Vitamins

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. 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.

Antioxidants: Pros and Cons

Description of 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 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.
• 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.

Some evidence also indicates that high doses of vitamin C may speed up atherosclerosis, or hardening of the arteries.

Some researchers speculate that certain immune factors generate oxidants to fight bacteria. The antioxidant vitamin E may block that action. Further study is necessary.

Protection against Heart Disease

Vitamins and Heart Protection.

• Antioxidant Vitamins A, C, and E. A low dietary intake of vitamins A, C, E, and beta carotene has been linked to heart disease. All of these nutrients have antioxidant effects and other properties that should benefit the heart. However, there is now clear evidence that supplements of these vitamins, singly or in combination, do not protect against heart disease or cancer.
• 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. However, there is now clear evidence that supplements of these vitamins do not reduce the risk of heart disease.
• Niacin. Niacin (vitamin B3) is used for improving unhealthy cholesterol levels, though very high doses are required. 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. [For more information, 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 Diets low in lycopene (particularly from tomatoes) were associated with a significantly higher risk of heart disease and stroke.

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 heart protective. 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 contribute to the heart protective effects in red wine. Ethanol, the alcohol found in wine, beer, and spirits is likely to be the most beneficial ingredient -- as long as the "dose" is only low or moderate.
• Organosulfurs. Organosulfurs found in onions and garlic have been under investigation for possible beneficial effects on cholesterol levels.
• Isoflavones. Soy protein is the most studied source of isoflavones (known as phytoestrogens, or plant estrogens). Not all studies are consistent, but some have shown an improvement in at least one of the cholesterol components in people who consumed at least 25 grams of soy protein. A 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. Soy may also reduce other heart risk factors, at least in certain populations. For example, in one study, soy was beneficial for controlling blood sugar and lowering LDL in postmenopausal women with type 2 diabetes. In a study of overweight men and postmenopausal women, soy protein reduced blood pressure and arterial stiffness. 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.

Protection against Stroke

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 (vitamins C or E, or beta carotene) on stroke have been studied extensively. Most studies have found that these vitamins do not help protect against stroke.

Recent studies have indicated that while B vitamin supplements help lower homocysteine levels, they have no effect on heart disease outcomes. A large randomized controlled trial is underway to evaluate the benefit of vitamins on reducing stroke risk.

Protection against Cancer

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)

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 recent studies found a connection between folate supplements and colorectal cancer. A large 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 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. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos.

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 that multivitamin and mineral supplements 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. 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.
• 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 in all women, however, 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. 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 and genetic factors, and more.

Evidence of Protection against Other Diseases with Vitamins, Carotenoids, and Phytochemicals
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.) Most studies performed since 2002 challenge this finding, while others agree with it. B Vitamins. 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. While some studies have described a benefit with administration of fully, vitamin B12, or vitamin B6, there is no good evidence from randomized controlled trials that these supplements prevent Alzheimer's disease.
Infectious Disease	Studies are mixed whether vitamin supplements protect against upper respiratory infections. The weight of evidence suggests there is little or no benefit. 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.
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. 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.)	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.
Osteoporosis	Vitamin D. A combination of calcium and vitamin D can reduce the risk of osteoporosis. (For strong bones, people need enough of both calcium and vitamin D.) The National Osteoporosis Foundation (NOF) recommends: Adults under age 50 should have 1,000 mg of calcium and 400 - 800 IU of vitamin D daily. Adults age 50 and older should have 1,200 mg of calcium and 800 - 1,000 IU of vitamin D daily.
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.

Highlights
Introduction
Carotenoids
Phytochemicals
Healthy Foods
Dietary Health Benefits
Resources
References

Review Date: 2/27/2009
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

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