The effect of vitamin D on fibroblast growth factor 23: a systematic review and meta-analysis of randomized controlled trials

The phosphaturic hormone fibroblast growth factor 23 (FGF23) is a risk marker of cardiovascular and all-cause mortality. We therefore aimed to synthesize the evidence for the effect of vitamin D administration on circulating FGF23 concentrations. We performed a systematic review and meta-analysis of randomized, placebo-controlled trials (RCTs) in several databases from inception to January 2020. A total of 73 records were identified for full-text review, and 21 articles with 23 studies were included in the final analysis. The selected studies included 1925 participants with 8-156 weeks of follow-up. The weighted mean difference in FGF23 in the vitamin D versus placebo group was +21 pg/ml (95% CI: 13-28 pg/ml; P < 0.001) with considerable heterogeneity among studies (I² = 99%). The FGF23 increment was higher in patients with end-stage kidney/heart failure than in other individuals (+300 pg/ml [95% CI: 41-558 pg/ml] vs. +20 pg/ml [95% CI: 12-28 pg/ml], P_interaction = 0.03), and if baseline 25-hydroxyvitamin D concentrations were <50 nmol/l instead of ≥50 nmol/l (+34 pg/ml [95% CI: 18-51 pg/ml] vs. +9 pg/ml [95% CI: 3-14 pg/ml]; P_interaction = 0.002). Moreover, the FGF23 increment was influenced by vitamin D dose/type (vitamin D dose equivalent ≤ 2000 IU/day: +2 pg/ml [95% CI: 0-3 pg/ml]; vitamin D dose equivalent > 2000 IU/day: +18 pg/ml [95% CI: 6-30 pg/ml]; administration of activated vitamin D: +67 pg/ml [95% CI: 16-117 pg/ml]; P_interaction = 0.001). Results were not significantly influenced by study duration (P_interaction = 0.14), age class (P_interaction = 0.09), or assay provider (P_interaction = 0.11). In conclusion, this meta-analysis of RCTs demonstrates that vitamin D administration of >2000 IU/d vitamin D or activated vitamin D significantly increased concentrations of the cardiovascular risk marker FGF23, especially in patients with end-stage kidney/heart failure.