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

2021 ◽  
Vol 8 ◽  
Author(s):  
Gabriele Zaromskyte ◽  
Konstantinos Prokopidis ◽  
Theofilos Ioannidis ◽  
Kevin D. Tipton ◽  
Oliver C. Witard

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.

2015 ◽  
Vol 173 (1) ◽  
pp. R25-R34 ◽  
Author(s):  
Jorn Trommelen ◽  
Bart B L Groen ◽  
Henrike M Hamer ◽  
Lisette C P G M de Groot ◽  
Luc J C van Loon

BackgroundThough it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis ratesin vivoin humans.ObjectiveTo assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults.DesignA systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects.ConclusionsFrom the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50 000 pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults.


2018 ◽  
Vol 74 (10) ◽  
pp. 1598-1604 ◽  
Author(s):  
Melissa M Markofski ◽  
Kristofer Jennings ◽  
Kyle L Timmerman ◽  
Jared M Dickinson ◽  
Christopher S Fry ◽  
...  

Abstract Background Essential amino acids (EAA) and aerobic exercise (AE) acutely and independently stimulate skeletal muscle protein anabolism in older adults. Objective In this Phase 1, double-blind, placebo-controlled, randomized clinical trial, we determined if chronic EAA supplementation, AE training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis. Methods We phone-screened 971, enrolled 109, and randomized 50 independent, low-active, nonfrail, and nondiabetic older adults (age 72 ± 1 years). We used a 2 × 2 factorial design. The interventions were: daily nutritional supplementation (15 g EAA or placebo) and physical activity (supervised AE training 3 days/week or monitored habitual activity) for 24 weeks. Muscle strength, physical function, body composition, and muscle protein synthesis were measured before and after the 24-week intervention. Results Forty-five subjects completed the 24-week intervention. VO2peak and walking speed increased (p < .05) in both AE groups, irrespective of supplementation type, but muscle strength increased only in the EAA + AE group (p < .05). EAA supplementation acutely increased (p < .05) muscle protein synthesis from basal both before and after the intervention, with a larger increase in the EAA + AE group after the intervention. Total and regional lean body mass did not change significantly with any intervention. Conclusions In nonfrail, independent, healthy older adults AE training increased walking speed and aerobic fitness, and, when combined with EAA supplementation, it also increased muscle strength and EAA-stimulated muscle protein synthesis. These increases occurred without improvements in muscle mass.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 80-81
Author(s):  
Tanja Hess ◽  
Emily Kent ◽  
Renan Regatieri Casagrande ◽  
Christine Levihn ◽  
Grace Romo ◽  
...  

Abstract Antioxidant supplementation has been shown to decrease post exercise oxidative stress but can lead to decreased post-exercise muscle protein synthesis. The objective of this study was to compare the effects of the supplementation with a control feed with low antioxidant content (CONT) to a high antioxidant feed (AO), versus a high antioxidant and branched chain amino acid feed (BCAO) on post-exercise protein synthesis and oxidative stress. Our hypothesis is that supplementing AO with BCAO will reduce oxidative stress without hindering muscle protein synthesis. Eighteen mixed breed conditioned polo horses were assigned to one of the three treatments. All horses consumed CONT for 30 days and were then submitted to a lactate threshold test (LT). One hour after this and all LT, each group was assigned and given their treatments. LT were done at 15 and 30 days of supplementation. Blood was collected before, two and four hours after LT, and analyzed for oxidative stress based on glutathione peroxidase, superoxide dismutase and malondialdehyde concentrations by ELISA. Muscle biopsies were taken before and 4 hours after LT and analyzed for the expression of protein synthesis by RT-PCR. Results were analyzed in a mixed model by ANOVA and compared by LSM. A reduction of oxidative stress was found over time (P &lt; 0.050) with no treatment effect (P &gt;0.50). An upregulation of protein synthesis after exercise was found for muscle primers CD36, CPT1, DK4, MyF5, and Myogenin (P &lt; 0.050). There was a treatment by time effect for MyoD (P = 0.027), where AO was upregulated the most after exercise compared to BCAO and CONT. DK4 had a treatment by time effect trend (P = 0.073), where AO and BCAO were upregulated and CONT was unchanged after exercise. This study demonstrated post exercise muscle synthesis with no advantage of AO plus BCAO compared to AO.


Geriatrics ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 6 ◽  
Author(s):  
Susan Morris ◽  
James D. Cater ◽  
Mark A. Green ◽  
Alexandra M. Johnstone ◽  
Jeffrey M. Brunstrom ◽  
...  

The current dietary recommendation for protein intake in the UK is 0.75 g/kg/day, however, this population-wide recommendation does not necessarily reflect altered requirements for older adults to maintain muscle protein synthesis, nor does it encompass the potential impact of intake timing. Optimal muscle protein synthesis in older adults requires both higher intake requirements and a distribution of protein intake above a 25 g threshold, three times across the day. This study aimed to describe the protein intake of older adults in a UK region and compare the results to recommendations. The study re-assessed two existing datasets with rich diet information for older adults in the South Yorkshire area. Data were extracted from food diaries of 256 adults aged between 65 and 89 years old (mean ± SD 72.4 ± 5.3 years). Quantity and timing of intake were coded using Nutritics software and compared to recommendations. The relationship between body mass index (BMI), age, and protein intake was explored. Fewer than 50% of the participants met current UK recommendations (0.75 g/kg/day) and fewer than 15% met the ESPEN 1.2 g/kg/day age-specific recommendation. Only one participant met the 25 g/meal recommendation across three meals. These findings suggest that the older adult population is not achieving recommendations to maintain muscle protein synthesis. Nonetheless it identifies several straightforward opportunities for improvement, notably elevation of morning intake.


