Saturday, March 22, 2014

Anti-Oxidants & Resistance Training: In the Elderly We See Minimal Benefits. In the Young and Fit Potential Detriments ➯ Could ROS Management, Not Eradication Be the Key?

Health, performance, longevity: It's all about ROS-management. The age-diffe- rence that's showing in the contemporary evidence pro/against the negative effects of vitamin C + E on exercise induced adapation actually confirms that.
I am pretty sure, the results of the Paulsen study I wrote about in " Study Confirms Antioxidants (C+E) Are Bad For Healthy People Who Train, But in Some Subjects C+E Increase the Fat Loss Effects of HIIT + HIT by a Whopping 60%" (read more) in February will still resonate in your ears. Impaired adaptation, but increased fat loss!? That sounds strange, but if you think of the inhibitory effects "bad inflammation" (see box below) will have on your body composition it is logical to assume that the provision of the simple reactive oxygen specimen (ROS) scavengers vitamin C & E would reduce the baseline inflammation and restore a person's sensitivity to "good inflammation" - the same ROS signalling, Nobel laureate James D Watson recently labeled as "a positive force for life." (Watson in Tarr. 2014).
Illustration 1: Reactive oxygen specimen can become a problem at both high and low levels. But don't worry, you can use exercise, your diet and (if necessary!) dietary supplements to manage them.
What's that all about "good and bad ROS": As Nobel Laureate Watson pointed out only recently, the often-heard claim that reactive oxygen species are dangerous terrorists that have to be exterminated at every cost is absolutely unwarranted. Their important role in apopotosis (=the controlled death of degenerate / old cells), for example, is of utmost importance in your bodies natural fight against cancer. As Radak et al. (2013) point out, ROS are also important exercise-induced modulators of muscle contraction, antioxidant protection, and oxidative damage repair, which trigger many of the health responses we associate with working out. Managing not extinguishing ROS is thus the key to ultimate health.
If we take a look at the results of pertinent studies, like the one researchers from the University of Sherbrooke (Bobeuf. 2011) presented in 2011, the corresponding findings clearly support my previously voiced hypothesis that it's the baseline inflammation status which decides whether the addition of the notorious 1,000mg of vitamin C and 400IU of vitamin E almost the average subject of the corresponding studies ingested will or won't impair the beneficial effects on the outcome of his / her training.
Figure 1: Changes in body composition in response to resistance training (RT), anti-oxidant supplementation (C+E) and resistance training + anti-oxidant supplementation (RT+C+E); no sign. differences in strength gains (Bobeuf. 2011)
Apropos "beneficial effects", if we take a closer look at both the previously referenced study by Paulsen (young people, read more) and the 2011 study by Bobeuf (see Figure 1), in the course of which 57 subjects (27 men and 30 women) between the age of 59 and 73 (mean: 65.6  ±  3.8yrs) performed 1h resistance training sessions thrice a week (3 sets @ 80% 1RM, linear progression, full body workouts; eg press, bench press, leg extension, shoulder press, seated row, triceps extension and biceps curl) we do have to realize, though, that these effects are body composition specific.

Is fat loss the only benefit of soothing the fire?

In view of the fact that reactive oxygen specimen activate both, UCP1 and UCP2, which are the "switches" for mitochondrial energy wasting and thus powerful (up-)regulator fatty acid oxidation and energy expenditure, this seems strange.
Illustration 2: The fact that the "energy wasting" uncoupling proteins (UCP1 & 2) are controlled by ROS (Mailloux. 2011) and glutathione is a potential explanation for the beneficial effects of anti-oxidants on exercise induced fat loss.
This is at least the case if we don't take into account that the activation and deactivation of these uncoupling proteins is controlled by glutathione (Mailloux. 2011), the production / recycling of which is in turn promoted by vitamin C + E and would thus obviously be increased in a scenario where someone uses anti-oxidant supplements to restore normal glutathione levels.

Figure 2: Glucose infusion rates and adiponectin before (white) and after (grey) the exercise +/- vitamin C + E intervention in the Ristow study (Ristow. 2009).
It is still difficult to reconcile these results with Ristow et al.'s 2009 study, which made it into the evening news and has been (officially) cited by more than 500 peer-reviewed papers, already (Ristow. 2009). With a combined cardio + circuit training regimen and sedentary, as well as previously trained subjects, there is little room to argue that the blunted increase in insulin sensitivity (see Figure 2) the researchers from the Universities of Jena and Leipzig measured in their 40 subjects were brought about by 'insufficient eu-stress' or a result of a training status, where any additional ROS buffer would reduce the incentive to metabolic, mitochondrial or endocrine adaptations to zero.

Now increases in insulin sensitivity do not necessarily translate into fat loss. If you think about the PPAR-gamma activating diabetes drugs, there are actually several examples, where the exact opposite is the case. And with stimulants like caffeine the temporary increase in fatty acid oxidation is paid for by decreases in insulin sensitivity (more free fatty acids in the blood ➯ lower insulin sensitivity, but higher fatty acid oxidation). It's thus a real pity that Ristow et al. didn't measure (or report) the changes in body composition and/or rates of fatty acid oxidation at rest and during exercise.

