Vitamin D supplementation in infertile men: a systematic review and meta-analysis of effects on semen quality and endocrine function

Vitamin D boosted sperm motility by 6.96% and testosterone slightly, but had no measurable effect on pregnancy or live birth rates (n=1,168)

Journal: PeerJ | Published: 2026-04-13 | Type: Systematic Review, Meta-Analysis | PMID: 42004696 Authors: Zhang Guoqing, Nelli Giribabu, Hoe See Ziau, Hamdan Mukhri (Universiti Malaya, Kuala Lumpur) Funding/COI: Funding not reported. Giribabu is an editorial board member of PeerJ but was excluded from the peer review decision for this manuscript.

Summary

Eleven studies (eight RCTs, three observational; n=1,168) found that oral vitamin D supplementation produces small but statistically significant improvements in semen volume, sperm concentration, progressive motility, and testosterone in infertile men. The catch: none of that translated into clinical pregnancy or live birth rates in the two trials that actually measured them. Whether lab-level sperm improvements mean anything for real-world fertility remains unanswered.

Claims

• Semen volume improved by +0.36 mL
• Sperm concentration increased by +3.74 ×10⁶/mL
• Progressive sperm motility improved by +6.96% — the authors note this exceeds their proposed minimum clinically important difference (MCID), which they describe as predictive of higher natural pregnancy rates
• Serum testosterone increased by +0.28 nmol/L
• LH declined marginally by −0.15 IU/L
• Normal sperm morphology showed a statistically significant decline of −0.69%, but one study (Blomberg Jensen et al., 2018) contributed 98.2% of the pooled weight for that outcome and had substantial baseline imbalances between groups
• No significant effect on clinical pregnancy rate or live birth rate
• Higher doses (>4,000 IU/day) showed no additional benefit over standard doses

Study Quality

This is a pre-registered (PROSPERO: CRD420251017427), PRISMA 2020-compliant meta-analysis drawing from five databases and using validated risk-of-bias tools (RoB 2.0 for RCTs, ROBINS-I for observational studies). Subgroup and sensitivity analyses were conducted, including stratification by dose, duration (≤3 months vs. 5–6 months), and baseline vitamin D status. The 5–6 month follow-up window is biologically appropriate given human spermatogenesis requires roughly 64–74 days.

Eleven studies and 1,168 participants is a thin evidence base. Heterogeneity across included studies was substantial and not fully resolved by subgroup analyses, and the authors did not conduct a formal GRADE assessment. Several trials co-administered calcium alongside vitamin D, complicating attribution of observed effects to vitamin D alone.

Red Flags

• Only 2 of 11 studies reported clinical pregnancy rates — the outcome that actually matters for infertile men
• No GRADE certainty-of-evidence assessment conducted
• High heterogeneity not resolved by subgroup analyses
• Multiple trials co-supplemented with calcium, confounding the vitamin D signal; the authors acknowledge this but sensitivity analysis couldn't fix it
• Gheflati et al. (2021) excluded from several sensitivity analyses due to small sample size (n=22 intervention arm) and outlier-level effects — its influence is disproportionate and incompletely characterized
• The −0.69% morphology decline is almost entirely an artifact of one study's baseline imbalance; it appeared in the abstract before the caveats arrived
• Most included trials had no predefined adverse event monitoring, making the reported absence of serious adverse events uninterpretable
• Funding source for the meta-analysis itself is not disclosed

Strengths

• First meta-analysis to simultaneously examine semen parameters, reproductive hormones, and fertility outcomes for vitamin D in infertile men
• Five-database search screening 20,888 records; PROSPERO-registered before data collection
• Biologically appropriate follow-up windows aligned with spermatogenesis timeline
• Authors correctly distinguish statistical significance from clinical relevance in their conclusions, stating deficiency-unconfirmed supplementation has "limited evidence of benefit"
• Sensitivity analyses included removal of high-influence outlier studies

Verdict

The sperm metrics moved; the pregnancies didn't. That gap is the paper's most important finding, and credit to the authors for stating it plainly rather than overselling. The meta-analysis is competently assembled within its constraints — pre-registration, proper bias tools, multiple sensitivity analyses — but two pregnancy endpoints across eleven studies is too thin a foundation for clinical inference. The heterogeneity problem is acknowledged but unsolved, calcium co-supplementation muddies the mechanism, and Gheflati et al. is doing enough work across pooled analyses to matter more than its n=22 deserves. Worth reading for the motility and testosterone data; treat the sperm morphology finding as noise.