL, Marsiske M, Ball K, Elias J, Koepke KM, et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA. 2006 Dec 20;296(23):2805-14.

Wilson RS, Krueger KR, Arnold SE, Schneider JA, Kelly JF, Barnes LL, et al. Loneliness and risk of Alzheimer disease. Arch Gen Psychiatry. 2007 Feb;64(2):234-40.

Review Date:
7/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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adam.com

Hepatitis

FitSugar — Wed, 08 Oct 2008 17:35:31 -0700

In This Report

Highlights

Introduction

Diagnosis

Hepatitis A

Hepatitis B and D

Hepatitis C

Autoimmune Hepatitis

Symptom Management

Outlook

Resources

References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2006, the FDA approved telbivudine (Tyzeka), a new type of nucleoside analog drug, for treatment of chronic hepatitis B. There are now six drugs approved for hepatitis B treatment.

In 2007, the FDA approved HepaGam B, an intravenous immune globulin drug, for preventing hepatitis B recurrence following liver transplantation.

Drug Warning

In 2007, the FDA revised the prescribing label for entecavir (Baraclude), a drug used to treat hepatitis B. The new label advises against using entacavir in patients infected with both hepatitis B and HIV who are not receiving antiretroviral (anti-HIV) therapy.

Hepatitis C May Increase Lymphoma Risk

Hepatitis C infection increases the risk for developing non-Hodgkin’s lymphoma (NHL) by 20 - 30%, according to a 2007 study of male war veterans published in the Journal of the American Medical Association.

Causes of Death in Hepatitis B and C

Liver disease in general, and liver cancer in particular, is the leading cause of death in patients infected with hepatitis B, according to a 2006 study in the Lancet. Hepatitis B is the leading cause of liver cancer.

Patients with hepatitis C are also at high risk for death from liver disease. However, the Lancet study indicated that young women with hepatitis C face an even higher risk of dying from illegal intravenous drug use.

Drug Research

Adefovir (Hepsera) is commonly used to treat hepatitis B, but many patients eventually develop drug resistance. A 2006 study suggested that adefovir works well for about 5 years, with resistance occurring in about 20% of patients.

Combination treatment with pegylated interferon and ribavirin is an effective treatment for hepatitis C, but causes many side effects. Researchers are studying whether some patients may be able to succeed with a shorter course of treatment. Unfortunately, a 2007 New England Journal of Medicine study suggested that 16 weeks of treatment does not work as well as the standard 24-week course.

Introduction

Hepatitis is a disorder in which viruses or other mechanisms produce inflammation in liver cells, resulting in their injury or destruction. The liver is the largest organ in the body, occupying the entire upper right quadrant of the abdomen. It performs over 500 vital functions including:

The liver processes all of the nutrients the body requires, including proteins, glucose, vitamins, and fats.

The liver manufactures bile, the greenish fluid stored in the gallbladder that helps digest fats.

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

Old red blood cells are removed from the blood by the liver and spleen, and the iron contained in them is recycled to the bone marrow to make new red blood cells.

The esophagus, stomach, large and small intestine -- aided by the liver, gallbladder, and pancreas -- convert the nutritive components of food into energy and break down the non-nutritive components into waste to be excreted.

Damage to the liver can impair these and many other processes. Hepatitis varies in severity from a self-limited condition with total recovery to a life-threatening or life-long disease. It can occur from many different causes:

In the most common hepatitis cases (viral hepatitis), specific viruses incite the immune system to fight off infections. Specific immune factors become over-produced that cause injury.

Hepatitis can also result from an autoimmune condition, in which abnormal immune factors attack the body's own liver cells.

Inflammation of the liver can also occur from medical problems, drugs, alcoholism, chemicals, and environmental toxins.

No matter what the cause of hepatitis, it can take either an acute (short term) or chronic (long term) form. In some cases, acute hepatitis develops into a chronic condition, but chronic hepatitis can also occur on its own. Although chronic hepatitis is generally the more serious condition, patients having either condition can experience varying degrees of severity.

Acute Hepatitis. Acute hepatitis can begin suddenly or gradually, but it has a limited course and rarely lasts beyond 1 or 2 months. Usually, there is only spotty liver cell damage and evidence of immune system activity. Rarely, acute hepatitis can cause severe, even life-threatening, liver damage.

Chronic Hepatitis. The chronic forms of hepatitis last for prolonged periods. Doctors usually categorize chronic hepatitis by indications of severity:

Chronic persistent hepatitis is usually mild and nonprogressive or slowly progressive, causing limited damage to the liver.

Chronic active hepatitis involves extensive liver damage and cell injury beyond the portal tract.

Click the icon to see an image of aggressive hepatitis.

Most cases of hepatitis are caused by viruses that infect liver cells and begin replicating. They are defined by the letters A through G:

Hepatitis A, B, and C are the most common viral forms of hepatitis. Investigators are still looking for additional viruses that may be implicated in hepatitis unexplained by the current known viruses.

Other hepatitis viruses include hepatitis E and hepatitis G. Like hepatitis A, hepatitis E is caused by contact with contaminated food or water. It is not serious except in pregnant women, when it can be life threatening. Hepatitis G is always chronic and most likely has the same modes of transmission as hepatitis C. It does not appear to have serious effects.

Scientists do not know exactly how these viruses actually cause hepatitis (inflammation in the liver). As the virus reproduces in the liver, several proteins and enzymes, including many that attach to the surface of the viral protein, are also produced. Some of these may be directly responsible for liver damage. Researchers are investigating elevated levels of specific immune factors, including T cell sub-types in the liver of hepatitis C and B patients. T cells are important infection fighters in the immune system that in some cases release powerful inflammatory substances (tumor necrosis factor and interferon gamma) that can cause considerable damage leading to hepatitis B or C.

Autoimmune chronic hepatitis accounts for about 20% of all chronic hepatitis cases. Like other autoimmune disorders, this condition develops because a genetically defective immune system attacks the body's own cells and organs (in this case the liver). The attack is triggered by an environmental factor, probably a virus. Suspects 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 susceptible individuals. In about 30% of cases, autoimmune hepatitis is associated with other disorders that involve autoimmune attacks on other parts of the body.

Alcohol. About 10 - 35% of heavy drinkers develop alcoholic hepatitis. In the body, alcohol breaks down into various chemicals, some of which are very toxic to the liver. After years of drinking, liver damage can be very severe, leading to cirrhosis in about 10 - 20% of cases. Although heavy drinking itself is the major risk factor for alcoholic hepatitis, genetic factors may play a role in increasing a person's risk for alcoholic hepatitis. Women who abuse alcohol are at higher risk for alcoholic hepatitis and cirrhosis than are men who drink heavily. High-fat diets may also increase the risk in heavy drinkers.

Drugs. Because the liver plays such a major role in metabolizing drugs, hundreds of medications can cause reactions that are similar to those of acute viral hepatitis. Symptoms can appear anywhere from 2 weeks to 6 months after starting drug treatment. In most cases, they disappear when the drug is withdrawn, but in rare circumstances they may progress to serious liver disease. Drugs most noted for liver interactions include halothane, isoniazid, methyldopa, phenytoin, valproic acid, and the sulfonamide drugs. Very high doses of acetaminophen (Tylenol) have been known to cause severe liver damage and even death, particularly when used with alcohol.

Nonalcoholic fatty liver disease (NAFLD) affects between 10 - 24% of the population. It covers several conditions, including nonalcoholic steatohepatitis (NASH). NAFLD has features similar to alcoholic hepatitis, particularly a fatty liver, but it occurs in individuals who drink little or no alcohol. Severe obesity and diabetes are the major risk factors for NAFLD as well as complications from NAFLD. NAFLD is usually benign and very slowly progressive. In certain patients, however, it can lead to cirrhosis, liver failure, or liver cancer. [For more information, see In-Depth Report #75: Cirrhosis.]

Diagnosis

In people suspected of having or carrying viral hepatitis, doctors will measure certain substances in the blood.

Bilirubin. Bilirubin is one of the most important factors indicative of hepatitis. It is 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. (High levels of bilirubin cause the yellowish skin tone, known as jaundice.)

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.)

Blood is drawn from a vein (venipuncture), usually from the inside of the elbow or the back of the hand. A needle is inserted into the vein, and the blood is collected in an air-tight vial or a syringe. Preparation may vary depending on the specific test.

Radioimmunoassays. To identify the particular virus 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 which can be targeted by antibodies.) Some of these tests can pinpoint hepatitis antigens directly. These tests, however, have limitations:

There may not be sufficient numbers of antibodies to be detectable by blood tests for up to weeks or months after hepatitis develops. Blood tests that are taken too early may miss these signs of infection.

Antibodies also linger 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. PCR is able to make multiple copies of the virus’ genetic material to the point where it is detectable.

A liver biopsy may be performed for acute viral hepatitis caught in a late stage or for severe cases of chronic hepatitis. No laboratory tests for enzyme or viral levels can truly determine the actual damage to the liver. A biopsy helps determine treatment possibilities, the extent of damage, and the long-term outlook.

The biopsy requires abdominal surgery, most often laparoscopy. This procedure takes about an hour. It requires general anesthesia and involves the following steps:

The surgeon makes one or more small incisions (about 0.5 - 1.0 inch) in the abdomen.

Carbon dioxide or nitrous oxide is delivered through the incision to inflate the abdomen so that the involved area is visible.

The surgeon inserts a thin tube, called a laparoscope, which contains a tiny camera. Surgical instruments are also inserted through the incision to remove the liver tissue for biopsy.

Click the icon to see an explanation of liver biopsy.

A less invasive procedure, called a minilaparoscopy, uses a smaller scope and may prove to reduce the time of the procedure.

Patients with cirrhosis are usually screened for liver cancer using tests for a substance called alpha-fetoprotein (AFP) and ultrasound. It is not known, however, if such screening has much impact on survival, since 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.

Hepatitis A

About a third of the U.S. population has antibodies to hepatitis A, indicating previous infection by the virus. The hepatitis A virus infects up to 200,000 Americans every year and causes symptoms in about 134,000 of them. Almost 30% are children under age 15.

Hepatitis A (formerly called infectious hepatitis) is excreted in feces and transmitted by contaminated food and water. Eating shellfish taken from sewage-contaminated water is a common means of contracting hepatitis A. Infected people can transmit it to others if they do not take strict sanitary precautions. Hepatitis A is infectious for 2 - 4 weeks before symptoms develop and for a few days afterward.

People at risk for passing the infection along or being infected include:

International travelers. Hepatitis A is the hepatitis strain people are most likely to encounter in the course of international travel. In fact, in spite of the availability of a vaccine, the increase in travel to underdeveloped countries has kept the incidence of hepatitis A steady in Western nations. The incidence may even be increasing.

