Vitamin E, C and Exercise

A question of balance… and prejudice?  Recent publication of a research article from Germany has created lots more controversy around antioxidant supplements, though vitamin C and vitamin E were the only compounds studied, and there are a great many more antioxidants both in foods and in supplements that have not been looked at in this context.

The article, published in the on-line version of Proceedings of the National Academy of Sciences (PNAS) showed that 500 mg of vitamin C twice daily and 400 IU of d-alpha tocopherol (1 of the 8 forms of the vitamin E complex) taken once daily by 20 young healthy men who performed supervised exercise for 85 minutes Monday thru Friday for 4 weeks, decreased the beneficial effects that this exercise program had on insulin sensitivity in the 20 unsupplemented men (control group). What this study appears to have discovered is that the oxygen free radicals produced by exercise produce beneficial effects on glucose metabolism, and may help decrease development of diabetes. However, the title of the article “Antioxidants prevent health-promoting effects of physical exercise in humans” overstates the case quite a bit, since their findings related ONLY to insulin sensitivity, and did not at all investigate the other known benefits of exercise, such as improving cardiovascular function, immune response, stress handling, mood, cognitive function, etc. etc. There was also no detriment shown in the supplemented group

Antioxidant vitamins such as vitamin C and E are different from many of the other antioxidants found in foods, herbs, spices, and teas, in that they can become free radicals themselves, if the diet is low in antioxidants and the individuals are under high oxidative stress. The “burst” of oxygen free radicals associated with an hour of exercise are quite different from the continuous barrage of free radicals associated with smoking for instance. So this study tells us only about the effect of 2 specific vitamin antioxidants, in a group of healthy young men, in terms of markers of insulin sensitivity, 1 of many known positive benefits of exercise.


This is not to minimize the importance of these findings, but simply to put them in context. Unfortunately, a controversy loving and science undereducated press will generalize and draw unwarranted conclusions, and the anti-supplement folks will point and say, see we told you so—supplements are no good….


It is important to document that at least in this context, the oxygen free radicals generated by an hour of intensive exercise have some beneficial effects that we would be better off not to block. We don’t know if other antioxidants such as co-q-10, alpha lipoic acid, OPCs, and other polyphenolic compounds would have similar effects or not. We also don’t know if a high antioxidant diet vs a low antioxidant diet has impact on the system they studied (diet is a major confounding influence on any studies of antioxidant supplements, and notoriously difficult to control for). But its probably the case that if you’re a young healthy man who exercises, or someone with risk factors for metabolic syndrome or diabetes who exercises, its probably best not to take vitamins C and E along with your exercise.


In biology there is always a question of balance. Its almost always possible to have too much of a good thing, whether that be oxygen free radicals or antioxidants—having the RIGHT AMOUNT is key, which probably varies with age, sex, state of health, environment, diet, level of physical activity, etc. I would predict that if the investigators studied antioxidants (optimally a much larger number in much smaller amounts, because that is how nutrients work) in people training for marathons and triathlons, where the oxidative stress is much greater, they would find a net BENEFIT for antioxidants supplements. My rule of thumb in 35 years of experience prescribing and formulating nutritional supplements has been to use many nutrients together, and avoid megadoses of any one, as that is most likely to create imbalances. My hope is that before too many more decades scientists will develop a model to study nutritional supplements in humans as networks of many interacting compounds that support and supplement the diet to support health, rather than as a few compounds in large doses and in isolation.


Below are some quotes from other experts that illustrate the points I’m making (borrowed from

The design of randomized clinical trials to study isolated nutrient factors, following the drug- or evidence-based model in general has received much criticism.

Andrew Shao, PhD, vice president of scientific & regulatory affairs for the Council for Responsible Nutrition (CRN), a trade association, said: “The current drug-based approach used in randomized clinical trials may not be the best approach to assess the health benefits of antioxidants, or other nutrients for that matter, and that researchers need to rethink how to design and execute such trials.”

“I do think more clinical trials are needed for antioxidants, but it is critical that they are designed and conducted to truly test the question(s) of interest, with the results interpreted and communicated appropriately,” added Dr Shao.

Jeff Blumberg, professor of nutrition science and policy at Tufts University said: “I think that when we look at  the idea of a single gold standard, like the randomized clinical trial, for evaluating nutrients, foods and diets, it  just doesn’t work.

“Sometimes it’s useful for answering for some very specific questions, but I think at other times we must go and use the approach that we have been using for the last generation or two, of looking at all of the research strategies and the information they can give us, from basic research using cell cultures and animal models, from clinical experience looking at how patients respond in the clinic, to observational studies of large populations followed for long times consuming different types of diets, as well as the intervention clinical trials.”

Understanding antioxidants

The criticisms of the drug-model for testing nutrients highlight fundamental issues with the understanding of antioxidants, and nutrients in general. Professor Blumberg added that it was important to understand how nutrients work.

“When we look at nutrients, nutrients are distributed throughout the body. Essential nutrients like vitamins and minerals have to be in every cell in every tissue in our body,” he said. “But in fact the body concentrates those nutrients in higher amounts in some tissues and in lower amounts in other tissues, it uses them in combination with other nutrients. They are designed in a system of synergies and networks.”