I have skeptical confession to make. I was once a panacea-seeking antioxidant-taker. As background, I’m a marathon runner and occasional triathlete. Several years ago, I was training for an Ironman triathlon, and banking 20+ hours of intense exercise per week. That may sound absurd to many (it does to me, now that I have kids) but that kind of training is necessary for the long races. So what did this pharmacist-wannabe-triathlete with access to discount vitamins do? He stocked up on the fancy bottles of multivitamins, the “endurance” version, of course — with extra antioxidants. Why did I supplement? I wanted to maximize my workouts, speed recovery, and minimize downtime and the risk of injury. Oxidation sounds bad — like a rusting car. Anti-oxidants sounded like the ultimate in preventative medicine. My workouts may have been more extreme, but the practice of supplementing if you exercise is common among athletes.
As it turns out, not only were the antioxidants likely ineffective, they may have compromised some of the gains I was seeking with all that training. That I didn’t evaluate the evidence at the time was my critical-thinking blind spot. Over the the past several years, more data on antioxidants and exercise have emerged. A recent review article, profiled by sports & science blogger Alex Hutchinson at his blog Sweat Science, was an opportunity to get caught up on the evidence. And there’s a lot, nicely summarized by Tina-Tinkari Peternelj and Jeff S. Coombes in this month’s Sports Medicine: Antioxidant Supplementation during Exercise Training: Beneficial or Detrimental?
Multivitamin supplementation has been getting a rough ride in the medical literature, as evidence emerges that routine supplementation for most is, at best, unnecessary. Some individual vitamins are earning their own unattractive risk/benefit profiles: Products like folic acid, calcium, and beta-carotene all seem inadvisable for routine supplementation in the absence of deficiency or medical indication. Vitamin E, already on the watch list, looks increasingly problematic, with data recently published confirming the suspected association of supplementation with an elevated risk of prostate cancer.
When it comes to health decisions about vitamin supplements, the history of medicine teaches us a valuable lesson: The danger of assuming therapeutic benefits based on intermediate or “surrogate” measures. Vitamin supplement have the patina of safety and of health, a feature that’s reinforced when you purchase them: You don’t need a prescription, you don’t get counseled by the pharmacist, and there isn’t a long list of frightening potential side effects to accompany the product. You can pull a bottle off the shelf at the health food store, and take any dose you want. After all, how harmful can vitamins be when you can buy 5 pounds of vitamin C at a time, or vitamin E capsules in a 1000-pack? But the research signals seem to be getting stronger, and most are pointing in the same direction: what we though we knew about antioxidants was based on simplistic hypotheses about nutrition and health. And while we thought we were doing ourselves good with antioxidant supplements, we may have been doing harm.
Let me address the biggest limitation of the paper first. This is just a review paper — not a systematic review, like a Cochrane Review. The benefit of a systematic review is the structured approach that minimizes the risk of bias, and especially the “cherry picking” of data. In this paper, while the authors describe using systematic search strategy, there’s no methodology described for the articles selected, nor is there a systematic appraisal of the literature selected. And as Travis Saunders at the excellent Obesity Panacea blog recently pointed out, a review article with the right amount of cherry picking can be used to support even the most implausible hypothesis, such as the potential benefits of smoking to distance runners. I couldn’t locate any published systematic reviews on this topic, so perhaps it’s more appropriate to consider the paper as a launching point for a review, but not a definitive statement on the evidence.
There’s good data from observational studies of large populations to suggest that a diet rich in foods that are naturally high in antioxidants is associated with better health outcomes. So if some antioxidants are good, more might be better, right? At a minimum, supplements might allow the kale-haters to get all the health benefits their cruciferous-vegetable-loving friends could be enjoying.
Oxidation (electron loss) and reduction (electron gain) are ubiquitous in biochemical reactions. While oxygen is essential to life, the outputs of respiration have the potential to do cellular damage in the form of “reactive oxygen species” or ROS. The ROS can damage cell membranes and other components. The imbalance is sometimes called “oxidative stress.” Antioxidants work to eliminate the oxidative stress by neutralizing ROS when they develop, preventing cell damage. We have evolved complex systems to produce several antioxidants (e.g., glutathione, uric acid, coenzyme q-10) onour own — the process is too critical to rely solely on the consumption of dietary antioxidants like vitamin C, vitamin E, and beta-carotene, which also play a role in managing ROS.
