Study of Effect of Vitamin D Supplementation on the Clinical, Hormonal and Metabolic Profile of the PCOS Women.
Gupta Taru,Rawat Mukta,Gupta Nupur,Arora Sarika
Journal of obstetrics and gynaecology of India
INTRODUCTION:Insulin resistance is one of the most common features of polycystic ovary syndrome, and some studies suggest that vitamin D deficiency may have role in insulin resistance. OBJECTIVE:To study the effect of vitamin D supplementation on the clinical, hormonal and metabolic profile of the PCOS women. STUDY DESIGN:Randomized, placebo-controlled, interventional, double-blind study. MATERIALS AND METHODS:PCOS women were evaluated and enrolled after considering inclusion and exclusion criteria. They were randomized by block randomization with sealed envelope system done in two groups. In the study group ( = 25), patients were supplemented with vitamin D 60,000 IU weekly for 12 weeks, whereas control group ( = 25) was given placebo weekly for the same period. Both the groups were compared pre- and post-supplementation for variables like clinical profile, biochemical profile and metabolic profile. Statistical analysis was performed by the SPSS program for Windows, version 10.1 (SPSS, Chicago, IL). RESULT:In the study ( = 50), PCOS patients were enrolled; 34 patients (68%) were vitamin D deficient (≤20 ng/ml) out of which 10 patients (29%) were severely deficient (<10 ng/ml). Twelve patients (24%) were vitamin D insufficient showing high prevalence of vitamin D deficiency in the PCOS women. The difference in mean serum fasting glucose pre- and post-supplementation of vitamin D in study group was found to be statistically significant with value of 0.041. There was significant difference seen in insulin resistance (IR) (2.38 ± 4.88-1.00 ± 0.58, = 0.003), serum fasting insulin (10.34 ± 20.00-5.00 ± 3.25, = 0.021), and increase in insulin sensitivity determined by QUICKI (0.37 ± 0.04-0.394 ± 0.009, = 0.001) after supplementation with vitamin D. CONCLUSION:The study concluded that there was a beneficial effect of vitamin D supplementation on ovulatory dysfunctions and blood pressure. Post-supplementation, there were decrease in insulin resistance and increase in insulin sensitivity. In the study decreased serum fasting insulin level and fasting blood sugar after vitamin D supplementation suggest underlying role of vitamin D in glucose homeostasis.
10.1007/s13224-017-1008-1
The role of vitamin D in breast cancer risk and progression.
Endocrine-related cancer
The active form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is primarily known as a key regulator of calcium and phosphate homeostasis. It exerts its biological functions by binding to the vitamin D receptor (VDR), a transcription factor that regulates gene expression in vitamin D-target tissues such as intestine, kidney and bone. Yet, the VDR is expressed in many additional normal and cancerous tissues, where it moderates the antiproliferative, prodifferentiating and immune-modulating effects of 1,25(OH)2D3. Interestingly, several epidemiological studies show that low levels of 25(OH)D, a biological marker for 1,25(OH)2D3 status, are associated with an increased risk of breast cancer (BC) development. Mendelian randomization studies, however, did not find any relationship between single-nucleotide polymorphisms in genes associated with lower serum 25(OH)D and BC risk. Nevertheless, multiple and in vivo preclinical studies illustrate that 1,25(OH)2D3 or its less calcaemic structural analogues influence diverse cellular processes in BC such as proliferation, differentiation, apoptosis, autophagy and the epithelial-mesenchymal transition. Recent insights also demonstrate that 1,25(OH)2D3 treatment impacts on cell metabolism and on the cancer stem cell population. The presence of VDR in the majority of BCs, together with the various anti-tumoural effects of 1,25(OH)2D3, has supported the evaluation of the effects of vitamin D3 supplementation on BC development. However, most randomized controlled clinical trials do not demonstrate a clear decrease in BC incidence with vitamin D3 supplementation. However, 1,25(OH)2D3 or its analogues seem biologically more active and may have more potential anticancer activity in BC upon combination with existing cancer therapies.
