Routine empirical antioxidant supplementation for male infertility is difficult to justify given non-converging and largely null trial evidence, but this does not establish universal inefficacy; future trials should test which biologically defined (redox-phenotyped) men, if any, benefit from which intervention.
The 2025 WHO infertility guideline made no recommendation for or against antioxidant supplementation in men with infertility and abnormal semen parameters.
The Cochrane review evidence base on antioxidants for male infertility is large but provides very low-certainty evidence for live birth.
The MOXI trial found no benefit of a multicomponent antioxidant formulation on semen or reproductive outcomes.
The FAZST trial found no benefit of folic acid and zinc and an increase in sperm DNA fragmentation.
The SUMMER trial found no improvement in ongoing pregnancy with a combined antioxidant supplement.
Contemporary trial results make routine empirical antioxidant supplementation difficult to justify but do not establish that redox-modulating interventions are universally ineffective.
Most trials enrolled men by clinical infertility or semen criteria rather than a prospectively defined, standardized redox phenotype and rarely tested treatment effect modification.
Several factors may dilute true treatment effects in antioxidant trials.
The authors propose that future trials move from empirical supplementation to phenotype-directed therapy.
This review looks at whether antioxidant supplements help men who have fertility problems. The idea is reasonable: oxidative stress can damage sperm, and antioxidants might counter it. But after decades of research, studies have not shown a consistent benefit for outcomes that matter most, such as pregnancy and live birth. A large Cochrane review covered 90 trials with over 10,000 men, but only 12 reported live births, and the certainty of that evidence was very low. The 2025 WHO guideline made no recommendation for or against antioxidants. Recent large randomized trials did not help much. The MOXI trial found no improvement in semen quality, sperm DNA damage, pregnancy, or live birth. The FAZST trial found no benefit of folic acid and zinc, and sperm DNA fragmentation actually rose. The SUMMER trial found no improvement in ongoing pregnancy. This research suggests that taking antioxidants routinely, without a clear reason, is hard to justify. The authors caution that this does not prove antioxidants never work. Most trials enrolled men based on general infertility or semen test results, not on whether they actually had a measured oxidative stress problem, so any benefit in a specific subgroup could be hidden. The authors call for future trials that identify men by standardized oxidative-stress profiles, confirm that the treatment hits its biological target, test whether benefit differs by profile, and measure real outcomes like live birth.
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Upload Your LabsZafar M, Qu M. (2026). Antioxidants in male infertility: from empirical supplementation to phenotype directed therapy.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1971018