Muscles and antioxidants

I’m trying to get my head around whether my daily antioxidant supplements are likely to interfere with muscle building. (Yes, I know that stimulating MTOR is counterindicated for longevity, but I’d like healthspan as well.)

Right now I am daily taking GlyNAC (6g glycine and 100g NACET which supposedly is 1-2g NAC equivalent) and starting this summer 12mg astraxanthin (for the sun protection but not sure if it does anything there, plus it is touted for many longevity and protective effects). Both are strong antioxidants, and I’m not sure either are doing anything. But when I lift weights, isn’t the signalling that my body should make more muscle a Reactive Oxidative Species (ROS)? So won’t having ample antioxidants flowing through by blood blunt these potentially positive impacts (including mitochondrial biosynthesis)? (I was ignorant to the fact that many weightlifters take vitamin C to aid their recovery.)

So what do you think? Should I drop astraxanthin on heavy lifting days? Should I drop GlyNAC on heavy lifting days? Should I drop either/both altogether? Should I stay the course? My gut is to drop astraxanthin (as the original intent was sun protection and it seems to be nil) and keep GlyNAC.

I must say if I am blunting mitochondrial biosynthesis with use of antioxidants, this could be a highly negative outcome: isn’t mitochondrial health a key marker for longevity (and healthspan)? That seems counterproductive for me.

There is building evidence that antioxidant supplementation can attenuate endurance training‐induced and ROS/RNS‐mediated enhancements in antioxidant capacity, mitochondrial biogenesis, cellular defence mechanisms and insulin sensitivity. However, this is not a universal finding, potentially indicating that there is redundancy in the mechanisms controlling skeletal muscle adaptation to exercise, meaning that in some circumstances the negative impact of antioxidants on acute exercise response can be overcome by training. Antioxidant supplementation has been more consistently reported to have deleterious effects on the response to overload stress and high‐intensity training, suggesting that remodelling of skeletal muscle following resistance and high‐intensity exercise is more dependent on ROS/RNS signalling. Importantly there is no convincing evidence to suggest that antioxidant supplementation enhances exercise‐training adaptions. Overall, ROS/RNS are likely to exhibit a non‐linear (hormetic) pattern on exercise adaptations, where physiological doses are beneficial and high exposure (which would seldom be achieved during normal exercise training) may be detrimental.


Experimental evidence does not support the “common knowledge” that antioxidant treatment greatly improves exercise performance and recovery. On the contrary, studies with antioxidant supplementations generally show no effect on muscle function during and after exercise. The exception is NAC treatment, which has been found to improve performance during submaximal exercise. The limited effects of ROS/RNS and antioxidants during exercise are unexpected in that increases in ROS/RNS are likely to occur and these are potentially harmful. It appears that muscle fibers are in some way protected against deleterious effects of oxidants during exercise and fibers are generally much more sensitive to exposure to oxidants in the rested state than during fatigue. For instance, experiments on single mouse muscle fibers have shown that application of 10 μM hydrogen peroxide did not affect fatigue development (Place et al., 2009), whereas concentrations as low as 100 pM hydrogen peroxide affected contraction and Ca2+ handling in rested fibers (Andrade et al., 2001). Thus, numerous questions remain to be answered in relation to the effects of oxidants during and after exercise.

Eric Trexler says…
"I feel pretty confident suggesting that consuming a diet rich in antioxidants is a good idea, and that high-dose antioxidant supplementation (particularly with vitamin C and E) is generally inadvisable based on the lack of meaningful benefit and small risk of detriment. Any enthusiastic calls for the avoidance of high-dose vitamin C and E supplements are probably more forceful than the evidence warrants, but in my opinion, the potential upside is too limited to justify the gamble. The justification for using polyphenols and other phytonutrients with antioxidant properties is a bit more compelling, with some degree of evidence supporting enhancements in blood flow, performance, and recovery, with limited reason to believe that impairment of training adaptations is likely. See well written article.

"Antioxidants blunt muscle hypertrophy?


Great article, thank you @Joseph_Lavelle . I’m embarrassed that I didn’t find it in my searching. I’m (appropriately) responding to this in between my deadlifts so I apologize for the disjuncture response.

So as far as I read the article (since my listening comprehension has recently been called into question): studies are mixed, but younger athletes see negative impact and older athletes may see positive impact. So in general, given there may be positive longevity and other healthspan impacts, some antioxidant supplementation appears positive.

“ Generally speaking, high-dose supplementation with vitamin C or E doesn’t seem to be an advisable strategy. It doesn’t appear to consistently lead to any particularly terrible outcomes in terms of performance, recovery, or training adaptations, but the evidence suggesting meaningful benefits from high-dose supplementation with vitamin C or E is weak, and there is at least some evidence pointing toward a modest impairment of select training adaptations. Conversely, the story for polyphenols and other phytonutrients with antioxidant properties is a bit more promising.”

