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Effects of Vitamin D Supplementation on Semen Quality, Reproductive Hormones, and Live Birth Rate: A Randomized Clinical Trial
Open accessAbstract
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.
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“Similar to the MOXI trial, the high quality trials included in the Cochrane review did not find a benefit to antioxidants on live birth. (25, 26)”
From The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial (2020) · cites this paper as [25]
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Sparks, A., Johnston, S., Handel, I., Pilkington, J., Berry, J., Pemberton, J., Nussey, D., & Mellanby, R. (2020) · bioRxiv · doi:10.1111/mec.16318 · Cited by 10
Is vitamin D status reflected by testosterone concentration in elite athletes?
Krzywański, J., Pokrywka, A., Młyńczak, M., & Mikulski, T. (2020) · Biology of Sport · doi:10.5114/biolsport.2020.95633 · Cited by 13
“There is some evi - dence of the positive influence of vitamin D status on sperm motili - ty [83, 84], as well as the effect of its supplementation on semen quality and male fertility [85, 86].”
BackgroundGlobal Andrology Forum Clinical Guidelines on Antioxidant Use in the Treatment of Male Infertility.
Agarwal, A., Mostafa, T., Hashimi, M. A., Çayan, S., Pescatori, E., Singh, K., Şahin, B., Zini, A., Chung, E., Arafa, M., et al. (2026) · The World Journal of Men's Health · doi:10.5534/wjmh.250290 · Cited by 9
Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity
Andreassen, C. H., Holt, R., Mortensen, L. J., Knudsen, N. K., Nielsen, J. E., Poulsen, N. N., Yahyavi, S. K., Boisen, I. M., Cui, Z., Ongaro, L., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101783 · Cited by 12
“17 In an exploratory post hoc analysis of a subgroup of men with serum AMH R 38 pmol/L at baseline (corresponding to 41% of all men), a significantly higher sperm concentration (5 million/mL) was observed in individuals treated with denosumab compared with placebo.”
Self-citationVitamin D Levels and Risk of Male Factor Infertility: A Mendelian Randomization Study
Chi, Y., Xiang, L., Jian, Z., & Liao, B. (2023) · The World Journal of Men s Health · doi:10.5534/wjmh.220109 · Cited by 9
“The results of this MR study support the protective role of VD in MFI, which complements the previous RCTs. Blomberg Jensen’s team found no significant improvement in sperm parameters in VD deficient men ( 25 nmol/L, n=66) treated with VD [12].”
InfluentialLeo, V. D., Tosti, C., Morgante, G., Ponchia, R., Luddi, A., Governini, L., & Piomboni, P. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11071991 · Cited by 8
Krog, M. C., Madsen, M. E., Bliddal, S., Bashir, Z., Vexø, L. E., Hartwell, D., Hugerth, L. W., Fransson, E., Hamsten, M., Boulund, F., et al. (2022) · Human Reproduction Open · doi:10.1093/hropen/hoac015 · Cited by 13
“…..DNA integrity based on the sperm chromatin structure assay) test (Blomberg Jensen et al., 2018) and the COMET (microgel electrophoresis technique) assay or TUNEL assay (terminal deoxynucleotidyl transferase dUTP nick-end…”
[Vitamin D and reproductive health].
Gorelova, I., Popova, P., & Rulev, M. V. (2020) · Problemy Endokrinologii · doi:10.14341/probl12468 · Cited by 9
The Impact of Vitamin D on Androgens and Anabolic Steroids among Adult Males: A Meta-Analytic Review
Abu-Zaid, A., Saleh, S. A. K., Adly, H. M., Baradwan, S., Alharran, A. M., Alhatm, M., Alzayed, M. M., Alotaibi, M. N., Saad, A. R., Alfayadh, H. M., et al. (2024) · Diseases · doi:10.3390/diseases12100228 · Cited by 11
Humla, E. C., Bergh, C., Akouri, R., & Tsiartas, P. (2022) · Human Reproduction Open · doi:10.1093/hropen/hoac036 · Cited by 8
“…secretion and vitamin D synthesis, all important parameters for the reproductive efficacy (Kauppila et al., 1987; Lam and Miron, 1991; Rojansky et al., 1992; Reiter, 1993; Levine, 1994; Bronson, 1995; Levine, 1999; Cummings, 2003, 2007, 2010a,b; Reiter et al., 2014; Blomberg Jensen et al., 2018).”
