Effects of Vitamin D Supplementation on Semen Quality, Reproductive Hormones, and Live Birth Rate: A Randomized Clinical Trial
What this study found
Vitamin D plus calcium did not improve the main fertility outcomes in infertile vitamin D-insufficient men. At day 150, 25-OHD increased to 89 nmol/L versus 51 nmol/L with placebo, and inhibin B was higher (169 vs 154 pg/mL), but total sperm count, sperm concentration, motility, morphology, and overall live-birth outcomes were not improved. A subgroup signal suggested higher live-birth rates in men with oligozoospermia (35.6% vs 18.3%), but this finding was exploratory and not definitive.
- Study & population
- Randomized 1:1, placebo-controlled clinical trial conducted at a single center in Copenhagen, Denmark.
- Intervention
- Participants received an initial oral dose of 300,000 IU cholecalciferol, followed by cholecalciferol 1400 IU plus calcium 500 mg once daily for 150 days.
- Key limitation
- Single-center trial with a modest sample size and a 150-day follow-up limits power to detect clinical fertility effects.
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Open PDFOriginal abstract
Context Results of animal models and cross-sectional cohort studies have suggested a beneficial role for vitamin D in male reproduction. Objective Determine the effect of vitamin D and calcium supplementation on semen quality in infertile men with serum 25-hydroxyvitamin-D (25OHD) levels ≤50 nmol/L. Design A single-center, triple-blinded, randomized clinical trial. Participants A total of 1427 infertile men were screened to include 330; 1002 men did not meet inclusion criteria and 95 did not wish to participate. Intervention The active group received cholecalciferol 300,000 IU initially, then 1400 IU cholecalciferol and 500 mg of calcium daily for 150 days; the other group received placebo. Results Serum concentrations of 25OHD and 1,25-dihydroxyvitamin D3 were significantly higher in men in the treatment group compared with the placebo group. Vitamin D supplementation was not associated with changes in semen parameters, although spontaneous pregnancies tended to be higher in couples in which the man was in the treatment group [7.3% vs 2.4%, Δ5.0% (-0.6%; 10.5%)]. Vitamin D treatment in a subgroup of oligozoospermic men increased the chance for a live birth compared with placebo [35.6% vs 18.3%, Δ17.3% (1.6%; 32.9%)]. Moreover, serum inhibin B levels were higher in men deficient in vitamin D who were randomly assigned to receive high-dose vitamin D [193 pg/mL vs 143 pg/mL, Δ49 pg/mL (8; 91 pg/mL)]; however, the increase in sperm concentration was not significantly higher than in the placebo group (P = 0.07). Conclusion High-dose vitamin D supplementation did not improve semen quality in vitamin D-insufficient infertile men. The positive impact of vitamin D supplementation on live birth rate and serum inhibin B in oligozoospermic and vitamin D-deficient men may be of clinical importance and warrant verification by others.