The effect of vitamin D-calcium co-supplementation on inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials

Data on the effect of vitamin D-calcium co-supplementation on inflammatory biomarkers, compared to placebo or intake of calcium and vitamin D supplements alone, are conflicting. The current systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize available findings on the effect of vitamin D-calcium co-supplementation on inflammatory biomarkers in adults. Online databases including PubMed, Scopus, ISI Web of Science and Google Scholar were searched using relevant keywords up to June 2019. We included RCTs investigating the effect of vitamin D-calcium co-supplementation, compared to placebo or intake of calcium and vitamin D supplements alone, on inflammatory biomarkers. In total, 8 RCTs that enrolled 706 participants, aged >= 18 years, were included. Pooling 9 effect sizes from 8 RCTs on C-reactive protein (CRP) levels revealed a significant reducing effect of vitamin D-calcium co-supplementation on serum CRP concentrations compared to placebo intake (WMD: -0.82, 95% CI: -1.56, -0.07 mg/L, P = 0.03). However, this beneficial effect became non-significant when compared to the intake of calcium and vitamin D supplements alone. Also, we found that the associations of vitamin D-calcium dosages and duration of intervention with the reduction in CRP concentrations were in a non-linear fashion. Combining 5 effect sizes for IL-6 and 3 effect sizes for TNF-alpha, we found no significant effect of joint calcium and vitamin D supplementation on serum concentrations of IL-6 (WMD: -1.45, 95% CI: -5.31, 2.41 pg/mL, P = 0.46) and TNF-alpha (WMD: -0.79, 95% CI: -2.19, 0.61 pg/mL, P = 0.26). We found a beneficial effect of vitamin D-calcium co-supplementation on serum CRP concentrations. However, such a beneficial effect was not seen for IL-6 and TNF-alpha concentrations.