BackgroundYahyavi, S., Holt, R., Mortensen, L. J., Petersen, J., Jørgensen, N., Juul, A., & Jensen, M. B. (2022) · Trials · doi:10.1186/s13063-022-06478-4 · Cited by 8
Self-citationEffect of Vitamin D3 Supplement on the Semen Quality in Human Patients with Vitamin D Deficiency
Abed, H. H., Ali, A. M., & Mahdi, Z. S. (2022) · HAYATI Journal of Biosciences · doi:10.4308/hjb.29.5.562-569 · Cited by 8
“The findings of this study corroborate with those of prior studies that have found a specific role for vitamin D in sperm motility (Blomberg Jensen et al. 2018).”
ResultVitamins as primary or adjunctive treatment in infertile men with varicocele: A systematic review
Tsampoukas, G., Gkeka, K., Dellis, A., Brown, D., Katsouri, A., Alneshawy, A., Moussa, M., Papatsoris, A., & Buchholz, N. (2021) · Arab Journal of Urology · doi:10.1080/2090598x.2021.1932124 · Cited by 8
Tiosano, D., Abrams, S., & Weisman, Y. (2021) · Journal of NutriLife · doi:10.1093/jn/nxaa380 · Cited by 7
Holzer, M., Massa, E., & Ghersevich, S. A. (2022) · Current Urology · doi:10.1097/cu9.0000000000000075 · Cited by 8
“[44] In conclusion, our results suggest that vitD could affect male reproductive function and that its deficiency may be related to infertility.”
BackgroundMortensen, L. J., Lorenzen, M., Jørgensen, A., Albrethsen, J., Jørgensen, N., Møller, S., Andersson, A., Juul, A., & Jensen, M. B. (2021) · Cancers · doi:10.3390/cancers13061329 · Cited by 8
“The Copenhagen-Bone-Gonadal Study is a cohort of 307 infertile men with no serious co-morbidities referred from 2011 to 2015 to our andrological outpatient clinic and included a total of 1427 men [21,22].”
BackgroundMethodSelf-citationChen, Y.-L., Liu, D.-F., Zeng, L., Xu, H.-Y., Jiang, H., Yang, R., Wang, H.-N., Yan, L.-Y., Li, R., Qiao, J., et al. (2020) · Andrology · doi:10.1111/andr.12818 · Cited by 6
Yahyavi, S. K., Wall-Gremstrup, G., Probst-Drejer, B., Toft, F. B., Jorsal, M. J., Holt, R., Aksglæde, L., Jørgensen, N., Juul, A., & Jensen, M. B. (2024) · Human Reproduction · doi:10.1093/humrep/deae293 · Cited by 7
Self-citationPreconceptual care for couples seeking fertility treatment, an evidence-based approach
Chronopoulou, E., Seifalian, A., Stephenson, J., Serhal, P. F., Saab, W., & Seshadri, S. (2020) · F&S Reviews · doi:10.1016/j.xfnr.2020.09.001 · Cited by 5
Vitamin D receptor expression in sperm of males with unexplained infertility.
Sagheb, Z. A., Mohammadnia‐Afrouzi, M., Shafi, H., Esmailzadeh, S., Ganji, K. S., & Shahbazi, M. (2023) · PubMed Central · doi:10.22088/cjim.14.1.94 · Cited by 4
Lengyel, B., Armos, R., Bojtor, B., Kiss, A., Tóbiás, B., Pikó, H., Illés, A., Horvath, E. M., Putz, Z., Takács, I., et al. (2025) · Pharmaceuticals · doi:10.3390/ph19010054 · Cited by 3
“Another consistent result was that vitamin D levels show a positive correlation with fertility, with infertile men having considerably lower vitamin D levels [209,210,212].”
The Intimate Relationship between Adipose Tissue, Fertility, and Bone
Michalopoulou, O., Kostoglou-Athanassiou, I., Troupis, G. T., & Mastorakos, G. (2026) · Journal of Frailty, Sarcopenia and Falls · doi:10.22540/jfsf-11-080 · Cited by 3
“Low serum 25(OH)D is associated with reduced sperm count and motility in population studies, while supplementation modestly improves reproductive hormones and semen parameters in men with such deficiency 102,103 .”
