To C or not to C? That is my question

(Vitamin C)

I will be the first to admit, inflammation is not always something I look forward to feeling when I step out of bed in the morning.  Whether it is an inflamed toe from cutting a nail too short, an inflamed and swollen ligament from training to hard, or something as simple as sore muscles, it can be uncomfortable.  In the case of muscle soreness, inflammation is often attributed to the generation of reactive oxygen species (ROS) which can damage cellular structures, impairing muscle function and result in fatigue.  ROS are generated during exercise through oxidative metabolism within the mitochondria, as well as in response to changes in oxygen availability and pH in the local microenvironment.   Importantly, ROS can be quenched by antioxidants such as Resveratrol, Quercitin, Vitamin E, and Vitamin C, and in the 90s antioxidants were heavily promoted to reduce muscle fatigue and enhance exercise performance.

                That being said, antioxidants supplementation is very common in exercise supplements, take a look at your favorite brand of gel or sports drink, does it contain Vitamin C or E?  I know several of my favorite products such as Gu, Succeed! Ultra and Amino, Cytomax, and Powerbars contain one or both.  Not surprisingly, studies suggest approximately 50% of elite and 40% of non-elite athletes take a daily vitamin supplement, usually in quantities well above the recommended levels (1).  Antioxidants work almost entirely independent of NSAIDs (Ibuprofen, Aspirin, Tylenol) to alleviate inflammation, quenching ROS produced during exercise by donating an electron to the ROS, preventing the generation of inflammatory signals.  In turn, this causes the anti-oxidant to become a pro-oxidant itself; however, anti-oxidants such as vitamin C and vitamin E are rapidly converted back into stable forms by natural enzymatic pathways (2).  While there is strong evidence suggesting much of the cardioprotective effects of certain foods such as tea, chocolate and wine are due to high levels of antioxidants, there is also a substantial body of evidence suggesting antioxidant use during exercise may also impair the critical training adaptations resulting from exercise.

                  The first step to understanding this hypothesis begins with understanding that ROS can be both beneficial and harmful for an endurance athlete.  There is significant data supporting the concept that the generation of ROS during exercise is an important step in initiating the adaptations that result from periods of training (3, 4).   ROS production during exercise has been found to be important for the upregulation of several genes important for the increasing generation of mitochondria, the mini power plants within muscle cells.  One of the defining features of elite or highly trained athletes is mitochondrial density.  Muscle biopsies from these athletes show a much greater number of mitochondria per cell, theoretically indicating a greater capacity to produce ATP, the fuel source for exercising muscles.  To clarify, both carbohydrate and fat can be used as fuel for muscle, but these fuel sources must first be converted to ATP within the mitochondria before they are available for use by muscle. 

                Skeletal muscle adaptations from training have been linked to the increase in the activity of several regulatory pathways within the muscle cell, including a protein central to the biogenesis or formation of new mitochondria within the muscle cell. (4)  This protein, peroxisome proliferator-activated receptor γ coactivator 1α (PCG-1α) promotes formation of new mitochondria through activating other proteins that bind to DNA and regulate gene expression (3).  Furthermore, this protein is found at much higher levels in slow-twitch oxidative muscle fibers (4), understandable as these fibers have a relatively high number of mitochondria and are responsible for sustaining endurance exercise (see my blog of fat oxidation in Type I muscle fibers).   Most importantly, the activation of PCG-1α is redox sensitive; ROS activate PCG-1α (3)!  Thus, this has lead to a hypothesis proposing that antioxidant consumption during training periods, results in the quenching of ROS, in turn impairing the activation of PCG-1α, and blunting mitochondrial biogenesis. 

