"The Well-Connected Board of Editors   Vitamin Overview"

Harvey Simon, M.D., Editor-in-Chief Massachusetts Institute of Technology; Physician, Massachusetts General Hospital
Masha J. Etkin, M.D., Gynecology Harvard Medical School; Physician, Massachusetts General Hospital
John E. Godine, M.D., Ph.D., Metabolism Harvard Medical School; Associate Physician, Massachusetts General Hospital
Daniel Heller, M.D., Pediatrics Harvard Medical School; Associate Pediatrician, Massachusetts General Hospital; Active Staff, Children's Hospital
Irene Kuter, M.D., D. Phil., Oncology Harvard Medical School; Assistant Physician, Massachusetts General Hospital
Paul C. Shellito, M.D., Surgery Harvard Medical School; Associate Visiting Surgeon, Massachusetts General Hospital
Theodore A. Stern, M.D., Psychiatry Harvard Medical School; Psychiatrist and Chief, Psychiatric Consultation Service, Massachusetts General Hospital
Carol Peckham, Editorial Director
Cynthia Chevins, Publisher

Vitamins and Carotenoids. Deficiencies in Vitamins C, E, A, and beta carotene have been linked to heart disease. All of these nutrients have antioxidant effects and other properties that may benefit the heart. For example, vitamin E may prevent blood clots and the formation of fatty plaques and cell proliferation on the walls of the arteries. Vitamin C may help maintain blood vessel flexibility and so have benefits on blood pressure. Generally such findings have occurred in the laboratory. Many studies have been undertaken to determine if such actions are powerful enough protect the heart in people. The evidence for protection from vitamin or other supplements, however, is quite weak, and in fact each of these supplements in high doses may be harmful. Long-term studies of people who took vitamin E supplements (which are usually composed of the form alpha tocopherol) are mixed. While population studies, such as a major study of nurses, reported benefit for the heart from high vitamin E levels (usually only found in supplements), others are finding little or no benefits for men or women and some have even reported harmful effects. On the other hand, studies are fairly consistent in indicating that eating foods rich in natural vitamin E (known as gamma tocopherol) may be protective. (Such foods, which include nuts, monounsaturated oils, and wheat germ, may also have other beneficial properties that account for these results.) The evidence for heart protection from vitamin C and beta carotene supplements is even weaker. In two major studies that demonstrated some benefit from vitamin E, vitamin C was not protective. One study found some benefits against stroke but not heart disease. Studies have reported that a high intake of beta carotene and other carotenoids from fruits and vegetables may reduce the risk of heart attack. It should be stressed, however, that studies are continuing to indicate that high doses of supplements of any of these antioxidants have pro-oxidant effects that can harm the arteries and incur other damage.

Several important studies have demonstrated a link between deficiencies in the B vitamins folic acid, B6, and B12 and elevated blood levels of an amino acid homocysteine, a risk factor for atherosclerosis. Studies further indicate that taking these vitamins can decrease homocysteine levels. It is not clear yet, however, that reducing homocysteine levels will actually protect against heart disease. Another B vitamin, niacin (vitamin B3), is used for lowering unhealthy cholesterol levels; although vitamin B3 is available over the counter, a physician should prescribe niacin in order to ensure its safety and effectiveness.

Phytochemicals. Flavonoids, particularly those found in both black and green tea, onions, red wine, and apples, may protect against damage done by cholesterol and help prevent blood clots. The first trial of flavonoid supplements reported that they had a significant effect on preventing blood clots. Drinking as little as a cup of tea a day appeared to help protect against heart disease. Some studies have suggested that the organosulfurs found in onions and garlic may have beneficial effects on cholesterol levels, although two well-conducted recent ones found no heart-benefits from taking capsules equivalent to between one and one and half garlic cloves a day. The preparation of these products, however, may be responsible for the lack of effect. Another recent study reported that heating garlic blocks its health-protective effects. By allowing crushed fresh garlic to stand 10 minutes before heating, however, beneficial chemicals are released and not lost when the garlic is cooked. It is known that human estrogens have a beneficial effect on cholesterol levels, and soy protein, high in the phytoestrogens (plant estrogens) isoflavones, has been associated in some studies with lower levels of total cholesterol, LDL, and triglycerides. Some researchers suggest that the well-known protective effect of red wine against cardiovascular disease may be due, in part, to the phytoestrogen resveratrol, which is found in grape skin.

