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Stuart M. Phillips - One of the best experts on this subject based on the ideXlab platform.
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consumption of high leucine containing protein bar following breakfast impacts Aminoacidemia and subjective appetite in older persons
Current developments in nutrition, 2021Co-Authors: Daniel A Traylor, Matthew J Lees, T Prior, Stefan H M Gorissen, Michael Kamal, Everson Araujo Nunes, Fran Gesel, Changhyun Lim, Stuart M. PhillipsAbstract:Background Limited data are available examining dietary interventions for optimizing protein and leucine intake to stimulate muscle protein synthesis (MPS) in older humans. Objectives We aimed to investigate the Aminoacidemia and appetite responses of older adults after consuming breakfast, a meal frequently consumed with high-carbohydrate and below-par amounts of protein and leucine for stimulating MPS. Methods Five men and 3 women (means ± SD; age: 74 ± 7 y, BMI: 25.7 ± 4.9 kg/m2, fat- and bone-free mass: 63 ± 7 kg) took part in this experiment in which they consumed breakfasts with low-protein (LP = 13 ± 2 g), high-protein (HP = 32 ± 5 g), and LP followed by a protein- and leucine-enriched bar formulation 2 h later (LP + Bar = 29 ± 2 g). The LP, HP, and LP + Bar breakfast conditions contained 519 ± 86 kcal, 535 ± 83 kcal, and 739 ± 86 kcal, respectively. Blood samples were drawn for 6 h and analyzed for amino acid, insulin, and glucose concentrations. Visual analog scales were assessed for hunger, fullness, and desire to eat. Results The net AUC for essential amino acid (EAA) exposure was similar between the LP + Bar and HP conditions but greater in the HP condition compared with the LP condition. Peak leucinemia was higher in the LP + Bar condition compared with the HP, and both were greater than the LP condition. Net leucine exposure was similar between HP and LP + Bar, and both were greater than LP. Hunger was similarly reduced in LP + Bar and HP, and LP + Bar resulted in a greater hunger reduction than LP. Both LP + Bar and HP resulted in greater net fullness scores than LP. Conclusions Consuming our bar formulation increased blood leucine availability and net exposure to EAAs to a similar degree as consuming a high-protein meal. High-protein at breakfast results in a greater net exposure to EAAs and leucine, which could support MPS in older persons. This study was registered at clinicaltrials.gov as NCT03712761.
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Aminoacidemia following ingestion of native whey protein micellar casein and a whey casein blend in young men
Applied Physiology Nutrition and Metabolism, 2019Co-Authors: Daniel A Traylor, Chris Mcglory, T Prior, Stefan H M Gorissen, Hannah Hopper, Stuart M. PhillipsAbstract:We examined the aminoacidemic, glycemic, and insulinemic responses following ingestion of 25 g of native whey protein, micellar casein, and a 1:1 blend of whey and casein in randomized order in young adult men. Blood samples were drawn at baseline and at regular intervals for 6 h following ingestion. Area under curve and peak plasma essential amino acid concentrations after the ingestion of the protein blend were similar to whey and greater compared with casein.
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Recent perspectives regarding the role of dietary protein for the promotion of muscle hypertrophy with resistance exercise training
Nutrients, 2018Co-Authors: Tanner Stokes, Amy J. Hector, Robert W. Morton, Chris Mcglory, Stuart M. PhillipsAbstract:Skeletal muscle supports locomotion and serves as the largest site of postprandial glucose disposal; thus it is a critical organ for physical and metabolic health. Skeletal muscle mass is regulated by the processes of muscle protein synthesis (MPS) and muscle protein breakdown (MPB), both of which are sensitive to external loading and Aminoacidemia. HyperAminoacidemia results in a robust but transient increase in rates of MPS and a mild suppression of MPB. Resistance exercise potentiates the Aminoacidemia-induced rise in MPS that, when repeated over time, results in gradual radial growth of skeletal muscle (i.e., hypertrophy). Factors that affect MPS include both quantity and composition of the amino acid source. Specifically, MPS is stimulated in a dose-responsive manner and the primary amino acid agonist of this process is leucine. MPB also appears to be regulated in part by protein intake, which can exert a suppressive effect on MPB. At high protein doses the suppression of MPB may interfere with skeletal muscle adaptation following resistance exercise. In this review, we examine recent advancements in our understanding of how protein ingestion impacts skeletal muscle growth following resistance exercise in young adults during energy balance and energy restriction. We also provide practical recommendations for exercisers who wish to maximize the hypertrophic response of skeletal muscle during resistance exercise training.
