Abstract
Background: Branched-chain amino acids (BCAAs: leucine, isoleucine, valine) account for 35% of skeletal muscle essential amino acids (AAs). As such, they must be provided in the diet to support peptide synthesis and inhibit protein breakdown. Although substantial evidence has been collected about the potential usefulness of BCAAs in supporting muscle function and structure, dietary supplements containing BCAAs alone may not be effective in controlling muscle protein turnover, due to the rate-limiting bioavailability of other AAs involved in BCAAs metabolism. Methods: We aimed to evaluate the in vivo/ex vivo effects of a 4-week treatment with an oral formulation containing BCAAs alone (2:1:1) on muscle function, structure, and metabolism in a murine model of physiological exercise, which was compared to three modified formulations combining BCAAs with increasing concentrations of L-Alanine (ALA), an AA controlling BCAAs catabolism. Results: A preliminary pharmacokinetic study confirmed the ability of ALA to boost up BCAAs bioavailability. After 4 weeks, mix 2 (BCAAs + 2ALA) had the best protective effect on mice force and fatigability, as well as on muscle morphology and metabolic indices. Conclusion: Our study corroborates the use of BCAAs + ALA to support muscle health during physiological exercise, underlining how the relative BCAAs/ALA ratio is important to control BCAAs distribution.
Highlights
Branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) are three proteinogenic essential amino acids (EAAs) accounting for about 21% of total protein content in the human body [1].Skeletal muscle tissue is our major reservoir of the BCAAs, which is provided by diet
We evaluated the effects exerted in vivo and ex vivo by an oral formulation containing BCAAs upon muscle function, structure, and metabolism in C57BL/6J wild type (WT) mice subjected to a protocol of incremental, non-harmful exercise on a horizontal treadmill
Our head-to-head comparison showed that the formulation with the greatest overall efficacy on the main in vivo and ex vivo parameters related to exercise was mix 2, containing BCAAs (2:1:1) + 2ALA, in relation to increased systemic and tissue action of the AA
Summary
Branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) are three proteinogenic essential amino acids (EAAs) accounting for about 21% of total protein content in the human body [1].Skeletal muscle tissue is our major reservoir of the BCAAs, which is provided by diet. The leucine metabolite β-hydroxy-β-methyl butyrate (HMB) exerts a parallel inhibitory effect on proteolysis by suppressing the ubiquitin–proteasome system [8], while branched-chain keto acids (BCKAs) prevent protein degradation in vitro [9]. These actions have beneficial effects on muscle mass in health and muscle-wasting conditions [3,4]. 35% of skeletal muscle essential amino acids (AAs) As such, they must be provided in the diet to support peptide synthesis and inhibit protein breakdown. Conclusion: Our study corroborates the use of BCAAs + ALA to support muscle health during physiological exercise, underlining how the relative BCAAs/ALA ratio is important to control BCAAs distribution
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