Vitamin D Supplementation and Testosterone

[madman]

Reviewing the Evidence on Vitamin D Supplementation in the Management of Testosterone Status and Its Effects on Male Reproductive System (Testis and Prostate): Mechanistically Dazzling but Clinically Disappointing

Heitor O. Santos, RD ; Scott Howell, PhD ; Keith Nichols, MD ; and Filipe J. Teixeira, RD, PhD




ABSTRACT

Purpose: Vitamin D supplementation has been suggested to increase testosterone levels. The primary purpose of this literature review was to critically assess the physiologic effects of vitamin D supplementation on serum testosterone concentrations in men and the secondary purpose was to evaluate the feasibility of vitamin D status toward urologic health (testis and prostate).

Methods: A structured literature review was performed using the Cochrane, MEDLINE, and Web of Science databases. The literature search encompassed studies published between 2011 and 2019.

Findings: Observational studies suggest an association between higher testosterone and serum vitamin D concentrations. Conversely, most randomized clinical trials that investigated the effect of vitamin D administration on testosterone levels have failed to detect any significant effect. Physiologically, vitamin D is engaging in spermatogenesis, but it remains unclear whether vitamin D is a determinant of fertility. With prostate support, the management of vitamin D status has been associated with a decreased prevalence of benign prostatic hyperplasia and symptoms (ie, lower urinary tract symptoms). However, with prostate cancer, there is a paucity of evidence pertaining to vitamin D supplementation.

Implications: Mechanistically, vitamin D exhibits essential roles in the testis and prostate; otherwise, there is no apparent evidence to support the use of vitamin D supplementation to increase testosterone levels and to improve clinical outcomes related to the male reproductive system.








CONCLUSION

Mechanistically, VitD has several essential roles in various organs (eg, heart, muscle, bone, and gut), including organs of the male reproductive system, such as testis and prostate. Thus far, despite physiologic importance of VitD in modulating the testicular steroidogenesis, there is no sound evidence for the use of VitD supplementation as a testosterone adjuvant, as detailed in this structured literature review. The evidence on VitD supplementation remains inconsistent in urologic conditions, particularly as an adjuvant to improve sperm and prostate parameters. Practitioners should refrain from any enthusiasm regarding VitD supplementation and 25(OH)D screening for urologic heath. The evidence presented in this review represents another nail in the coffin for VitD as a magic bullet. Definitive long-term clinical trials are needed to confirm the effects of VitD supplementation on diseases critical to urologic health with an emphasis on hypogonadism, BPH, and prostate cancer.

 

[madman]

Figure 2. The active form of vitamin D (VitD) increases the expression of androgen metabolism enzymes (ie, P450scc, and SRD5A1). 25-Hydroxyvitamin D3 (1,25[OH]2D3) binds to its membrane receptor and consequently further binds to the nuclear receptor, forming the VitD receptor (VDR) retinoid X receptor (RXR) heterodimer. There are VitD-dependent genes in the nucleus, and when the VDR-RXR heterodimer is activated, the vitamin D response element (VDRE) signals the expression of androgen enzymes in the mitochondria. P450scc acts primarily on the hormone cascade, which is responsible for converting cholesterol into pregnenolone. After pregnenolone is synthesized, several enzymatic actions lead to testosterone formation, whose processes occur in the endoplasmic reticulum. Increased expression of SRD5A1 by virtue of 1,25(OH)2D3 signaling enhances the conversion of testosterone to dihydrotestosterone. The proposed pathway for the association between the active form of VitD and increased testosterone levels in humans occurs in the Leydig cells, whereas the association with increased levels of dihydrotestosterone occurs in cells that predominantly express isoforms of 5a-reductase, one of which is SRD5A1. Some precursors of the testosterone pathway should be investigated through randomized clinical trials for better clinical insight. DHEA, dehydroepiandrosterone.