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VITAMINS & SUPPLEMENTS · GUIDE

Antioxidants Beyond Neutralizing Free Radicals: Signaling and Hormesis

Free radicals are not only harmful: the body also uses them as signals. What that means for antioxidant supplements, hormesis, and training adaptation, and what small trials found.

Content last updated . This page has not been medically reviewed.

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Quick answer
"Antioxidant" describes what a chemical can do in a test tube: interact with and neutralize free radicals. [1] It does not tell you what a pill does inside a person. The National Cancer Institute (NCI) says free radicals are formed naturally and play an important role in many normal cell processes. [1] The NIH National Center for Complementary and Integrative Health (NCCIH) adds that larger-than-usual amounts of antioxidants may not always be beneficial and may interfere with defense mechanisms and normal signaling in the cell. [2]

This page explains that idea, what "hormesis" means, and what a handful of small exercise trials found. It does not tell anyone what to take.

Signaling: why the body keeps some free radicals

The NCCIH describes oxidative stress as overproduction of reactive oxygen-containing substances, and says the body has preventive and repair systems, with antioxidant enzymes being the most important part of that defense. [2] A 2021 review in Nature Reviews Drug Discovery describes how antioxidant defenses can be raised through physiological signaling and dietary components, and notes that antioxidants that looked useful in preclinical studies have given disappointing clinical trial results. [3]

Hormesis in plain words

Hormesis is the general idea that a small, manageable stress can trigger a protective response. One 2011 review (written by a researcher who has published trials in this area) uses the term "mitohormesis": it proposes that a rise in reactive oxygen species from the mitochondria (the cell's energy units) acts as a signal that switches on the body's own defenses. [4] That review also argues that antioxidant supplements which block these signals could interfere with benefits of exercise and calorie restriction. [4] This is a hypothesis built mostly from animal and cell work plus a few human studies. Label: preclinical, with limited human data.

What the human exercise studies found

All of the studies below used vitamins C and E together or polyphenols. None tested food, and none can be applied to other antioxidants.
5 findings · 3 supported · 1 mixed · 1 limited or unclearThe colour follows the evidence label on each card.

  1. Ristow et al., 2009 [5]

    Promising but limited (small trial; insulin sensitivity and markers, not disease)

    Insulin sensitivity and some gene-activity markers rose with exercise only in men not taking the vitamins

    Who and what: 39 healthy young men, 4 weeks of exercise; study amounts of 1,000 mg vitamin C plus 400 IU vitamin E a day

  2. Bjornsen et al., 2016 [6]

    Promising but limited

    Lean mass gain was smaller with the vitamins; strength (one-repetition maximum) improved in both groups

    Who and what: 34 men aged 60 to 81, 12 weeks of strength training; study amounts of 500 mg vitamin C and 117.5 mg vitamin E around training

  3. Study of bone density, 2017 [7]

    Promising but limited

    Hip bone density rose in the placebo group; the authors said high doses may constrain bone benefits

    Who and what: 33 men, 12 weeks of strength training; study amounts of 1,000 mg vitamin C plus 235 mg vitamin E a day

  4. Review of muscle soreness [8]

    Insufficient evidence

    Soreness was lower at all time points in only 3 of 14 studies

    Who and what: 14 trials, 280 healthy people aged 16 to 30; vitamin C and/or E

  5. Meta-analysis of polyphenols [9]

    Mixed

    No effect on strength, peak power or VO2max; better exercise capacity; resveratrol may have impaired adaptation in two studies (not statistically significant)

    Who and what: 22 trials, 2 or more weeks of supervised training

"Study amounts" are what researchers gave volunteers. They are not recommendations.

Frequently asked questions

Are free radicals always bad?

No. The NCI says free radicals are formed naturally and play an important role in many normal cellular processes, though at high concentrations they can damage cells. [1]

What is hormesis?

It is the idea that a mild stress can switch on protective responses. One review applies it to the mitochondria and calls it mitohormesis. [4] It is not proven to apply to antioxidant pills in everyday life.

Do antioxidant supplements blunt the benefits of exercise?

Some small trials of vitamin C plus E found smaller gains in insulin sensitivity, lean mass or bone density, while others, such as the soreness review, found little effect either way. [5][6][7][8] The evidence is mixed and limited to those vitamins.

Does eating fruit and vegetables have the same effect?

The sources we read did not test that. NCCIH says people who eat more fruits and vegetables have lower risks of chronic disease, but that this may be due to other substances in the foods or to lifestyle. [2]

Should I stop my supplement because of this page?

This page cannot answer that. Do not stop a prescribed medicine. For any supplement, ask a clinician or pharmacist who knows your health and medicines.

More details: evidence, limits and cautions

The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.

How to read the evidence labels

Labels used on this page: promising but limited, mixed, insufficient evidence, preclinical. For the basics see Antioxidants Explained and What Are Free Radicals and Reactive Oxygen Species?.

Limits and uncertainty
  • The trials are small and short, and most enrolled men. Blood or gene-activity changes are not the same as long-term health outcomes.
  • Results for vitamins C and E in these trials do not transfer to other antioxidants, other forms, or to antioxidant-rich foods. NCCIH notes that purified antioxidants and the high doses in supplements may act differently than the smaller amounts in foods. [2]
  • The sources we read do not show that normal amounts from food interfere with training. Proper evidence not found on that question; we searched PubMed reviews on vitamin C and E, polyphenols and training adaptation.
  • A large body of evidence does not yet settle whether signaling effects matter for health in people. Hormesis is a working idea, not a proven reason to avoid or to take any supplement.
Safety and who should ask first
Antioxidant supplements can interact with medicines and some cause harm at high doses; NCCIH says they are not necessarily safe. [2] If you are pregnant or nursing, giving a child a supplement, taking medicines, living with kidney or liver conditions, or facing surgery or cancer treatment, talk to a clinician or pharmacist first. [2] See Antioxidants and Exercise, Recovery After Exercise, Medication Interactions and Quality Testing and Certifications.
References
  1. National Cancer Institute, Antioxidants and Cancer Prevention. Read 2026-10-23.
  2. NCCIH, Antioxidant Supplements: What You Need To Know (last updated July 2023). Read 2026-10-23.
  3. Forman and Zhang, Targeting oxidative stress in disease: promise and limitations of antioxidant therapy (Nat Rev Drug Discov 2021). Read 2026-10-23.
  4. Ristow and Schmeisser, Extending life span by increasing oxidative stress (Free Radic Biol Med 2011). Read 2026-10-23.
  5. Ristow et al., Antioxidants prevent health-promoting effects of physical exercise in humans (PNAS 2009). Read 2026-10-23.
  6. Bjornsen et al., Vitamin C and E supplementation blunts increases in total lean body mass in elderly men after strength training (Scand J Med Sci Sports 2016). Read 2026-10-23.
  7. Vitamin C plus E and strength training-induced areal bone mineral density in elderly men (Eur J Appl Physiol 2017). Read 2026-10-23.
  8. Supplementation with vitamins C and E and exercise-induced delayed-onset muscle soreness: a systematic review (Antioxidants 2021). Read 2026-10-23.
  9. The effect of dietary (poly)phenols on exercise-induced physiological adaptations: a systematic review and meta-analysis (Crit Rev Food Sci Nutr 2022). Read 2026-10-23.
Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.