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preexercise Aminoacidemia and muscle protein synthesis after resistance exercise
Medicine and Science in Sports and Exercise, 2012Co-Authors: Louise M Burke, Stuart M. Phillips, John A Hawley, Daniel R Moore, Trent Stellingwerff, Megan L Ross, Gary Slater, Kevin D Tipton, Andrew GarnhamAbstract:PURPOSE: We have previously shown that the Aminoacidemia caused by the consumption of a rapidly digested protein after resistance exercise enhances muscle protein synthesis (MPS) more than the amino acid (AA) profile associated with a slowly digested protein. Here, we investigated whether differential feeding patterns of a whey protein mixture commencing before exercise affect postexercise intracellular signaling and MPS. METHODS: Twelve resistance-trained males performed leg resistance exercise 45 min after commencing each of three volume-matched nutrition protocols: placebo (PLAC, artificially sweetened water), BOLUS (25g of whey protein + 5g of leucine dissolved in artificially sweetened water; 1x500 mL), or PULSE (15x33-mL aliquots of BOLUS drink every 15 min). RESULTS: The preexercise rise in plasma AA concentration with PULSE was attenuated compared with BOLUS (P BOLUS (P < 0.05). MPS throughout 5 h of recovery was higher with protein ingestion compared with PLAC (0.037 ± 0.007), with no differences between BOLUS or PULSE (0.085 ± 0.013 vs. 0.095 ± 0.010% h(-1), respectively, P = 0.56). CONCLUSIONS: Manipulation of Aminoacidemia before resistance exercise via different patterns of intake of protein altered plasma AA profiles and postexercise intracellular signaling. However, there was no difference in the enhancement of the muscle protein synthetic response after exercise. Protein sources producing a slow AA release, when consumed before resistance exercise in sufficient amounts, are as effective as rapidly digested proteins in promoting postexercise MPS.
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rapid Aminoacidemia enhances myofibrillar protein synthesis and anabolic intramuscular signaling responses after resistance exercise
The American Journal of Clinical Nutrition, 2011Co-Authors: Daniel W D West, Nicholas A Burd, Vernon G Coffey, Steven K Baker, Louise M Burke, John A Hawley, Daniel R Moore, Trent Stellingwerff, Stuart M. PhillipsAbstract:Ingestion of whey or casein yields divergent patterns of Aminoacidemia that influence whole-body and skeletal muscle myofibrillar protein synthesis (MPS) after exercise. Direct comparisons of the effects of contrasting absorption rates exhibited by these proteins are confounded by their differing amino acid contents.
Philip J Atherton - One of the best experts on this subject based on the ideXlab platform.
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human skeletal muscle is refractory to the anabolic effects of leucine during the postprandial muscle full period in older men
Clinical Science, 2017Co-Authors: Kyle W Mitchell, Bethan E Phillips, Daniel J Wilkinson, Kenneth Smith, John P Williams, Debbie Rankin, Jonathan N Lund, Ian G Hill, Paul L Greenhaff, Philip J AthertonAbstract:Leucine modulates muscle protein synthesis (MPS), with potential to facilitate accrual/maintenance of muscle mass. Animal models suggest that leucine boluses shortly after meals may prolong MPS and delay onset of a “muscle-full” state. However, the effects of nutrient “top-ups” in humans, and particularly older adults where deficits exist, have not been explored. We determined the effects of a leucine top-up after essential amino acid (EAA) feeding on anabolic signaling, MPS, and muscle energy metabolism in older men. During 13C6-phenylalanine infusion, 16 men (∼70 years) consumed 15 g of EAA with (n=8, FED + LEU) or without (n=8, FED) 3 g of leucine top-up 90 min later. Repeated blood and muscle sampling permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling including mTOR complex 1 (mTORC1) substrates, cellular ATP and phosphorylocreatine, and MPS. Oral EAA achieved rapid insulinemia (12.5 iU·ml−1 25 min post-feed), essential Aminoacidemia (3000 μM, 45–65 min post-feed), and activation of mTORC1 signaling. Leucine top-up prolonged plasma EAA (2800 μM, 135 min) and leucine availability (1050 μM, 135 min post-feed). Fasting FSRs of 0.046 and 0.056%·h-1 (FED and FED + LEU respectively) increased to 0.085 and 0.085%·h-1 90–180 min post-feed and returned to basal rates after 180 min in both groups. Phosphorylation of mTORC1 substrates returned to fasting levels 240 min post-feed in both groups. Feeding had limited effect on muscle elongation factor 2 (eEF2) phosphorylation. We demonstrate the refractoriness of muscle to nutrient-led anabolic stimulation in the postprandial period; thus, leucine supplements should be taken outside of meals, or with meals containing suboptimal protein in terms of either amount or EAA composition.
