Role of vitamin C and E supplementation on IL-6 in response to training
Journal Title (Medline/Pubmed accepted abbreviation):  J. Appl. Phyiol.
Year: 2012
Volume: 112
Page Numbers: 990-1000
doi: 10.1152/japplphysiol.01027.2010

Summary of background and research design:

Background: The increased cellular metabolism associated with exercise increases production of free radicals. Because of the damaging effects of free radicals on cells, increased free radical production has historically been viewed as a negative consequence of exercise. However, it is now recognized that free radicals and other reactive species play important signaling roles in the cellular response and adaptation to exercise. The immune system is one such system that is responsive to this type of signaling. The authors wanted to know if antioxidant supplementation, which would theoretically reduce free radicals/oxidative stress in cells, could actually have a negative impact on the adaptation to exercise training.

Hypothesis: Supplementation with vitamins C and E will reduce the rate at which the body adapts to routine exercise. Therefore, without supplementation, exercise-induced IL-6 production will decrease after a 16 week exercise program whereas with supplementation, there will be less of a decrease.

Subjects: 21 healthy males that exercise between 2-4 times per week, age about 25-35 y.

Experimental Design: randomized, placebo-controlled, double-blinded

Vitamins- tablets that contain 500 mg ascorbic acid (vitamin C) and 400 IU RRR-α-tocopheryl succinate (vitamin E)
Placebo- tablets made of starch, cellulose, and calcium hydrogen anhydrous (no vitamins)

Protocol: The participants were first evaluated for VO2max (maximum consumption of oxygen) and Pmax (maximum power) and randomized to one of the two groups. Subsequently, vitamin (or placebo) supplementation commenced, lasting 16 wks. Four weeks into the supplementation period, all participants performed an acute exercise trial where they cycled at 65% Pmax on a stationary bicycle for 1 hr. Blood samples and muscle biopsies were collected before and after training as well as 3 hrs after training. Then, participants engaged in a cycling exercise protocol 5 times per week for the remaining 12 wks. Training intensity was based on the individuals’ Pmax that was determined at the start of every week. Training was different on different days of the week and included both interval training and less intense, longer rides of “cardio” training. Training length or intensity was increased every week. Another acute exercise trial was completed within 3-4 days of the last training session. Blood was analyzed for vitamin C and E concentrations, IL-6, IL-1ra, cortisol, and protein carbonyls (used to assess oxidative injury). Biopsies were analyzed for mRNA concentration for specific genes, the concentration of various proteins, and malondialdehyde (MDA; an indicator of oxidative stress).

Summary of research findings:
  • Supplementation with vitamins C and E effectively increased concentrations of these vitamins in the blood at 4 wks. Concentrations remained elevated at 16 wks.
  • Exercise training for 12 wks increased VO2max and Pmax with no difference between groups. Participants in both groups exhibited an average decrease in body weight.
  • Exercise stimulated an increase in IL-6 in both groups before and after the exercise training. There was statistically significant attenuation in stimulation in the placebo group but not the vitamin group. There were large individual differences, especially before training in the placebo group, so it is unknown if this difference is practically significant.
  • Exercise training attenuated the increase of mRNA expression of IL-6 after acute exercise with no difference between groups.
  • Acute exercise increased MDA concentrations in the blood and muscle. In general, there was a greater concentration of MDA after the 12 wk exercise training compared to before the 12 wk training period.
  • After the 12 wk training period, the concentration of plasma carbonyls was higher in the vitamin group than the placebo group before and after acute exercise.
  • After the 12 wk training period, expression of antioxidant enzyme (ex. glutathione peroxidase) was higher in the vitamin group compared to the placebo group before and after acute exercise. However, there was no difference in the protein content of the antioxidant enzymes.

Key practice applications: This study provides evidence that supplementation with vitamins C and E may attenuate the immune response to exercise. However, there were only very small differences between the vitamin group and the placebo group in regard to markers assessing the adaptive response to exercise. The authors concluded that there were no beneficial effects of vitamins C and E supplementation in their study.

Limitations It would have been interesting if the study design included a performance measurement to assess whether the 12 wk exercise training allowed the placebo group to improve more than the vitamin group (or not).
- There is a chance that some of the athletes in the supplement group were vitamin deficient before supplementation. Therefore, supplementation would lead to gains in performance and body functionality, where it may have a different effect in vitamin-replete athletes.

Key search terms for this article (5-7 terms): antioxidants, vitamin C, vitamin E, ascorbic acid, tocopherol, oxidative stress, adaptation

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