Determining Ideal Balance Among Branched-Chain Amino Acids (BCAA) as a Proof of Concept Study in Healthy Children

Abstract

Abstract Objectives Medical foods for children with in-born errors of metabolism (propionic academia, PROP) are formulated with imbalanced mixture of the BCAA (high leucine, to minimal or no valine and isoleucine), and therefore their use is controversial. The objective of the current study was to determine an ideal BCAA ratio at which total body protein synthesis is optimized in healthy children using the indicator amino acid oxidation (IAAO) method. Methods The study design was based on the oxidation of the stable isotope L-[1–,13C] phenylalanine to ,13CO2 to compare protein synthesis among seven different BCAA ratios. Leucine intake was gradually reduced from current high doses in medical foods; isoleucine and valine were kept constant. This study was done as a proof of concept in healthy children, to allow characterization of the metabolic responses to wide range of leucine test intakes, to help design narrow BCAA ratio range to test in children with PROP. Results A total of 8 healthy children were studied, completing 42 study days. ANOVA showed significant differences in F13CO2 with different BCAA ratios; P value <0.001. A BCAA ratio of (leucine: Isoleucine: Valine = 1:0:0) was associated with the highest F13CO2 compared to other ratios (p value <0.001), indicating low total body protein synthesis. By reducing leucine intake, with BCAA ratio between (1: 0.26: 0.28 to 1:0.35:0.4) protein synthesis was optimized. Conclusions Using the IAAO method in healthy children, we tested for the first time the effect of different BCAA ratios on protein synthesis. Results from this study confirmed that the BCAA ratio of (leucine: Isoleucine: Valine = 1:0:0), which is similar to the ratio in medical foods, limited total body protein synthesis. Furthermore, a balanced BCAA ratio that optimized protein synthesis was found to be between (1: 0.26: 0.28) and (1: 0.35:0.4). Thus, we propose reformulating the BCAA mixture in medical foods, by reducing leucine content by 50%. Future research in children with PROP with our proposed BCAA ratio is necessary to confirm improved patient growth outcomes. Funding Sources Faculty of Applied Medical Sciences, Department of Clinical Nutrition, King Abdulaziz University and BC Children's Hospital Research Institute.