When Antioxidants Backfire

When Antioxidants Backfire

The free radicals from exercise are not the enemy — they are the adaptation signal, and new ISSN evidence shows high-dose antioxidants can shut it down.

The Paradox Nobody Talks About

The muscle soreness, the fatigue, the oxidative stress your body generates during a hard training session — those are not just damage. They are the signal that tells your muscles to adapt.

A 2026 position stand from the International Society of Sports Nutrition (ISSN) [1] makes this case in detail across a comprehensive review of the evidence on dietary antioxidants in exercise and sport. The central message is simple: the reactive oxygen species (ROS) and reactive nitrogen species (RNS) that exercise produces are not purely harmful. At moderate levels, they trigger a cascade of beneficial adaptations — stronger endogenous antioxidant defenses, mitochondrial biogenesis, improved cellular repair.

This follows a pattern biologists call hormesis: a dose-dependent response that traces an inverted-U curve. Too little stress — a sedentary lifestyle — produces insufficient ROS to trigger any adaptive signal. Moderate stress — a well-designed training programme with adequate recovery — lands in the sweet spot where ROS and RNS act as molecular messengers, telling cells to build more mitochondria, upregulate endogenous antioxidant enzymes, and repair stronger than before. Excessive stress — overtraining, chronic under-fuelling, inadequate sleep — overwhelms the body's repair capacity, tipping from productive eustress into damaging distress.

This is where the hormesis model becomes practically important: Let's say you are training at the right intensity with adequate recovery, the oxidative stress you generate sits in the middle of that inverted-U curve — the sweet spot where ROS and RNS drive adaptation. If you were to take high-dose antioxidant supplements, they would chemically neutralise the ROS and RNS from training, before those molecules can deliver their signalling role. The effect is like sliding yourself back toward the left side of the curve — the "too little stress" zone — even though you did the work to be in the middle. Your muscles experienced the load, but the chemical signal that tells them to adapt has been dampened. You pay the cost of training without collecting the full return.

The Evidence That High-Dose Supplements Can Blunt Training Gains

The strongest evidence for this "backfire" effect comes from vitamins C and E — the two antioxidants most people associate with the term. The ISSN review notes that despite being FDA-recognised dietary antioxidants, the data for their use in sport show overwhelmingly mixed or limited performance benefits [1].

The most striking finding comes from Ristow et al. (2009) [2], who gave 39 untrained healthy young men 400 IU/day of vitamin E and 1000 mg/day of vitamin C for four weeks during an exercise programme. The supplemented group showed blunted induction of PGC-1α — a key regulator of mitochondrial biogenesis — along with reduced upregulation of endogenous antioxidant enzymes. In other words, the supplements prevented the body from building its own defences in response to training.

This is not an isolated result. A review of ten investigations on vitamins E and C during chronic exercise by Nikolaidis et al. (2012) [3] found that only two showed an ergogenic (performance-enhancing) effect, two showed an ergolytic (performance-impairing) effect, and six showed no effect at all. The overall picture is that at doses substantially above the Recommended Daily Allowance, these vitamins are more likely to interfere with adaptation than to help it.

An important nuance: this does not mean vitamins C and E are harmful in general. Athletes eating a balanced diet will naturally consume these nutrients from food sources, and that appears to be fine — even beneficial. The concern is specifically with isolated, high-dose supplementation that pushes intake well beyond what food provides.

When Antioxidant Support Does Make Sense

If the story ended there, the message would be simple: skip the supplements. But biology is not that neat. The ISSN position stand identifies specific scenarios where antioxidant supplementation appears beneficial — primarily when the goal shifts from long-term adaptation to short-term recovery.

During planned overreaching phases, back-to-back competition days, or periods of elevated environmental stress (altitude training, air pollution), oxidative stress can tip from productive eustress into damaging distress. In these windows, targeted antioxidant support may help an athlete recover faster and prepare for the next effort without meaningfully blunting the adaptive process. The key word is targeted — context-specific rather than year-round.

