Vitamin D Deficiency and Its Association with Iron Deficiency in African Children

Abstract

Vitamin D regulates the master iron hormone hepcidin, and iron in turn alters vitamin D metabolism. Although vitamin D and iron deficiency are highly prevalent globally, little is known about their interactions in Africa. To evaluate associations between vitamin D and iron status we measured markers of iron status, inflammation, malaria parasitemia, and 25-hydroxyvitamin D (25(OH)D) concentrations in 4509 children aged 0.3 months to 8 years living in Kenya, Uganda, Burkina Faso, The Gambia, and South Africa. Prevalence of iron deficiency was 35.1%, and prevalence of vitamin D deficiency was 0.6% and 7.8% as defined by 25(OH)D concentrations of <30 nmol/L and <50 nmol/L, respectively. Children with 25(OH)D concentrations of <50 nmol/L had a 98% increased risk of iron deficiency (OR 1.98 [95% CI 1.52, 2.58]) compared to those with 25(OH)D concentrations >75 nmol/L. 25(OH)D concentrations variably influenced individual markers of iron status. Inflammation interacted with 25(OH)D concentrations to predict ferritin levels. The link between vitamin D and iron status should be considered in strategies to manage these nutrient deficiencies in African children.

Keywords: Africa; Vitamin D deficiency; anemia; children; ferritin; hemoglobin; hepcidin; iron; iron deficiency; transferrin saturation.

Figure 1

How the metabolism of vitamin D and iron is interlinked from in vitro and animal studies. 1,25(OH)₂D may influence iron status by reducing hepcidin levels through directly binding to the vitamin D response element (VDRE) in the promoter region of the hepcidin gene (HAMP), decreasing pro-inflammatory cytokines (e.g., IL6, IL1B) and support erythropoiesis [5,6,13,14]. Low iron status may also influence vitamin D status by decreasing the activity of vitamin D activation enzymes (25- and 1α-hydroxylase) [7] and increasing FGF23 [8]. High levels of FGF23 suppress 1α-hydroxylase activity thus reducing 1,25(OH)₂D concentrations [9,15]. Abbreviations: sTfR, soluble transferrin receptor; DMT1, divalent metal transporter 1; DBP vitamin D binding protein; Cp, ceruloplasmin; FGF23, fibroblast growth factor 23; RBC, red blood cell; 7-DHC, 7-dehydrocholesterol.

Figure 2

Map of Africa showing study sites (A), meta-analyses of associations between low vitamin D status (25(OH)D <50 nmol/L) and iron deficiency, iron deficiency anemia and anemia by study site (B) and meta-analyses of associations between low vitamin D status (25(OH)D <50 nmol/L) and individual markers of iron status (C). Abbreviations: sTfR, soluble transferrin receptors; TSAT, transferrin saturation. The map colors represent the predicted posterior predictions of age-standardized P. falciparum prevalence (PfPR2–10) as previously published by Snow et. al. [11]. Regression estimates were obtained from multivariable logistic regression analyses evaluating the effect of vitamin D status (25(OH)D <50 nmol/L against >75 nmol/L) on iron deficiency, iron deficiency anemia and anemia and on individual markers of iron status. Regression models were adjusted for age, sex, season, and inflammation. Meta-analysis of site-specific odd ratios was performed using metan package in STATA. Estimates for the meta-analyses for analyses using vitamin D status defined by 25(OH)D levels of 50–75 nmol/L are presented in Table S1. The map is adapted with permission from Snow et. al. (2008) [11].