Vitamin D Supplementation Decreases TGF-β1 Bioavailability in PCOS: A Randomized Placebo-Controlled Trial

Irani, Mohamad; Seifer, David B.; Grazi, Richard V.; Julka, Nitasha; Bhatt, Devika; Kalgi, Bharati; Irani, Sara; Tal, Oded; Lambert-Messerlian, Geralyn; Tal, Reshef

doi:10.1210/jc.2015-2580

Cited by 90 publications

(107 citation statements)

References 52 publications

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“…Taken together, vitamin D supplementation in vitamin D-deficient women with PCOS could reduce serum VEGF levels, thus improving PCOS characteristic clinical manifestations. Of note, this is an extension of our previous work in the same patient cohort showing that transforming growth factor-β1 bioavailability decreases following vitamin D treatment [23]. …”

Section: Introductionsupporting

confidence: 58%

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Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial

et al. 2017

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Vascular endothelial growth factor (VEGF) has been suggested to play a role in the pathophysiology of polycystic ovary syndrome (PCOS) and may contribute to increased risk of ovarian hyperstimulation syndrome (OHSS) in affected individuals. Vitamin D (VitD) supplementation improves multiple clinical parameters in VitD-deficient women with PCOS and decreases VEGF levels in several other pathologic conditions. Unveiling the basic mechanisms underlying the beneficial effects of vitamin D on PCOS may enhance our understanding of the pathophysiology of this syndrome. It may also suggest a new treatment for PCOS that can improve it through the same mechanism as vitamin D and can be given regardless of vitamin D levels. Therefore, we aimed to explore the effect of VitD supplementation on serum VEGF levels and assess whether changes in VEGF correlate with an improvement in characteristic clinical abnormalities of PCOS. This is a randomized placebo-controlled trial conducted between October 2013 and March 2015. Sixty-eight VitD-deficient women with PCOS were recruited. Women received either 50,000 IU of oral VitD3 or placebo once weekly for 8 weeks. There was a significant decrease in serum VEGF levels (1106.4 ± 36.5 to 965.3 ± 42.7 pg·mL–1; p < 0.001) in the VitD group. Previously reported findings of this trial demonstrated a significant decrease in the intermenstrual intervals, Ferriman-Gallwey hirsutism score, and triglycerides following VitD supplementation. Interestingly, ∆VEGF was positively correlated with ∆triglycerides (R2 = 0.22; p = 0.02) following VitD supplementation. In conclusion, VitD replacement significantly decreases serum VEGF levels correlating with a decrease in triglycerides in women with PCOS. This is a novel molecular explanation for the beneficial effects of VitD treatment. It also suggests the need to investigate a potential role of VitD treatment in reducing the incidence or severity of OHSS in VitD-deficient women with PCOS.

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Section: Introductionsupporting

confidence: 58%

“…This study was a randomized, single-blind, placebo-controlled trial designed to assess the impact of vitamin D supplementation on serum VEGF levels and PCOS characteristic clinical manifestations in vitamin D-deficient women with PCOS [23]. All participants signed an informed consent form at the time of recruitment.…”

Section: Methodsmentioning

confidence: 99%

Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial

et al. 2017

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“…These findings suggest that vitamin D induced decrease in TGF-β1 bioavailability in PCOS subjects might be a novel mechanism through which vitamin D exerts its beneficial effects on certain aspects of PCOS. 93 In conclusion, despite the abundance of existing literature data regarding supplementation studies, their results are inconsistent and no clear conclusion can be drawn about the effect of vitamin D administration on metabolic and reproductive parameters of PCOS. The aforementioned intervention studies are subject to several limitations, which partially explain the lack of apparent concordance.…”

Section: 95mentioning

confidence: 98%

“…92 Apart from AGEs, TGF-β dysregulation may possibly be im plicated in the pathophysiology of PCOS, given its role in angiogenesis, fibroblast activation and tissue fibrosis, which could explain morphological and vascular alterations of PCOS ovaries. 93 PCOS women display an abnormal increase in TGF-β1 bioavailability, which is mainly attributed to the decreased levels of soluble endoglin (sENG), a circulating receptor that binds TGF-β1.…”

Section: Ii) 25(oh)vitd Status and Hyperandrogenism Markersmentioning

confidence: 99%

Vitamin D and aspects of female fertility

Voulgaris

Papanastasiou

Piaditis

et al. 2017

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The role of vitamin D in female reproduction has been intensively examined over the last few decades. A large body of evidence suggests that vitamin D might have beneficial effects on metabolic/hormonal parameters of PCOS and endometriosis, while it appears to be associated with IVF outcomes. However, due to the heterogeneity among observational and interventional studies, no cause-effect relationship has yet been established. The aim of this review is to analyze recent in vitro animal and human studies which examined the association of vitamin D with disease entities affecting female fertility potential. Recent research data strongly imply that vitamin D is implicated in female reproduction and might represent a beneficial and inexpensive therapeutic approach, in combination with first-line medical treatments, to female infertility.

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“…Vitamin D supplementation in vitamin D-deficient women with reproductive disorder significantly decreases the bioavailability of TGF-β1 28. To test the effect of vitamin D deficiency on fibrosis-related receptor expression, we performed Western blot analysis using myometrial tissues from two groups.…”

Section: Resultsmentioning

confidence: 99%

Diet-induced vitamin D deficiency triggers inflammation and DNA damage profile in murine myometrium

Elhusseini

Elkafas

Abdelaziz

et al. 2018

IJWH

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BackgroundPreviously, we reported a significantly higher prevalence of uterine fibroids (UFs) in African American women. This minority group also commonly suffers from vitamin D deficiency. We have demonstrated that 1,25(OH)2D3 attains a fibroid growth inhibitory impact through its ability to block the G1/S (gap 1/synthesis) phase of the cell cycle. Vitamin D is involved in DNA damage as well as in immune response regulation, anti-inflammation, autoimmunity and cancer. Since most of the prior data on vitamin D and UF were generated in vitro via established cell lines, it was necessary to verify and validate this observation in vivo using a diet-induced vitamin D-deficient mouse model.Materials and MethodsOur model of vitamin D lacking function was established using 8-week exposure of C57/BL6 mice to vitamin D-deficient diet provides evidence of different functions accomplished by vitamin D in the regulation of myometrium homeostasis disrupted in the context of uterine fibroid.ResultsWe found that vitamin D deficiency was associated with increased expression of sex steroid receptors in murine myometrium, increased expression of proliferation related genes, the promotion of fibrosis and enhanced inflammation, and promoted immunosuppression through Tregs expansion in murine myometrium. We also showed that a vitamin D deficient diet enhanced DNA damage in murine myometrium.ConclusionOur model mimics the effects in humans that a lack of vitamin D has and propels the study of in vivo interaction between inflammation, genomic instability and cell proliferation in the myometrium.

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Vitamin D Supplementation Decreases TGF-β1 Bioavailability in PCOS: A Randomized Placebo-Controlled Trial

Cited by 90 publications

References 52 publications

Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial

Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial

Vitamin D and aspects of female fertility

Diet-induced vitamin D deficiency triggers inflammation and DNA damage profile in murine myometrium

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