Supplementation also makes sense when correcting an actual nutrient deficiency. Paschalis et al. (2018) [4] found that N-acetylcysteine (NAC) improved aerobic and anaerobic performance by 11–15% in individuals with low baseline glutathione levels, while doing nothing for those with adequate levels. The implication is that some athletes may benefit substantially from supplementation — but only if they are starting from a deficit.

There is also a broader point about individual variability. Not everyone's body responds to the same exercise with the same amount of oxidative stress. Margaritelis et al. (2014) [5] tested 98 young males performing the same muscle-damaging eccentric exercise protocol and measured their oxidative stress markers afterward. More than one in three showed minimal or no increase in oxidative stress at all — and some actually showed a shift in the opposite direction, toward an excess of antioxidant activity relative to the stress produced. If an athlete is already generating little oxidative stress from a given workout, adding an antioxidant supplement on top of that has no upside — there is nothing to neutralise — and may further suppress the already-weak adaptive signal. This is why the ISSN emphasises that a person's redox status and baseline antioxidant capacity matter more than any one-size-fits-all dosing recommendation.

The Four Antioxidants With the Strongest Evidence

The ISSN review evaluated 24 dietary antioxidants and rated them by the strength of evidence for both performance and antioxidant effects. The results are sobering: most fall into the weak or low-evidence category. Only four emerged with moderate-to-high support, and notably, none of them appear to interfere with training adaptations at the doses studied [1].

Creatine monohydrate is not traditionally thought of as an antioxidant, but the review highlights emerging evidence for indirect antioxidant and anti-inflammatory properties. Beyond its well-established role in performance, creatine supplementation has been associated with increased antioxidant enzyme activity and reduced post-exercise levels of pro-inflammatory markers like TNF-α. Santos et al. (2004) [6] reported that creatine supplementation (20 g/day for 5 days) attenuated changes in PGE2 and TNF-α among runners, while placebo recipients showed substantial increases in both markers. Its performance evidence is rated high; its antioxidant evidence is rated weak-to-moderate, suggesting the antioxidant benefit is a bonus rather than the primary reason to use it [1].

Omega-3 fatty acids (EPA and DHA) have moderate evidence for both performance and antioxidant outcomes. They activate the Nrf2 pathway — a master regulator of the body's own antioxidant defence system — and have been shown to reduce markers of inflammation and muscle damage after exercise. A meta-analysis by Heshmati et al. (2019) [7], covering 39 trials with over 28,000 participants, found improvements in total antioxidant capacity and glutathione peroxidase activity along with reductions in malondialdehyde, a marker of lipid peroxidation. The ISSN notes that at least 1000 mg/day of combined EPA and DHA, taken for 6–12 weeks, is the threshold where antioxidative effects consistently appear [1].

Tart cherry, consumed as juice concentrate or powder, is rich in anthocyanins and polyphenols. Its performance evidence is rated moderate-to-high, driven largely by its effectiveness in reducing delayed onset muscle soreness (DOMS) and improving endurance performance metrics. A meta-analysis by Gao and Chilibeck (2020) [8] found that consuming tart cherry for 7 days before and up to 1.5 hours before endurance exercise improved time trials, time to exhaustion, and total work performed.

Astaxanthin, a lipid-soluble carotenoid, has a unique molecular structure that allows it to span the entire cell membrane, neutralising free radicals both inside and outside the lipid bilayer. Djordjevic et al. (2012) [9] found that elite soccer players who ingested 4 mg/day of astaxanthin for 90 days showed a blunted increase in post-exercise creatine kinase compared to placebo, while Baralic et al. (2013) [10] reported increased antioxidant enzyme activity in the same population. Like tart cherry, astaxanthin appears to enhance recovery without impairing adaptation [1].

