{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:02:48Z","timestamp":1789988568796,"version":"4.0.1"},"reference-count":40,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: 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. Objective: 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. Methods: 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\u2013Knapp adjustment. Results: 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 \u22120.50 to 1.44; I2 = 24.1%). No clear effects were observed for SHBG (MD 0.27 nmol\/L, 95% CI \u22122.14 to 2.68), FAI (MD \u22120.37, 95% CI \u22124.28 to 3.55), calculated FT sensitivity evidence (MD \u22120.0096 nmol\/L, 95% CI \u22120.0525 to 0.0332), or BAT exploratory evidence (MD \u22120.47 nmol\/L, 95% CI \u22121.77 to 0.83). GRADE certainty was low for TT, SHBG, and FAI, and very low for calculated FT and BAT. Conclusions: 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.<\/jats:p>","DOI":"10.3390\/nu18132090","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T08:43:57Z","timestamp":1782463437000},"page":"2090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.3390","volume":"18","author":[{"given":"Loreto","family":"Paez-Allendes","sequence":"first","affiliation":[{"name":"Departamento de Ciencias y Geograf\u00eda, Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Valpara\u00edso 2360072, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"Valenzuela-Fuenzalida","sequence":"additional","affiliation":[{"name":"Escuela de Medicina, Facultad de Medicina, Universidad Andr\u00e9s Bello, Vi\u00f1a del Mar 2520000, Chile"},{"name":"Departamento de Ciencias Qu\u00edmica y Biol\u00f3gicas, Facultad de Ciencias de la Salud, Universidad Bernardo O\u2019Higgins, Santiago 8370993, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda P.","family":"Moya","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Universidad Aut\u00f3noma de Chile, Santiago 8910060, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Oyanedel","sequence":"additional","affiliation":[{"name":"Faculty of Health and Social Sciences, University of the Americas, Santiago 8370040, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6497-3480","authenticated-orcid":false,"given":"Gloria","family":"Cifuentes-Suazo","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Carrera de Odontolog\u00eda, Universidad Cat\u00f3lica de la Sant\u00edsima Concepci\u00f3n, Av. Alonso de Ribera 2850, Concepci\u00f3n 4090541, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Figueroa-Puig","sequence":"additional","affiliation":[{"name":"Escuela de Kinesiolog\u00eda, Facultad de Medicina, Universidad Mayor, Santiago 7500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1781-062X","authenticated-orcid":false,"given":"Mathias","family":"Orellana-Donoso","sequence":"additional","affiliation":[{"name":"Escuela de Medicina, Universidad Finis Terrae, Santiago 7501015, Chile"},{"name":"Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Lota 2465, Santiago 7510157, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Mateluna-Valls","sequence":"additional","affiliation":[{"name":"Acad\u00e9mico Carrera de Kinesiolog\u00eda, Departamento de Salud, Comunidad y Gesti\u00f3n, Facultad de Ciencia de la Salud, Universidad de Playa Ancha, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jose","family":"Cabezas-Salgado","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Cat\u00f3lica del Maule, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2599-8474","authenticated-orcid":false,"given":"Juan","family":"Sanchis-Gimeno","sequence":"additional","affiliation":[{"name":"GIAVAL Research Group, Department of Anatomy and Human Embryology, Faculty of Medicine, University of Valencia, 46001 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7697-419X","authenticated-orcid":false,"given":"Alejandro","family":"Bruna-Mejias","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias y Geograf\u00eda, Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Valpara\u00edso 2360072, Chile"},{"name":"Escuela de Medicina, Facultad de Medicina, Universidad Andr\u00e9s Bello, Vi\u00f1a del Mar 2520000, Chile"},{"name":"Programa de Doctorado en Investigaci\u00f3n Aplicada a las Ciencias Sanitarias, Escuela de Doctorado, Universidad de Las Palmas de Gran Canaria, 35001 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.chembiol.2013.12.016","article-title":"Vitamin D metabolism, mechanism of action, and clinical applications","volume":"21","author":"Bikle","year":"2014","journal-title":"Chem. