Methionine requirement of the enterally fed term infant in the first month of life in the presence of cysteine

Background: The essential amino acid methionine can be used for protein synthesis but also serves as a precursor for homocysteine and cysteine. Objective: The objective of this study was to determine the minimal obligatory methionine requirement of infants in the presence of excess cysteine (91 mg . kg(-1) . d(-1)) by using the indicator amino acid oxidation (IAAO) method with L-[1-C-13]phenylalanine as the indicator. Design: Fully enterally fed term infants <1 mo of age were randomly assigned to methionine intakes that ranged from 3 to 59 mg . kg(-1) . d(-1) as part of an elemental formula. After 1 d of adaptation to the test diet, [C-13]bicarbonate and L[1-C-13]phenylalanine tracers were given enterally. Breath samples were collected at baseline and during isotopic plateaus. The mean methionine requirement was determined by using biphasic linear regression crossover analysis on the fraction of (CO2)-C-13 recovery from L-[1-C-13]phenylalanine oxidation ((FCO2)-C-13). Data are presented as means +/- SDs. Results: Thirty-three neonates (gestational age: 39 +/- 1 wk) were studied at 13 +/- 6 d. With increasing methionine intakes, (FCO2)-C-13 decreased until a methionine intake of 38 mg . kg(-1) . d(-1); additional increases in methionine intake did not affect (FCO2)-C-13. The mean methionine requirement was determined at 38 mg . kg(-1) . d(-1), and the upper and lower CIs were 48 and 27 mg . kg(-1) . d(-1) respectively (P <0.0001, r(2) = 0.59). Conclusions: Although the current recommended methionine intake of 28 mg kg(-1) . d(-1) is within the CIs of our study, the estimated mean requirement is substantially higher. However, most of the infant formulas provide a methionine intake of 49-80 mg . kg(-1) . d(-1), which is above the upper Cl of our study. This trial was registered at www.trialregister.nl as NTR1610. Am J Clin Nutr 2012;95:1048-54