Vitamin D and anemia: insights into an emerging association

Abstract

Purpose of review: The current review highlights recent findings in the emerging association between vitamin D and anemia through discussion of mechanistic studies, epidemiologic studies, and clinical trials.

Recent findings: Vitamin D has previously been found to be associated with anemia in various healthy and diseased populations. Recent studies indicate that the association may differ between race and ethnic groups and is likely specific to anemia of inflammation. The mechanism underlying this association involves the reduction of proinflammatory cytokines by vitamin D and the direct suppression of hepcidin mRNA transcription. There is also evidence that vitamin D may be protective against anemia by supporting erythropoiesis. Other calciotropic hormones including fibroblast growth factor 23, and parathyroid hormone have also been found to be associated with iron homeostasis and erythropoiesis.

Summary: Recent advances in our understanding of the association between vitamin D and anemia suggest that maintenance of sufficient vitamin D status may be important in preventing anemia, particularly in diseases characterized by inflammation. Early clinical trials have been promising, but further research is needed to define the efficacy of vitamin D as a future approach for the treatment of anemia.

Conflict of interest statement

Conflicts of interest

None

Figures

Figure 1. Alterations in Iron Recycling in Anemia of Inflammation and Proposed Role of Vitamin D

A. Alterations in Iron Recycling in Anemia of Inflammation: Iron recycling, under non-pathologic conditions, involves transferrin-bound iron in circulation traveling to the bone marrow to support erythropoiesis. Upon senescence, red blood cells (RBCs) are engulfed by macrophages and iron is recycled back into circulation to support further erythropoiesis. Dietary iron may also enter the circulating pool from absorption in the duodenum based on the body’s needs. In anemia of inflammation, elevations in pro-inflammatory cytokines suppress erythropoiesis in the bone marrow and shorten RBC lifespan due to increased macrophage activation and erythrophagocytosis. Cytokines IL-6 and IL-1β stimulate the liver to up-regulate expression of hepcidin antimicrobial peptide (HAMP). Hepcidin inhibits iron egress from cells of the reticuloendothelial system, including enterocytes and macrophages, by binding and eventual degradation of the cellular iron exporter, ferroportin, resulting in decreased iron absorption and increased iron sequestration in the macrophage. Collectively, depressed erythropoiesis, shortened RBC lifespan, iron sequestration in the macrophage, and reduced iron absorption impairs iron recycling and results in insufficient iron available for erythropoiesis and hemoglobin synthesis, ultimately leading to anemia. B. Proposed Role of Vitamin D in Counteracting Anemia of Inflammation: Vitamin D has been shown to promote erythropoiesis by increasing erythroid progenitor proliferation and decreasing pro-inflammatory cytokines. Additionally, by decreasing hepcidin-stimulatory pro-inflammatory cytokines, and through direct transcriptional regulation of the HAMP gene, vitamin D may suppress hepcidin expression. Decreases in pro-inflammatory cytokines and hepcidin may increase iron bioavailability for erythropoiesis and hemoglobin synthesis by restoring iron recycling, preventing iron sequestration in macrophages, and removing impairments on iron absorption, thus protecting against anemia.

Figure 1. Alterations in Iron Recycling in Anemia of Inflammation and Proposed Role of Vitamin D

A. Alterations in Iron Recycling in Anemia of Inflammation: Iron recycling, under non-pathologic conditions, involves transferrin-bound iron in circulation traveling to the bone marrow to support erythropoiesis. Upon senescence, red blood cells (RBCs) are engulfed by macrophages and iron is recycled back into circulation to support further erythropoiesis. Dietary iron may also enter the circulating pool from absorption in the duodenum based on the body’s needs. In anemia of inflammation, elevations in pro-inflammatory cytokines suppress erythropoiesis in the bone marrow and shorten RBC lifespan due to increased macrophage activation and erythrophagocytosis. Cytokines IL-6 and IL-1β stimulate the liver to up-regulate expression of hepcidin antimicrobial peptide (HAMP). Hepcidin inhibits iron egress from cells of the reticuloendothelial system, including enterocytes and macrophages, by binding and eventual degradation of the cellular iron exporter, ferroportin, resulting in decreased iron absorption and increased iron sequestration in the macrophage. Collectively, depressed erythropoiesis, shortened RBC lifespan, iron sequestration in the macrophage, and reduced iron absorption impairs iron recycling and results in insufficient iron available for erythropoiesis and hemoglobin synthesis, ultimately leading to anemia. B. Proposed Role of Vitamin D in Counteracting Anemia of Inflammation: Vitamin D has been shown to promote erythropoiesis by increasing erythroid progenitor proliferation and decreasing pro-inflammatory cytokines. Additionally, by decreasing hepcidin-stimulatory pro-inflammatory cytokines, and through direct transcriptional regulation of the HAMP gene, vitamin D may suppress hepcidin expression. Decreases in pro-inflammatory cytokines and hepcidin may increase iron bioavailability for erythropoiesis and hemoglobin synthesis by restoring iron recycling, preventing iron sequestration in macrophages, and removing impairments on iron absorption, thus protecting against anemia.