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the impact of delivery profile of essential amino acids upon skeletal muscle protein synthesis in older men clinical efficacy of pulse vs bolus supply
American Journal of Physiology-endocrinology and Metabolism, 2015Co-Authors: Kyle W Mitchell, Bethan E Phillips, Daniel J Wilkinson, Kenneth Smith, John P Williams, Debbie Rankin, Jonathan N Lund, Philip J AthertonAbstract:Essential amino acids (EAA) are responsible for skeletal muscle anabolic effects after nutrient intake. The pattern of appearance of EAA in blood, e.g., after intake of “slow” or “fast” protein sources or in response to grazing vs. bolus feeding patterns, may impact anabolism. However, the influence of this on muscle anabolism is poorly understood, particularly in older individuals. We determined the effects of divergent feeding profiles of EAA on blood flow, anabolic signaling, and muscle protein synthesis (MPS) in older men. Sixteen men (∼70 yr) consumed EAA either as a single dose (bolus, 15 g; n = 8) or as small repeated fractions (pulse, 4 × 3.75 g every 45 min; n = 8) during 13C6 phenylalanine infusion. Repeated blood samples and muscle biopsies permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling, and MPS. Muscle blood flow was assessed by contrast-enhanced ultrasound (Sonovue). Bolus achieved rapid insulinemia (12.7 μiU/ml 25-min postfeed), essential Aminoacidemia (∼3,000 μM, 45–65 min postfeed), and mTORC1 activity; pulse achieved attenuated insulin responses, gradual low-amplitude Aminoacidemia (∼1,800 μM 80–195 min after feeding), and undetectable mTORC1 signaling. Despite this, equivalent anabolic responses were observed: fasting FSRs of 0.051 and 0.047%/h (bolus and pulse, respectively) increased to 0.084 and 0.073%/h, respectively. Moreover, pulse led to sustainment of MPS beyond 180 min, when bolus MPS had returned to basal rates. We detected no benefit of rapid Aminoacidemia in this older population despite enhanced anabolic signaling and greater overall EAA exposure. Rather, apparent delayed onset of the “muscle-full” effect permitted identical MPS following low-amplitude-sustained EAA exposure.
