Causal association between 25-Hydroxyvitamin D and risk of abnormal spermatozoa: a bidirectional Mendelian randomization study
Reprod Toxicol. 2024 Apr 19:108597. doi: 10.1016/j.reprotox.2024.108597 PDF behind paywall
Nannan Li 1, Ke Yang 1, Youjie Zeng 2, Si Cao 3, Liang Deng 4
Previous studies indicated conflicting findings regarding the association between vitamin D and abnormal spermatozoa. Herein, we assessed the causal association between circulating 25-Hydroxyvitamin D (25OHD) levels and the risk of abnormal spermatozoa by utilizing bidirectional Mendelian randomization (MR) analysis. Genome-wide association study summary statistics for 25OHD and abnormal spermatozoa were obtained from publicly accessible databases. Single nucleotide polymorphisms (SNPs) associated with 25OHD and SNPs associated with abnormal spermatozoa were used as instrumental variables (IVs) for forward MR analysis and reverse MR analysis, respectively. Inverse variance weighted (IVW) was the main MR approach, while weighted median, MR-Egger and maximum likelihood methods were employed to supplement IVW. In addition, several sensitivity tests assessed the reliability of MR analysis. Forward MR analysis showed that elevated 25OHD levels significantly reduced abnormal spermatozoa risk (odds ratio [OR] = 0.75, 95% confidence interval [CI]: 0.56-1.00, P = 4.98E-02), and the effect remained statistically significant after excluding SNPs associated with confounders (OR = 0.73, 95% CI: 0.54-0.98, P = 3.83E-02) or only utilizing SNPs located near 25OHD-associated genes only as IVs (OR = 0.58, 95% CI: 0.41-0.81, P = 1.67E-03). Reverse MR analysis indicated abnormal spermatozoa not affecting 25OHD level (P > 0.05). Sensitivity tests showed that MR analyses were not affected by heterogeneity and horizontal polytropy.
Overall, the present MR study supports that elevated 25OHD levels reduce the risk of abnormal spermatozoa. Therefore, ensuring adequate vitamin D intake and maintaining stable levels of 25OHD may be effective strategies to optimize reproductive outcomes.
VitaminDWiki – Vitamin D greatly improves Fertility
- Vitamin D is needed for human fertility – goal is 50 ng – Sept 2018
- In-vitro Fertilization costs at least 10,000 dollars, Vitamin D costs 5 dollars
- Infertile patients 1.7X more-likely to become pregnant if take Vitamin D – meta-analysis Feb 2023
- Live birth 1.7 X more likely after IVF if good level of vitamin D – meta-analysis Aug 2020
- If diagnosed infertile, more likely to have live birth if Vitamin D fortification – Feb 2020
- Preconception vitamin D is great - every extra 10 ng associated with 10 percent more likely to have live birth – Aug 2018
- Women with more than minimum vitamin D were 3.4 X more likely to achieve pregnancy and 1.6 X more likely to have live births – June 2017
- Assisted Reproduction – 5 studies concluded vitamin D repletion helps – Review March 2015
- Pregnancy success increased 30 percent if sunny (or vitamin D) one month earlier – June 2015
- IVF 4X more successful for white women with lots of vitamin D – many studies
Increased male Vitamin D increases fertility
- Birth rates doubled with Vitamin D - 300,000 for infertile men – RCT Nov 2017
- Higher vitamin D results in 22% fewer abnormal sperm (Mendelian analysis) – May 2024
- Conception was 3.7X more likely if the male had a good level of Vitamin D – July 2022
- Far better sperm in fertility clinic if more than 30 ng of Vitamin D - June 2022
- Fertility (sperm) associated with vitamin D – meta-analysis Sept 2019
- Infertility - 71 percent of the time of BOTH partners had less than 20 ng of Vitamin D – Aug 2017
- Male fertility 4 X higher if high Vitamin D – Nov 2015
- Vitamin D somewhat assists reproduction – both the mother and the father – May 2014
Decreased Fertility if decreased Vitamin D Receptor
- Unexplained infertility 4X more likely if poor vitamin D receptor – Dec 2020
- Male Infertility is associated with poor Vitamin D Receptor – July 2021