Administration of Antioxidants in the Infertile Male: When it may have a Beneficial Effect?

Background: Reactive Oxygen Species (ROS) are required for intact spermatogenesis and sperm function, but excessive levels will cause oxidative stress, impairing sperms and sperm function due to membrane damage and DNA fragmentation. Objective: Theoretically, antioxidant supplementation may act as a protection system against free radicals. Since infertile males have higher levels of ROS, nutritional supplements are widely used for protecting sperms. In the recent review, the authors summarize the most recent data regarding the effect of antioxidant treatment and draw the attention of the limitations of antioxidant use in male infertility. Methods: The recent review gives an update of antioxidant treatment in male infertility. Results: Improvement of sperm parameters was reported in the majority of studies. Comparing different antioxidants versus placebo showed low certainty of evidence with a serious risk of bias, and there is a lack regarding certain doses, pregnancy rate, and live birth rate outcomes. Various clinical studies and randomized control trials reported negative outcomes. Conflicting findings lead the attention to the study of biochemical features of the oxidant vs. antioxidant equilibrium. Higher exposure to antioxidants will result in “reductive stress”, which has harmful effects on sperm function, moreover can negatively influence embryo development. Reductive stress is as dangerous as oxidative stress and may act as a cause of different human pathologies. Conclusion: An intact balance of oxidant and antioxidant systems is required for normal sperm function. No guideline exists for the antioxidant dose regimen and treatment duration. Overdosing can result in reductive stress, which is also harmful to fertility and can cause several diseases. Assessment of the pre-treatment redox status can be recommended before the administration of exogenous antioxidants.