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a dose rather than delivery profile dependent mechanism regulates the muscle full effect in response to oral essential amino acid intake in young men
Journal of Nutrition, 2015Co-Authors: William Kyle Mitchell, Kenneth Smith, John P Williams, Debbie Rankin, Jonathan N Lund, B E Phillips, Philip J AthertonAbstract:Background: The anabolic response of skeletal muscle to essential amino acids (EAAs) is dose dependent, maximal at modest doses, and short lived, even with continued EAA availability, a phenomenon termed “muscle-full.” However, the effect of EAA ingestion profile on muscle metabolism remains undefined. Objective: We determined the effect of Bolus vs. Spread EAA feeding in young men and hypothesized that muscle-full is regulated by a dose-, not delivery profile–, dependent mechanism. Methods: We provided 16 young healthy men with 15 g mixed-EAA, either as a single dose (“Bolus”; n = 8) or in 4 fractions at 45-min intervals (“Spread”; n = 8). Plasma insulin and EAA concentrations were assayed by ELISA and ion-exchange chromatography, respectively. Limb blood flow by was determined by Doppler ultrasound, muscle microvascular flow by Sonovue (Bracco) contrast-enhanced ultrasound, and phosphorylation of mammalian target of rapamycin complex 1 substrates by immunoblotting. Intermittent muscle biopsies were taken to quantify myofibrillar-bound 13C6-phenylalanine to determine muscle protein synthesis (MPS). Results: Bolus feeding achieved rapid insulinemia (13.6 μIU · mL−1, 25 min after commencement of feeding), Aminoacidemia (∼2500 μM at 45 min), and capillary recruitment (+45% at 45 min), whereas Spread feeding achieved attenuated insulin responses, gradual low-amplitude Aminoacidemia (peak: ∼1500 μM at 135 min), and no detectable capillary recruitment (all P < 0.01 vs. Bolus). Despite these differences, identical anabolic responses were observed; fasting fractional synthetic rates of 0.054% · h−1 (Bolus) and 0.066% · h−1 (Spread) increased to 0.095% and 0.104% · h−1 (no difference in increment or final values between regimens). With both Spread and Bolus feeding strategies, a latency of at least 90 min was observed before an upswing in MPS was evident. Similarly with both feeding strategies, MPS returned to fasting rates by 180 min despite elevated circulating EAAs. Conclusion: These data do not support EAA delivery profile as an important determinant of anabolism in young men at rest, nor rapid Aminoacidemia/leucinemia as being a key factor in maximizing MPS. This trial was registered at clinicaltrials.gov as NCT01735539.
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pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions
American Journal of Physiology-endocrinology and Metabolism, 2014Co-Authors: Bethan E Phillips, Philip J Atherton, Krishna K Varadhan, Daniel J Wilkinson, Marie C Limb, Anna Selby, M J Rennie, Kenneth Smith, John P WilliamsAbstract:Skeletal muscle anabolism associated with postprandial plasma Aminoacidemia and insulinemia is contingent upon amino acids (AA) and insulin crossing the microcirculation-myocyte interface. In this ...
Louise M Burke - One of the best experts on this subject based on the ideXlab platform.
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effect of intake of different dietary protein sources on plasma amino acid profiles at rest and after exercise
International Journal of Sport Nutrition and Exercise Metabolism, 2012Co-Authors: Louise M Burke, David Cameronsmith, Julie A Winter, Marc Enslen, Michelle M Farnfield, Jacques DecombazAbstract:The authors undertook 2 crossover-designed studies to characterize plasma amino acid (AA) responses to the intake of 20 g of protein. In Study 1, 15 untrained and overnight-fasted subjects consumed 20 g protein from skim milk, soy milk, beefsteak, boiled egg, and a liquid meal supplement. In Study 2, 10 fasted endurancetrained subjects consumed 20 g protein from a protein-rich sports bar at rest and after a 60-min submaximal ride. Plasma AA concentrations were measured immediately before and for 180 min after food ingestion using a gas-chromatography flame-ionization detection technique. A pharmacokinetic analysis was undertaken for profiles of total AAs (TAA), essential AAs, branched-chain AAs (BCAA), and leucine. Although areaunder-the-curve values for plasma TAA were similar across protein sources, the pattern of Aminoacidemia showed robust differences between foods, with liquid forms of protein achieving peak concentrations twice as quickly after ingestion as solid protein-rich foods (e.g., ~50 min vs ~100 min) and skim milk achieving a significantly faster peak leucine concentration than all other foods (~25 min). Completing exercise before ingesting protein sources did not cause statistically significant changes in the pattern of delivery of key AAs, BCAAs, and leucine apart from a 20–40% increase in the rate of elimination. These results may be useful to plan the type and timing of intake of protein-rich foods to maximize the protein synthetic response to various stimuli such as exercise.
