Selenium supplementation and male fertility: Mechanistic insights and therapeutic potential.

Organic selenium demonstrated superior bioavailability and enhanced GPx4 and SELENOP activity, thereby reducing lipid peroxidation in germ cells.

• Organic selenium forms showed enhanced activity of glutathione peroxidase 4 (GPx4) and selenoprotein P (SELENOP) compared to inorganic forms.
• The reduction in lipid peroxidation was specifically noted in germ cells.
• Literature reviewed spanned 2000–2025 using PubMed, Scopus, and Web of Science.

Optimal dietary selenium concentrations in animal models maximize spermatogenesis, with elemental nano-selenium showing the best effects relative to sodium selenite and seleno-yeast.

• Optimal concentrations were found to be 0.25–0.35 mg Se/kg in breeder roosters and 0.5–1.0 mg/kg in other animal models.
• Elemental nano-selenium was found superior to both sodium selenite and seleno-yeast in animal research.
• These findings were derived from animal research studies identified in the literature review.

Selenium deficiency induces cell apoptosis via the PI3K/AKT pathway.

• The PI3K/AKT signaling pathway was identified as the mechanistic route through which selenium deficiency triggers apoptosis.
• This apoptotic effect was relevant to germ cells and spermatogenesis.
• This finding was synthesized from the reviewed literature (2000–2025).

Human trials revealed that a daily intake of 100 µg selenium improved sperm motility and resulted in an 11% increase in paternity.

• Improvement in sperm motility was statistically significant (p = 0.023).
• Paternity rate increased by 11% with selenium supplementation at 100 µg/day.
• These results were drawn from human clinical trials identified in the systematic literature review.

Selenium supplementation at concentrations of 2–5 µg/ml enhanced sperm viability, but excessive intake above 300 µg/day impaired motility.

• In vitro or supplementation concentrations of 2–5 µg/ml were associated with enhanced sperm viability.
• Intake exceeding 300 µg/day was associated with impaired sperm motility, demonstrating a U-shaped dose-response relationship.
• This toxicity threshold highlights the narrow therapeutic window for selenium supplementation.

Co-supplementation of selenium with vitamin E or zinc further enhanced antioxidant defense in the context of male fertility.

• Both vitamin E and zinc were identified as micronutrients that synergistically improved antioxidant outcomes when combined with selenium.
• The review specifically examined dose-response relationships and co-supplementation with vitamin E and zinc.
• Markers assessed included superoxide dismutase, catalase, malondialdehyde, and reactive oxygen species.

Structured clinical trials are needed to determine the optimal form, dosage, and combination of selenium with other micronutrients to enhance fertility while mitigating U-shaped toxicity risk.

• The review identified a gap in current evidence regarding optimal selenium form (organic vs. inorganic vs. nano-selenium) for human supplementation.
• The U-shaped toxicity profile of selenium necessitates careful dosage determination in clinical settings.
• Monitoring strategies in clinical settings were identified as a key area requiring further research.