Common metabolic profile in infants indicating impaired cobalamin status responds to cobalamin supplementation

OBJECTIVE. 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. METHODS. 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 mu g 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. RESULTS. 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 mu mol/ L) and methylmalonic acid ( from 0.58 to 0.20 mu mol/ L) levels, whereas levels of both metabolites were essentially unchanged during the follow-up period in the control group. CONCLUSIONS. 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.