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preexercise Aminoacidemia and muscle protein synthesis after resistance exercise
Medicine and Science in Sports and Exercise, 2012Co-Authors: Louise M Burke, Stuart M. Phillips, John A Hawley, Daniel R Moore, Trent Stellingwerff, Megan L Ross, Gary Slater, Kevin D Tipton, Andrew GarnhamAbstract:PURPOSE: We have previously shown that the Aminoacidemia caused by the consumption of a rapidly digested protein after resistance exercise enhances muscle protein synthesis (MPS) more than the amino acid (AA) profile associated with a slowly digested protein. Here, we investigated whether differential feeding patterns of a whey protein mixture commencing before exercise affect postexercise intracellular signaling and MPS. METHODS: Twelve resistance-trained males performed leg resistance exercise 45 min after commencing each of three volume-matched nutrition protocols: placebo (PLAC, artificially sweetened water), BOLUS (25g of whey protein + 5g of leucine dissolved in artificially sweetened water; 1x500 mL), or PULSE (15x33-mL aliquots of BOLUS drink every 15 min). RESULTS: The preexercise rise in plasma AA concentration with PULSE was attenuated compared with BOLUS (P BOLUS (P < 0.05). MPS throughout 5 h of recovery was higher with protein ingestion compared with PLAC (0.037 ± 0.007), with no differences between BOLUS or PULSE (0.085 ± 0.013 vs. 0.095 ± 0.010% h(-1), respectively, P = 0.56). CONCLUSIONS: Manipulation of Aminoacidemia before resistance exercise via different patterns of intake of protein altered plasma AA profiles and postexercise intracellular signaling. However, there was no difference in the enhancement of the muscle protein synthetic response after exercise. Protein sources producing a slow AA release, when consumed before resistance exercise in sufficient amounts, are as effective as rapidly digested proteins in promoting postexercise MPS.
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rapid Aminoacidemia enhances myofibrillar protein synthesis and anabolic intramuscular signaling responses after resistance exercise
The American Journal of Clinical Nutrition, 2011Co-Authors: Daniel W D West, Nicholas A Burd, Vernon G Coffey, Steven K Baker, Louise M Burke, John A Hawley, Daniel R Moore, Trent Stellingwerff, Stuart M. PhillipsAbstract:Ingestion of whey or casein yields divergent patterns of Aminoacidemia that influence whole-body and skeletal muscle myofibrillar protein synthesis (MPS) after exercise. Direct comparisons of the effects of contrasting absorption rates exhibited by these proteins are confounded by their differing amino acid contents.
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rapid Aminoacidemia enhances myofibrillar protein synthesis and anabolic intramuscular signaling responses after resistance exercise
Faculty of Health, 2011Co-Authors: Daniel W D West, Nicholas A Burd, Vernon G Coffey, Steven K Baker, Louise M Burke, John A Hawley, Daniel R Moore, Trent Stellingwerff, Stuart M. PhillipsAbstract:Background: Ingestion of whey or casein yields divergent patterns of Aminoacidemia that influence whole-body and skeletal muscle myofibrillar protein synthesis (MPS) after exercise. Direct comparisons of the effects of contrasting absorption rates exhibited by these proteins are confounded by their differing amino acid contents. Objective: Our objective was to determine the effect of divergent Aminoacidemia by manipulating ingestion patterns of whey protein alone on MPS and anabolic signaling after resistance exercise. Design: In separate trials, 8 healthy men consumed whey protein either as a single bolus (BOLUS; 25-g dose) or as repeated, small, "pulsed" drinks (PULSE; ten 2.5-g drinks every 20 min) to mimic a more slowly digested protein. MPS and phosphorylation of signaling proteins involved in protein synthesis were measured at rest and after resistance exercise. Results: BOLUS increased blood essential amino acid (EAA) concentrations above those of PULSE (162% compared with 53%, P < 0.001) 60 min after exercise, whereas PULSE resulted in a smaller but sustained increase in Aminoacidemia that remained elevated above BOLUS amounts later (180-220 min after exercise, P < 0.05). Despite an identical net area under the EAA curve, MPS was elevated to a greater extent after BOLUS than after PULSE early (1-3 h: 95% compared with 42%) and later (3-5 h: 193% compared with 121%) (both P < 0.05). There were greater changes in the phosphorylation of the Akt-mammalian target of rapamycin pathway after BOLUS than after PULSE. Conclusions: Rapid Aminoacidemia in the postexercise period enhances MPS and anabolic signaling to a greater extent than an identical amount of protein fed in small pulses that mimic a more slowly digested protein. A pronounced peak Aminoacidemia after exercise enhances protein synthesis.