Day care employees and children. It is estimated that between 11 - 16% of hepatitis A cases occur among day care employees and children who attend day care. The risk for children attending day care is very low, however, if hygienic precautions are used, particularly when changing babies and handling diapers.

Sexually active homosexual men.

Intravenous drug users.

Health care, food industry, and sewage workers.

A fly may act as a mechanical vector of diseases such as hepatitis A, which means the fly carries the infective organism on its feet or mouth parts and contaminates food or water which a person then consumes. A biological vector actually develops an infective organism in its body and passes it along to its host, usually through its saliva. A fly can be a biological vector, as in the transmission of leishmaniasis by the sandfly.

Symptoms of acute viral hepatitis may begin suddenly or develop gradually. They may be so mild that patients mistake the disease for the flu. They include:

Nearly all patients experience some fatigue and often have mild fever.

Gastrointestinal problems are very common, including nausea, vomiting, a general feeling of discomfort in the abdomen, or a sharper pain that may occur in the upper right area of the abdomen. This pain tends to increase during jerking movements, such as climbing stairs or riding on a bumpy road.

Gastrointestinal problems can also lead to loss of appetite, weight loss, and dehydration.

After about 2 weeks, dark urine and jaundice (a yellowish color in the skin and whites of the eyes) develops in some, but not all, patients. (Children tend not to develop jaundice.)

About half of all patients have light colored stools, muscle pain, drowsiness, irritability, and itching, usually mild.

Diarrhea and joint aches occur in about a quarter of patients.

The liver may be tender and enlarged, and most people have mild anemia.

In about 10% of patients, the spleen is enlarged.

Travelers should take the following precautions:

Get vaccinated against hepatitis A and possibly B if traveling for long periods of time to countries where epidemics occur.

Use only carbonated bottled water for brushing teeth and drinking. (Remember that ice cubes can carry infection.) Boiling water is the best method for eliminating infectious organisms. Bringing the water to a good boil for at least a minute generally renders it safe to drink.

Heated food should be hot to the touch and eaten promptly.

Don’t buy food from street vendors.

Beware of sliced fruit that may have been washed in contaminated water. Travelers themselves should peel all fresh fruits and vegetables.

Avoid dairy products.

Avoid raw or undercooked meat and fish.

Two vaccines (Havrix, Vaqta) are now available, both very safe and effective for preventing hepatitis A (HAV). They can be given along with immune globulin and other vaccines. A combination Hep A - Hep B vaccine (Twinrix) that contains both Havrix and Engerix-B (a hepatitis B vaccine) is also available.

Click the icon to see a discussion of hepatitis A vaccine.

Candidates for HAV Vaccinations. Vaccinations for hepatitis A are recommended for:

Children age 12 - 23 months (the U.S. Centers for Disease Control and Prevention recommends that children receive the first dose of the hepatitis A vaccine when they are 12 months old, and a second dose 6 months later). Hepatitis A used to affect mostly children, but now occurs mostly in adults.

Travelers to developing countries. (Travelers should also receive immune globulin if they are visiting high-risk areas within 4 weeks of the vaccination.)

Sexually active homosexual men

Illegal drug users, especially those who inject drugs

Health care workers

People with chronic liver disease

People with hemophilia or other blood-clotting disorders

Side Effects. Although there are few side effects, allergic responses from the vaccination can occur. Hair loss has been reported in very few people after a second administration. There may be pain at the injection site. (Havrix causes more pain at the injection site than Vaqta.)

Symptoms are usually mild, especially in children, and generally appear between 2 - 6 weeks after exposure to the virus. Adult patients are more likely to have fever, jaundice, and itching that can last up to several months.

Hepatitis A is the least serious of the common hepatitis viruses. It does not directly kill liver cells, and there is no risk for a chronic form. Severe (fulminant) hepatitis is the only major concern, but even if it develops, it is almost always less dangerous than with other viral types. Only 1 in a 1,000 patients is at risk for death from this complication. If hepatitis A infection occurs in patients with hepatitis C, however, superinfections can occur, even without cirrhosis, leading to a life-threatening form of fulminant hepatitis. (Infection of patients with hepatitis B who do not have cirrhosis does not appear to be as dangerous.)

Radioimmunoassays are generally used to identify IgM antibodies, first produced to fight hepatitis A. They appear early in the course of the disease and usually can be identified as soon as symptoms appear. IgM antibodies disappear during recovery, but those known as IgG antibodies persist, and their presence can be used to indicate a previous infection.

The primary goals for managing acute viral hepatitis are to provide adequate nutrition, to prevent additional damage to the liver, and to prevent transmission to others.

Precautions for Preventing Transmission of Hepatitis A. Because hepatitis A and hepatitis E are usually passed through contaminated food, people with these viruses should not prepare food for others. Unfortunately, these viruses are most contagious before symptoms appear.

Using hot water when cleaning utensils or clothing is essential. Heating a contaminated article for 1 minute kills the virus. Simple household bleach is effective for disinfecting hard surfaces. Sterilizing is not necessary. Still, even with strong precautions, utensils used by the patient for eating and cooking should be kept separate from those used by others.

Abstain from sexual activity or take strict precautions.

Abstain from alcohol. Moderate drinking after recovery is not harmful for most people.

Hepatitis B and D

Hepatitis B and D were formerly called serum hepatitis. Hepatitis B is mainly transmitted through blood transfusions, contaminated needles, and sexual contact. Blood screening has reduced the risk from transfusions. It can also be passed from cuts, scrapes, and other breaks in the skin. Hepatitis D virus can replicate only by attaching to hepatitis B and therefore cannot exist without the B virus being present.

Risk Factors for Hepatitis B. About 1.2 million Americans are chronically infected with hepatitits B and between 20 - 30% acquired the infection when they were children. Men are at higher risk than women. Among ethnic groups living in the United States, Asians are at highest risk, due to the high rate of hepatitits B in Asian countries. Fortunately, in the US the number of new infections has declined dramatically -- by 67% between 1990 and 2002. In 2003, 7,526 cases were reported compared to over 20,000 in 1990. The greatest decrease has occurred in children. Among young adults and people living in the Northeast, however, the incidence has increased since 1999. This may indicate that sexual activity is an important route for viral transmission and that the protective effect of the vaccine has not yet reached older, high-risk groups. Also, as with hepatitis A, the increase in travelers to underdeveloped nations may be responsible for the steady rate.

Hepatitits B is far more common overseas and about 600,000 people die each year from conditions, such as liver cancer or cirrhosis, that are related to chronic hepatitis B. Nearly 70% of these infections were acquired during infancy or early childhood.

People at risk include:

Drug users who share needles.

Children of infected mothers. Pregnant women with hepatitis B can transmit the virus to their babies. Even if they are not infected at birth, unvaccinated children of infected mothers run a 60% risk of developing hepatitits B before age 5. Children are more likely than adults to become chronic carriers, although between 6 - 12% of children spontaneously recover each year.

People with multiple sex partners or other high-risk sexual behavior.

Hospital workers and others exposed to blood products. Contaminated medical instruments, including fingerstick devices used for more than one individual, have been known to transmit the virus.

Staff members and clients of institutions for the developmentally disabled.

Prisoners.

Immigrants from areas where the disease rate is high. (International travelers who spend long periods in such areas may also be at risk.)

People at highest risk for becoming chronic carriers of the virus include:

Children infected before age 5, including newborns, most of whom become carriers.

Infected people with damaged immune systems, such as AIDS patients.

Risk Factors for Hepatitis D. Hepatitis D occurs only in people with hepatitis B. It is not common in the U.S. and the incidence of this hepatitis is declining rapidly overseas. Experts anticipate that it will be extremely rare in the near future. Those who recover from hepatitis B are immune to further infection from both hepatitis B and D viruses.

The following are some precautions for preventing the transmission of hepatitits B or hepatitits C:

All objects contaminated by blood from patients with hepatitis B or C must be handled with special care. (Restrictions on food preparation are not necessary for these hepatitis viruses.)

Patients with viral hepatitis should abstain from sexual activity or take strict precautions. Infected patients should use condoms and contraceptives that prevent passage of the virus, possibly even in relationships that last for years. Women partners or infected women should abstain from sexual activity during menstruation. Either partner with infections that cause bleeding in the genital or urinary areas should avoid sexual activity until the infection is no longer active.

Couples with an infected partner or people sharing household with an infected person should avoid sharing personal items, such as razors or toothbrushes.

Note: There is no evidence that the viruses can be passed through casual contact, or other contact without exposure to blood, including kissing, hugging, sneezing, or coughing or by sharing eating utensils or drinking glasses. People infected with chronic hepatitis B or C should not be excluded from work, school, play, childcare or any social or work settings on the basis of their infection.

Symptoms appear long after the initial infection, usually 4 - 24 weeks. Many patients may not even experience them or they may be mild and flu-like. About 10 - 20% of patients have a fever and rash. Nausea is not common. Sometimes there is general aching in the joints. The pain can resemble arthritis, affecting specific joints and accompanied by redness and swelling.

Most people with hepatitis B recover from the virus. The risk of progressing to the chronic form of hepatitis B is age dependent. Only 2 - 6% of people who are older than 5 years old when they acquire the virus will develop chronic hepatitis B. The risk for chronic hepatitis in children age 1 - 5 years is 30%, and the risk for infants under the age of 1 is up to 90%. In the U.S., about 1.25 million people are chronically infected with hepatitis B. Worldwide, about 400 million people are chronically infected.

Chronic hepatitis B infection significantly increases the risk for liver damage, including cirrhosis and liver cancer. In fact, hepatitis B is the leading cause of liver cancer worldwide. According to a 2006 Lancet study, liver disease, especially liver cancer, is the main cause of death in people with chronic hepatitis B. Because of these high risks, it is very important that patients with chronic hepatitis B receive regular screenings for liver cancer.

Patients with hepatitis B who are co-infected with hepatitis D may develop a more severe form of acute infection than those who have only hepatitis B. Co-infection with hepatitis B and D increases the risk of developing acute liver failure. Patients with chronic hepatitis B who develop chronic hepatitis D also face high risk for cirrhosis. Hepatitis D occurs only in people who are already infected with hepatitis B.

A diagnosis of hepatitis B relies on measuring the liver enzymes aspartate (AST) and alanine (ALT) -- released when the liver is damaged -- assays to identify the viral DNA, and a liver biopsy.

