A lot of people still try to understand aging as a kind of accumulated damage, or wear-and-tear. Theories of oxidative damage are one poular version, and anti-oxidants have been promoted as a remedy for aging by people who should know better. One trouble with the damage theories is the of things that increase damage, but that lengthen life span. Exercise is the best example, but there are many others.
For twenty years and more, it has been clear that anti-oxidants don’t lead to longer life. More recently, there is evidence that anti-oxidants can actually take away the benefits of exercise. The latest such study was reported just last week.
Writing in her NYTimes column this week, Gretchen Reynolds reported on a Norwegian study* combining vitamin C and E supplements with a vigorous exercise program. The study recruited people who were already exercising, and intensified their aerobic program for 11 weeks, with both endurance exercise and interval training. The outcome that they highlighted was in the mitochondrial metabolism. Mitochondria are tiny “organelles”, hundreds of them in each cell, burning sugar to supply the cell with energy. One of the things that happens to increase strength and endurance in response to exercise is that the cells grow new mitochondria, and the existing mitochondria become more efficient. In the Norwegian study, this seemed to be happening on schedule in the test subjects who exercised without vitamin supplements, but not in the group taking vitamins. Nevertheless, endurance capacity of both groups was imroved by the exercise program.
The first result of this type (that I am aware of) was reported from a German study in 2009 **. In this study, non-exercisers were given an exercise program for just 4 weeks, and their insulin sensitivity and glutathione both improved; but supplementation with vitamins E and C blocked these benefits. I think both these are pretty good markers for aging – more basic and more closely-related to aging than mitochondrial markers. Of course, what we really would like to see would be long-term effects on mortality and longevity.
In between, there have been a number of studies confirming the effect. Here’s one that found that generation of new mitochondria is blocked by alpha lipoic acid. Another one related glutathione and mitochondrial markers to vitamin C. There are studies of old and young people, people who did no exercise prior to the experiment, and people who had exercised regularly, and were challenged with more. There were also some studies that failed to find an effect [ref for rats; ref for humans]
In one study of mice, very large doses of resveratrol seemed to give the mice great strength and endurance. However, in a human study last year (from this same Norwegian group), resveratrol diminished the benefits of exercise.
The theory is that temporary elevation of ROS (= free radicals, sources of oxidative damage) is a signal that tells the body to build new muscle, to proliferate mitochondria, and to improve the sensitivity to insulin. All these changes are plausibly related to better strength and health, and perhaps youthfulness. The fact that the effects appear when measuring a variety of outcomes from a variety of anti-oxidants (vitamins A, C, E, CoQ10 and resveratrol) lends to the credibility of this idea. Vitamin C, in particular, is intimately related to the energy metabolism of the mitochondria, lending plausibility to results for vitamin C in particular.
The bottom line, for me, is that results are still quite sketchy, that we don’t know the full story, that some physiological benefits of exercise seem to be blunted for some people, if certain anti-oxiadants are taken in combination with the exercise program. But the broader context is clear: Anti-oxidant vitamins have never been shown to increase life span in rodents, or to reduce mortality in humans. But exercise robustly increases life span in animal studies, and reduces mortality in humans. For me, the evidence is clear enough to advise against vitamin E and C supplements for people who exercise. For resveratrol and CoQ10, I remain uncertain.
* I get error messages when I try to pull up the original study in the Journal of Physiology. If I get a good web reference to the study, I’ll link it above and erase this footnote.
** There are precursors that go back to 1971, when competitive swimmers were given vitamin E, and it was reported to slow them down. Here’s a 1997 study that reported CoQ10 supplementation dragged down performance improvements from high-intensity sprint training.