10.1530/ERC-21-0182
Associations between 25 hydroxyvitamin D concentration and spontaneous abortion.
BMC public health
BACKGROUND:Spontaneous abortion is a common complication of pregnancy that can lead to adverse physical and psychological outcomes for women. Vitamin D is reported to be associated with reproductive functions, whereas its casual effects on abortion remains unclear. MATERIALS AND METHODS:In this study, a two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between serum 25 hydroxyvitamin D [25(OH)D] concentration and the risk of spontaneous abortion. GWAS summary data of 25(OH)D were used as exposure, and data of spontaneous abortion was considered as outcome. A retrospective study was additionally conducted to verify the MR results. RESULTS:MR estimates showed that a higher 25(OH)D level was potentially associated with decreased risk of spontaneous abortion (IVW, OR = 0.98, 95%CI = 0.90-1.06; MR Egger, OR = 0.94, 95%CI = 0.84-1.05; Weighted median, OR = 0.93, 95%CI = 0.82-1.06; Weighted mode, OR = 0.93, 95%CI = 0.84-1.03), though the P-value was not statistically significant. The retrospective study also produced consistent result of Vitamin D's protective role to spontaneous abortion. The P-value was very close to statistical significance (P = 0.053). CONCLUSIONS:This study reports the potential protective role of serum 25(OH)D concentration to spontaneous abortion, suggesting that increased vitamin D levels may decrease the risk of abortion. Further larger prospective studies and/or even randomized controlled trials are needed to confirm causal relationship between vitamin D and abortion.
10.1186/s12889-024-19078-5
Review of Recent Advances in Understanding the Role of Vitamin D in Reducing Cancer Risk: Breast, Colorectal, Prostate, and Overall Cancer.
Grant William B
Anticancer research
This article is a narrative review of recent epidemiological findings regarding ultraviolet-B (UVB) dose or exposure, serum 25-hydroxyvitamin D [25(OH)D] concentrations, vitamin D supplementation, and genetic variations in 25(OH)D concentration for incidence, survival, and mortality rates of overall and breast, colorectal, and prostate cancer. According to ecological studies, solar UVB doses are inversely correlated with incidence/mortality rates for about 20 cancer types. Observational studies support a role of higher 25(OH)D concentrations in reducing risk of breast and colorectal cancer incidence and mortality rates but, for prostate cancer, in increasing incidence rates while reducing mortality rates. Mendelian randomization studies offer little support for vitamin D in reducing cancer risk. Their primary limitation is that they only investigate small variations in genetically predicted 25(OH)D concentration near the population mean value. The secondary analyses from the VITAL clinical trial indicated significant reductions from 2000 IU/d of vitamin D supplementation in all-cancer incidence and mortality rates for selected subgroups. Thus, Hill's criteria for causality in a biological system are now largely satisfied for supporting the claim that vitamin D reduces the risk of cancer incidence and death.
10.21873/anticanres.13977
Maternal vitamin D during pregnancy and offspring autism and autism-associated traits: a prospective cohort study.
Molecular autism
BACKGROUND:There has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive. METHODS:We used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits. The association between each outcome with seasonal and gestational age-adjusted maternal serum 25-hydroxyvitamin D during pregnancy was estimated using confounder-adjusted regression models. Multiple imputation was used to account for missing data, and restricted cubic splines were used to investigate nonlinear associations. Mendelian randomization was used to strengthen causal inference. RESULTS:No strong evidence of an association between maternal serum 25-hydroxyvitamin D during pregnancy and any offspring autism-associated outcome was found using multivariable regression analysis (autism diagnosis: adjusted OR = 0.98, 95% CI = 0.90-1.06), including with multiple imputation (autism diagnosis: adjusted OR = 0.99, 95% CI = 0.93-1.06), and no evidence of a causal effect was suggested by Mendelian randomization (autism diagnosis: causal OR = 1.08, 95% CI = 0.46-2.55). Some evidence of increased odds of autism-associated traits at lower levels of maternal serum 25-hydroxyvitamin D was found using spline analysis. LIMITATIONS:Our study was potentially limited by low power, particularly for diagnosed autism cases as an outcome. The cohort may not have captured the extreme lows of the distribution of serum 25-hydroxyvitamin D, and our analyses may have been biased by residual confounding and missing data. CONCLUSIONS:The present study found no strong evidence of a causal link between maternal vitamin D levels in pregnancy and offspring diagnosis or traits of autism.