Doctors must then determine if the condition is chronic but inactive or whether it is more aggressive. This is done by identifying a specific antigen called HBsAg, which is a protein that is found in the blood in early stages of hepatitis B and suggests the presence of a viral replication. Most people develop antibodies to this antigen during convalescence. Their condition is referred to as HBeAG negative, or anti-HBe, and suggests that infection is on the wane. About 5 - 10% of people do not clear the infection but become carriers of the antigen (called HBsAG-positive). Evidence of its persistence for more than 6 months suggests that the condition is chronic.

Tests can identify specific genetic types of hepatitis B virus (designated A to G). It is not clear how significant they are in treating patients with hepatitits B.

It is important to remember, however, that viral levels are not an accurate measure of actual liver damage. Only a biopsy can determine this.

To diagnose hepatitis D using an antibody test, hepatitis B must already have been identified.

General precautions for preventing hepatitis B when traveling are the same as those for hepatitis A. In infected people, precautions for preventing transmission are similar to those for hepatitis C.

Vaccinations for Prevention of Hepatitis B. Several inactivated virus vaccines, including Recombivax HB, GenHevac B, Hepagene, and Engerix-B, can prevent hepatitis B and are safe even for infants and children. A triple-antigen hepatitis B vaccine (Hepacare) is proving to be effective for people who do not respond to the standard vaccines. Vaccination programs are also helping to reduce the risk for liver cancer. A combination vaccine (Twinrix) that contains Engerix-B and Havrix, a hepatitis A vaccine, is now approved for people with risk factors for both hepatitis A and B.

Click the icon to see an image discussing hepatitis B vaccine.

Until recently, the vaccine contained a mercury-based preservative called thimerosal. In response to concerns, professional organizations recommended suspending vaccinations in infants with noninfected mothers. In 1999, a thimerosal-free vaccine became available, and medical centers are now urged to continue vaccinations. Unfortunately, even after the thimerosal-free vaccine became available, a number of hospitals still have not restored vaccination of all infants. This is a safe vaccine. Parents should be sure their children are immunized.

Candidates for Hepatitits B Vaccinations. Experts now recommend that all infants and children not previously vaccinated be immunized by the time they reach seventh grade.

Typical schedules for hepatitis B vaccinations in childhood are as follows:

All infants should receive the hepatitis B vaccine soon after birth and before hospital discharge. (The first dose may be given by age 2 months if the mother has no evidence of infection. Infants of mothers infected with hepatitits B should be treated with immune globulin plus the hepatitis vaccine within 12 hours of birth. Vaccinating the newborn prevents infection from being transmitted from mother to child.)

The second dose should be given at least 4 - 6 weeks after the first dose. The third dose is given at least 8 weeks after the second dose (typically when the baby is 6 - 23 months old).

Children who are 11 - 12 years old and who have not been immunized should receive two or three doses of the vaccine (depending on the brand) given over a few months.

Hepatitis B vaccine protection lasts at least 10 years. Booster shots after that may be recommended, depending on continuing risk such as sexual exposure.

The following adults are at very high risk and should be vaccinated:

Health care and public safety workers who may be exposed to blood products. Such individuals have a risk for hepatitis B virus that ranges from 15 - 30%.

People in the same household as hepatitits B infected individuals. (Unvaccinated people who have had intimate exposure to people with hepatitits B may be protected with immune globulin, which is sometimes administered with the vaccine.)

Travelers to developing countries.

Patients who require transfusions and have not been infected with hepatitits B. (Those with blood clotting disorders should have the vaccination administered under the skin, not injected in the muscle.)

Sexually active homosexual or heterosexual individuals with multiple partners or who engage in high-risk sexual behavior.

People with any sexually transmitted diseases.

Other people at risk who may benefit from vaccinations include:

Patients and workers in mental institutions and morticians.

Patients on hemodialysis. (People on hemodialysis may need larger doses or boosters. They also may need to be re-vaccinated if blood tests indicate they are losing immunity.)

People who use injected drugs.

Pregnant women at risk for the virus should be vaccinated. There is no evidence that the vaccine is dangerous to the fetus.

People receiving treatments or who have conditions that suppress the immune system may need the vaccination, although its benefits for this group are unclear except for those at high risk, such as people with HIV or spleen abnormalities.

The regimen in adults is typically three doses given over 6 months. People with alcoholism may need high doses.

Soreness at the injection site is the most common side effect. There have been some reports of nerve inflammation after vaccinations for hepatitis B, and there has been some concern about three small studies associating the vaccine with an insignificant increase in multiple sclerosis. Recent studies, however, have found no evidence to support these concerns. Nonetheless, some groups oppose the vaccination in children who are not in high-risk groups. It should be strongly stressed that worldwide 65 million people with chronic hepatitis are expected to die from liver disease. Vaccinations save lives. For example, in Taiwan, where infection rates are high and infants are at risk for hepatitis B from infected mothers, vaccination programs have significantly reduced the risk for liver cancer.

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 hepatitits 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 FDA approved entecavir (Baraclude) for treatment of adults with chronic hepatitis B. In clinical trials, entecavir worked better than lamivudine for treating hepatitits 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 hepatitits 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 hepatitits B. The HIV drug tenofovir (Viread) should not be used to treat patients with HIV who are co-infected with hepatitits B as the drug may increase hepatitis severity. The lymphoma drug rituximab (Rituxan) may reactivate hepatitits B. Patients with lymphoma should be screened for hepatitits B. In 2007, the FDA revised the label for entecavir (Baraclude); patients who are co-infected with hepatitits B and HIV should take entecavir only if they are also taking antiretroviral HIV drugs.

Investigational Drugs.

Emtricitabine is a nucleoside analog drug used to treat HIV and AIDS. It is being investigated for chronic hepatitits 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 hepatitits 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.

Liver Transplantation. If the disease progresses to liver failure, liver transplantation may be an option. It is not foolproof, however. Viral recurrence is high in patients with hepatitis B. However, regular, lifelong injections of hepatitis B immune globulin (HepaGam B) can reduce the risk for re-infection following liver transplantation.

Hepatitis C

Hepatitis C is spread by contact with infected human blood. It is the most common blood-borne infection in the country. Until blood screening began in 1990, the hepatitis C virus was primarily transmitted through blood transfusions. Now, hepatitis C is transmitted mainly through intravenous drug use and sharing needles. Nearly half of people infected with hepatitis C have a history of injecting drugs. People who received a blood transfusion before 1992 are also at high risk, as are people who have had 20 or more sexual partners. Hepatitis C can also be passed from an infected mother to her baby during birth. (Breast-feeding does not increase the risk of transmission.)

Click the icon to see an image discussing hepatitis C.

About 4 million Americans have had an initial hepatitis C infection and an estimated 3.2 million have chronic hepatitis C. Hepatitis C affects about 170 million people worldwide. Most people with chronic hepatitis C are unaware that they have it. It is not possible to predict which patients will develop the chronic form of hepatitis C.

Ethnic Groups. In general, hepatitis C occurs most commonly in non-Caucasian men ages 30 - 49 years. Over 6% of African-Americans are infected with hepatitis C, about two to three times the risk for Caucasians.

Most patients with hepatitis C do not experience symptoms. If they appear at all, symptoms develop about 1 – 2 months after a person is infected. Symptoms of progressive chronic viral hepatitis may be very subtle. In some patients, itchy skin is the first symptom. Overall, fatigue is the most common symptom. Many patients do not experience any symptoms at all. Chronic hepatitis C can be present for 10 - 30 years, and cirrhosis or liver failure can sometimes develop before patients experience any clear symptom.

Some evidence suggests, however, that patients with chronic hepatitis C often experience an impaired quality of life, mostly from fatigue. Fatigue can impair daily function, vitality, and mood in ways that are similar to other chronic diseases. The severity of the fatigue is not necessarily related to the degree of liver injury. Some patients develop pain in small joints in the body (such as the hand) that may be nearly indistinguishable from symptoms of rheumatoid arthritis, fibromyalgia, or carpal tunnel syndrome. Recent research suggests that sexual dysfunction may be common among men with chronic hepatitis C. Other nonspecific symptoms include abdominal discomfort, loss of appetite, depression, and difficulty concentrating.

Acute Form. Acute hepatitis C is rarely recognized, since there are no symptoms in up to 80% of patients. About 15 - 45% of acute cases clear up on their own without becoming chronic. Early treatment with interferon drugs can significantly reduce the risk for progression to chronic hepatitis.

Chronic Form. About 55 - 85% of infected people develop chronic hepatitis. Chronic hepatitis C poses a risk for cirrhosis, liver cancer, or both.

Five - 20% of patients with chronic hepatitis C develop cirrhosis over a period of 20 – 30 years. The longer the patient has had the infection, the greater the risk. Patients who have had hepatitis C for more than 60 years have a 70% chance of developing cirrhosis.

Seventy percent of patients with chronic hepatitis C eventually develop chronic liver disease.

Of these patients, 4% eventually develop liver cancer. (Liver cancer rarely develops without cirrhosis first being present.)

About 1 - 5% of people with chronic hepatitis C eventually die from liver diseases (cirrhosis or liver cancer). However, according to a 2006 Lancet study, intravenous drug-related deaths are more common than liver-related deaths among younger female patients (ages 15 - 24) infected with hepatitis C or hepatitis C and B.

Patients with chronic hepatitis C may also be at higher risk for non-liver disorders, including the following:

Cryoglobulinemia (a disorder in which protein clumps form in the blood). This can cause skin rash and ulcers, kidney problems, arthritis, and sensations (such as tingling or pain) in the hands and feet. People with such symptoms may have particular difficulties with interferon, which can have similar side effects.

Porphyria cutanea tarda (a disorder that causes skin color and texture changes and sensitivity to light).

Certain autoimmune disorders, particularly hypothyroidism and rheumatoid arthritis.

Type 2 diabetes, particularly among younger people with hepatitis C who are overweight.

Some experts believe that hepatitis C may infect the central nervous system in certain patients, possibly accounting for the fatigue, depression, or both experienced by patients who have even relatively mild cases.

Certain types of lymphomas (cancers of the lymphatic system). According to a 2007 study in the Journal of the American Medical Association, hepatitis C infection increases the risk of developing non-Hodgkin’s lymphoma by 20 - 30%. The risk for a particular type of non-Hodgkin’s lymphoma, Waldenstrom’s macroglobulinemia, increases by 300%. However, this study only evaluated male Vietnam War veterans, so these risks may not apply to the general public.

Tests for Liver Enzymes. Blood tests showing elevated liver enzymes, particularly alanine aminotransferase (ALT), plus symptoms of hepatitis (jaundice, fatigue) are often first signs of acute hepatitis. In chronic hepatitis, however, liver enzymes may be normal or fluctuate. They also can be elevated even after the virus has cleared.