Protection Against Stroke Some studies including a 1999 one on stroke patients suggested that vitamin E may protect against ischemic stroke (caused by blocked arteries) and an animal study reported that high levels of vitamin E in the diet reduced the amount of brain tissue injured by a stroke. (This vitamin may increase the risk for hemorrhagic stroke -- a far less common form of stroke.) Studies are also indicating that people who have higher blood levels of folic acid have a lower than average risk for stroke. Two 1995 studies found that high intake vitamin C intake was associated with a lower risk for death from stroke (but not from coronary artery disease).

Protection Against Cancer Any protective effects of vitamins or specific phytochemicals against cancer appear to depend on a cooperative effort between them and other nutrients found diets rich in fresh fruits and vegetables. For example, although premenopausal women who ate foods rich in vitamin A and carotenes appeared to have a reduced risk of breast cancer, supplements of vitamins A, C, and E had no effect.

Vitamins and Carotenoids. Folic acid and B12 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 regulary drink alcohol. (In the study, folic acid had no other effect on breast cancer.) Because many cancers are thought to be initiated by the effects of oxygen-free radicals on DNA, the antioxidant vitamins E, C, and A and beta carotene have been intensively studied. One study reported that people with the lowest blood levels of vitamin E are at higher risk for all types of cancer than those with the highest levels. One study found that tocotrienol, a vitamin E compound found in unrefined palm oil, inhibits cancer cell proliferation and causes cancer cell death. (The standard vitamin E supplement, tocopherol, had much weaker effects.) Palm oil sold in the U.S. is refined and does not contain tocotrienol. Most studies, however, have found no evidence that vitamin E or C supplements protect people from a first or a recurring cancer. In fact, studies are now reporting that excessive use of a single supplement, such as beta carotene, may interfere with other nutrients or convert into pro-oxidants and become harmful. Synthetic forms of vitamin A are being studied for their protective effects and even for treating some cancers. It should be stressed, however, that vitamin A supplements can be very toxic, even in amounts not much higher than the RDA levels. Of particular concern are the many studies that have found an increase in lung cancer and overall mortality rate among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, a recent animal study reported that beta carotene increased enzymes in the lungs that actually promote cancerous changes. Another study suggested that beta carotene taken as a supplement may interfere with other, protective forms of vitamin A. Fruits and vegetables rich in carotenoids, show protection against cancer. The carotenoid lycopene, found in tomatoes -- particularly when they are cooked -- may have particular value in protection against prostate, colon, and bladder cancer.

Phytochemicals. Isothiocyanates and sulforaphane found in cruciferous vegetables may block the effects of carcinogens and suppress tumor growth. Young sprouts of broccoli and cauliflower, compared to the mature counterparts, contain much higher levels of isothiocyanates. Plant estrogens, including daidzein, equol, and enterolactone, which are found in soy beans, whole wheat, berries, and flax seed, may help reduce the risk for certain hormone-stimulated cancers, such as breast and prostate, by replacing human estrogen with the benign plant estrogens they contain. They may also inhibit the proliferation of existing cancer cells. Because of the lower risk for reproductive and breast cancers in Asian women, most studies on plant estrogens are being conducted using soy. The effects on cancer are not entirely clear, however. One reported that when taken with high doses of estrogen replacement therapy, soy protects against breast and uterine cell proliferation. However, when combined with low doses of estrogen replacement therapy, soy causes breast cell proliferation. Other studies have indicated that some phytoestrogens, such as black cohosh, also cause cell proliferation in the uterus under certain circumstances. Some experts advise that until more is known about when or even if phytoestrogens protect against breast cancer, women who are on hormone replacement therapy and at risk for breast cancer should also avoid plant products with known high levels of phytoestrogens. Some evidence suggests the genistein in soy may have properties that are protective against lung cancer. Flavonoids, including those found in apples, onions, tea, and red wine, are coming under scrutiny for possible cancer fighting properties. In one 24-year study, people who ate flavonoid-rich foods had a 20% lower risk for cancer in general. (For lung cancer the risk was reduced by 46%.) Laboratory and animal studies have indicated that compounds in green tea have the capacity to selectively kill cancer cells. Some experts recommend that drinking four cups of green tea daily may be protective against certain cancers; black tea does not appear to have these particular benefits. Resveratrol, a substance found in grapes, has been found to fight tumor promotion and progression in mice. The organosulfur compounds found in the onion and garlic family may have very potent properties in suppressing or blocking carcinogenic substances.

