Saturday, October 26, 2013

Antioxidant Supplementation With 1g of Vitamin C + 400IU Vitamin E Hampers Muscle Gains in Older Men (60-81y)

Human study shows: Antioxidant supplements hamper "gains" in elderly individuals, as well. The effects appears to be less pronounced than in younger trainees, though.
Most of you will be aware that I have been following and at least in parts subscribing to the hormesis hypothesis as it was proposed by Ristow and Zarse who proposed in 2010, already, that the mitohormesis hypothesis would provide "a common mechanistic denominator for the physiological effects of physical exercise" (Ristow. 2010). If we subscribe to the fundamental principles of this theory, any exogenous manipulation of the exercise induced stress would be expected to block or at least reduce the beneficial effects of exercise - and guess what!? Ristow et al. have already shown that (learn more about hormesis).

The previous research

By then, Ristow, Zarse, Oberbach et al. had already gotten quite some public attention, when they published the results of an experiment that involved 19 prevously untrained and 20 pretrained healthy young men, a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day), 4 weeks of training and an analysis of the effects on blood glucose management:
"Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPARgamma), and PPARgamma coactivators PGC1alpha and PGC1beta only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation." (Ristow. 2009)
Despite the fact that these results clearly indicate that antioxidant supplementation (in high enough doses) is counter-indicated, researchers and more importantly practitioners have long returned to their old habits, conducting study after study on the benefits of antioxidants and popping the corresponding pills a whole industry whose sales this year are worth $31,000,000,000 and who expects to add another billion $US to its sales over the next 4-5 years.
"Antioxidants - Yes or No?" - Will we ever find the answer? Not too long after Ristow et al. presented their results other researchers came up with counter evidence from endurance training base studies in mice and men (learn more). I would thus be surprised if the whole issue would be settled anywhere in the close future. If anything, I'd suppose we may identify an age- and exercise-dependent inflammation threshold you have to exceed before additional antioxidants eventually make sense.
A study like the one by Thomas Bjørnsen would thus be bad news and it's probably no coincidence that it was up to master student and his supervisors, Sveinung Berntsen Stølevik, Gøran Paulsen, Ken Joar Hetlelid to generate further evidence that the halo of health, longevity and endless youth that surrounds the use of antioxidant supplements could be nothing but an optical illusion.

What does damage in the young, does not help in the elderly

If you have been following my previous posts on the mitohormesis concept you may have read me write that logic dictates that elderly individuals are the ones who are more likely to benefit from the use of antioxidants. Their weakened immune system does not allow for the a similarly rapid and complete restoration of muscular and cellular damage in general.

 Against that background it appears only reasonable that older physical culturists would be well advised to keep the damage to their mitochondria in check; and 1000 mg of vitamin C and 235 mg of vitamin E per day don't sound like the worst way to do just that. It is thus only reasonable that Bjørnsen's research hypothesis reads:
"Supplementation with vitamin C and E in high daily dosages (1000 mg and 235 mg
per day, respectively) will enhance adaptations to resistance training, i.e. increased
muscle thickness, lean mass and one repetition maximum in the exercises: leg press,
leg extension and scott curl." (Bjørnsen. 2013; my emphasis)
So, if there was a hidden agenda or a bias to deliver the expected results, it would not have favored an outcome like this:
Figure 1: Difference of training effects in vit C + E group compared to placebo; all values rel. to placebo (Bjørnsen. 2013)
An outcome that indicates that the provision of the said supplements to the 30 elderly men (age 60-81y) who had not been resistance training in the past 6 months before they embarked on a resistance training regimen with the following characteristics:
  • Table 1: Overview of the exercise program - certainly not a bad one (Bjørnsen. 2013)
    an undulating periodized profile,
  • 3 full-body sessions per week, 
  • an emphasis on free weight exercises where all the major muscle groups were included,
  • two of the sessions each week were “moderate” → 8-10 rep, with 1 min break between sets), one was varied between “heavy” → 3- 5 rep, with 2 min break between sets and “light” → 13-15 rep, with 45 seconds break between sets every second week.
  • the number of sets per exercise was increased progressively from 1 to 4 sets during the first 10 weeks, and then reduced with 1 set each of the last 2 weeks of the intervention (tapering). 
Subjects conducted one additional “warm-up” set at 50 % of their target weight in each exercise before the main sets started. All exercise sessions were supervised by two experienced instructors supervised all resistance exercise sessions and the loads were weekly adjusted. The res between sets was timed and synchronized for the all participants and the movement velocity was also instructed to a minimum of 1 second in the concentric phase, and 2 seconds in the eccentric phase.

Maximal growth? Only with proper stress
As Bjørnsen points out, the resistance exercise program was "designed to give large metabolic stress (i.e., oxidative stress) and the intention was to stimulate as much muscle growth as possible." Moreover, all subjects had to keep an individual exercise diary to ensure that the resistance could be  adjusted before the next session, whenever they reached the prescribed number of reps on their last set.
Inflammation won't build muscle, but without it, your body won't notice that it's time to adapt (learn more)
It's always worth working out - with and without anti-oxidant supplements: I guess you'd agree that there is little reason to complain about the training regimen - is there? I don't think so. After all, even in the anti-oxidant group the gains were significantly more pronounced than the average size and strength gains in the studies with even older subjects Stewart et al. reviewed only recently (see SuppVersity Facebook News).

If there was no other take home message, it would thus be that the beneficial effects of a well designed workout are not lost, when you take a daily "high performance multi" - and that notwithstanding that the study at hand provides further evidence that  the term "high performance mulitvitamin supplement" is an oxymoron (a figure of speech that juxtaposes apparently contradictory elements).
Despite the fact that the study at hand provides further evidence for the negative effects of antioxidant supplementation on the exercise induced adaptation processes, we still need more data before we can definitely say whether or not antioxidants hamper your gains.
At least for vitamin C, vitamin E, and as you've already learned here at the SuppVersity, n-acetyl-cysteine (learn more & even more) - the "kamikaze oxidants" and real free radical scavengers - it wouldn't be unreasonable to have one or another second thought before you add them to your supplement regimen.
  • Baird et al. Vitamins and nutrition supplements sales in U.S. Health, Nutrition & Fitness Report 2012.
  • Bjørnsen T. The effect of supplementation with vitamin C and E on muscle growth and maximal strength during 12 weeks of resistance exercise in elderly men. University of Agder, 2013.
  • Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Blüher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009 May 26;106(21):8665-70.
  • Ristow M, Zarse K. How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis). Exp Gerontol. 2010 Jun;45(6):410-8. 
  • Stewart VH, Saunders DH, Greig CA. Responsiveness of muscle size and strength to physical training in very elderly people: A systematic review. Scand J Med Sci Sports. 2013 Oct 24.