Daniel R Moore - One of the best experts on this subject based on the ideXlab platform.
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preexercise Aminoacidemia and muscle protein synthesis after resistance exercise
Medicine and Science in Sports and Exercise, 2012Co-Authors: Louise M Burke, Stuart M. Phillips, John A Hawley, Daniel R Moore, Trent Stellingwerff, Megan L Ross, Gary Slater, Kevin D Tipton, Andrew GarnhamAbstract:PURPOSE: We have previously shown that the Aminoacidemia caused by the consumption of a rapidly digested protein after resistance exercise enhances muscle protein synthesis (MPS) more than the amino acid (AA) profile associated with a slowly digested protein. Here, we investigated whether differential feeding patterns of a whey protein mixture commencing before exercise affect postexercise intracellular signaling and MPS. METHODS: Twelve resistance-trained males performed leg resistance exercise 45 min after commencing each of three volume-matched nutrition protocols: placebo (PLAC, artificially sweetened water), BOLUS (25g of whey protein + 5g of leucine dissolved in artificially sweetened water; 1x500 mL), or PULSE (15x33-mL aliquots of BOLUS drink every 15 min). RESULTS: The preexercise rise in plasma AA concentration with PULSE was attenuated compared with BOLUS (P BOLUS (P < 0.05). MPS throughout 5 h of recovery was higher with protein ingestion compared with PLAC (0.037 ± 0.007), with no differences between BOLUS or PULSE (0.085 ± 0.013 vs. 0.095 ± 0.010% h(-1), respectively, P = 0.56). CONCLUSIONS: Manipulation of Aminoacidemia before resistance exercise via different patterns of intake of protein altered plasma AA profiles and postexercise intracellular signaling. However, there was no difference in the enhancement of the muscle protein synthetic response after exercise. Protein sources producing a slow AA release, when consumed before resistance exercise in sufficient amounts, are as effective as rapidly digested proteins in promoting postexercise MPS.
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rapid Aminoacidemia enhances myofibrillar protein synthesis and anabolic intramuscular signaling responses after resistance exercise
The American Journal of Clinical Nutrition, 2011Co-Authors: Daniel W D West, Nicholas A Burd, Vernon G Coffey, Steven K Baker, Louise M Burke, John A Hawley, Daniel R Moore, Trent Stellingwerff, Stuart M. PhillipsAbstract:Ingestion of whey or casein yields divergent patterns of Aminoacidemia that influence whole-body and skeletal muscle myofibrillar protein synthesis (MPS) after exercise. Direct comparisons of the effects of contrasting absorption rates exhibited by these proteins are confounded by their differing amino acid contents.
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rapid Aminoacidemia enhances myofibrillar protein synthesis and anabolic intramuscular signaling responses after resistance exercise
Faculty of Health, 2011Co-Authors: Daniel W D West, Nicholas A Burd, Vernon G Coffey, Steven K Baker, Louise M Burke, John A Hawley, Daniel R Moore, Trent Stellingwerff, Stuart M. PhillipsAbstract:Background: Ingestion of whey or casein yields divergent patterns of Aminoacidemia that influence whole-body and skeletal muscle myofibrillar protein synthesis (MPS) after exercise. Direct comparisons of the effects of contrasting absorption rates exhibited by these proteins are confounded by their differing amino acid contents. Objective: Our objective was to determine the effect of divergent Aminoacidemia by manipulating ingestion patterns of whey protein alone on MPS and anabolic signaling after resistance exercise. Design: In separate trials, 8 healthy men consumed whey protein either as a single bolus (BOLUS; 25-g dose) or as repeated, small, "pulsed" drinks (PULSE; ten 2.5-g drinks every 20 min) to mimic a more slowly digested protein. MPS and phosphorylation of signaling proteins involved in protein synthesis were measured at rest and after resistance exercise. Results: BOLUS increased blood essential amino acid (EAA) concentrations above those of PULSE (162% compared with 53%, P < 0.001) 60 min after exercise, whereas PULSE resulted in a smaller but sustained increase in Aminoacidemia that remained elevated above BOLUS amounts later (180-220 min after exercise, P < 0.05). Despite an identical net area under the EAA curve, MPS was elevated to a greater extent after BOLUS than after PULSE early (1-3 h: 95% compared with 42%) and later (3-5 h: 193% compared with 121%) (both P < 0.05). There were greater changes in the phosphorylation of the Akt-mammalian target of rapamycin pathway after BOLUS than after PULSE. Conclusions: Rapid Aminoacidemia in the postexercise period enhances MPS and anabolic signaling to a greater extent than an identical amount of protein fed in small pulses that mimic a more slowly digested protein. A pronounced peak Aminoacidemia after exercise enhances protein synthesis.
