(OR14-03-26) Limited Anabolic Response to High Amounts of Essential Amino Acids Feeding Measured by a Novel Stable Isotope Pulse Approach

Objectives: Essential amino acid (EAA)-rich protein is vital for muscle health in older adults, but it’s unclear whether anabolic resistance to high EAA intake occurs. Methodological challenges, such as underestimating the true appearance of amino acids, hinder anabolic response calculations. We developed a novel stable-isotope pulse approach¹ with compartmental modeling to estimate the intracellular appearance of EAA and non-essential amino acids (NEAAs) post high EAA intake.

Methods: Eleven healthy adults (60-80y) participated in a randomized, placebo-controlled, single-blind, crossover study over three non-consecutive days, where they consumed an oral mixture via sip feeding every 20 minutes for 6 hours: EAA-normal (20g), EAA-high (45g), and water (placebo). Three hours into feeding, a stable-isotope tracer pulse (labeled EAA, branched-chain amino acids (BCAA), keto acids (BCKA), and NEAAs) was given intravenously (IV) to evaluate whole-body and compartmental kinetics. Blood samples were collected pre/post IV pulse and analyzed by LC-MS/MS and GC-MS. Data are mean (µmol/min) stats by GLMM. <

Results: EAA-high, compared to EAA-normal, decreased plasma concentrations of asparagine, glycine, and serine, but increased EAAs, HMB, and BCKAs (all p< 0.001). EAA-high proportionally increased intracellular disposal of EAAs, HMB, KMV, KIC, glutamine, and tyrosine (TYR) (p < 0.001). EAA-high showed higher phenylalanine (PHE) metabolism compared to EAA-normal (85 vs 38 consumed, 104 vs 46 disposed, 64 vs 22 to TYR, 40 vs 24 for Protein Synthesis (PS); p< 0.001). However, the % available for PS decreased from 63 to 47%. EAA-high increased the extracellular (Q₁) and intracellular (Q₂) pool of EAAs (except histidine), BCKAs, HMB, and TYR (p < 0.001) but reduced Q₁ and Q₂for glycine and ornithine (p < 0.001).

Conclusions: The pulse tracer approach measures intracellular amino acid metabolism during consumption of free amino acids¹. Doubling EAA intake didn’t double the anabolic response, likely because the EAA mixtures lacked TYR, increasing the need for PHE-to-TYR conversion to meet the TYR requirement for PS. We hypothesize that endogenous NEAA availability limits EAAs anabolic gains, especially at high levels. Compartmental modeling increases our insights in metabolism of net PS after amino acid and protein meal intakes.

¹ Deutz et al CN2025

Funding Sources: N/A