Protection Against Infectious Diseases A 1993 study found that older people who took a multivitamin had fewer sick days than those who did not. One analysis of studies found that large doses of vitamin C reduced the duration of the cold by 21%, and another found that it reduced the severity and length of respiratory infections in a group of ultramarathon athletes, who are normally at risk for these infections. Fewer incidents of infectious diseases have been observed in people taking large supplements of vitamin E. In a study of elderly people whose immune system had deteriorated, B6 restored them to normal levels, and in those taking large doses the immune response was close to that seen in young people. It was not clear from the study if vitamin B6 actually protected against disease, and it should be noted that large doses of this vitamin can cause nerve damage so should be taken only under advisement from a physician. Major studies in underdeveloped countries where immunization programs are limited and risks for infectious diseases are high, children with infectious diseases who were given vitamin A have lower mortality rates. Vitamin A supplements, however, are toxic in children in amounts close to normal adult doses and should never be given to children with normal diets. Saponins extracted from ginseng and allicin found in garlic also have properties that boost the immune system. Both ginseng and garlic have long been traditionally used for their health benefits. Lycopene, found in tomatoes, appears to have properties that protect infection-fighting white blood cells.

Protection Against Respiratory Disorders Some people with exercise-induced asthma may benefit from taking vitamin C one hour before strenuous physical activity, although antioxidant vitamins do not appear to reduce the risk of adult-onset asthma. Vitamin C and E may even counteract the negative effects of ozone on lung function in athletes. Studies have indicated that diets rich in antioxidant vitamins and carotenoids improve lung functions in everyone and may provide some protection against lung damage from chronic obstructive pulmonary disease (COPD) among smokers if their diets are healthy throughout their smoking years. (Smokers should never take beta carotene supplements.) One new study reported that vitamin C may lower the risk of emphysema, chronic bronchitis, and other forms of chronic lung disease.

Protection Against Eye Disorders Oxygen-free radicals play a role in cataract formation. Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk of cataracts. Vitamins E and C and the B vitamins niacin and riboflavin (vitamin B2) might protect against cataracts. Carotenoids, especially lutein and zeaxantin found in dark, green, leafy vegetables, may also help prevent macular degeneration, which is the most common cause of irreversible blindness in the elderly. Protection Against Skin Disorders and Wrinkles There is some evidence that topical products (e.g., lotions and creams) containing vitamins A, E, C, and beta carotene help protect the skin when applied before sun exposure -- although they have no benefits if they are applied afterward. Researchers are also interested in the possible protective effects of combined forms of topical vitamins A and D. One small study found that taking a combination of vitamins C and E may help reduce sunburn reactions, and another reported that such supplements were associated with a lower risk for basal cell carcinoma. (Vitamin A supplements should never be taken, however, to cure skin problems without a doctor's recommendation.) Drinking green or black tea, which contain powerful flavonoids, helped block the carcinogenic effects of UVB radiation in one study.

Protection Against Osteoporosis Postmenopausal women who have very limited exposure to sunlight and low amounts of vitamin D in their diet are at increased risk for osteoporosis and hip fracture. Although everyone, particularly postmenopausal women, should have sufficient vitamin D, doses beyond the recommended daily allowance do not appear to stimulate additional bone mass. One study indicated that 1 mg of additional Vitamin K (ten times the U.S. RDA levels) reduced urinary calcium loss by 33% in postmenopausal women. Supplements are not recommended at this time; clinical trials to confirm this finding and to determine the toxicity levels of vitamin K are still required. In one study bone density increased in postmenopausal women who ate foods rich in soy protein, which contain isoflavones (phytoestrogens). Some experts recommend 25 to 45 milligrams of isoflavones a day. Soy powders, soluble in juice or milk, that list amounts of isoflavones per serving are now available in health food stores. Tofu prepared with calcium may be particularly beneficial. Ipriflavone, a synthetic derivative of isoflavones is currently being investigated for preventing bone loss. Studies are reporting a positive effect on bone density with very mild side effects (mostly gastrointestinal symptoms).