Pro and contra - it's all about cherry picking your "evidence"

But there is more evidence to support my "baseline inflammation hypothesis" and studies supporting the arguments of both, the advocates and opponents of anti-oxidant supplementation for active, inactive, young and old individuals. And what makes the whole issue even more complicated you can find a "pro" and a "contra" study for almost all claims you can make:
  • Vitamin C supplementation impairs recovery in the days after a bout of eccentric exercise despite  / due to reduced ROS production (Close. 2006); and acute Vitamin C supplementation does not reduce muscle damage or soreness after prolonged intermittent shuttle-running (Thompson. 2001)
  • The acute reduction in muscle performance is reduced after eccentric exercise with previous vitamin C & E supplementation (Shafat. 2004)
  • Antioxidant supplementation prevents exercise-induced lipid peroxidation, but not inflammation, in ultramarathon runners (Childs. 2001)
  • Antioxidants do not prevent postexercise peroxidation and may delay muscle recovery (Teixeira. 2009)
  • Supplementation with CoQ10 (ubiquinone) causes cellular damage during intense exercise (Malm. 1996)
  • Supplemental CoQ10 boost peak power increases in young elite athletes (Alf. 2013 | learn more)
  • Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise (Childs. 2001)
  • N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals (Medved. 2005)
I am pretty sure that I could go on for hours searching and finding study pairs like this, but in the end, I just want you to realize that the answer to the "anti-oxidants for athletes question" (if there even is one) is still out there.
Figure 3: The results of a recent study by Bouzid et al. suggest that age is one of the most important determinants of the width of the margin between "too little" and "too much" eu-stress: The same incremental cycle ergometer test to exhaustion that's a eu-stressor (=generate beneficial effects) in the young can only be compensated in the elderly, but does not induce a supercompensatory increases in anti-oxidant enzyme activity.
Overall it would appear as if it was a constant balancing act between too much and too little ROS - a process that may require well-timed temporary / acute vs. chronic (I am not talking about away from workouts, but rather about taking your anti-oxidants only in the days before a meet, for example) an above all minimimalist antioxidant supplementation according to your individual needs.

With age, training status, diet, psychological stress, sleep, acute vs. chronic supplementation, training volume, intensity and the other 500 potential parameters you would have to take into account to figure out, how much vitamin C, E, A, ... you have to consume every X, Y, or Z hours it's unrealistic to assume that anything but some sort of yet not available physical test would be the only way to ensure that you are neither consuming to few, nor too many free radical scavengers. Against that background any general recommendation like "take 1g of vitamin C and 400IU of mixed tocopherols" appears to be over-simplistic - if you insist on supplementing, though, I would suggest not to take more than that ;-)
References:
  • Alf, D., Schmidt, M. E., & Siebrecht, S. C. (2013). Ubiquinol supplementation enhances peak power production in trained athletes: a double-blind, placebo controlled study. Journal of the International Society of Sports Nutrition, 10(1), 24.
  • Bobeuf, F., et al. "Combined effect of antioxidant supplementation and resistance training on oxidative stress markers, muscle and body composition in an elderly population." The journal of nutrition, health & aging 15.10 (2011): 883-889. 
  • Bouzid, Mohamed Amine, et al. "Changes in Oxidative Stress Markers and Biological Markers of Muscle Injury with Aging at Rest and in Response to an Exhaustive Exercise." PloS one 9.3 (2014): e90420.
  • Childs, A., et al. "Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise." Free Radical Biology and Medicine 31.6 (2001): 745-753.
  • Close, Graeme L., et al. "Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process." British journal of nutrition 95.05 (2006): 976-981.
  • Gomez-Cabrera, Mari-Carmen, et al. "Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance." The American Journal of Clinical Nutrition 87.1 (2008): 142-149.
  • Ji, Li Li. "Exercise‐induced modulation of antioxidant defense." Annals of the New York Academy of Sciences 959.1 (2002): 82-92.
  • Mailloux, Ryan J., and Mary-Ellen Harper. "Uncoupling proteins and the control of mitochondrial reactive oxygen species production." Free Radical Biology and Medicine 51.6 (2011): 1106-1115. 
  • Paulsen, G, et al. "Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind randomized control trial." Journal of Physiology (February 2014; accepted manuscript).
  • Radak, Zsolt, et al. "Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling." Antioxidants & redox signaling 18.10 (2013): 1208-1246. 
  • Ristow, Michael, et al. "Antioxidants prevent health-promoting effects of physical exercise in humans." Proceedings of the National Academy of Sciences 106.21 (2009): 8665-8670. 
  • Shafat, A., et al. "Effects of dietary supplementation with vitamins C and E on muscle function during and after eccentric contractions in humans." European journal of applied physiology 93.1-2 (2004): 196-202.
  • Tarr, Peter. "Nobel laureate James Watson publishes novel hypothesis on curing late-stage cancers." Cold Spring Harbor Laboratory - Press Release. Monday, 07 January 2013.
  • Teixeira, VITOR H., et al. "Antioxidants do not prevent postexercise peroxidation and may delay muscle recovery." Med Sci Sports Exerc 41.9 (2009): 1752-1760.
  • Thompson, D., et al. "Muscle soreness and damage parameters after prolonged intermittent shuttle-running following acute vitamin C supplementation." International journal of sports medicine 22.01 (2001): 68-75.