Evaluating the Leucine Trigger Hypothesis to Explain the Post-prandial Regulation of Muscle Protein Synthesis in Young and Older Adults: A Systematic Review

Abstract

Background: The “leucine trigger” hypothesis was originally conceived to explain the post-prandial regulation of muscle protein synthesis (MPS). This hypothesis implicates the magnitude (amplitude and rate) of post-prandial increase in blood leucine concentrations for regulation of the magnitude of MPS response to an ingested protein source. Recent evidence from experimental studies has challenged this theory, with reports of a disconnect between blood leucine concentration profiles and post-prandial rates of MPS in response to protein ingestion.Aim: The primary aim of this systematic review was to qualitatively evaluate the leucine trigger hypothesis to explain the post-prandial regulation of MPS in response to ingested protein at rest and post-exercise in young and older adults. We hypothesized that experimental support for the leucine trigger hypothesis will depend on age, exercise status (rest vs. post-exercise), and type of ingested protein (i.e., isolated proteins vs. protein-rich whole food sources).Methods: This qualitative systematic review extracted data from studies that combined measurements of post-prandial blood leucine concentrations and rates of MPS following ingested protein at rest and following exercise in young and older adults. Data relating to blood leucine concentration profiles and post-prandial MPS rates were extracted from all studies, and reported as providing sufficient or insufficient evidence for the leucine trigger hypothesis.Results: Overall, 16 of the 29 eligible studies provided sufficient evidence to support the leucine trigger hypothesis for explaining divergent post-prandial rates of MPS in response to different ingested protein sources. Of these 16 studies, 13 were conducted in older adults (eight of which conducted measurements post-exercise) and 14 studies included the administration of isolated proteins.Conclusion: This systematic review underscores the merits of the leucine trigger hypothesis for the explanation of the regulation of MPS. However, our data indicate that the leucine trigger hypothesis confers most application in regulating the post-prandial response of MPS to ingested proteins in older adults. Consistent with our hypothesis, we provide data to support the idea that the leucine trigger hypothesis is more relevant within the context of ingesting isolated protein sources rather than protein-rich whole foods. Future mechanistic studies are warranted to understand the complex series of modulatory factors beyond blood leucine concentration profiles within a food matrix that regulate post-prandial rates of MPS.

Impact of Optimal Timing of Intake of Multi-Ingredient Performance Supplements on Sports Performance, Muscular Damage, and Hormonal Behavior across a Ten-Week Training Camp in Elite Cyclists: A Randomized Clinical Trial

“…This could be explained by the fact that the leucine trigger hypothesis, from whey protein isolate, is insufficient for muscle protein synthesis (MPS) in our study. The leucine trigger hypothesis is because protein administration, especially whey protein isolate, increases blood concentrations of essential amino acids, mainly leucine, and promotes MPS mediated by activation of the target complex of rapamycin 1 (mTORC1) [46,47]. However, there are some considerations that would modify leucine concentration (the dose and source of protein; the type and intensity of exercise), derived from protein supplementation, which could alter MPS [46].…”

“…The leucine trigger hypothesis is because protein administration, especially whey protein isolate, increases blood concentrations of essential amino acids, mainly leucine, and promotes MPS mediated by activation of the target complex of rapamycin 1 (mTORC1) [46,47]. However, there are some considerations that would modify leucine concentration (the dose and source of protein; the type and intensity of exercise), derived from protein supplementation, which could alter MPS [46]. Therefore, the differences observed in the groups supplemented with MIPS compared to GC would justify supplementation with MIPS, because MPS would be increased attenuating muscle damage.…”

Increased protein intake derived from leucine-enriched protein enhances the integrated myofibrillar protein synthetic response to short-term resistance training in untrained men and women: a 4-day randomized controlled trial

“…Recently, we reported that consuming a protein and leucine-enriched bar -formulated with 16 g of a blend of micellar casein, whey protein, and whey protein hydrolysate -induced aminoacidemia comparable to consuming a single higher-protein-containing meal (0.5g of protein/kg) (Traylor et al 2021). Previous studies also reported that higher leucine-containing proteins enhance MyoPS and whole-body protein synthesis in young and older adults (Glynn et al 2010;Zaromskyte et al 2021). The effect of leucine on daily MyoPS can be independent of daily protein intake (Devries et al 2018a(Devries et al , 2018bMurphy et al 2016).…”

Peripheral Amino Acid Appearance Is Lower Following Plant Protein Fibre Products, Compared to Whey Protein and Fibre Ingestion, in Healthy Older Adults despite Optimised Amino Acid Profile

“…Overall, beyond differences in intake, our data indicate that the peripheral AA appearance of threonine, methionine, and cysteine, and to a lesser extent, leucine and isoleucine, are dependent on the protein sources in older adults. Although in this study, leucine concentrations were enough to stimulate MPS in healthy older adults based on previous findings [ 96 , 97 ], the remaining IAA (e.g., methionine and threonine), more so than NIAA [ 98 , 99 ], must also be present in adequate concentrations at the same time to act as precursors and allow efficient protein accretion; otherwise, they are referred to as limiting AA [ 100 , 101 ]. Therefore, a delay in and/or insufficient IAA availability, as seen in this and other studies examining plant protein postprandial curves [ 18 , 19 , 23 , 48 , 73 , 74 , 76 ], combined with an ageing effect hindering digestion and absorption [ 84 , 102 ], is expected to have a detrimental impact on the optimal utilisation of all the other AA in the PPF products.…”