Background & aims: An anabolic state can be achieved upon intravenous amino acid administration during the immediate postnatal phase despite a low energy intake. The optimal dosing of amino acid and energy intake has yet to be established. The aim was to quantify the efficacy of early initiation of parenteral lipids and increased amounts of amino acids on metabolism and protein accretion in very low birth weight infants. Methods: 28 very low birth weight infants were randomized to receive parenteral nutrition with glucose and either 2.4 g amino acids/(kg.d) (control group), 2.4 g amino acids/(kg.d) plus 2-3 g lipid/(kg.d) (AA + lipid group), or 3.6 g amino acids/(kg.d) plus 2-3 g lipid/(kg.d) (high AA + lipid group) from birth onward. On postnatal day 2, we performed a stable isotope study with [1-C-13]phenylalanine, [ring-D-4] tyrosine, [U-C-13(6),N-15]leucine, and [methyl-D-3]alpha-ketoisocaproic acid to quantify intermediate amino acid metabolism. Results: The addition of lipids only had no effect on phenylalanine metabolism, whereas the addition of both lipids and additional amino acids increased the amount of phenylalanine used for protein synthesis. In addition, high amino acid intake significantly increased the rate of hydroxylation of phenylalanine to tyrosine, increasing the availability of tyrosine for protein synthesis. However, it also increased urea concentrations. Increasing energy intake from 40 to 60 kcal/(kg.d) did not increase protein efficiency as measured by phenylalanine kinetics. The leucine data were difficult to interpret due to the wide range of results and inconsistency in the data between the phenylalanine and leucine models. Conclusions: High amino acid and energy intakes from birth onwards result in a more anabolic state in very low birth weight infants, but at the expense of higher urea concentrations, which reflects a higher amino acid oxidation. Long-term outcome data should reveal whether this policy deserves routine implementation. (C) 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.