The antioxidant-exercise hypothesis is simple: exercise more, breathe more, oxidize more. Exercise can also damage muscle tissue. So the idea of boosting the antioxidant reserves to offset the perceived negative effects of exercise emerged. The expected results: better workouts and faster recovery. But like the t-shirt says, it’s a bit more complicated than that.
So let’s look at the data in the paper. The authors found 150 studies, but most were small and had weak methodologies:
As commonly found in sports nutrition research, the vast majority do not adhere to all the accepted features of a high-quality trial (e.g. placebo-controlled, double-blind, randomized design with an intent-to-treat analysis). Indeed, most studies fail to provide sufficient detail regarding inclusion and exclusion criteria, justification of sample size, adverse events, data gathering and reporting, randomization, allocation and concealment methods, and an assessment of blinding success. The poor quality of the majority of studies in this field increases the possibility for bias and needs to be always considered when evaluating the findings.
Summarizing the data is complicated by different supplements, different endpoints, varied durations and doses, and a lack of hard outcomes. The most common endpoint was some measure of oxidative stress, and on balance (though not always consistently) the data suggest that antioxidants do reduce this parameter. It’s been shown with vitamin C, vitamin E, beta carotene, and other antioxidants. Good news? Not really. It’s an endpoint without any demonstrated relationship to something meaningful — like performance or recovery.
Evaluations of the effects of antioxidant supplements on exercise-induced muscle damage are disappointing. The usual research approach is to look at measures of muscle damage in the bloodstream — enzymes like creatine kinase, which are a indicator of cell rupture. But the evidence is mixed — there’s no strong evidence to suggest supplements have any meaningful effect on muscle damage. What’s more concerning is that some studies have suggested that supplements may induce muscle injury and actually delay recovery.
So do antioxidants have any acute benefits on exercise? Should the weekend warrior be selecting the energy bar with extra vitamins? The data are more consistent here — there does not appear to be strong evidence of a performance-enhancing effect when antioxidants are consumed during exercise. With some exceptions, single ingredient and multiple-product supplements including vitamins E, C, coenzyme Q10, quercetin and polyphenol resveratrol have generally failed to demonstrate consistent effects in animal and human studies. Again, the quality of the studies and the lack of reproduction of many of the trials precludes firm conclusions.
Let’s consider the post-workout period now, and it’s here where we get to the most concerning data. Antioxidant supplements seem to be working against the beneficial cardiovascular effects of exercise. Mechanisms could include:
- Promoting, rather than reducing, oxidative stress: In some cases, supplements appear to raise indicators of inflammation, rather than reduce them.
- Reducing the ability to adapt to exercise-induced oxidative stress: Cells will naturally adapt to increases in ROS by upregulating endogenous enzyme systems. Supplements may inhibit this endogenous adaptation.
- Affecting physiologic processes like muscle contraction and insulin sensitivity: Supplementation, by affecting the concentration of ROS, may interfere with muscle function and recovery from the effects of exercise. A study by Ristow identified that supplementation with vitamins E and C inhibited the usual insulin-sensitizing effects of exercise. Becoming more insulin-sensitive is an important benefit to diabetics. The result, for diabetics that exercise and take antioxidants, could mean an elimination of the expected benefits.
So what does the science say about antioxidants and exercise?
Simple solutions can be the wrong ones. Surrogate, or intermediate endpoints, like those that measure oxidative stress, can’t be extrapolated to infer positive health effects in the absence of good confirmatory data. Like other areas of CAM, our ability to draw firm conclusions is limited by a lack of good data. The evidence is inconsistent and generally unimpressive when it comes to the effects of antioxidant supplements on exercise. So we’re challenged to make decisions based on incomplete information. In light of what we know about antioxidants and exercise, the trend in the data is strongly suggestive of zero benefit, at best, with the real possibility that there may be negative consequences to supplementation. Overlay the larger studies that looked at mortality, cancer, and other health measures, and the attractiveness of antioxidant supplements drops even further. The best advice, whether you exercise or not, may be to focus on consuming a diet rich in fruits and vegetables, and leave the antioxidant bottles on the shelf. There appears to be little that is complementary about them.
Peternelj TT, & Coombes JS (2011). Antioxidant Supplementation during Exercise Training: Beneficial or Detrimental? Sports medicine (Auckland, N.Z.), 41 (12), 1043-69 PMID: 22060178