Update on Antioxidants & Exercise - Neither Vitamin C Nor E Have ANY Effect on the Response to Intense Exercise.

Image 1: If you add some reactive oxygen species to this mitochondrium, this will trigger beneficial, (mito-)hormetic adaptations, that could be blunted by too many antioxidants.

As a diligent reader of the SuppVersity, you have probably been following my posts on antioxidants and their potentially negative effect on the adaptive (hormetic) response to the exercise induced formation of reactive oxygen specimen. Although, I still believe that the theory may have its merit - especially in metabolically deranged people, where the exercise induced ROS formation would initially have to overcome the low-grade chronic "background" stress - it appears that for healthy people, and "moderately trained young men" on an intense exercise protocol, in particular, the ingestion of reasonable amounts (<1g of vitamin C and <400IU of vitamin E) does not pose a problem. At least this is what the results of two relatively recent studies by scientists from Washington School of Medicine (Higashida. 2011) and researchers from universities in Denmark and France (Yfanti. 2011) would suggest.

The hormetic benefits of inflammation

According to the mitohormesis hypothesis, the beneficial effects of exercise on health, in general, and glucose metabolism, in particular, are at least partly mediated by an increase in reactive oxygen species, which triggers downstream "hormetic" adaptation processes which result in increased oxidative capacity and insulin sensitivity, as well as a reduction in total inflammation (cf. previous posts on the work of S. Schmeisser and M. Ristow from the Department of Human Nutrition at the University of Leipzig. If this theory held true, or let's be more specific, if this theory which is largely based on observations in metabollically derranged, i.e. obese and/or type II diabetic subjects, was applicable to healthy people and athletes, as well, this could mean that the multi-vitamin, the vitamin C pills, the alpha-tocopherol (vitamin E) and all the other little helpers you have been taking religiously to increase your exercise performance would actually have hampered, not promoted your muscle gains, fat loss and whatever else you may have had in mind, when you hit the gym, the road, the field, the court or the green ;-)

Figure 1: Neither the high-dose supplementation protocol in rodents (HED: Human Equivalent Dose for 80kg), nor the moderate dose protocol in humans did block any of the measured beneficial adaptations to exercise in the studies by Higashida (2011) and Yfanti. (2011), respectively.

Let me say this right away: As long as you have not been following the recommendations of dubious nutritional gurus and self-proclaimed fitness "experts" to take 10g+ of vitamin C and vitamin E supplements in the 3000IU+ range, the little vitamin pills and powders are probably not the reason that your biceps is not growing and your belly is just as fat as it was, when you began training.

Figure 2: Serum vitamin C and vitamin E levels (µmol/L) in 21 subjects before, at the beginning and after 12 weeks of 5x a week strenuous cycling exercise with and without supplemental vitamin C & E (adapted from Yfanti. 2011)

As you can see in figure 2, supplementation with 500mg of vitamin C and 400 IU of vitamin E (more on the protocols used in the studies in figure 1) before and during 12 weeks of strenuous bicycle exercise training with a frequency of 5 sessions per week (HIIT, HIT and stead state, cf. figure 6) did increase the concentration of antioxidants in the blood of the 21 healthy, physically active subjects (age 18-40years) of the Yfanti study, who had not participated in physical exercise more than twice a week before the experiment. Despite higher vitamin C and E plasma levels, and contrary to the research hypothesis of the scientists, who had expected that the anti-oxidant supplementation would blunt the adaptive response to the exercise protocol,

[...] the present study showed that combined supplementation with vitamins C and E before and during 12 weeks of supervised, strenuous bicycle exercise training of a frequency of 5 days/week had no effect on maximal oxygen consumption, maximal power output, workload at lactate threshold, glycogen content, and CS and β-HAD activity in muscle.

In other words, supplementing with "reasonable" amounts of vitamin C and vitamin E had absolutely NO EFFECT (!) on the exercise induced metabolic adaptations or performance increases - that does yet also imply that taking anti-oxidants is of little benefit as long as the minimal dietary requirements are met... and if you still insist to poor money down the literally rat hole, you may be interested to hear that (assuming that the results from Higashida's rat study translate to humans), even 10g of vitamin C and 3000IU of vitamin E a day probably would not really make a difference - as long as you train heavy enough.

Figure 4: Exercise induced changes in GLUT-4 expression (arbitrary units) and 2DG transport (µmol/ml/20min) in rats subjected to 8 weeks of high dose antioxidant supplementation and 6days/week swimming exercise in the last 3 weeks (data adapted fro Higashida. 2011)

Of particular interest in this context is the effect of "mega-dosing" anti-oxidants on the exercise induced increase in insulin sensitivity, which has been reported to be impaired in previous studies (Ristow. 2009). As the data in figure 3 shows, the increase in glucose transporter (GLUT4) expression is slightly greater in the non-supplemented rats, BUT neither this difference nor the difference in measured 2-Deoxy-D-glucose (2DG) transport reach statistical significance.

Figure 5: Exercise induced changes in MDA, SOD and PGC-1α in rats subjected to 8 weeks of high dose antioxidant supplementation and 6days/week swimming exercise in the last 3 weeks (data adapted fro Higashida. 2011)

Moreover, Higashida et al. found no statistically significant differences in the increases of malondialdehyde (MDA), superoxide dismutase (SOD1 & SOD2) or PGC-1α, a marker for the mitochondrial fatty acid oxidation, between the rats in the two groups (cf. figure 5).

Now, I a confused and don't know what to believe

So what does all that tell us? Well, we can now be relatively certain that supplementing with vitamin C and vitamin E is a waste of time and money for most of us. What we still cannot say for sure, though is why the Ristow study from 2009, which even made it to mainstream media news, found detrimental effects of supplementing with 1g of vitamin C and 400IU of vitamin E on the adaptive response to 4 weeks of 5days/week 20min steady state aerobic training + 45 minute circuit training + 20 min warm up + cool down (Ristow. 2009), while the Yfanti study, with 500mg of vitamin C and 400IU of vitamin E did not find any effects of supplementation...

Figure 6: Exercise protocol that was used in the Yfanti study.

...the only reasonable explanation I have is that the protocol in the Ristow study may not have been intense enough. Unfortunately there is no detailed information on what the subjects did in the course of the "circuit training", but if that was your usual sissy type walk from one machine to the next, chances are that the level of ROS that was induced by this "exercise" protocol was so low that it was completely blocked by the supplemental anti-oxidants. The "cycling protocol" in the Yfanti study, on the other hand, is pretty intense. If you look at the schedule in figure 6 you will concede that this is almost the way athletes (and maybe you) train.

All that being said, it appears that all is coming back to what I have been writing (and also saying on SHR) several times before: Controlled oxidation is likely to be beneficial. It's like the fire in the oven that keeps you warm - the one you carefully take care of, in order to prevent your whole house to catch fire... if you are a marathon runner, the latter can happen pretty quickly and you will need (tons of ;-) antioxidants and even that will probably not suffice. If you are the housewife on the treadmill, who walks at 5km/h for 20min two times a week, on the other hand, even a few milligrams of vitamin C and a few units of vitamin E will blunt the little oxidative "damage" that you do and your "efforts" to increase your insulin sensitivity or whatever your intentions may be will be sabotaged by your vitamin supplements.