Network meta-analysis uncovers dose-dependent glycemic improvements from vitamin D in adults with prediabetes, indicating extremely high doses best reduce insulin resistance.
Context It is evident that the supplementation of vitamin D has been identified as a potential intervention strategy with the objective of reducing the incidence of type 2 diabetes (T2D). However, the optimal dosage of vitamin D supplementation to improve prediabetes in intervention studies remains to be elucidated. Objective The objective of this study was to evaluate the effects vitamin D supplement dose in adults with prediabetes, by conducting a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs). Data Sources The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to March 2025. Data Extraction An NMA of multiple doses, including low (LDS) (<1000 IU d–1), medium (MDS) (1000-2000 IU d–1), high (HDS) (2000-4000 IU d–1), and extremely high (EHDS) (≥4000 IU d–1) dosing strategies, was conducted. Data Analysis Our NMA of 21 RCTs suggested that, compared with control, LDS decreased fasting blood glucose (FBG) and was ranked as the most effective in decreasing FBG (surface under the cumulative ranking curve = 87.9%). In terms of decreasing fasting insulin (FIN) level, EHDS (mean difference [MD] = −0.30; 95% CI –0.56 to −0.03) was more effective than control. And EHDS (MD = −2.82; 95% CI, –5.06 to −0.57) was more efficacious than LDS in reducing the homeostasis model assessment for insulin resistance (HOMA-IR) value. The EHDS was the top-ranked strategy in reducing FIN, HOMA-IR, HOMA of β-cell function, 2-h postload glucose, and new-onset T2D, and for improving normal glucose regulation. Conclusion The findings suggest that vitamin D supplementation at different doses in adults with prediabetes may improve glycemic parameters in different dimensions. However, there are few low-dose studies, and more high-quality studies are needed to confirm this. Systematic Review Registration PROSPERO registration no. CRD420251108418.
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