Tests to Identify the Virus. The standard first test for diagnosing hepatitis C is known as enzyme-linked immunosorbent assay (ELISA or EIA). The antibody for hepatitis C is used to identify the virus. The antibody may not show up for 6 weeks to 1 year after the onset of the disease, however, so its absence is not necessarily an indication of a healthy liver. A test called an immunoblot assay (called RIBA) may also be used to confirm the presence of the virus. An accurate home test (Hepatitis C Check) is now available. It supplies a lancet for obtaining a drop of blood, which is sent to the laboratory for EIA and possibly RIBA analysis. Results take about a week.

Tests to Identify Genetic Types and Viral Load. Additional tests called hepatitis C RNA assays may be used to confirm the diagnosis. They use a polymerase chain reaction (PCR) to detect the RNA (the genetic material) of the virus. Such tests may be performed if there is some doubt about a diagnosis but the doctor still firmly believes the virus is present.

hepatitis C RNA assays also determine virus levels (called viral load). Such levels do not reflect the severity of the condition or speed of progression, as they do for other viruses, such as HIV. However, high viral loads suggest a poorer response to treatment with interferons.

Such techniques may also help determine the genotype of the virus, which can be helpful in determining a treatment approach. There are six main genetic types of hepatitis C and more than 50 subtypes. They do not appear to affect the rate of progression of the disease itself, but they can differ significantly in their effects on response to treatment. Genotype 1 is the most difficult to treat and is the cause of up to 75% of the cases in the U.S. The other common genetic types are types 2 (15%) and 3 (7%), which are more responsive to treatment. People with hepatitis C need to have their genotype tested so that doctors can make appropriate treatment recommendations.

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.

Liver Biopsy. Only a biopsy can determine the extent of injury in the liver. Some doctors now recommend biopsies for all patients with chronic hepatitis C, regardless of severity, because of the risk for liver damage even in patients without symptoms. If a biopsy does not show any scarring and liver enzymes are normal, patients can be assured that the outlook is very favorable.

No vaccines are available, but immune globulin helps protect against developing hepatitis C after transfusions. Periodic doses of immune globulin in sexual partners of infected people also appear to be protective. In infected people, preventing transmission is similar to those for hepatitis B.

Interferons. Interferons are natural proteins that activate certain immune functions in the body and have anti-viral properties. The natural interferons used for chronic hepatitis B and C are called type I interferons. They are given by injection, need to be taken three times a week, and include the following:

Interferon alfa 2b (Intron A). Used for both hepatitis B and C.

Interferon alfa 2a (Roferon-A). Mostly used for hepatitis C.

Interferon alfa-n1 (Wellferon). Approved but mostly used in Canada for hepatitis C.

Newer synthetic interferons have been developed that are showing some advantages over the natural forms:

Pegylated interferon (PegINF). Pegylated interferons use a small molecule called polythelene glycol (PEG), which attaches to a protein and extends the activity of the interferon. This action allows the drug to be taken only once a week. Drugs available include pegylated interferon alfa-2b (Peg-Intron) and alfa-2a (Pegasys).

Interferon alfacon-1 (Infergen). This drug is called a consensus interferon (CIFN) because it was genetically developed using the most commonly occurring amino acid sequences from each of the natural type 1 alpha interferons. It is 5 - 10 times more biologically active than natural type 1 interferons. CIFN is usually given three times a week when used as initial treatment for hepatitis C.

Interferon Candidates. The best candidates for interferon treatments are patients who are at greatest risk for cirrhosis. Factors suggesting a higher risk for cirrhosis include:

Detectable virus levels as determined by an assay test.

High levels of aminotransferase enzyme for more than 6 months.

Indication of liver scarring on biopsy.

Patients who are not good candidates for interferon and are usually ineligible include:

Women who are pregnant or planning to become pregnant soon.

Patients with advanced cirrhosis. (It is unclear if the drug improves survival in patients with advanced cirrhosis and, in any case, it may be dangerous for them.)

Patients with fluid in the abdomen (ascites).

Patients with anemia or risk factors for anemia should not take the combination treatments, although they may be candidates for interferon alone.

Several kinds of patients are ineligible for treatment because of the high risk for noncompliance and the severe psychiatric effects of the drugs. They include patients with psychiatric and medical problems and substance abusers. Some doctors believe that these patients could benefit from treatment.

Side Effects and Complications of Treatment with Interferon. Common side effects of any interferon are flu-like symptoms (fever, chills, muscle aches) that usually occur within 6 hours and gradually decline over 1 - 2 weeks. (Pegylated interferon may pose a higher risk for these symptoms than the natural interferons.)

Chronic or more serious effects include:

Emotional and mental changes. Depression can be very severe, and cases of suicidal thoughts have been reported. Other mental and emotional symptoms include anxiety, amnesia, confusion, irritability, impaired concentration, decreased alertness, memory problems, and mental slowing.

Changes in sensation.

Weight loss.

Skin rashes.

Hair loss.

Gastrointestinal problems, including nausea, vomiting, and diarrhea, and, in severe cases intestinal bleeding and ulcers.

Fatigue and general weakness.

Back pain.

Complications in the lungs, including worsening of asthma. In severe cases, interferon can cause shortness of breath, inflammation in the lungs, and pneumonia.

Possible negative effects on cholesterol and lipid levels.

Heart rhythm disturbances, which, in rare cases, can be serious.

Mild anemia.

Drop in platelet and white blood cell counts, increasing susceptibility to bacterial infections.

May trigger an autoimmune response, possibly causing anemia, diabetes, lupus-like symptoms, hypothyroidism, or even autoimmune hepatitis.

Complications in the eye, including bleeding that, in some cases, may lead to loss of vision if not detected promptly.

Rare reports of acute pancreatitis.

In children, interferon therapy temporarily disrupts growth.

Patients have a difficult time with prolonged therapy. Over 20% drop out if treatment lasts longer than 2 years. Depression is the most common reason for stopping the treatment.

Several different methods of administering interferons are under investigation to help reduce some of the problems associated with injections. These methods include pills, pumps, and controlled release implants.

Interferons in Combination with Ribavirin. Ribavirin, a nucleoside analog drug, does not work alone, but it can double sustained response rates when combined with an interferon.

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 hepatitis C 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 ribavirin.

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 ribavirin treatment, particularly anemia, researchers are actively investigating how to identify which patients may be able to succeed with shorter treatment duration.

PegINF combinations may help 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.

Determining Treatment Success. Doctors measure treatment success and approaches based on the patient’s response to the treatments:

Early Response. These are patients who respond to the drug right away. This means that their viral count drops very rapidly within the first few weeks of treatment and is still undetectable at 12 weeks. (One difficulty in deciding when to stop treatment, even in responders, is the inability to predict at 12 weeks which of these patients will relapse and which ones will have a sustained response.)

Sustained Response. Patients who are free of the virus longer than 6 months are considered to be sustained responders. The overall sustained response rates with the current standard combination of pegylated interferon and ribavirin is over 50%, with certain factors predicting higher or lower response rates.

Relapse. In relapse, the virus comes back again and requires retreatment. This is usually due to the development of mutant strains that are resistant to the drugs or because the original dose was too low.

Nonresponse. Patients are considered to be nonresponders if the virus is still detectable 12 weeks after interferon alone or after 24 weeks of combination therapy. Treating these patients again has achieved only a 15% response.

People at Risk for Poor Response to Combination Treatment. The following patients have a greater risk for not responding to combination treatment with interferon and ribavirin:

People at high risk for aggressive hepatitis C.

Having a high viral count.

Having a specific genetic type of the virus. Patients with genotype 1 do not respond as well to combination treatment as patients with genotypes 2 or 3.

Older age (especially older than 60 years).

African-Americans are less responsive to treatment than Caucasians or Asians. The reasons for this are unclear.

Failure can be due to other, modifiable factors, which should be assessed before stopping treatment, particularly in patients who had interferon alone. They include:

Interferon dose was too low.

Patient did not comply fully with the treatment.

Patient was consuming alcohol.

Treatment time was too short. Some evidence suggests that response can significantly improve for many patients with genotype 1 if treatment time is extended to 48 weeks.

Even if viral levels linger, interferon treatment may still have benefits. For example, patients with normal liver enzyme levels appear to have almost no risk for liver damage, even if viral levels persist after treatment. Evidence also suggests that interferon reduces liver scarring and may reduce the risk for liver cancer in some patients, even if the treatment does not eliminate the virus. More research is needed, however, to confirm these findings.

Investigational Drugs for Hepatitis C. 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 that may show 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 ribavirin 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 combinations 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.

Other drugs under investigation include vaccines, genetic therapies known as antisense oligonucleotides or monoclonal antibodies, and drugs that will help prevent or reduce progression of liver scarring or progression to liver cancer. Even if successful, none of these drugs will be available for many years.

Liver Transplantation for Hepatitis C. If the disease progresses to the point where it becomes life-threatening, liver transplantation may be an option. Nearly 40% of liver transplant patients are infected with hepatitis C. However, liver transplantation is not a cure for hepatitis C. The virus nearly always returns. One study of patients with hepatitis C reported 5-year risks for viral recurrence of 80% and for cirrhosis of 10%. A 2004 study found that the hepatitis C virus comes back with more severity in livers from living donors than livers taken from cadavers. Researchers are investigating retreatment with antiviral drugs.

In both hepatitis B and C, the disease often persists or returns despite treatment. The virus continually generates many “mutant viruses” that differ just slightly from the parent virus. These mutated viruses may be resistant to interferons and so, over time, the drugs become ineffective.

Autoimmune Hepatitis

Autoimmune chronic hepatitis typically occurs in women ages 20 - 40 who have other autoimmune diseases, including:

Systemic lupus erythematosus

Rheumatoid arthritis

Sjögren's syndrome

Inflammatory bowel disease

Glomerulonephritis

Hemolytic anemia

Some research indicates that the postmenopausal period may be another peak in incidence of autoimmune hepatitis among women. About 30% of patients are men, however, and in both genders there is often no relationship to another autoimmune disease. In general, researches have not discovered major risk factors for this condition.

About 85% of people with chronic active autoimmune hepatitis do not have severe symptoms. When symptoms occur, they range from minimal to severe, and include fatigue, jaundice, fever, and weight loss. The liver and spleen are often enlarged. In addition, patients with this condition may experience skin disorders, including palmar erythema (red palms) and spider angioma (a blood-red spot, the size of a pinhead, from which tiny blood vessels radiate like spider legs). Itching is not common, however. The abdomen or legs may be swollen due to the accumulation of fluid.

