Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health

Highlights

• Protein-restricted (PR) and branched-chain amino acid (BCAA)-restricted diets improve metabolic health

• Decreasing dietary BCAAs recapitulates many of the benefits of a PR diet

• Low BCAA diet improves metabolic health independently from changes in energy balance

• Dietary protein quality regulates metabolic health independently from protein quantity

Summary

Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.