Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review...

Vitamin D has traditionally been recognized for its role in calcium homeostasis and skeletal health, but vitamin D receptor expression and vitamin D-metabolizing enzymes have also been identified in extra-skeletal tissues, including components of the male reproductive tract. Observational evidence has suggested associations between vitamin D status and androgen-related markers; however, whether vitamin D supplementation has a measurable effect on androgen bioavailability remains uncertain.

This systematic review and meta-analysis evaluated the effects of vitamin D supplementation on total testosterone (TT) and androgen bioavailability markers in adult men, including sex hormone-binding globulin (SHBG), free androgen index (FAI), calculated free testosterone (calculated FT), and bioactive testosterone (BAT) where methodologically compatible.

The review was registered in PROSPERO (CRD420261365005) and conducted according to PRISMA 2020 and Cochrane methodological guidance. Searches were conducted from database inception to April 2026 in PubMed, Web of Science, Scopus, ClinicalTrials.gov, and the WHO ICTRP. Embase was initially planned but was not searched because institutional access was unavailable; this amendment was made before screening, extraction, risk-of-bias assessment, and synthesis. Records were deduplicated in Zotero, screened in a structured matrix, and converted from report-level records into independent comparison-level datasets where appropriate. Meta-analyses used random-effects REML models with Hartung-Knapp adjustment.

The official search set comprised 2854 records, of which 703 duplicates were removed, leaving 2151 records for title and abstract screening. The full-text screening file was reconciled to 162 PRISMA-countable reports/records: 135 reports were assessed, 27 reports could not be assessed because the full text was unavailable or had not been obtained for review, and 27 reports/studies were retained for qualitative synthesis. Eighteen reports were considered candidate sources for quantitative synthesis and were operationalized into 21 comparison-level records. The primary TT model included 11 comparisons and showed no clear effect of vitamin D supplementation on final TT (MD 0.47 nmol/L, 95% CI -0.50 to 1.44; I² = 24.1%). No clear effects were observed for SHBG (MD 0.27 nmol/L, 95% CI -2.14 to 2.68), FAI (MD -0.37, 95% CI -4.28 to 3.55), calculated FT sensitivity evidence (MD -0.0096 nmol/L, 95% CI -0.0525 to 0.0332), or BAT exploratory evidence (MD -0.47 nmol/L, 95% CI -1.77 to 0.83). GRADE certainty was low for TT, SHBG, and FAI, and very low for calculated FT and BAT.

Current randomized evidence does not demonstrate a statistically clear or reproducible effect of vitamin D supplementation on total testosterone or androgen bioavailability markers in adult men. GRADE certainty was low for total testosterone, SHBG, and FAI, and very low for calculated free testosterone and bioactive testosterone. Because directly measured and calculated free testosterone are not analytically equivalent, free testosterone was not pooled as a primary outcome; method-compatible calculated FT was handled as sensitivity evidence and BAT as exploratory evidence.