If a patient has symptoms of chronic active hepatitis for 6 months or more and a virus cannot be identified, doctors usually suspect autoimmune hepatitis. Other autoimmune liver diseases, however, can confuse a diagnosis. To help confirm this condition, test results may show high levels of immune factors called serum globulins or certain antibodies to liver proteins. In some cases, a successful trial of steroid drugs may be the only way to diagnose autoimmune hepatitis.

Autoimmune hepatitis is usually benign and causes little trouble. There is a very small risk that it can evolve into the active form. One study reported a 10-year survival rate of 95%, which was similar to the same age group in the general population. However, it the condition evolves into the chronic active form, 5-year survival may be only 50% if the disease is not treated. (The survival rate can be higher in people with milder symptoms and less liver damage.)

Although very uncommon, severe autoimmune hepatitis can be life-threatening and require intensive therapy, possibly including liver transplantation. The risk for liver failure and bleeding in the stomach and esophagus is highest in the early years after disease onset. This risk diminishes over time but is replaced by an increase in liver cancer rates and bleeding in the stomach and intestines. The risk for liver cancer is not as high, however, as with chronic viral hepatitis.

Patients with autoimmune hepatitis who have mild symptoms and slight inflammation of the liver do not require any treatment except to relieve symptoms. They should be monitored, however, for any signs of disease progression. Severe autoimmune hepatitis is a life-threatening condition and requires intensive therapy.

Because of effective treatment options and in spite of a high rate of relapse, long-term survival rates in patients with autoimmune hepatitis are excellent. Drugs that block factors in the immune system and help reduce inflammation and symptoms of autoimmune hepatitis are most often used.

Corticosteroids. The corticosteroid prednisone (Deltasone, Orasone, Sterapred, generic) is the standard drug for treating autoimmune hepatitis. It produces remission of symptoms in about 80% of patients with autoimmune hepatitis. For most patients, steroids also reduce symptoms within 3 months, improve liver function within 6 months, and restore liver health within 2 years. Between 10 - 20% of patients continue to deteriorate despite steroid treatment, although higher doses may help some of these people. (Steroids are generally not useful for chronic hepatitis B or C. Suppressing the immune system in these patients can actually encourage the viruses to multipy more quickly.)

Treatment usually needs to continue for about 2 years before the disease is in complete remission. Usually, steroids are stopped when disease symptoms have disappeared, when blood tests show that aminotransferase (AST) levels are less than two times normal, and liver biopsies reveal no active cell damage. Steroid medications must be withdrawn very slowly. Patients who are very elderly or who have advanced (decompensated) cirrhosis are not good candidates for this treatment.

Unfortunately, remission rarely lasts more than 3 years. About half of patients relapse within 6 months, and only about 20% of patientsare disease-free for more than 5 years. A 2007 study indicated that AST, gamma-globulin, and immunoglobulin-G (IgG) levels are helpful in predicting which patients may relapse and which patients have the best chance for maintaining remission. Still, most patients with autoimmune hepatitis will eventually have a relapse. Re-administering prednisone therapy after relapse achieves another remission in about 80% of patients.

Corticosteroid side effects can be very distressing and sometimes serious. They include weight gain, skin problems, moon-shaped face, high blood pressure, diabetes, cataracts, mental disturbances, infections, and osteoporosis.

Azathioprine. Doctors often prescribe the drug azathioprine (Imuran) along with steroids to help reduce severe side effects caused by using steroids alone. When azathioprine is given in combination with prednisone, the prednisone dose can be reduced, thereby lowering the corticosteroid’s side effects. Azathioprine also suppresses the immune system and helps prevent relapse, but the drug will not induce remission by itself.

Other Drugs. Other immunosuppressant drugs, such as mycophenylate mofetil (MMF), cyclosporine (Neoral), or tacrolimus (Prograf) are sometimes prescribed for patients who are not helped by standard treatment.

Liver Transplantation and Autoimmune Hepatitis. If all therapies fail and the disease becomes life threatening, liver transplantation may be performed. Liver transplantation can be a successful option for many people. Survival rates are about 90% after 1 year, and 70 - 80% after 5 years.

Symptom Management

The primary goals for managing viral hepatitis are to provide adequate nutrition, to prevent additional damage to the liver, and to prevent transmission to others. For mild cases of acute viral hepatitis, no drug therapy or other treatment is either available or necessary. Hospitalization is needed only for people at high risk for complications such as pregnant women, elderly people, patients with other serious conditions, or those who have severe nausea and vomiting and need to have fluids administered intravenously.

The following tips may be useful:

All patients should abstain from alcohol and sexual contact during the acute phase.

Although most patients with hepatitis experience fatigue and require more rest than usual, they can be as physically active as they want without affecting recovery. In fact, patients should be encouraged to be as active as they can.

Depression is common, particularly in people used to an active life. Patients should be reassured that in the majority of hepatitis cases, recovery is complete.

The liver processes many types of medications. As soon as hepatitis is diagnosed, patients should stop taking all drugs (including over-the-counter-medication) except those prescribed or recommended by their doctors. Specific nonsteroidal anti-inflammatory drugs (NSAIDs) that should be avoided include ibuprofen (Advil, Motrin) and acetaminophen (Tylenol). Ibuprofen (Advil, Motrin) may increase liver enzymes and cause liver damage in patients with hepatitis C. Acetaminophen (Tylenol) may cause sudden liver failure in patients with hepatitis A or B. Acetaminophen can also damage the liver if taken in combination with alcohol.

After the onset of acute hepatitis, periodic visits to the doctor for repeat blood tests are necessary, the frequency of which depends on how well the patient feels. If symptoms still occur after 3 months and laboratory tests still indicate active presence of the virus, the patient should be evaluated every month. If symptoms persist beyond 6 months, a liver biopsy may be required to determine any liver damage.

Dietary Factors to Protect the Liver. In general, no vitamins or special diets have been proven to be particularly beneficial. The following may be helpful, however:

Eating many small snacks during the day, with larger ones in the morning, may help prevent weight loss while reducing the severity of nausea. Patients might be able to tolerate high-caloric drinks to supplement their regular diet.

One small Japanese study suggested that vitamin E might help protect against liver damage in patients with hepatitis C.

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. Pork is high in the vitamin, but more healthy sources include dried fortified cereals, oatmeal, corn, nuts, cauliflower, sunflower seeds and vitamin pills.

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

Higher coffee intake has been shown to reduce the risk for cirrhosis.

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.

Popular herbal remedies for hepatitis include ginseng, glycyrrhizin (a compound in licorice), catechin (found in green tea), and silymarin (found in milk thistle). Aside from milk thistle, there has been no evidence that these herbs are helpful for hepatitis. Studies on milk thistle’s benefit have been mixed. Some studies have indicated that milk thistle may help improve liver enzyme levels. However, a 2005 review found that the herb did not reduce deaths from liver disease caused by hepatitis B or C.

Patients with hepatitis should be aware that some herbal remedies may cause liver damage. In particular, kava (an herb used to relieve anxiety and tension) may be dangerous for people with chronic liver disease.

Outlook

In most cases of acute viral hepatitis, recovery is complete and the liver returns to normal within 2 - 8 weeks. In a small number of cases of hepatitis B or C, the condition can be prolonged and recovery may not occur for a year. About 5 - 10% of these patients will have a flare-up of milder symptoms before full recovery. A few of these patients may go on to develop chronic hepatitis. People who have been infected with a hepatitis virus continue to produce antibodies to that specific virus. This means that they cannot be reinfected with the same hepatitis virus again. Unfortunately, they are not protected from other types.

Serious consequences of acute viral hepatitis are rare, but can be life threatening if they occur. Pregnant women with acute hepatitis B, C, or E are at higher risk for complications of acute hepatitis.

In very rare cases, within 2 months of onset of acute hepatitis, a very serious condition known as fulminant hepatitis can develop. In this event, the liver fails with catastrophic consequences. The following events may develop:

A large swollen abdomen (known as ascites) and a peculiar hand-flapping tremor (called asterixis).

These symptoms may be followed by stomach and intestinal bleeding and mental confusion, stupor, or coma caused by brain injury (encephalopathy).

No medications, including corticosteroids, have any effect against the condition itself. Liver transplantation is currently the only life-saving treatment for fulminant acute hepatitis and has survival rates of up to 60%. Without liver transplantation, the chance of survival is only 20%.

Other serious and rare consequences of acute viral hepatitis are aplastic anemia (which can be fatal), pancreatitis, hypoglycemia, and polyarteritis, a serious inflammation of blood vessels.

Chronic Persistent Hepatitis. Chronic persistent hepatitis is usually mild and nonprogressive or slowly progressive, causing limited damage to the liver. Cell injury in such cases is usually limited to the region of portal tracts, which contains vessels that carry blood to the liver from the digestive tract. In some cases, however, more extensive liver damage can occur over long periods of time and progress to chronic active hepatitis.

Chronic Active Hepatitis. If damage to the liver is extensive and cell injury occurs beyond the portal tract, chronic active hepatitis can develop. Significant liver damage has usually occurred by this time. Nearly every bodily process is affected by a damaged liver, including digestive, hormonal, and circulatory systems. Symptoms can significantly impair daily life.

Cirrhosis. If liver cells are destroyed between the portal tract and the central veins in the liver, progressive cell damage can build a layer of scar tissue over the liver, resulting in the condition known as cirrhosis. In such cases, the entire liver is threatened with malfunction and failure. If cirrhosis develops, the average survival time is about 10 years. The risk for cirrhosis is much higher in patients with hepatitis C than in those with hepatitis B. [For more information, see In-Depth Report #75: Cirrhosis.]

Liver Cancer. The risk for liver cancer in patients with cirrhosis is about 14% but varies widely depending on the cause of hepatitis. (Liver cancer is rare in patients who do not develop cirrhosis.)

Click the icon to see an image of cirrhosis of the liver.

Liver transplantation may be indicated for the following patients:

Those 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.

Current 5-year survival rates after liver transplantation are 55 - 80%, depending on different factors. Patients report improved quality of life and mental functioning after liver transplantation. Unfortunately, in about half of all patients with chronic hepatitis, the disease recurs after transplantation.

Patients should consider medical centers that have performed more than 50 transplants per year and produced better-than-average results. Unfortunately, there are far more people waiting for liver donors than there are available organs. [For more information on liver transplantation, see In-Depth Report #75: Cirrhosis.]