John P Williams - One of the best experts on this subject based on the ideXlab platform.
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human skeletal muscle is refractory to the anabolic effects of leucine during the postprandial muscle full period in older men
Clinical Science, 2017Co-Authors: Kyle W Mitchell, Bethan E Phillips, Daniel J Wilkinson, Kenneth Smith, John P Williams, Debbie Rankin, Jonathan N Lund, Ian G Hill, Paul L Greenhaff, Philip J AthertonAbstract:Leucine modulates muscle protein synthesis (MPS), with potential to facilitate accrual/maintenance of muscle mass. Animal models suggest that leucine boluses shortly after meals may prolong MPS and delay onset of a “muscle-full” state. However, the effects of nutrient “top-ups” in humans, and particularly older adults where deficits exist, have not been explored. We determined the effects of a leucine top-up after essential amino acid (EAA) feeding on anabolic signaling, MPS, and muscle energy metabolism in older men. During 13C6-phenylalanine infusion, 16 men (∼70 years) consumed 15 g of EAA with (n=8, FED + LEU) or without (n=8, FED) 3 g of leucine top-up 90 min later. Repeated blood and muscle sampling permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling including mTOR complex 1 (mTORC1) substrates, cellular ATP and phosphorylocreatine, and MPS. Oral EAA achieved rapid insulinemia (12.5 iU·ml−1 25 min post-feed), essential Aminoacidemia (3000 μM, 45–65 min post-feed), and activation of mTORC1 signaling. Leucine top-up prolonged plasma EAA (2800 μM, 135 min) and leucine availability (1050 μM, 135 min post-feed). Fasting FSRs of 0.046 and 0.056%·h-1 (FED and FED + LEU respectively) increased to 0.085 and 0.085%·h-1 90–180 min post-feed and returned to basal rates after 180 min in both groups. Phosphorylation of mTORC1 substrates returned to fasting levels 240 min post-feed in both groups. Feeding had limited effect on muscle elongation factor 2 (eEF2) phosphorylation. We demonstrate the refractoriness of muscle to nutrient-led anabolic stimulation in the postprandial period; thus, leucine supplements should be taken outside of meals, or with meals containing suboptimal protein in terms of either amount or EAA composition.
