Phosphate concentration is exceptionally high in seminal fluid and is linked with semen quality but not influenced by vitamin D and calcium supplementation

Abstract Objective This study aims to determine the link between seminal fluid (SF) concentrations of phosphate with semen quality parameters, corresponding serum phosphate concentration, and possible influence of high-dose cholecalciferol and calcium supplementation. Materials and methods In a single-center, double-blinded, randomized clinical trial (NCT01304927), 307 infertile men were assigned to receive a single dose of vitamin D (cholecalciferol) 300 000 IU initially followed by 1400 IU and 500 mg of calcium daily for 150 days or placebo. Change in SF phosphate was a predefined secondary endpoint while effect on semen parameters was the primary endpoint. Results At baseline, SF phosphate concentration was 25-fold higher but not associated with serum phosphate concentration (median 24.0 mmol/L [IQR 17, 30] vs 0.93 mmol/L [IQR 0.83, 1.05]). Men with the highest concentration of SF phosphate (≥29 mmol/L) had fewer motile spermatozoa (AB%: median 27% [IQR 14, 39] vs 37% [IQR 17, 56]; P = .007) and morphologically normal spermatozoa (1.9% [IQR 0.8, 3.8] vs 2.5% [IQR 1.4, 6.5]; P = .014) than men having SF phosphate < 19 mmol/L. Seminal fluid concentrations of phosphate remained stable and were unaffected by vitamin D and calcium supplementation (SF phosphate in placebo median 21.4 [IQR 15.9, 28.4] vs treatment 21.1 [IQR 14.5, 29.8]). Conclusion Seminal fluid phosphate concentration may be of importance for reproductive function as infertile men with the lowest SF phosphate concentration had higher percentage of motile and morphologically normal spermatozoa. Serum phosphate concentration was not associated with seminal phosphate levels, and cholecalciferol and calcium supplementation did not influence SF phosphate.