Saberivand, A., Sarvarzadeh, F., Peighambarzadeh, S., Saberivand, M., Pakizehvand, H., Rashidi, S., Rahbar, M., & Khoshniyat, M. (2022) · Theriogenology · doi:10.1016/j.theriogenology.2022.06.017 · Cited by 3
Reproductive history of patients with hereditary 1,25-dihydroxyvitamin D–resistant rickets
Tiosano, D., & Weisman, Y. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2019.02.028 · Cited by 5
Melhem, S. J., Melhem, M., Haddad, R., Alghurabi, O., Mousa, R., Massad, E. M., Almomani, H., Alrashdan, Y., & Melhem, J. (2026) · Andrology · doi:10.1111/andr.70266 · Cited by 2
“Jensen et al. [ 24 ] enrolled 330 infertile men with baseline vitamin D insufficiency and randomized them to cholecalciferol with calcium or placebo for 5 months.”
InfluentialYahyavi, S. K., Toft, F. B., Probst-Drejer, B., Boisen, I. M., Priskorn, L., Jørgensen, N., Juul, A., & Jensen, M. B. (2026) · Andrology · doi:10.1111/andr.70172 · Cited by 2
“Second, many of the screened men for the RCT were not eligible to participate in the study due to exclusion criteria [ 24 ], which could limit generalizability to other studies.”
InfluentialSelf-citationWen, Q., Xu, H.-Y., Zou, H., Wang, P., Xing, X., Chen, Y., Zhu, Q.-L., Chen, Y., Tan, M.-H., Zhang, M.-M., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1418936 · Cited by 2
Dialameh, H., Nikoobakht, M., Oskouie, I. M., Rahimdoost, N., Nazarpour, M., Mousavi, S. H., Lotfi, M., Esmaeilpanah, S., & Inanloo, H. (2023) · Urologiâ · doi:10.1177/03915603231162394 · Cited by 2
Effect of Adding Different Vitamin D3 Concentrations on Chilled Storage of Awassi Ram Semen
Bresm, M. H. A., & Habeeb, H. M. H. (2022) · IOP Conference Series: Earth and Environment · doi:10.1088/1755-1315/1060/1/012084 · Cited by 2
“However, This is in contrast to the study conducted by [36] who reported that a low level of VD decreases sperm motility.”
ResultRole of vitamin D in common urological conditions: a narrative review of past decade literature
Brown, D., Gkeka, K., Narayan, Y., Katsouri, A., Tsampoukas, G., & Buchholz, N. (2021) · Longhua Chinese Medicine · doi:10.21037/lcm-21-49 · Cited by 2
“Notably, treatment with vitamin D has also been associated with higher live-birth rates in couples in which the man had oligozoospermia compared with those men taking placebo (77).”
BackgroundImpact of Vitamin D on Male Iraqi Patients with Infertility
Aziz, A. S. A., Al-Sharifi, Z. A. R., & Dulaime, H. K. A. (2020) · Annals of Tropical Medicine and Public Health · doi:10.36295/asro.2020.232240 · Cited by 2
The effect of lipid disturbance and vitamin D on the fertility in male albino rats
Hikal, S. M., Bayoumi, M. E., Ibrahim, S. E., & el Shawwa, M. (2020) · Journal of Recent Advances in Medicine/Journal of Recent Advances in Medicine · doi:10.21608/jram.2020.30036.1058 · Cited by 2
Medikamentöse Therapie primär nichthormonell bedingter männlicher Fertilitätsstörungen
Haidl, G., Allam, J., Köhn, F., Haidl, F., & Schuppe, H. (2019) · Gynäkologische Endokrinologie · doi:10.1007/s10304-019-00273-2 · Cited by 2
Zhang, G., Nelli, G., Hoe, S., & Hamdan, M. (2026) · PeerJ · doi:10.7717/peerj.21002 · Cited by 1
“The study by Blomberg Jensen et al. (2018) , contributing 98.2% of the weight, showed the most precise effect estimate.”
InfluentialYahyavi, S., Holt, R., Jorsal, M., Árting, L. B., Eldrup, E., Juul, A., Jørgensen, N., & Jensen, M. B. (2024) · Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2024.106640 · Cited by 1
“This study utilizes secondary outcome data from a previously conducted randomized clinical trial [19] to describe and compare the association of serum levels of total 25OHD, free 25OHD, and free 25OHD % on various calciotropic, bone, and metabolic outcomes.”