The Bigger Picture

The thread running through the entire ISSN review is that the body's first line of antioxidant defence is not something you buy — it is something you build. Regular endurance training alone increases the activity of superoxide dismutase (one of the body's key antioxidant enzymes) by 20–112% and glutathione peroxidase by 20–177% [1]. In other words, consistent training makes the body progressively better at handling its own oxidative stress. On top of that foundation, the ISSN advocates what they call a "food-forward" approach: whole foods rich in flavonoids, polyphenols, carotenoids, vitamins, and minerals deliver antioxidants in the complex matrix that the body evolved to absorb, without the risks of isolated high-dose compounds. Supplements, in this framework, are not the baseline — they are a targeted tool for filling specific gaps when diet or circumstances fall short.

The position stand also covers special considerations for masters athletes, tactical/occupational populations, sex-based differences in redox biology, and the role of antioxidants in traumatic brain injury — all of which warrant their own treatment and which we may cover in future articles.

What stands out from the review is how much the answer to "should I take an antioxidant supplement?" depends on context: what phase of training you are in, what your baseline nutritional status looks like, what your specific goal is (recovery versus adaptation), and even your individual redox response to exercise. The era of blanket recommendations — take vitamin C because it is good for you — is giving way to something more nuanced, more individual, and ultimately more honest about what the science does and does not yet know.

References

  1. Gonzalez DE, Dickerson BL, Roberts BM et al. "International Society of Sports Nutrition position stand: effects of dietary antioxidants on exercise and sports performance", Journal of the International Society of Sports Nutrition 23 (2026) 2629828. doi.org/10.1080/15502783.2026.2629828
  2. Ristow M, Zarse K, Oberbach A et al. "Antioxidants prevent health-promoting effects of physical exercise in humans", Proceedings of the National Academy of Sciences 106 (2009) 8665–8670. doi.org/10.1073/pnas.0903485106
  3. Nikolaidis MG, Kerksick CM, Lamprecht M et al. "Does vitamin C and E supplementation impair the favorable adaptations of regular exercise?", Oxidative Medicine and Cellular Longevity 2012 (2012) 707941. doi.org/10.1155/2012/707941
  4. Paschalis V, Theodorou AA, Margaritelis NV et al. "N-acetylcysteine supplementation increases exercise performance and reduces oxidative stress only in individuals with low levels of glutathione", Free Radical Biology and Medicine 115 (2018) 288–297. doi.org/10.1016/j.freeradbiomed.2017.12.007
  5. Margaritelis NV, Kyparos A, Paschalis V et al. "Reductive stress after exercise: the issue of redox individuality", Redox Biology 2 (2014) 520–528. doi.org/10.1016/j.redox.2014.02.003
  6. Santos RV, Bassit RA, Caperuto EC et al. "The effect of creatine supplementation upon inflammatory and muscle soreness markers after a 30km race", Life Sciences 75 (2004) 1917–1924. doi.org/10.1016/j.lfs.2003.11.036
  7. Heshmati J, Morvaridzadeh M, Maroufizadeh S et al. "Omega-3 fatty acids supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials", Pharmacological Research 149 (2019) 104462. doi.org/10.1016/j.phrs.2019.104462
  8. Gao R, Chilibeck PD. "Effect of tart cherry concentrate on endurance exercise performance: a meta-analysis", Journal of the American College of Nutrition 39 (2020) 657–664. doi.org/10.1080/07315724.2020.1713246
  9. Djordjevic B, Baralic I, Kotur-Stevuljevic J et al. "Effect of astaxanthin supplementation on muscle damage and oxidative stress markers in elite young soccer players", Journal of Sports Medicine and Physical Fitness 52 (2012) 382–392.
  10. Baralic I, Djordjevic B, Dikic N et al. "Effect of astaxanthin supplementation on paraoxonase 1 activities and oxidative stress status in young soccer players", Phytotherapy Research 27 (2013) 1536–1542. doi.org/10.1002/ptr.4898