Vitamin D Supplementation Ameliorates Metabolic Dysfunction in Patients with PCOS: A SystematicReview of RCTs and Insight into the Underlying Mechanism

Abstract

Objective: Evidence suggests that vitamin D deficiency correlated with metabolic disorders in women with polycystic ovary syndrome (PCOS). We conducted this systematic review and meta-analysis to evaluate the impact of vitamin D supplementation alone on glucose, lipid, and androgen parameters and inflammation biomarkers in women with PCOS.

Methods: Literature research was conducted in Pubmed, Embase, Web of Science, Clinical Trials, and Cochrane Library to identify relevant randomized controlled trials (RCTs) up to March 2020. The effect of vitamin D supplementation alone on women with PCOS was compared with administration of placebo. The systematic review and meta-analysis protocol was registered in the International Prospective Register of Systematic Reviews (Prospero) as number CRD42020157444.

Results: Thirteen randomized controlled trials with 824 patients in total were included. Serum FPG, fasting insulin, HOMA-IR, and VLDL-C were significantly decreased in the vitamin D group versus placebo. Vitamin D supplementation group also showed a significantly elevated level of QUICKI. No significant impact was seen on serum triglyceride, total-C, LDL-C, HDL-C, total testosterone, DHEAS, SHBG, or hs-CRP. Subgroup analysis demonstrated that oral vitamin D intake had significantly decreased serum triglyceride and total-C level in women with PCOS who have vitamin D deficiency (serum vitamin D < 20 ng/ml).

Conclusion: The findings of the present meta-analysis indicate that vitamin D supplementation exerted favorable effects among women with PCOS on glucose metabolism and lipid metabolism, especially in vitamin D deficient women, but had no significant effect on the androgenic profile or inflammation status.

Figure 1

Flowchart of search strategy.

Figure 2

Quality assessment for randomized controlled trials included on basis of Cochrane risk of bias assessment tool.

Figure 3

Forest plot of vitamin D concentration in experimental and placebo groups.

Figure 4

(a) Forest plot of FPG level in experimental and placebo groups. (b) Forest plot of FPG level in women with PCOS supplemented by day, week, and 20 days. (c) Forest plot of FPG level in women with PCOS who have vitamin D deficiency or insufficiency. (d) Forest plot of FPG level in women with PCOS supplemented with low- or high-dose vitamin D.

Figure 5

(a) Forest plot of fasting insulin level in experimental and placebo groups. (b) Forest plot of HOMA-IR in experimental and placebo groups. (c) Forest plot of QUICKI in experimental and placebo groups.

Figure 6

(a) Forest plot of total-C level in experimental and placebo groups. (b) Forest plot of LDL-C level in experimental and placebo groups. (c) Forest plot of VLDL-C level in experimental and placebo groups. (d) Forest plot of HDL-C level in experimental and placebo groups. (e) Forest plot of triglycerides in experimental and placebo groups. (f) Forest Plot of triglycerides in women with PCOS who have vitamin D deficiency or insufficiency. (g) Forest plot of total-C in women with PCOS who have vitamin D deficiency or insufficiency. (h) Forest plot of triglycerides in women PCOS supplemented by day, week, two weeks, and 20 days. (i) Forest plot of total-C in women with PCOS supplemented by day, week, and 20 days. (j) Forest plot of triglycerides in women with PCOS supplemented with a low or high dose. (k) Forest plot of total-C in women with PCOS supplemented with a low dose or high dose. (l) Forest plot of LDL-C in women with PCOS supplemented with a low dose or high dose.

Figure 7

(a) Forest plot of total testosterone level in experimental and placebo groups. (b) Forest plot of DHEAS level in experimental and placebo groups. (c) Forest plot of SHBG level in experimental and placebo groups. (d) Forest plot of hs-CRP level in experimental and placebo groups.

Figure 8

Funnel plot of standard error by standard differences in the means of plasma: (a) vitamin D; (b) FPG; (c) fasting insulin; (d) HOMA-IR; (e) QUICKI; (f) triglycerides; (g) total-C; (h) HDL-C; (i) LDL-C; (j) VLDL-C; (k) total testosterone; (l) DHEAS; (m) SHBG; (n) hs-CRP in selected trials.

Figure 9

Potential mechanism of therapeutic effect of vitamin D on women with PCOS.