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1210\/endrev\/bnae009","article-title":"Consensus statement on vitamin D status assessment and supplementation: Whys, whens, and hows","volume":"45","author":"Giustina","year":"2024","journal-title":"Endocr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1210\/clinem\/dgae290","article-title":"Vitamin D for the prevention of disease: An Endocrine Society clinical practice guideline","volume":"109","author":"Demay","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41574-021-00593-z","article-title":"The health effects of vitamin D supplementation: Evidence from human studies","volume":"18","author":"Bouillon","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bendotti, G., Biamonte, E., Leporati, P., Goglia, U., Ruggeri, R.M., and Gallo, M. (2025). Vitamin D supplementation: Practical advice in different clinical settings. Nutrients, 17.","DOI":"10.3390\/nu17050783"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1210\/jc.2018-00229","article-title":"Testosterone therapy in men with hypogonadism: An Endocrine Society clinical practice guideline","volume":"103","author":"Bhasin","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1210\/jcem.84.10.6079","article-title":"A critical evaluation of simple methods for the estimation of free testosterone in serum","volume":"84","author":"Vermeulen","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/cen.14633","article-title":"Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism","volume":"96","author":"Jayasena","year":"2022","journal-title":"Clin. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1210\/jc.2017-02360","article-title":"Reassessing free-testosterone calculation by liquid chromatography-tandem mass spectrometry direct equilibrium dialysis","volume":"103","author":"Fiers","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1093\/humrep\/deq024","article-title":"Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract","volume":"25","author":"Nielsen","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1530\/REP-12-0064","article-title":"Vitamin D metabolism, sex hormones, and male reproductive function","volume":"144","year":"2012","journal-title":"Reproduction"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Dimitriadis, F., Zachariou, A., and Sofikitis, N. (2026). When testosterone fades: Leydig cell aging shaped by environmental toxicants, metabolic dysfunction, and testicular niche crosstalk. Cells, 15.","DOI":"10.3390\/cells15020158"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Luo, D., Qi, X., Xu, X., Yang, L., Yu, C., and Guan, Q. (2023). Involvement of p38 MAPK in Leydig cell aging and age-related decline in testosterone. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1088249"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1530\/EJE-11-0743","article-title":"Association of hypogonadism with vitamin D status: The European Male Ageing Study","volume":"166","author":"Lee","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1365-2265.2009.03777.x","article-title":"Association of vitamin D status with serum androgen levels in men","volume":"73","author":"Wehr","year":"2010","journal-title":"Clin. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1055\/s-0030-1269854","article-title":"Effect of vitamin D supplementation on testosterone levels in men","volume":"43","author":"Pilz","year":"2011","journal-title":"Horm. Metab. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1007\/s00394-018-1858-z","article-title":"Effects of vitamin D supplementation on androgens in men with low testosterone levels: A randomized controlled trial","volume":"58","author":"Lerchbaum","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/cen.12711","article-title":"Vitamin D supplementation and testosterone concentrations in male human subjects","volume":"83","author":"Heijboer","year":"2015","journal-title":"Clin. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/cen.13507","article-title":"Vitamin D and calcium supplementation, skeletal muscle strength and serum testosterone in young healthy adult males: Randomized control trial","volume":"88","author":"Saha","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1159\/000516636","article-title":"Serum testosterone levels are not modified by vitamin D supplementation in dialysis patients and healthy subjects","volume":"145","author":"Ulrich","year":"2021","journal-title":"Nephron"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1080\/15502783.2022.2100718","article-title":"Seven-month wintertime supplementation of 1200 IU vitamin D has no effect on hand grip strength in young, physically active males: A randomized, controlled study","volume":"19","author":"Rips","year":"2022","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mielgo-Ayuso, J., Calleja-Gonz\u00e1lez, J., Urdampilleta, A., Le\u00f3n-Guere\u00f1o, P., C\u00f3rdova, A., Caballero-Garc\u00eda, A., and Fernandez-L\u00e1zaro, D. (2018). Effects of vitamin D supplementation on haematological values and muscle recovery in elite male traditional rowers. Nutrients, 10.","DOI":"10.3390\/nu10121968"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Michalczyk, M.M., Go\u0142a\u015b, A., Maszczyk, A., Kaczka, P., and