Selenium supplementation and male fertility: Mechanistic insights and therapeutic potential

To comprehensively review the role of selenium (Se) in male reproductive health, placing this review above the previous reviews synthesizing selenium forms, mechanistic pathways, and actionable supplementation/monitoring strategies in clinical settings,focusing on its biochemical forms, antioxidant functions, and effects on sperm parameters, fertility outcomes, and interactions with other micronutrients.

A literature review was conducted using PubMed, Scopus, and Web of Science (2000-2025) to identify studies examining Se metabolism, selenoprotein activity (GPx1/4 and SELENOP), dose-response relationships, and co-supplementation with vitamin E and zinc. Data pertaining to selenium (Se) forms, modulation of antioxidant enzymes (such as superoxide dismutase and catalase), markers of oxidative stress (including malondialdehyde and reactive oxygen species), sperm function, hormone synthesis, and toxicity thresholds were collected and synthesized.

Organic selenium (Se) demonstrated superior bioavailability and enhanced GPx4 and SELENOP activity, thereby reducing lipid peroxidation in germ cells. Animal research has found that dietary Se in the best concentrations (0.25-0.35 mg Se/kg in breeder roosters; 0.5-1.0 mg/kg in other models) maximizes the process of spermatogenesis, and elemental nano-selenium has the best effects relative to sodium selenite and seleno-yeast, whereas Se deficiency induces cell apoptosis via the PI3K/AKT pathway. Human trials revealed that a daily intake of 100 µg Se improved sperm motility (p = 0.023) and resulted in an 11 % increase in paternity. Se supplementation at concentrations of 2-5 μg/ml enhanced sperm viability; however, excessive intake of > 300 µg/day impaired motility. Co-supplementation with vitamin E or zinc further enhanced the antioxidant defense.

Selenium plays a crucial role in male reproductive health through its dose-dependent antioxidant and endocrine function. Structured clinical trials are essential to determine the optimal form, dosage, and combination of selenium with other micronutrients to enhance fertility while mitigating the risk of U-shaped toxicity.