Self-citationLi, N.-N., Yang, K., Zeng, Y., Cao, S., & Deng, L. (2024) · Reproductive Toxicology · doi:10.1016/j.reprotox.2024.108597 · Cited by 1
Decline in human sperm parameters: How to stop?
Mohamed, E. A. (2023) · Clinical Journal of Obstetrics and Gynecology · doi:10.29328/journal.cjog.1001122 · Cited by 1
Highlights from the 22nd Workshop on Vitamin D in New York City, May 2019.
Fleet, J., Bernal-Mizrachi, C., Hewison, M., Jorde, R., White, J. H., Cantorna, M., Schoenmakers, I., & Erben, R. (2020) · Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2020.105747 · Cited by 1
JawdatKadhim, M., & Al-Dabbagh, A. (2020) · doi:10.36295/asro.2020.231805 · Cited by 1
“Calcium is needed to commence the acrosome reaction liberating enzymes necessary for effective sperm-ovum communication (18) , and vitamin D through activation of VDR raised the intracellular calcium from its store in the sperm’s neck stimulating sperm motility and acrosome reaction (19), therefore calcium action on m…”
BackgroundResultInfluentialAssessment of Sperm DNA Integrity and Implications for the Outcome of ICSI Treatments
Christensen, P., & Birck, A. (2018) · Springer eBooks · doi:10.1007/978-3-319-70497-5_6 · Cited by 1
Filho, D. R., Nogueira‐de‐Almeida, C. A., & Filho, A. E. D. O. (2019) · International Journal of Nutrology · doi:10.1055/s-0040-1709661 · Cited by 8
Sengupta, P., Dutta, S., Alaee, S., Mishra, D., Selvam, M. K. P., Rosas, I. M., & Roychoudhury, S. (2026) · Frontiers in Veterinary Science · doi:10.3389/fvets.2026.1920393
Vitamin D in male reproduction: molecular mechanisms and pharmacological perspectives
Liu, J., Liu, B., Qiu, X.-Y., Lv, M.-M., Liu, S.-S., & Zhou, D. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1849299
Puia, D., Ivănuță, M., Corlade-Andrei, M., Tory, H., Majeru, A.-G., Doroftei, B., Ștefăniu, R., Elena, V., & Pricop, C. (2026) · Endocrines · doi:10.3390/endocrines7030051
Nazarpour, M., Hamidi, M., Gholipour, F., Dialameh, H., Dehaki, M. G., Kazemi-Galougahi, M., & Namdari, F. (2026) · Journal of Research in Medical Sciences · doi:10.4103/jrms.jrms_1064_25
The 24,25(OH)2D3-TLCD3B signaling complex and reproductive function in mice and men
Kooij, I., Mitrofanov, K., Rehfeld, A., Andreassen, C. H., Madsen, S. K., Janssen, A. M., St‐Arnaud, R., Jørgensen, A., & Jensen, M. B. (2026) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2026.107060
Metadata
- Authors
- Blomberg Jensen, M., Lawaetz, J. G., Petersen, J. H., Juul, A., & Jørgensen, N.
- Affiliations
- Department of Growth and Reproduction, International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- University of Copenhagen (DK)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2017-11-03
- Volume
- 103
- Issue
- 3
- Pages
- 870-881
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2766252936
- Cited by
- 129
- References
- 35
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 15 · 2023: 17 · 2022: 17 · 2021: 16 · 2020: 17 · 2019: 15 · 2018: 7
- FWCI
- 12.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Hørslev-Fonden
- Novo Nordisk
- Novo Nordisk Fonden (NNF17OC0026096)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
- Health Sciences › Medicine › Urology › Male Reproductive Health Studies
- Keywords
- vitamin D supplementation, vitamin D3, calcium supplementation, male infertility, semen quality, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D3, inhibin B, live birth rate, oligozoospermia, vitamin D deficiency, male reproductive hormones
- MeSH terms
- Adult, Calcium, Cholecalciferol, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Infertility, Male, Male, Middle Aged, Oligospermia, Pregnancy, Pregnancy Outcome, Sperm Count, Sperm Motility, Vitamin D, Vitamin D Deficiency, Pregnancy Rate, Dietary Supplements, Semen Analysis
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