Zaj\u0105c, A. (2020). Influence of sunlight and oral D3 supplementation on serum 25(OH)D concentration and exercise performance in elite soccer players. Nutrients, 12.","DOI":"10.3390\/nu12051311"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1080\/17461391.2020.1713218","article-title":"Effects of vitamin D3 supplementation for 12 weeks on serum levels of anabolic hormones, anaerobic power, and aerobic performance in active male subjects: A randomized, double-blind, placebo-controlled trial","volume":"20","author":"Mohammadshahi","year":"2020","journal-title":"Eur. J. Sport Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e000856","DOI":"10.1136\/bmjnph-2023-000856","article-title":"Effects of vitamin D and L-cysteine cosupplementation on circulating bioavailable and total 25-hydroxy-vitamin D, the free\/total testosterone ratio and inflammatory biomarkers in healthy vitamin D-deficient African Americans: A placebo-controlled double-blind clinical trial","volume":"7","author":"Jain","year":"2024","journal-title":"BMJ Nutr. Prev. Health"},{"key":"ref_27","first-page":"31","article-title":"Effects of vitamin D supplementation on semen quality and reproductive hormones in patients with asthenozoospermia: A randomized double-blind placebo-controlled clinical trial","volume":"6","author":"Gheflati","year":"2021","journal-title":"J. Nutr. Food Secur."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s12958-021-00789-y","article-title":"The effects of Vitamin D3 supplementation on Spermatogram and endocrine factors in asthenozoospermia infertile men: A randomized, triple blind, placebo-controlled clinical trial","volume":"19","author":"Mansoori","year":"2021","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102529","DOI":"10.1016\/j.ctim.2020.102529","article-title":"Evaluation of the effect of vitamin D3 supplementation on quantitative and qualitative parameters of spermograms and hormones in infertile men: A randomized controlled trial","volume":"53","author":"Amini","year":"2020","journal-title":"Complement. Ther. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4292","DOI":"10.1210\/jc.2017-01428","article-title":"Vitamin D and testosterone in healthy men: A randomized controlled trial","volume":"102","author":"Lerchbaum","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s00394-018-1666-5","article-title":"Vitamin D supplementation does not prevent the testosterone decline in males with advanced heart failure: The EVITA trial","volume":"58","author":"Zittermann","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1055\/s-0033-1345139","article-title":"Supplementation with vitamin D does not increase serum testosterone levels in healthy males","volume":"45","author":"Jorde","year":"2013","journal-title":"Horm. Metab. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/andr.13505","article-title":"Effects of vitamin D on sex steroids, luteinizing hormone, and testosterone to luteinizing hormone ratio in 307 infertile men","volume":"12","author":"Holt","year":"2024","journal-title":"Andrology"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Abu-Zaid, A., Saleh, S.A.K., Adly, H.M., Baradwan, S., Alharran, A.H., Alkhaldi, M.G., Alzayed, M.M., Alotaibi, M.N., Saad, A.R., and Alfayadh, H.M. (2024). The impact of vitamin D on androgens and anabolic steroids among adult males: A meta-analytic review. Diseases, 12.","DOI":"10.3390\/diseases12100228"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1002\/jbmr.2252","article-title":"Standardizing vitamin D assays: The way forward","volume":"29","author":"Binkley","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.5740\/jaoacint.17-0258","article-title":"Baseline assessment of 25-hydroxyvitamin D assay performance: A Vitamin D Standardization Program interlaboratory comparison study","volume":"100","author":"Wise","year":"2017","journal-title":"J. AOAC Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_38","unstructured":"Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J., and Welch, V.A. (2024). Cochrane Handbook for Systematic Reviews of Interventions, Version 6.5 (Updated August 2024), Cochrane. Available online: https:\/\/training.cochrane.org\/handbook."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_40","unstructured":"Sch\u00fcnemann, H., Bro\u017cek, J., Guyatt, G., and Oxman, A. (2013). GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations Using the GRADE Approach, GRADE Working Group."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/13\/2090\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:28:22Z","timestamp":1789986502000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/13\/2090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":40,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["nu18132090"],"URL":"https:\/\/doi.org\/10.3390\/nu18132090","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]}}}