10.1186/s13229-022-00523-4
Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study.
BMJ (Clinical research ed.)
OBJECTIVE:To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. DESIGN:One and two sample mendelian randomisation analyses. SETTING:Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). PARTICIPANTS:7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. EXPOSURES:Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. MAIN OUTCOME MEASURES:Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. RESULTS:In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels <25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level <75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels <50 nmol/L. CONCLUSIONS:No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed.
10.1136/bmj.k2167
Association of 25-Hydroxyvitamin D with Preterm Birth and Premature Rupture of Membranes: A Mendelian Randomization Study.
Nutrients
Low vitamin D (VitD) level is a risk factor for preterm birth (PTB), but the results of previous studies remained inconsistent, which may be influenced by the confounding factors and different types of PTB. We performed Mendelian randomization (MR) to uncover the association of 25-hydroxyvitamin D (25(OH)D) with PTB, premature rupture of membranes (PROM), and preterm premature rupture of membranes (PPROM). This study was conducted in Zhoushan Maternal and Child Health Hospital, Zhejiang, from August 2011 to March 2022. Plasma 25(OH)D levels in three trimesters of pregnancy were measured. We conducted an MR analysis utilizing a genetic risk score (GRS) approach, which was based on VitD-associated single-nucleotide polymorphisms. The prospective cohort study included 3923 pregnant women. The prevalence of PTB, PROM, and PPROM were 6.09%, 13.18%, and 1.33%, respectively. Compared to those without vitamin D deficiency (VDD), only vaginally delivering pregnant women with VDD had a 2.69 (1.08-6.68) times risk of PTB. However, MR analysis did not support the association. One-unit higher GRS was not associated with an increased risk of PTB, regardless of the trimesters (OR [95% CI]: 1.01 [0.93-1.10], 1.06 [0.96-1.18], and 0.95 [0.82-1.10], respectively). When further taking PROM and PPROM as the outcomes, the MR analysis also showed no consistent evidence of a causal effect of VitD levels on the risk of them. Our MR analyses did not support a causal effect of 25(OH)D concentrations in the three trimesters on PTB, PROM, and PPROM.
10.3390/nu15163593
25-hydroxyvitamin D and Endometriosis: A bidirectional Mendelian randomization study.
Reproductive sciences (Thousand Oaks, Calif.)
Numerous studies have demonstrated a correlation between serum 25-hydroxyvitamin D (25OHD) and endometriosis. However, the precise nature of this association remains elusive. The causal connection between 25OHD and endometriosis remains uncertain, as it is yet to be determined whether one directly influences the other. The objective of our research was to investigate the cause-and-effect connection between 25OHD and endometriosis. The study employed Mendelian randomization (MR) in a bidirectional two-sample investigation to examine the causal relationship between 25OHD and endometriosis. The analysis utilized the most recent publicly accessible statistics from the genome-wide association study (GWAS) encompassing 25OHD, endometriosis, and its five subtypes. The primary analytical approach employed was Inverse-Variance Weighting (IVW), accompanied by supplementary analysis methods including weighted median, MR-Egger, simple mode, and weighted mode. Furthermore, sensitivity analyses were conducted to assess the potential influence of heterogeneity and pleiotropy on the MR outcomes. MR primary analysis showed no significant causal effect of 25OHD on endometriosis (OR = 0.892, 95%CI = 0.745 ~ 1.068, P = 0.213). Similarly, there was no evidence to support a causal relationship of endometriosis on 25OHD (IVW Beta = 0.005, 95%CI = 0.993 ~ 1.018, P = 0.406). However, when conducting MR analysis on different subtypes of endometriosis and 25OHD, we found a positive correlation between endometriosis of ovary and 25OHD level (IVW Beta = 0.012, 95%CI = 1.002 ~ 1.022, P = 0.024). This study indicates that there is no causal relationship between serum 25OHD and endometriosis. However, it is important to note that serum 25OHD levels will increase in patients with endometriosis of the ovary. Further observational studies and clinical trials are indispensable.