2019 ◽  
Vol 49 (S1) ◽  
pp. 59-68 ◽  
Author(s):  
Nicholas A. Burd ◽  
Joseph W. Beals ◽  
Isabel G. Martinez ◽  
Amadeo F. Salvador ◽  
Sarah K. Skinner

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2285 ◽  
Author(s):  
Konstantinos Prokopidis ◽  
Mavil May Cervo ◽  
Anoohya Gandham ◽  
David Scott

The continuous population increase of older adults with metabolic diseases may contribute to increased prevalence of sarcopenia and obesity and requires advocacy of optimal nutrition treatments to combat their deleterious outcomes. Sarcopenic obesity, characterized by age-induced skeletal-muscle atrophy and increased adiposity, may accelerate functional decline and increase the risk of disability and mortality. In this review, we explore the influence of dietary protein on the gut microbiome and its impact on sarcopenia and obesity. Given the associations between red meat proteins and altered gut microbiota, a combination of plant and animal-based proteins are deemed favorable for gut microbiota eubiosis and muscle-protein synthesis. Additionally, high-protein diets with elevated essential amino-acid concentrations, alongside increased dietary fiber intake, may promote gut microbiota eubiosis, given the metabolic effects derived from short-chain fatty-acid and branched-chain fatty-acid production. In conclusion, a greater abundance of specific gut bacteria associated with increased satiation, protein synthesis, and overall metabolic health may be driven by protein and fiber consumption. This could counteract the development of sarcopenia and obesity and, therefore, represent a novel approach for dietary recommendations based on the gut microbiota profile. However, more human trials utilizing advanced metabolomic techniques to investigate the microbiome and its relationship with macronutrient intake, especially protein, are warranted.


2019 ◽  
Vol 49 (6) ◽  
pp. 1275-1286
Author(s):  
Milena Casagranda ◽  
Priscila Berti Zanella ◽  
Alexandra Ferreira Vieira ◽  
Rodrigo Cauduro Oliveira Macedo

Purpose The purpose of the study was to evaluate the acute effect of milk proteins supplementation, compared to another nitrogen compound on muscle protein synthesis. Design/methodology/approach The search was conducted on MEDLINE® (via PUBMED®), Cochrane and Embase databases, using the terms “whey proteins,” “caseins,” “milk proteins,” “protein biosynthesis,” “human” and its related entry terms. The selected outcome was fractional synthetic rate (FSR) before (0) and 3 h after consumption of milk proteins, compared to supplementation with other protein sources or isolated amino acids. Findings The results were expressed as mean difference (MD) of absolute values between treatments with confidence interval (CI) of 95 per cent. Of the 1,913 identified studies, 4 were included, with a total of 74 participants. Milk proteins generated a greater FSR (MD 0.03 per cent/h, CI 95 per cent 0.02-0.04; p < 0.00001), compared to control group. Acute consumption of milk proteins promotes higher increase in FSR than other protein sources or isolated amino acids. Originality/value This paper is a systematic review of the effects of milk proteins supplementation, which is considered an important subject because of its large consumption among athletes and physical exercise practitioners.


2010 ◽  
Vol 42 ◽  
pp. 75-76
Author(s):  
Charles Paul Lambert ◽  
B. Selma Mohammed ◽  
Dennis T. Villareal ◽  
Linda R. Peterson ◽  
Brian N. Finck ◽  
...  

1999 ◽  
Vol 31 (Supplement) ◽  
pp. S279
Author(s):  
W. J. Durham ◽  
S. M. Miller ◽  
C. W. Yeckel ◽  
K. D. Tipton ◽  
B. B. Rasmussen ◽  
...  

2013 ◽  
Vol 110 (6) ◽  
pp. 981-987 ◽  
Author(s):  
Atsushi Kanda ◽  
Kyosuke Nakayama ◽  
Tomoyuki Fukasawa ◽  
Jinichiro Koga ◽  
Minoru Kanegae ◽  
...  

It is well known that ingestion of a protein source is effective in stimulating muscle protein synthesis after exercise. In addition, there are numerous reports on the impact of leucine and leucine-rich whey protein on muscle protein synthesis and mammalian target of rapamycin (mTOR) signalling. However, there is only limited information on the effects of whey protein hydrolysates (WPH) on muscle protein synthesis and mTOR signalling. The aim of the present study was to compare the effects of WPH and amino acids on muscle protein synthesis and the initiation of translation in skeletal muscle during the post-exercise phase. Male Sprague–Dawley rats swam for 2 h to depress muscle protein synthesis. Immediately after exercise, the animals were administered either carbohydrate (CHO), CHO plus an amino acid mixture (AA) or CHO plus WPH. At 1 h after exercise, the supplements containing whey-based protein (AA and WPH) caused a significant increase in the fractional rate of protein synthesis (FSR) compared with CHO. WPH also caused a significant increase in FSR compared with AA. Post-exercise ingestion of WPH caused a significant increase in the phosphorylation of mTOR levels compared with AA or CHO. In addition, WPH caused greater phosphorylation of ribosomal protein S6 kinase and eukaryotic initiation factor 4E-binding protein 1 than AA and CHO. In contrast, there was no difference in plasma amino acid levels following supplementation with either AA or WPH. These results indicate that WPH may include active components that are superior to amino acids for stimulating muscle protein synthesis and initiating translation.


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