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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], Pinteraction = 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]; Pinteraction = 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]; Pinteraction = 0.001). Results were not significantly influenced by study duration (Pinteraction = 0.14), age class (Pinteraction = 0.09), or assay provider (Pinteraction = 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.

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Fig. 1: Flowchart of identified and selected studies.
Fig. 2: Effect of vitamin D on circulating FGF23 concentrations.
Fig. 3: Subgroup analyses of vitamin D on mean differences in circulating FGF23 concentrations between intervention and control groups.


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AZ designed the work that led to the submission, AZ and HKB acquired data, and SP played an important role in interpreting the results. AZ drafted the manuscript and HKB and SP revised the manuscript. AZ, HKB, and SP approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Armin Zittermann.

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Zittermann, A., Berthold, H.K. & Pilz, S. The effect of vitamin D on fibroblast growth factor 23: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr 75, 980–987 (2021).

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