Blood Manganese Modifies the Relationship Between Iron Status and Blood Lead in Ugandan Children

Abstract

ObjectivesNinety-seven % of children living in the Katanga area of Kampala, Uganda, have elevated blood lead (Pb), and 30% have elevated manganese (Mn). Children with iron deficiency (ID) may have higher blood concentrations of both metals as each share the same intestinal transported as iron (DMT1). We characterized the iron status of children living in Katanga and determined whether children with poorer iron status had elevated blood Pb and Mn. We hypothesized that higher concentrations of Pb and Mn will be associated with iron deficiency. MethodsWe measured plasma concentrations of iron biomarkers [hemoglobin (Hb), ferritin, soluble transferrin receptor (sTfR), hepcidin] in 100 children 6–59 months living in the Katanga urban settlement who had participated in a survey environmental metals exposure. We compared whole blood concentrations of Pb and Mn by different definitions of ID and by median hepcidin (Hb < 11.0 g/dL; sTfR > 8.3 mg/L; ferritin < 12.0 μg/L; hepcidin < 14.9 ng/mL) using t-test (Pb) and Wilcoxon rank-sum test (Mn). We examined the association of each iron marker with Pb and Mn while accounting for child age using multiple linear regression. ResultsMore than one-third of children had Hb < 11.0 g/dL [n (%): 36 (36.7)], and one in five were ID by either ferritin [20 (20.4)] or sTfR [23 (23.5)]. Median Mn was higher in children with ID defined by either sTfR or ferritin [(ID, not ID): sTfR (21.8 mg/L, 11.2 mg/L); ferritin (19.7 μg/L, 12.0 μg/L), p < 0.001 for both] and in children with low hepcidin [(low, high): (16.59 ng/mL, 10.6 ng/mL), p < 0.01]. In contrast, mean Pb level was lower in children with vs. without ID defined by sTfR [(5.0 mg/L, 6.5 mg/L), p = 0.01]. Having high Mn (>18.3 μg/L) modified the association between blood lead and ID: high Mn was associated with ID and lower Pb; low Mn was associated with no ID and higher Pb. ConclusionsID was prevalent in the Katanga area. Children with ID had higher Mn and lower Pb, suggesting preferential absorption of Mn over Pb in children with ID. Mn may inhibit Pb absorption in children with ID, but because both Mn and Pb are neurotoxic, immediate environmental remedies such as the use of low-Mn cement must be implemented. Funding SourcesThis research is supported by University of Minnesota School of Medicine Innovation Award (Dr. Sarah Cusick).