Resources

www.cdc.gov/hepatitis -- Centers for Disease Control and Prevention

www.hepfi.org -- Hepatitis Foundation International

www.hepb.org -- Hepatitis B Foundation

www.liverfoundation.org -- American Liver Foundation

www.aasld.org -- American Association for the Study of Liver Diseases

www.gastro.org -- American Gastrointestinal Association

www2.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases

www.immunize.org -- Immunization Action Coalition

www.hivandhepatitis.com -- Hepatitis and HIV

www.unos.org -- United Network for Organ Sharing

References

Amin J, Law MG, Bartlett M, Kaldor JM, Dore GJ. Causes of death after diagnosis of hepatitis B or hepatitis C infection: a large community-based linkage study. Lancet. 2006 Sep 9;368(9539):938-45.

Giordano TP, Henderson L, Landgren O, Chiao EY, Kramer JR, El-Serag H, et al. Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. JAMA. 2007 May 9;297(18):2010-7.

Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006 Dec;131(6):1743-51. Epub 2006 Sep 20.

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.

Montano-Loza AJ, Carpenter HA, Czaja AJ. Improving the end point of corticosteroid therapy in type 1 autoimmune hepatitis to reduce the frequency of relapse. Am J Gastroenterol. 2007 May;102(5):1005-12. Epub 2007 Feb 23.

Shiffman ML, Suter F, Bacon BR, Nelson D, Harley H, Sola R, et al. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2007 Jul 12;357(2):124-34.

Wang CS, Wang ST, Yao WJ, Chang TT, Chou P. Hepatitis C virus infection and the development of type 2 diabetes in a community-based longitudinal study. Am J Epidemiol. 2007 Jul 15;166(2):196-203. Epub 2007 May 11.

Review Date:
8/31/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, In-Depth Reports; Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Eczema

FitSugar — Wed, 08 Oct 2008 17:34:55 -0700

Overview

Signs and Symptoms

Causes

Risk Factors

Diagnosis

Prevention

Treatment

Other Considerations

Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Eczema is a chronic, inflammatory skin disorder. Its main features are blisters that dry to become scaly, itchy rashes. The skin becomes dry and itchy because too much moisture is lost from its upper layer. This leaves the skin without protection, making it easy for bacteria and viruses to penetrate. The disease occurs episodically; in other words, there may be periods when symptoms are severe (flares) and times when there are no symptoms at all (remission). Although eczema is not contagious, it is very common -- estimates are that more than 15 million people in the United States have eczema. People with eczema often have a personal or family history of allergic conditions like asthma or hay fever. There is no cure, but treatments can reduce symptoms and help prevent outbreaks.

Signs and Symptoms

Symptoms of eczema occur repeatedly. The most common signs of eczema are:

Dry, extremely itchy skin

Blisters with oozing and crusting

Redness of the skin around the blisters

Raw areas of the skin from scratching which may even lead to bleeding

Dry, leathery areas with more or less pigment than their normal skin tone (called lichenification)

Eczema in children under 2 years old generally begins on the cheeks, elbows, or knees. In adults, it tends to be located on the inside surfaces of the knees and elbows.

Causes

The cause of eczema is thought to be a combination of hereditary (genetic) and environmental factors. This means that factors such as allergies can cause eczema in susceptible people. Exposure to certain irritants and allergens in the environment can worsen symptoms, as can dryness of the skin, exposure to water, temperature changes, and stress.

Risk Factors

Young age -- infants and young children are most affected by eczema (about 65% of cases occur before age one, and about 90% occur before age 5)

Skin exposure to harsh conditions

Living in a climate with low humidity

Personal or family history of allergies to plants, chemicals, or food

Deficiencies of certain vitamins and minerals (for example, zinc)

Stress can make eczema worse

Irritants that may worsen eczema include:

Wool or synthetic fibers

Certain soaps and detergents as well as perfumes and some cosmetics

Dust or sand

Cigarette smoke

Diagnosis

Your doctor will most likely base a diagnosis on both the appearance of the skin and on personal and family history. To find the cause of your rash, your doctor may ask about stress in your life, your diet, drugs you are taking, soaps and detergents you use, and chemicals or materials you may be exposed to at work. A skin lesion biopsy (removal of a small piece of skin for examination in a laboratory) may be performed, but is not always required to make the diagnosis.

Prevention

Control of stress, nervousness, anxiety, and depression may help prevent flares of eczema. Mind-body techniques that have shown some success include cognitive-behavioral therapy and autogenic training. These two techniques can also be combined with learning about eczema.

Dietary restrictions that may help avoid flare ups include eggs, fish, peanuts, and soy. This is very individual and should be discussed with your health care provider. A doctor, dietitian, or naturopath, for example, can help you make these dietary changes and determine if the lack of these foods in your diet is reducing the incidence and severity of your eczema.

Although somewhat controversial, some studies have shown that children who are exclusively breast-fed for at least 4 months are less likely to get eczema. This is particularly true when the nursing mother has avoided cow's milk in her own diet.

Similarly, recent studies suggest that babies whose mothers used probiotics during pregnancy and while breastfeeding were less likely to have eczema at up to 2 years of age.

Preliminary studies suggest that pretreatment of skin with creams containing omega fatty acids can reduce the severity of eczema or prevent eczema entirely.

Treatment

The goals when treating eczema are to heal the skin, reduce symptoms, prevent skin damage, and prevent flares. Treatment may vary depending on age, symptoms, and general health. Developing skin care routines, identifying factors that trigger flares, and avoiding these triggers are a large part of any treatment plan.

Lifestyle

Avoid anything that aggravates the symptoms, such as allergens (substances to which the immune system overreacts) and irritants to the skin. Common allergens include pollen, dust mites, and animal dander. Common skin irritants include wool, synthetic fibers, soaps and detergents, perfumes, cosmetics, lanolin, certain chemicals such as chlorine and solvents (including mineral oil), cigarette smoke, dust, and sand.

Avoid scratching or rubbing affected areas.

Protect skin from rough clothing and irritants.

Be aware of emotional stress, and try stress-reducing techniques.

Keep your environment cool, with stable temperature and humidity.

Dry skin often makes the condition worse. Remember to:

Avoid hot baths or showers; lukewarm water is best.

Wash or bathe as quickly as possible to lessen water contact.

Use a mild soap or a nonsoap cleanser, or less soap than usual.

Moisturize. After bathing, it is important to trap the moisture in the skin by applying lubricating cream on the skin while it is damp (within 3 minutes of bathing).

Parents can help their children by:

Providing distractions to prevent them from scratching.

Keeping fingernails short to reduce chances of infection from scratching.

Being aware that there may well be social and emotional stress associated with visible skin lesions; additional support and encouragement may be needed.

Medications

Mild anti-itch lotions (Caladryl or Calamine) or topical corticosteroids (hydrocortisone) may soothe less severe or healing areas, or dry scaly lesions.

Chronic thickened areas may be treated with ointments or creams that contain tar compounds (such as Psoriasin), corticosteroids (medium to very high potency), and ingredients that lubricate or soften the skin.

Systemic corticosteroids may be prescribed to reduce inflammation in some severe cases. Examples include prednisone (Deltasone) and methylprednisolone (Medrol). In very rare instances, medications that suppress the immune system (called immunosuppressants), such as cyclosporine, may be considered in adults with extremely severe eczema who do not respond to oral steroids.

Antihistamines, such as diphenhydramine (Benadryl), may be recommended for nighttime use to prevent scratching. These medications may cause drowsiness. Topical (on the skin) antihistamines preparations are also available.

New treatments -- the latest treatment for eczema is a new class of skin medications called topical immunomodulators (TIMs). These medications are steroid-free. The most common are tacrolimus (Protoptic) and pimecrolimus (Elidel). Clinical studies have reported as high as an 80% success rate using these new medications.

Surgery and Other Procedures

Phototherapy and Photochemotherapy

Treatment with ultraviolet light waves may effectively treat mild-to-moderate cases of eczema in children over age 12 and adults. If phototherapy is ineffective alone, it may be combined with a drug called psoralen. It is then called photochemotherapy.

Nutrition and Dietary Supplements

Nutritional deficiencies may be addressed with the following supplements:

Eliminate potential food allergens, including dairy, wheat (gluten), corn, preservatives, and food additives. Your health care provider may want to test for food sensitivities. Identifying and treating hidden food allergies along with stress management are often the cornerstones of effective complimentary medical treatment of eczema.

A multivitamin daily, containing the antioxidant vitamins A, C, E, the B-vitamins, and trace minerals, such as magnesium, calcium, zinc, and selenium.

Omega-3 fatty acids, such as fish oil (1 - 2 capsules or 1 tablespoonful oil 2 - 3 times daily), to help decrease inflammation and improve immunity. Cold-water fish, such as salmon or halibut, are good sources, but supplementation is recommended.

Probiotic supplement (containing Lactobacillus acidophilus), 5 - 10 billion CFUs (colony forming units) a day, for maintenance of gastrointestinal and immune health. Some probiotic supplements may need to be refrigerated for best results. Your child may also take probiotic supplements. Consult with your health care provider before giving your child any dietary supplements.

Alpha-lipoic acid, 25 - 50 mg twice daily, for antioxidant support.

Vitamin C, 500 - 1,000 mg 1 - 3 times daily, as an antioxidant and for immune support.

L-glutamine, 500 - 1,000 mg 3 times daily, for support of gastrointestinal health and immunity.

Grapefruit seed extract (Citrus paradisi), 100 mg capsule or 5 - 10 drops (in favorite beverage) 3 times daily when needed, for antibacterial, antifungal, and antiviral activity, and for immunity.

Resveratrol (from red wine), 50 - 200 mg daily, to help decrease inflammation and for antioxidant effects.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink 2 - 4 cups per day. You may use tinctures alone or in combination as noted.

Green tea (Camellia sinensis) standardized extract, 250 - 500 mg daily, for antioxidant and anti-inflammatory effects. Use caffeine free products. You may also prepare teas from the leaf of this herb.

Cat's claw (Uncaria tomentosa) standardized extract, 20 mg 3 times a day, for inflammation and antibacterial, or antifungal activity.

Reishi mushroom (Ganoderma lucidum), 150 - 300 mg 2 - 3 times daily, for inflammation and for immunity. You may also take a tincture of this mushroom extract, 30 - 60 drops 2 - 3 times a day.

Olive leaf (Olea europaea) standardized extract, 250 - 500 mg 1 -3 times daily, for antibacterial or antifungal activity and immunity. You may also prepare teas from the leaf of this herb.

Evening primrose (Oenothera biennis) standardized oil extract (EPO), 500 mg - 8 grams daily in divided dosages, depending upon severity of symptoms. Ask a health care provider for more information on proper dosages of EPO.

Milk thistle (Silybum marianum) seed standardized extract, 80 - 160 mg 2 - 3 times daily, for detoxification support.

Homeopathy

Although very few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies for the treatment of eczema based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional -- your physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for each individual. Any remedy that causes aggravation of symptoms should be discontinued right away.