10.1007/s43032-024-01517-8
Causal association between low vitamin D and polycystic ovary syndrome: a bidirectional mendelian randomization study.
Journal of ovarian research
BACKGROUND:Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain. OBJECTIVE:We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms. METHODS:We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms. RESULTS:TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587-0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968-0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process. CONCLUSION:Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.
10.1186/s13048-024-01420-5
The association between vitamin D and uterine fibroids: A mendelian randomization study.
Frontiers in genetics
Uterine fibroids (UFs), the most common benign gynecological tumor, can bring severe negative impacts on a woman's life quality. Vitamin D, is thought to play an important role in regulating cell proliferation and differentiation. In recent years, several studies suggested that higher level of vitamin D has a negative effect on the occurrence of UFs, but the results of studies on the relationship between them are conflicting and further evidence needs to be studied. Here in, we used a two-sample Mendelian Randomization (2SMR) study to explore the causal relationship between genetically predicted vitamin D levels and the risk of UFs. The exposure data comes from a genome-wide association study (GWAS) summary dataset consisting of 441,291 individuals, which includes datasets from United Kingdom Biobank, FinnGen Biobank and the corresponding consortia. Single-nucleotide polymorphisms (SNPs) associated with vitamin D at a significant level of < 5 × 10 and low linkage disequilibrium (LD) level (r < 0.01) were selected. The outcome data comes from a GWAS dataset of IEU analysis of United Kingdom Biobank phenotypes consisting of 7,122 UFs cases and 455,811 controls. Our inverse-variance weight (IVW) analysis results support the causal association of genetically predicted vitamin D with the risk of UFs (OR = 0.995,95% CI = 0.990-0.999, = 0.024). In addition, heterogeneity and pleiotropy were not observed in statistical models. In summary, our results indicate that elevated serum vitamin D levels are in strong relationship with reduction of the risk of UFs, which indicates that the clinical treatment of UFs may have a new and excellent option.
10.3389/fgene.2022.1013192
Vitamin D and hyperemesis gravidarum: A mendelian randomization study.
Journal of gynecology obstetrics and human reproduction
BACKGROUND:The causality between vitamin D and hyperemesis gravidarum remains unknown. Our aim was to investigate the causal effect of vitamin D on hyperemesis gravidarum using the two-sample Mendelian randomization method. METHODS:Independent single nucleotide polymorphisms significantly associated with serum 25-hydroxyvitamin D levels served as instrumental variables. The corresponding effect estimates for hyperemesis gravidarum were obtained from the Finngen Biobank. For Mendelian randomization analysis, inverse variance weighting was used as the primary method. We also used weighted median, MR-Egger regression, simple mode, and weighted mode as complementary methods to inverse variance weighting. The MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis were performed to assess the horizontal pleiotropy, heterogeneity, and stability of the causal association between 25-hydroxyvitamin D levels and hyperemesis gravidarum. RESULTS:We found that an increase in 25-hydroxyvitamin D level was associated with a lower risk of hyperemesis gravidarum [odds ratio (OR): 0.568, 95 % CI: 0.403-0.800, p = 0.001]. The result demonstrates the causal relationship between 25-hydroxyvitamin D level and the risk of hyperemesis gravidarum in the European population. CONCLUSIONS:The large Mendelian randomization analysis suggests that vitamin D may be causally associated with risk of hyperemesis gravidarum.
10.1016/j.jogoh.2023.102678