Optimizing vitamin D status in polycystic ovary syndrome: a systematic review and dose-response meta-analysis

Context: Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder in women of reproductive age. Vitamin D supplementation is a promising complementary therapy for PCOS, yet there is no consensus on an optimal dose, leading to a lack of evidence-based supplementation guidelines. Objective: The objective of this study was to conduct a vitamin D dose-response meta-analysis among women with PCOS. Data sources: MEDLINE, CINAHL, and EMBASE data -bases from inception to November 2022 were searched for relevant articles. Data extraction: Study screening and bias assessment were conducted by 2 independent reviewers. Eight relevant studies were identified; data for serum 25(OH)D (nmol/L) at baseline and at 12 weeks in each intervention group (mean +/- SD) and vitamin D dose were extracted. Data analysis: Estimates across studies were used to create a pooled curve, using restricted cubic splines with knots at the 10th, 50th, and 90th percentiles of the distribution of doses, to estimate the mean difference in effect for serum 25(OH)D at each dose compared with 0 IU/day. Sensitivity analyses were conducted fixing knots at 4000 IU/day and 7000 IU/day, which were a priori identified as potentially important thresholds, and to assess model fit and estimate heterogeneity. The pooled analysis demonstrated strong evidence of a dose- response relationship (P < .001), suggesting an increasing effect with increasing dose. An initial increase in serum 25(OH)D was evident until doses of approximately 3000 IU/day; this was followed by a plateau in effect between approximately 3000 IU/day and 5000 IU/day. The effect of supplementation with >5000 IU/day was unclear, given the minimal data at higher doses. The curve produced robust results for moderate doses (3000 IU/day to 4000 IU/day), which were not sensitive to model specification. Conclusion: Women with PCOS are responsive to vitamin D supplementation, but the benefit of providing doses of >3000 IU/day appears mini -mal. Further data is required to determine dose-response at doses of >5000 IU/ day, and whether higher intakes provide a clinically meaningful advantage in this population.