Mechanisms of Vitamin B12 Absorption in Breast‐Fed Infants

Abstract

ABSTRACTObjectivesThe mechanisms of vitamin B12 absorption in infants are unknown. We investigated whether haptocorrin (HC), a vitamin B12‐binding protein in human milk, facilitates vitamin B12 absorption during the neonatal period or if it occurs by a process similar to that in adults involving another vitamin B12‐binding protein, intrinsic factor (IF).MethodsTo determine whether HC or IF can deliver vitamin B12 to the enterocyte, binding studies using Caco‐2 intestinal cells in culture and purified human milk HC‐[57Co]vitamin B12 or [125I]IF‐vitamin B12 were performed. Determination of IF secretion by infant stomach was investigated by a competitive ELISA on fecal extracts from breast‐fed infants. Determination of receptors specific for IF‐vitamin B12 or HC‐vitamin B12 in infant intestine was achieved by ligand blot analysis using isolated brush border membrane vesicles (BBMV) from fetal and adult intestine and Caco‐2 cells. PCR was performed to identify the IF receptor gene transcript in Caco‐2 cells and fetal intestine.ResultsLimited binding of both HC and IF to Caco‐2 cells was observed; however, HC displayed affinity to low molecular weight proteins in BBMV from fetal intestine and Caco‐2 cells while IF showed affinity for a 240 kDa protein in BBMV from fetal intestine and Caco‐2 cells. IF receptor gene transcript was identified in fetal intestine and Caco‐2 cells. An increase in IF excretion from breast‐fed infants throughout early life was observed.ConclusionsAn IF‐dependent vitamin B12 absorption mechanism appears to be in place in breast‐fed infants. However, IF levels may be too low in early life to participate in vitamin B12 absorption; therefore, haptocorrin may mediate vitamin B12 absorption until the absorption function can be taken over by a more mature IF system.