Calendula -- applied to the skin, particularly if the affected area is inflamed; this remedy soothes but does not cure the skin condition.

Sulphur -- for redness, burning, itching, and hot skin that tends to worsen with washing and scratching.

Urtica urens -- for large, red rashes (particularly those related to allergies) that itch and burn intensely.

Rhus toxicodendron -- used as a remedy for inflamed skin resulting from direct contact with an irritating substance; some homeopaths use it to treat eczema.

Massage and Physical Therapy

One clinical study evaluating essential oils for treating children with eczema concluded that massage with and without essential oils was effective in improving the dry, scaly skin lesions. Children with this scaly, itchy skin problem seem to experience less redness, scaling, and other symptoms if receiving massage between flares. Massage should not be used when this skin condition is actively inflamed. The essential oils most often chosen by the mothers in the study included sweet marjoram, frankincense, German chamomile, myrrh, thyme, benzoin, spike lavender, and Litsea cubeba.

Exercise

In one clinical study it was found that regular group sporting activities improved symptoms in those who participated for 3 weeks. The therapeutic effect of exercise may be related to the positive impact it has on the emotions. Sports should be avoided during the worst stages of an outbreak.

Climatotherapy

Climatotherapy is the use of sunlight and water (such as the ocean) as therapy. The Dead Sea in Israel is known for its healing properties, and many people with eczema go there to sit in the sun and swim in the water. Clinical studies suggest that this is a successful treatment for eczema. One clinical study looked at the experience of more than 1,500 people with eczema and found that 95% of skin was cleared in people who had previous stays at the Dead Sea and stays longer than 4 weeks.

Mind-Body Medicine

Flares of eczema are associated with anxiety and stress. Several clinical studies have shown that relaxation techniques to reduce stress and anxiety can successfully decrease the number of occurrences and relieve symptoms of eczema. Biofeedback seems to be a particularly useful technique.

Other Considerations

Starting an infant on solid foods conservatively and gradually may help prevent the food sensitivities that can cause eczema. Those who are allergic to ragweed, chrysanthemums, asters, echinacea, or feverfew should avoid chamomile because it is in the same plant family.

Pregnancy

Avoid the use of burdock and sulfur during pregnancy.

Warnings and Precautions

Although Chinese herbal treatments for eczema have been gaining popularity in both the United States and the United Kingdom, caution must be exercised when considering such remedies for this skin condition. Many of the Chinese herbal creams available in these two countries have been tested, and high amounts of steroid medications have been discovered. This is worrisome and potentially dangerous because the amount of the medication in such creams is not standardized or regulated. In a few rare instances, the use of oral Chinese herbs (like a tea) for eczema has led to kidney damage.

Prognosis and Complications

Although there may be complications of eczema, such as bacterial infections of the skin and permanent scar formation, eczema is usually just an annoyance that is easily controlled with treatment and by avoiding irritants. Call for an appointment with your health care provider if it does not respond to treatment or if signs of infection (such as fever, redness, pain) occur. Children with eczema, after a certain period of time, often go into remission for the rest of their lives, although skin may remain sensitive and dry.

Supporting Research

Abrahamsson TR, Jakobsson T, Bottcher MF, et al., Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2007;119(5):1174-80.

Anderson C, Lis-Balchin M, Kifk-Smith M. Evaluation of massage with essential oils in childhood atopic eczema. Phyother Res. 2000;14(6):452-456.

Berger MM, Shenkin A. Vitamins and trace elements: Practical aspects of supplementation. Nutrition. 2006; 22(9):952-5.

Billmann-Eberwein C, Rippke F, Ruzicka T, Krutmann J. Modulation of atopy patch test reactions by topical treatment of human skin with a fatty acid-rich emollient. Skin Pharmacol Appl SkinPhysiol. 2002;15(2):100-104.

Borrek S, Hildebrandt A, Forster J. Gamma-linolenic-acid-rich borage seed oil capsules in children with atopic dermatitis. A placebo-controlled double-blind study [Article in German]. Klin Padiatr. 1997;209(3):100-104.

Bruno EJ Jr, Ziegenfuss TN, Landis J. Vitamin C: research update. Curr Sports Med Rep. 2006; 5(4):177-81.

Byremo G, Rod G, Carlsen KH. Effect of climatic change in children with atopic eczema. Allergy. 2006;61(12):1403-10.

Cabrera C, Artacho R, Gimenez R. Beneficial effects of green tea -- a review. J Am Coll Nutr. 2006;25(2):79-99.

Cooper R, Morre DJ, Morre DM. Medicinal benefits of green tea: Part I. Review of noncancer health benefits. J Altern Complement Med. 2005; 11(3):521-8.

Doron S, Gorbach SL. Probiotics: their role in the treatment and prevention of disease. Expert Rev Anti Infect Ther. 2006; 4(2):261-75.

Dryden GW Jr, Deaciuc I, Arteel G, McClain CJ. Clinical implications of oxidative stress and antioxidant therapy. Curr Gastroenterol Rep. 2005;7(4):308-16.

Ernst E, Huntley A. Tea tree oil: a systematic review of randomized clinical trials. ForschKomplementarmed Klass Naturheilkd. 2000; 7(1):17-20.

Ernst E. Adverse effects of herbal drugs in dermatology. Br J Dermatol. 2000;143(5):923-929.

Fleischer AB Jr, Abramovits W, Breneman D, Jaracz E; US/Canada tacrolimus ointment study group. Tacrolimus ointment is more effective than pimecrolimus cream in adult patients with moderate to very severe atopic dermatitis. J Dermatol Treat. 2007;18(3):151-7.

Harari M, Shani J, Seidl V, Hristakieva E. Climatotherapy of atopic dermatitis at the Dead Sea: demographic evaluation and cost-effectiveness. Int J Dermatol. 2000;39(1):59-69.

Hederos CA, Berg A. Epogam evening primrose oil treatment in atopic dermatitis and asthma. Arch Dis Child. 1996;75(6):494-497.

Horrobin DF. Essential fatty acid metabolism and its modification in atopic eczema. Am J Clin Nutr. 2000;71(1 Suppl):367S-72S.

Johnston CS. Recommendations for vitamin C intake. JAMA. 1999;282(22):2118-2119.

Kalliomaki M, Kirjavainen P, Eerola E, Kero P, Salminen S, Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol. 2001;107(1):129-134.

Kalliomaki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomized placebo controlled trial. Lancet. 2001;357(9262):1076-1079.

Karamfilov T, Elsner P. Sports as a risk factor and therapeutic principle in dermatology [article in German]. Hautarzt. 2002;53(2):98-103.

Langan SM, Williams HC. What causes worsening of eczema? A systematic review. Br J Dermatol. 2006;155(3):504-14.

Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999;281(15):1415-1453.

Linde K, Hondras M, Vickers A, ter Riet G, Melchart D. Systematic reviews of complementary therapies - an annotated bibliography. Part 3: homeopathy. BMC Complement Altern Med. 2001; 1:4.

Magin PJ, Adams J, Heading GS, Pond DC, Smith W. Complementary and alternative medicine therapies in acne, psoriasis, and atopic eczema: results of a qualitative study of patients' experiences and perceptions. J Altern Complement Med. 2006;12(5):451-7.

McMenamy CJ, Katz RC, Gipson M. Treatment of eczema by EMG biofeedback and relaxation training: a multiple baseline analysis. J Behav Ther Exp Psychiatry. 1988;19(3):221-227.

Morse NL, Clough PM. A meta-analysis of randomized, placebo-controlled clinical trials of Efamol evening primrose oil in atopic eczema. Where do we go from here in light of more recent discoveries? Curr Pharm Biotechnol. 2006;7(6):503-24.

Osborn DA, Sinn J. Soy formula for prevention of allergy and food intolerance in infants. Cochrane Database Syst Rev. 2006;(4):CD003741.

Prescott SL, Bjorksten B. Probiotics for the prevention or treatment of allergic diseases. J Allergy Clin Immunol. 2007;120(2):255-62.

Rainone F. Milk thistle. Am Fam Physician. 2005 Oct 1; 72(7):1285-8.

Rautava S, Kalliomaki M, Isolauri E. Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant. J Allergy Clin Immunol. 2002;109(1):119-121.

Schmitt J, Schakel K, Schmitt N, Meurer M. Systemic treatment of severe atopic eczema: a systematic review. Acta Derm Venereol. 2007;87(2):100-11.

Schulz P, Bunselmeyer B, Brautigam M, Luger TA. Pimecrolimus cream 1% is effective in asteatotic eczema: results of a randomized, double-blind, vehicle-controlled study in 40 patients. J Eur Acad Dermatol Venereol. 2007;21(1):90-4.

Sezer E, Etikan I. Local narrowband UVB phototherapy vs. local PUVA in the treatment of chronic hand eczema. Photodermatol PhotoimmunolPhotomed. 2007;23(1):10-4.

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Review Date:
8/23/2007
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and 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., 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

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

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Viral encephalitis

FitSugar — Wed, 08 Oct 2008 17:35:11 -0700

Overview

Signs and Symptoms

Causes

Risk Factors

Diagnosis

Preventive Care

Treatment Approach

Other Considerations

Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Encephalitis is an inflammation of the brain caused, most often, by a viral infection. The specific viruses that cause encephalitis vary. Exposure to viruses that cause encephalitis occur mostly through insect bites. The virus enters through the blood stream and spreads to the brain, causing inflammation of the nerve cells (encephalitis) or the surrounding membranes (meningitis). Encephalitis is different from meningitis, but these two brain infections often occur together. Although the vast majority of individuals with encephalitis recover after a long period of time, inflammation may cause irreparable damage to the brain, bleeding within the brain, and even death. An estimated 10,000 - 20,000 cases of encephalitis are reported annually in the United States.

Signs and Symptoms

Ninety percent of people with encephalitis have flu-like symptoms, such as fever, sore throat, cough, and malaise.

If meningitis accompanies encephalitis, an individual may experience headache, stiff neck, intolerance to light, and vomiting.

A change in the level of consciousness, ranging from mild confusion to coma, develops in most people with encephalitis, often including disorientation and delusion with possible hallucinations, agitation, and personality changes.

Seizures occur in up to 50% of individuals with encephalitis.

Other signs and symptoms of encephalitis depend on which area of the brain is most affected. These may include an impaired ability to use or comprehend words or coordinate voluntary muscle movements, muscle weakness or partial paralysis on one side of the body, uncontrollable tremors or involuntary movements, and an inability to regulate body temperature.

