Effect of Calcium‑Vitamin D Co‑Supplementation on Insulin, Insulin Sensitivity, and Glycemia: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of calcium-vitamin D co‑supplementation on insulin, insulin sensitivity, and glycemia. A systematic search was carried out in Web of Science, PubMed, EMBASE, Scopus, and Cochrane library without any language and time restriction up to 12 August 2018, to retrieve the RCTs, which examined the effect of calcium and vitamin D co-supplementation on fasting blood glucose (FBG), insulin, HOMA-B, HOMA-IR, and QUICKI. Meta-analyses were carried out using a random effects model, and I2 indexes were used to evaluate the heterogeneity. Search yielded 2225 publications. Twelve RCTs with 4395 patients were eligible. Results demonstrated that calcium and vitamin D co‑supplementation had significantly reducing effects on FBG, HOMA-IR and circulating levels of insulin. As the subgroup analysis demonstrated, short-term (≤12 weeks) calcium and vitamin D co‑supplementation had a significant reducing effect on FBG. However, beneficial effects of calcium and vitamin D co‑supplementation on circulating level of insulin and HOMA-IR were seen in both short-term and long-term (>12 weeks) supplementations. Furthermore, we found that high doses of vitamin D and calcium co-supplementation (vitamin D≥2000 mg/day and calcium≥1000 mg/day) had significantly reducing effects on FBG, HOMA-IR and insulin. Present meta-analysis indicated the beneficial effects of high-dose and short-term combined vitamin D and calcium supplementation on insulin, insulin resistance and glycemia; however, further large-scale RCTs with adequate and multiple dosing schedules are needed.

Association between serum 25-hydroxy vitamin D level and metabolic associated fatty liver disease (MAFLD)—a population-based study

“…The new definition of MAFLD emphasizes on the metabolic disorder among patients with liver steatosis and aims to select patients at high risk of disease progression and to treat patients holistically, therefore the control of metabolic syndrome could be more important than the control of liver injury alone in MAFLD cases. Although the serum 25(OH)D level was not associated with fibrosis in MAFLD in this study, high dose of vitamin D and calcium co-supplementation can significantly reduce FBG and HOMA-IR [30], indicating the beneficial effect of vitamin D supplementation in MAFLD needs further investigation.…”

The Interplay Between Bone and Glucose Metabolism

“…Data from clinical studies showed that calcium and vitamin D supplementation might exert beneficial effect on glucose metabolism. However, different results have been observed among studies (116,117). The most recent meta-analysis including 12 studies with 4,395 participants in the intervention arm and 4,551 in the control group demonstrated that calcium and vitamin D supplementation significantly reduce fasting glucose, HOMA-IR, and insulin levels (116).…”

Effects of vitamin D3 on glucose metabolism in patients with severe osteoarthritis: A randomized double‐blind trial comparing daily 2000 with 800 IU vitamin D3

“…Interestingly, participants with an elevated CRP at baseline (>6.2 mg/L) improved only in the standard dose group. Although it might solely be attributable to chance, Asbaghi et al made a similar observation that higher vitamin D (>2000 IU/day) seemed to have less effect on HOMA‐IR and insulin 41 …”