                Because mitochondrial biogenesis is critical for the increase in aerobic capacity following training, there have been several studies attempting to address whether chronic antioxidant supplementation can reduce training induced gains in aerobic capacity.  While fairly consistent data exists in animal models (5, 6), there are mixed results in human studies as to whether this phenomenon holds true.  In one study, 4 week supplementation with a combination of vitamin C and vitamin E resulted in decreased expression of several markers of mitochondrial biogenesis following endurance training (7).  Furthermore, this study, and at least one other that I am aware of, have noted that other health benefits such as the upregulation of endogenous antioxidant enzymes as well as increased insulin sensitivity resulting from exercise training may also be subverted by antioxidant supplementation (7, 8).  However, scientists in another study supplemented 11 males with vitamin C and E while 10 received placebo.  The subjects were instructed to consume vitamin supplements with breakfast afterw hich they had the study participants undergo an intense exercise regime for 12 weeks.  Overall, the scientists that conducted this study observed marked increases in Vo2 max, maximum power, and power at lactic threshold following the 12 week training protocol, but found no differences between the group receiving antioxidant supplementation and the group receiving placebo leading them to conclude that in their study antioxidant supplementation did not impair training-induced gains (1).  However, the authors did not measure mitochondrial biogenesis, only examining factors influenced by mitochondrial density.   

                There definitely appears to be conflicting reports as to whether antioxidant supplementation impairs exercise-induced muscle adaptations.  I am of the opinion that the paucity of the data suggests that this concept is influenced heavily by one’s fitness status before beginning a training regime.  That is to say, less trained individuals taking an antioxidant supplement may observe fewer adaptations to training than someone of their same fitness level not taking supplements.  In highly trained individuals, the body has already considerably upregulated natural pathways to abolish ROS once they are produced, perchance making it more difficult to observe an effect of antioxidant supplementation.  While the data I have highlighted here is focused mainly on vitamin C and E, there have been reports that other antioxidants such as CoQ10 have the similar effect in dampening training induced gains (9).  After speaking with another Human Nutrition grad student, we both agreed that the take home message from this piece of word vomit is not that you should avoid your anti-oxidant rich blueberries, strawberries, glass of wine or piece of dark chocolate, but rather, think twice about taking pharmacological doses found in supplements (1000% Daily Value).  Interestingly, while Gu contains antioxidants, I noticed that Hammer Gel, Clif Shots, Powerbar Gel, and Honeystinger Gels do not.  Maybe my application of this principal will be to rely on Gu gels only when racing.  On a personal note, I enjoy basking in some good old soreness and encourage you to not shy away from feeling sore, because it is your body’s own way of telling itself to adapt.  Maybe there still is a place for antioxidants during exercise in order to increase performance and ward-off fatigue during racing when the goal is to just finish the damn thing or if it is your #1 A race of the year and its PR or fail – but that is a different blog all together!

Works Cited

1.            Yfanti C, Akerstrom T, Nielsen S, Nielsen AR, Mounier R, Mortensen OH, Lykkesfeldt J, Rose AJ, Fischer CP, Pedersen BK. Antioxidant supplementation does not alter endurance training adaptation. Med Sci Sports Exerc.  Jul;42:1388-95.

2.            Linster CL, Van Schaftingen E. Vitamin C. Biosynthesis, recycling and degradation in mammals. FEBS J. 2007 Jan;274:1-22.

3.            Kang C, O'Moore KM, Dickman JR, Ji LL. Exercise activation of muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling is redox sensitive. Free Radic Biol Med. 2009 Nov 15;47:1394-400.

4.            Suwa M, Nakano H, Radak Z, Kumagai S. Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1alpha protein expressions in rat skeletal muscle. Metabolism. 2008 Jul;57:986-98.

5.            Strobel NA, Peake JM, Matsumoto A, Marsh SA, Coombes JS, Wadley GD. Antioxidant supplementation reduces skeletal muscle mitochondrial biogenesis. Med Sci Sports Exerc.  Jun;43:1017-24.

6.            Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, Vina J. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr. 2008 Jan;87:142-9.

7.            Ristow M, Zarse K, Oberbach A, Kloting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Bluher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009 May 26;106:8665-70.

8.            Yfanti C, Nielsen AR, Akerstrom T, Nielsen S, Rose AJ, Richter EA, Lykkesfeldt J, Fischer CP, Pedersen BK. Effect of antioxidant supplementation on insulin sensitivity in response to endurance exercise training. Am J Physiol Endocrinol Metab.  May;300:E761-70.

9.            Malm C, Svensson M, Ekblom B, Sjodin B. Effects of ubiquinone-10 supplementation and high intensity training on physical performance in humans. Acta Physiol Scand. 1997 Nov;161:379-84.