The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes

Abstract

Chronic kidney disease affects 40% of adults aged 65 and older. Anemia of CKD is present in 30% of patients with CKD and is associated with increased cardiovascular risk, decreased quality of life, and increased mortality. Hepcidin-25 (hepcidin), the key iron regulating hormone, prevents iron egress from macrophages and thus prevents normal recycling of the iron needed to support erythropoiesis. Hepcidin levels are increased in adults and children with CKD. Vitamin D insufficiency is highly prevalent in CKD and is associated with erythropoietin hyporesponsiveness. Recently, hepcidin levels were found to be inversely correlated with vitamin D status in CKD. The aim of this study was to investigate the role of vitamin D in the regulation of hepcidin expression in vitro and in vivo. This study reports that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the hormonally active form of vitamin D, is associated with decreased hepcidin and increased ferroportin expression in lipopolysaccharide (LPS) stimulated THP-1 cells. 1,25(OH)2D3 also resulted in a dose-dependent decrease in pro-hepcidin cytokines, IL-6 and IL-1β, release in vitro. Further, we show that high-dose vitamin D therapy impacts systemic hepcidin levels in subjects with early stage CKD. These data suggest that improvement in vitamin D status is associated with lower systemic concentrations of hepcidin in subjects with CKD. In conclusion, vitamin D regulates the hepcidin-ferroportin axis in macrophages which may facilitate iron egress. Improvement in vitamin D status in patients with CKD may reduce systemic hepcidin levels and may ameliorate anemia of CKD.

Iron, Hematological Parameters and Blood Plasma Lipid Profile in Vitamin D Supplemented and Non-Supplemented Young Soccer Players Subjected to High-Intensity Interval Training

“…Of note, ferritin levels were not significantly altered either immediately post-test or 1, 6, or 24 h post-test (38). The serum 25-hydroxyvitamin D levels have been inversely correlated with hepcidin, which prevents iron efflux from macrophages, the key cells in iron metabolism, by binding to ferroportin receptor, the only iron exporter (52). It is plausible that vitamin D-supplemented subjects would manifest a greater increase in serum iron than unsupplemented ones in response to interval training; however, serum iron was not examined in the present study.…”

Vitamin D deficiency and the risk of anemia: a meta-analysis of observational studies

“…Vitamin D regulates the hepcidin-ferroportin axis in macrophages which may facilitate iron utilization. 31 Based on these, further mechanism researches need to be conducted to evaluate whether these is a direct causal effect of VDD on anemia.…”

Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial

“…14 Increased availability of iron through suppression of hepcidin may also play a role. 15 Given the potential risks 16,17 and costs associated with ESAs, reducing ESA dose is desirable, particularly if it can be accomplished safely and inexpensively.…”