Causes

Arboviruses, or viruses carried by insects, are among the most common causes of viral encephalitis. Some of the major arboviruses include:

Eastern equine encephalitis -- transmitted by mosquito, primarily affecting individuals along the eastern seaboard of the United States. One-third of infected individuals die of the condition, and many others suffer permanent brain damage.

European and Far Eastern (Russian) encephalitis -- transmitted by ticks. Although vaccine against this type of encephalitis is available in Europe, there is speculation that it may cause serious side effects.

Japanese encephalitis -- transmitted by mosquito and is widespread in Asia. Between 10 - 30% of infected individuals, primarily children, die of the condition.

La Crosse encephalitis -- transmitted by mosquito, and primarily affecting children under 16 years of age in the upper Midwestern United States. About 1% of infected individuals die of the condition.

St. Louis encephalitis -- transmitted by mosquito. Individuals in rural Midwestern and southern United States are primarily affected, with 7% of infected children and 30% of infected elderly dying of the condition.

Venezuelan equine encephalitis -- transmitted by mosquito and primarily affects individuals in Central and South America. Fatalities rare in humans but common in horses, with epidemics in people occasionally occur after an outbreak in horses.

West Nile encephalitis -- transmitted by mosquito, primarily affecting individuals in Africa and the Middle East, but outbreaks have also been recorded in the United States (New York City area and parts of New England). Infections are most common in children and the elderly, and as many as 10% of infected individuals die of the condition.

Western equine encephalitis -- transmitted by mosquito, primarily affecting individuals in western United States and Canada. It usually causes a mild infection in people, except in children under 1 year of age, who often suffer permanent complications. Almost % of infected individuals die of the condition.

Other viruses that commonly cause viral encephalitis include:

Herpes simplex virus type 1 (HSV1)

Measles

Enteroviruses (viruses that typically occur in the gastrointestinal tract)

Mumps

Less common causes include:

Cytomegalovirus

Epstein-Barr virus (EBV)

Human immunodeficiency virus (HIV)

Varicella-zoster virus (VZV)

Rabies virus

Not all cases of encephalitis are caused by viruses. Some nonviral causes of encephalitis include:

Bacterial infection

Fungal infection

Parasitic infection

Noninfectious causes, such as allergic reactions or toxins

Risk Factors

The following factors may increase your risk of becoming infected with viral encephalitis:

Very young or very old age

Exposure to mosquitoes or ticks

Compromised immune system

Not being immunized against measles, mumps, and rubella

Traveling to areas where viral encephalitis is prevalent

Handling potentially infected animals

Diagnosis

Encephalitis is a serious condition, so diagnosis and initial treatment usually take place in a hospital setting. After performing a physical exam, a doctor may take the following steps to diagnose the condition:

Blood test -- detects viruses in the blood

Spinal tap -- detects viruses in the cerebrospinal fluid

MRI and CT scan -- determines whether bleeding is present in the brain

Electroencephalogram (EEG) -- detects abnormal brain waves

Preventive Care

The most effective way to prevent encephalitis is to avoid contracting viruses that lead to encephalitis:

Take protective measures when working or playing outside, such as using insect repellant and wearing long pants and long sleeves. Some insect repellants are very toxic, so check with your health care provider about some alternatives.

Immunize against viruses that lead to encephalitis with vaccines such as the measles, mumps, rubella (MMR), and rabies.

Maintain a balanced diet to keep the immune system healthy.

An infectious disease specialist may recommend a particular Japanese encephalitis vaccine for those traveling to Asia during the summer, but serious allergic reactions have been reported with its use.

Treatment Approach

Viral encephalitis is a serious medical condition. Because encephalitis can cause severe complications, treatment usually occurs in the hospital and sometimes requires intensive care. Generally, there are no specific medications to treat the viruses causing encephalitis. HSV1, VZV, and EBV are exceptions to this rule, however, as acyclovir is an excellent treatment. Often, people with symptoms of encephalitis are treated with this medication until the virus causing the condition is identified. Behavioral techniques, such as those used to treat people with traumatic brain injury, have been recently explored in the treatment of those recovering from viral encephalitis. Although complementary and alternative therapies have not been extensively studied for the treatment of encephalitis, some studies indicate that scalp acupuncture, combined with proper medication, may aid the healing process. Careful observation and supportive care, including rest, proper nutrition, and fluids are a mainstay of treatment for encephalitis and allow the body to fight the infection.

Always tell your health care provider about the herbs and supplements you are using or considering using, as some supplements may interfere with conventional treatments.

Medications

Medications used to treat viral encephalitis include:

Acyclovir -- treats encephalitis caused by HSV, VZV, and EBV

Ganciclovir or foscarnet -- treats encephalitis caused by cytomegalovirus and HSV1

Anticonvulsant medications -- prevent and treat seizures associated with encephalitis

Nutrition and Dietary Supplements

Following these nutritional tips may help improve general health and well-being:

Try to eliminate potential food allergens, including dairy, wheat (gluten), corn, preservatives, and food additives. Your health care provider may want to test for food sensitivities.

Eat antioxidant foods, including fruits (such as blueberries, cherries, and tomatoes), and vegetables (such as squash and bell peppers).

Avoid refined foods, such as white breads, pastas, and especially sugar.

Eat fewer red meats and more lean meats, cold-water fish, tofu (soy, if no allergy), or beans for protein.

Use healthy oils in foods, such as olive oil or vegetable oil.

Reduce or eliminate trans-fatty acids, found in commercially baked goods such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.

Avoid coffee and other stimulants, alcohol, and tobacco.

Drink 6 - 8 glasses of filtered water daily.

Exercise at least 30 minutes daily, 5 days a week.

You may address deficiencies with the following supplements:

A multivitamin daily, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals, such as magnesium, calcium, zinc and selenium.

Omega-3 fatty acids, such as fish oil, one to two capsules or one to three tablespoonfuls oil, one to three times daily, to help decrease inflammation and help with immunity. Cold-water fish, such as salmon or halibut, are good sources but not substitutes for supplementation.

Vitamin C, 500 - 1000 mg one to three times daily, as an antioxidant and for immune support.

Coenzyme Q10, 100 - 200 mg at bedtime, for antioxidant, immune, and muscular support.

Acetyl-L-carnitine, 500 mg daily, for antioxidant and antiviral activity.

Probiotic supplement (containing Lactobacillus acidophilus), 5 - 10 billion CFUs (colony forming units) a day, for maintenance of gastrointestinal and immune health. You should refrigerate your probiotic supplements for best results.

L-glutamine, 500 - 1000 mg three times daily, for support of gastrointestinal health and immunity.

Resveratrol (from red wine), 50 - 200 mg daily, for antioxidant and antiviral effects.

L-theanine, 200 mg one to three times daily, for nervous system support.

Melatonin, 2 - 5 mg 1 hour before bedtime, for sleep and immune protection. Ask your health care provider about potential drug interactions with the use of melatonin.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink 2 - 4 cups per day.

Green tea ( Camellia sinensis) standardized extract, 250 - 500 mg daily, for antioxidant, anti-inflammatory, and immune effects. Use caffeine-free products. You may also prepare teas from the leaf of this herb.

Milk thistle (Silybum marianum) seed standardized extract, 80 - 160 mg two to three times daily, for detoxification support and antiviral effects.

Cat's claw (Uncaria tomentosa) standardized extract, 20 mg three times a day, for inflammation and antiviral activity.

Garlic (Allium sativum), standardized extract, 400 mg two to three times daily, for antibacterial or antifungal and immune activity.

Astragalus (Astragalus membranaceus) standardized extract, 250 – 500 mg four times daily for immune support and antiviral activity.

Maitake mushroom (Grifola frondosa) standardized extract (D-fraction), 600 mg twice daily, for immune and antiviral effects. You may also take a tincture of this mushroom extract, 30 - 60 drops two to three times a day.

Phyllanthus (Phyllanthus amarus) standardized extract, 200 mg two to four times daily for antiviral effects.

Elderberry (Sambucus nigra), one to two teaspoonfuls of standardized liquid extract two to four times daily, for immune support and antiviral activity.

Acupuncture

A study of a small number of people with complications from encephalitis suggests that acupuncture delivered to the scalp may lessen the severity of the complications and reduce the symptoms of the condition. Some researchers believe that scalp acupuncture is effective for people with encephalitis because all meridians converge at the head, and the method can stimulate and regulate qi (energy) throughout the entire body. More research is necessary.

Massage and Physical Therapy

Behavioral and Physical Training

Behavioral and physical training techniques recently have been explored in the treatment of individuals recovering from encephalitis. In one case, a woman experiencing poor short-term memory and decreased muscle coordination as a result of viral encephalitis began to improve significantly after participating in a behavioral rehabilitation training program. As a result of the program, she gained a high level of independence and was able to return home from the hospital with only minimal assistance from a caregiver. More studies are needed.

Other Considerations

Pregnancy

The most common cause of encephalitis in newborns is vaginal delivery by a mother who is infected with herpes simplex virus 2 (HSV2). This infection in newborns is often severe and fatal. For this reason, cesarean section may be advised for pregnant women with a history of HSV2, even if there is no sign of an active infection.

Prognosis and Complications

Full recovery from encephalitis can take weeks or months, during which time many individuals experience complications ranging from fatigue and difficulty concentrating to tremors and personality changes. The most severe problems associated with encephalitis result from the destruction of nerve cells in the brain that do not regenerate. The severity of complications depends on the condition of the immune system (whether it is healthy or weak) and the infection causing the encephalitis. For example, 80% of those infected with Eastern equine encephalitis, St. Louis encephalitis, and Japanese encephalitis have permanent neurologic impairments (such as memory, speech, vision, hearing, muscle control, and sensation) and a very low survival rate. Those infected with EBV or Venezuelan equine encephalitis rarely experience any serious complications. The long-term outlook for those with HSV encephalitis depends primarily on how quickly the condition is treated.

Between 80 - 95% of people infected with viral encephalitis will survive the condition, but 20% will experience debilitating side effects or complications, such as memory loss or severe personality changes. The survival rate for those with HSV encephalitis increases dramatically from 30 - 70% when the condition is detected early and treated with antiviral medications.

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Barak V, Halperin T, Kalickman I. The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. Eur Cytokine Netw. 2001;12(2):290-6.

Bhat KPL, Kosmeder JW 2nd, Pezzuto JM. Biological effects of resveratrol. Antioxid Redox Signal. 2001;3(6):1041-64.

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Bonilla E, Valero-Fuenmayor N, Pons H, Chacin-Bonilla L. Melatonin protects mice infected with Venezuelan equine encephalomyelitis virus. Cell Mol Life Sci. 1997;53(5):430-434.

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Review Date:
10/27/2006
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and 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., 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

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

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