Common Metabolic Profile in Infants Indicating Impaired Cobalamin Status Responds to Cobalamin Supplementation

Abstract

A metabolic profile consistent with impaired cobalamin status is prevalent in breastfed infants. We investigated whether this profile reflects immature organ systems or impaired cobalamin status. In a single-center, randomized, placebo-controlled trial, we studied 107 six-week-old infants. The infants were randomly assigned to receive either an intramuscular injection of 400 mug of cobalamin or no intervention. Concentrations of cobalamin and folate in serum and total homocysteine, methylmalonic acid, and cystathionine in plasma were determined at enrollment and at the age of 4 months. There were no significant differences between the intervention group (n = 54) and the control group (n = 53) in the concentrations of any vitamin marker at baseline (6 weeks). At 4 months, the supplement-treated infants had a 75% higher median serum cobalamin level and remarkable reductions in median plasma total homocysteine (from 7.46 to 4.57 micromol/L) and methylmalonic acid (from 0.58 to 0.20 micromol/L) levels, whereas levels of both metabolites were essentially unchanged during the follow-up period in the control group. Cobalamin supplementation changed all markers of impaired cobalamin status (low cobalamin, high total homocysteine, and high methylmalonic acid levels) toward a profile observed in cobalamin-replete older children and adults. Therefore, the high total homocysteine and methylmalonic acid levels reported for a large fraction of infants reflect not immature metabolism but rather insufficient cobalamin levels to fully sustain cobalamin-dependent reactions fully.