From the article:

(Vitamin C in lowish dowses seems to do nothing to exercise)
“ Of the eight human studies, vitamin C dosages ranged from 0.2g/day to 1.5g/day, and the duration of supplementation ranged from a single dose to 16 weeks. While the exact performance outcomes ranged significantly, they utilized endurance exercise modalities (running and cycling) across a variety of exercise intensities. None of the studies reported statistically significant effects in any direction; four of the studies reported small, non-significant impairments, while the other four reported small, non-significant improvements. ”

(NAC seems to positively impact athletic performance)
Multiple studies have shown that infusion of N-acetylcysteine enhances skeletal muscle function and endurance performance. For example, twoseparate infusion studies found N-acetylcysteine infusion to significantly improve cycling time to exhaustion at an intensity of 92% of VO2max. In contrast, a separate infusion study found no improvement in time to exhaustion at 130% of VO2max, using an experimental protocol resembling high-intensity interval exercise. These results cannot necessarily be used to make inferences about the effects of oral supplementation, but a few studies evaluating the performance effects of oral N-acetylcysteine supplementation are available. One studyfound that 1800mg/day for four days enhanced submaximal knee extensor endurance, and another studyfound that 150mg/kg enhanced submaximal handgrip strength endurance. A third study evaluated the effects of 1200mg/day for nine days, with results showing an improvement in repeated sprint performance during a simulated race on a cycle ergometer.”

(Antioxidant impact on mitochondrial biogenesis appears mixed)
“ Collectively, these studies have indicated that pre-exercise antioxidant supplementation does interfere with signaling pathways related to mitochondrial biogenesis, which is a key adaptation by which training enhances endurance capacity. While this would seem to pretty conclusively extinguish any existing optimism regarding antioxidant supplementation, the matter isn’t quite that simple. Despite the evidence showing an impairment in various signaling pathways, the evidence directly assessing training-induced changes in mitochondrial biogenesis is mixed; some studies report impairment, whereas others report no effect of antioxidants. While it may seem a bit paradoxical that the relationship between impaired signaling and impaired mitochondrial biogenesis is a bit tenuous, this lack of a consistent effect matches the results we’ve seen for the ultimate outcomes: aerobic capacity, and performance on endurance tasks. When it comes to endurance training adaptations, there doesn’t appear to be a consistent negative impact in trials lasting multiple weeks.”

(Muscle hypertrophic impact is mixed)
“ a recent meta-analysis summarizing the available literature provided minimal reason for concern, as vitamin C and E supplementation resulted in an effect size for muscle strength that actually favored the antioxidant group in comparison to placebo (effect size = 0.15, which was not statistically significant). That same meta-analysissummarized the available studies evaluating the effects of antioxidant supplementation on hypertrophy in response to resistance training; for a long-form discussion on its findings, Greg and I discussed some preliminary thoughts on the paper on the Stronger By Science Podcast shortly after its publication. The meta-analysis found that vitamin C or E supplementation did not significantly impact lean mass gains in response to resistance training. However, as Greg noted, not all of the studies included in the analysis are equally informative.”


“ Acutely, antioxidant supplementation interfered with anabolic signaling, but also reduced total ubiquitination levels (which are associated with protein degradation), with no significant impact on muscle protein fractional synthetic rate. Antioxidants did not significantly alter changes in lean mass, whole muscle cross-sectional area, or muscle fiber cross-sectional area. The study also reported a handful of strength-related outcomes; the placebo group improved biceps curl strength significantly more than the antioxidant group (+17.1 ± 17.0% versus +7.6 ± 5.0%), with non-significant results reported for the rest of the strength outcomes. While the placebo group tended to have slightly (and non-significantly) better gains than the antioxidant group, the overall differences were not large enough or consistent enough to get particularly concerned over.”

(Young athletes may have negative impact of antioxidants but older subjects may have positive impacts)
“ Taken together, the evidence linking antioxidant supplementation to impaired muscle growth is characterized by a small body of inconsistent findings. It would seem premature to conclude that antioxidant supplementation unequivocally and substantially impairs hypertrophy or strength gains. However, it’s also worth noting that the results, despite being modest in magnitude and relatively inconsistent, generally tend to show either no effect, or a negative effect, of high-dose supplementation with vitamins C and E. As noted in a very recent review by Ismaeel et al, the studies that do tend to report modest impairments related to muscle growth tend to be carried out in younger subjects, whereas the limited number of studies using older subjects (generally above 60 years of age) tend to show either no effect or a modest beneficial effect of vitamin C and E supplementation.”

As an aside (from the article) it seems that cocoa might be an interesting addition to creatine and beta-alanine for exercise.

“ supplementation. For example, a single dose of high-flavonol cocoa (701mg) significantly increased flow-mediated vasodilation and altered the blood pressure response to exercise in comparison to a low-flavonol cocoa (22mg) in overweight and obese individuals. “

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