Vitamin C and E Research

Should You Take Vitamin C and E Supplements?

Last year the Food and Nutrition Board of the National Academy of Sciences—the main authority in the U.S. for nutritional recommendations—published a major report on antioxidant nutrients, including vitamins C and E. It concluded that taking antioxidant supplements serves no purpose.

Recently the Editorial Board of this newsletter, along with Gladys Block (Professor of Public Health at UC Berkeley) and Bruce Ames (Professor Emeritus of Biochemistry and Microbiology), reviewed the Food and Nutrition Board report. Following this review, the recommendation has been modified for vitamin E to 200 to 400 IU a day (instead of up to 800 IU). It is widely recommended to ingest 250 to 500 milligrams of vitamin C, but suggest you get this from food, if possible.

Here is a review of the research behind the Food and Nutrition Board report, and important conclusions.

The different kinds of research

Much laboratory research has shown that as antioxidants, these vitamins help inactivate free radicals. The latter are unstable molecules (usually oxygen) produced in the normal process of "burning" oxygen for energy; they are also created by such environmental factors as tobacco smoke and radiation. Free radicals can damage the basic structure of cells and thus may lead to disease (notably cancer and heart disease) and accelerate the aging process. By mopping up free radicals, vitamins C and E could potentially protect against these disorders.

Many laboratory and animal studies suggest that vitamins C and E help reduce the risk of coronary artery disease in a number of ways. First, they inhibit the oxidation of LDL ("bad") cholesterol, both individually and through their interaction. Oxidation makes LDL more likely to promote the buildup of fatty plaque in coronary artery walls (atherosclerosis). Vitamin E may also reduce the blood's ability to clot, thus lowering the risk of heart attacks. Finally, E may help reduce inflammatory processes (inflammation has been linked with coronary artery disease).

Many large population studies have found that people who consume the most vitamin C from foods have a reduced risk of heart disease and various cancers. (Hence the recommendation to eat at least five fruits and vegetables a day.) Some population studies have found similar protective effects from C or E supplements. But other elements in foods rich in C, or something about the life-style of people who consume high levels of C or E as supplements, may account for their lower risk. These observational studies are unable to tease apart the effects of various dietary constituents and simply can't tell us whether taking large doses of E and/or C is beneficial.

What the clinical trials show

Some well-designed clinical trials, using human subjects under carefully controlled experimental conditions, have found that vitamins C and E do have the proposed health benefits. But others have found no effect. Different studies use different doses of vitamins, so it's often hard to compare the results. Most have focused on coronary artery disease.

Vitamin E. The results have been inconclusive. A study from Cambridge University, published in the Lancet in 1996, for in-stance, found that among men with heart disease, 400 to 800 IU of E supplements a day for an average of 1.5 years substantially reduced the risk of heart attack, but not death rates. (Later, however, the researchers reanalyzed the data and did find that vitamin E markedly reduced deaths from coronary artery disease.) But the Heart Outcomes Prevention Evaluation Study, a Canadian study published last year, found no benefit when those at high risk for cardiovascular disease took 400 IU of E a day for four years. An Italian study published in the Lancet in 1999 found no significant reduction in coronary risk from 300 IU of E. These studies, and several others, raised more questions than they answered. Most of the clinical trials have been done on patients with heart disease. It's possible that there would be a more consistently protective effect in healthy people.

Other research suggests that vitamin E supplements may lower the risk of some types of cancer, as well as arthritis, Parkinson's, one kind of stroke, diabetes, and Alzheimer's. But the evidence is inconsistent and/or preliminary.

Vitamin C. Several controlled studies have found that large doses of vitamin C help relax blood vessels and maintain blood flow (by increasing the amount of nitric oxide produced in the arterial walls). Theoretically, this should reduce the risk of cardiovascular disease. However, there have been no large-scale studies to demonstrate that high doses of vitamin C supplements actually prevent heart attacks.

Some grounds for concern

It's possible that antioxidant supplements in high doses, unlike the nutrients in food, may upset the antioxidant balance in the body. The many types of antioxidants do different kinds of work, and they often work together. Notably, vitamins C and E work well together to produce their antioxidant effect and help protect each other from oxidation. They may also help other antioxidants, such as beta carotene, do good work.

Some investigators have found that vitamin C can become a "pro-oxidant" (have the opposite effect and actually become a free radical) in the test tube. But there's no convincing evidence that this happens in the body. (Similarly, many other substances, often marketed as supplements, have antioxidant effects in the test tube, but probably not in the body.)

Since many people get 250 to 500 milligrams (or more) of vitamin C from a diet rich in fruits and vegetables, with no adverse effects, it's relatively safe to get that much from supplements. In the case of vitamin E, however, since few, if any, people get the recommended 200 to 400 IU from food, we must be concerned with safety. Nonetheless, long-term studies have found virtually no adverse effects from these levels of E. In fact, the report of the Food and Nutrition Board concluded that 1,000 IU per day is the safe upper limit for vitamin E supplements (the upper limit for C, it said, is 2,000 milligrams).

Scientists are only beginning to understand the importance of antioxidants and how they work. The evidence is still accumulating and may look different to different experts. Some important studies on C and E are underway and should answer many of the questions in the next few years.

The bottom line

• Consume 250 to 500 milligrams of vitamin C per day. Such levels are considered safe and the potential benefits are great. If you eat five or more servings of fruits and vegetables and their juices, as recommended, you can easily get that much vitamin C. If not, take a supplement.

•Take 200 to 400 IU of vitamin E supplements per day. You can't get that much from food unless you eat huge amounts of nuts, seeds, or vegetable oil, all high in fat. Not all experts agree that E supplements are advisable. But the majority believe that such levels are safe and potentially beneficial. Vitamin E is a complex group of related compounds. Look for "natural" vitamin E supplements (preferably those containing some "mixed tocopherols"), since synthetic E largely contains forms that are poorly utilized by the body.