FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study

Recent studies have described relationships between iron status and fibroblast growth factor-23 (FGF23) but the possible confounding effects of inflammation on iron status have not been considered. The aims of this study were a) to consider a relationship between FGF23 and inflammation b) to identify relationships between iron status and FGF23 whilst correcting for inflammation and c) to assess the relationship between changes in FGF23 and iron status after supplementation.

FGF23 was not significantly correlated with CRP. At baseline, all markers of iron status were significantly correlated with FGF23. Ferritin was the strongest independent inverse predictor of FGF23 in subjects with and without elevated CRP (coefficient (SE)): All subjects=−0.57 (0.12), R²=22.3%, P≤0.0001; subjects with CRP < 5 mg/dL=−0.89 (0.14), R²=38.9%, P≤0.0001. FGF23 was elevated in 28% of children at baseline and 16% post supplementation (P=0.1). Improved iron status was associated with a decrease in FGF23 concentration in univariate (ferritin =−0.41 (0.11), R²=14.1%, P=0.0004; haemoglobin=−2.22 (0.64), R²=12.5%, P=0.0008; zinc protoporphyrin=1.12 (0.26), R²=18.6%, P≤0.0001) and multivariate analysis (R²=33.1%; ferritin=−0.36 (0.10), P=0.0007, haemoglobin = −1.83 (0.61), P=0.004, zinc protoporphyrin=0.62 (0.26), P=0.02).

Iron status rather than inflammation is a negative predictor of plasma FGF23 concentration. Improvements in iron status following iron supplementation are associated with a significant decrease in FGF23 concentration.