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the impact of delivery profile of essential amino acids upon skeletal muscle protein synthesis in older men clinical efficacy of pulse vs bolus supply
American Journal of Physiology-endocrinology and Metabolism, 2015Co-Authors: Kyle W Mitchell, Bethan E Phillips, Daniel J Wilkinson, Kenneth Smith, John P Williams, Debbie Rankin, Jonathan N Lund, Philip J AthertonAbstract:Essential amino acids (EAA) are responsible for skeletal muscle anabolic effects after nutrient intake. The pattern of appearance of EAA in blood, e.g., after intake of “slow” or “fast” protein sources or in response to grazing vs. bolus feeding patterns, may impact anabolism. However, the influence of this on muscle anabolism is poorly understood, particularly in older individuals. We determined the effects of divergent feeding profiles of EAA on blood flow, anabolic signaling, and muscle protein synthesis (MPS) in older men. Sixteen men (∼70 yr) consumed EAA either as a single dose (bolus, 15 g; n = 8) or as small repeated fractions (pulse, 4 × 3.75 g every 45 min; n = 8) during 13C6 phenylalanine infusion. Repeated blood samples and muscle biopsies permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling, and MPS. Muscle blood flow was assessed by contrast-enhanced ultrasound (Sonovue). Bolus achieved rapid insulinemia (12.7 μiU/ml 25-min postfeed), essential Aminoacidemia (∼3,000 μM, 45–65 min postfeed), and mTORC1 activity; pulse achieved attenuated insulin responses, gradual low-amplitude Aminoacidemia (∼1,800 μM 80–195 min after feeding), and undetectable mTORC1 signaling. Despite this, equivalent anabolic responses were observed: fasting FSRs of 0.051 and 0.047%/h (bolus and pulse, respectively) increased to 0.084 and 0.073%/h, respectively. Moreover, pulse led to sustainment of MPS beyond 180 min, when bolus MPS had returned to basal rates. We detected no benefit of rapid Aminoacidemia in this older population despite enhanced anabolic signaling and greater overall EAA exposure. Rather, apparent delayed onset of the “muscle-full” effect permitted identical MPS following low-amplitude-sustained EAA exposure.
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a dose rather than delivery profile dependent mechanism regulates the muscle full effect in response to oral essential amino acid intake in young men
Journal of Nutrition, 2015Co-Authors: William Kyle Mitchell, Kenneth Smith, John P Williams, Debbie Rankin, Jonathan N Lund, B E Phillips, Philip J AthertonAbstract:Background: The anabolic response of skeletal muscle to essential amino acids (EAAs) is dose dependent, maximal at modest doses, and short lived, even with continued EAA availability, a phenomenon termed “muscle-full.” However, the effect of EAA ingestion profile on muscle metabolism remains undefined. Objective: We determined the effect of Bolus vs. Spread EAA feeding in young men and hypothesized that muscle-full is regulated by a dose-, not delivery profile–, dependent mechanism. Methods: We provided 16 young healthy men with 15 g mixed-EAA, either as a single dose (“Bolus”; n = 8) or in 4 fractions at 45-min intervals (“Spread”; n = 8). Plasma insulin and EAA concentrations were assayed by ELISA and ion-exchange chromatography, respectively. Limb blood flow by was determined by Doppler ultrasound, muscle microvascular flow by Sonovue (Bracco) contrast-enhanced ultrasound, and phosphorylation of mammalian target of rapamycin complex 1 substrates by immunoblotting. Intermittent muscle biopsies were taken to quantify myofibrillar-bound 13C6-phenylalanine to determine muscle protein synthesis (MPS). Results: Bolus feeding achieved rapid insulinemia (13.6 μIU · mL−1, 25 min after commencement of feeding), Aminoacidemia (∼2500 μM at 45 min), and capillary recruitment (+45% at 45 min), whereas Spread feeding achieved attenuated insulin responses, gradual low-amplitude Aminoacidemia (peak: ∼1500 μM at 135 min), and no detectable capillary recruitment (all P < 0.01 vs. Bolus). Despite these differences, identical anabolic responses were observed; fasting fractional synthetic rates of 0.054% · h−1 (Bolus) and 0.066% · h−1 (Spread) increased to 0.095% and 0.104% · h−1 (no difference in increment or final values between regimens). With both Spread and Bolus feeding strategies, a latency of at least 90 min was observed before an upswing in MPS was evident. Similarly with both feeding strategies, MPS returned to fasting rates by 180 min despite elevated circulating EAAs. Conclusion: These data do not support EAA delivery profile as an important determinant of anabolism in young men at rest, nor rapid Aminoacidemia/leucinemia as being a key factor in maximizing MPS. This trial was registered at clinicaltrials.gov as NCT01735539.
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pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions
American Journal of Physiology-endocrinology and Metabolism, 2014Co-Authors: Bethan E Phillips, Philip J Atherton, Krishna K Varadhan, Daniel J Wilkinson, Marie C Limb, Anna Selby, M J Rennie, Kenneth Smith, John P WilliamsAbstract:Skeletal muscle anabolism associated with postprandial plasma Aminoacidemia and insulinemia is contingent upon amino acids (AA) and insulin crossing the microcirculation-myocyte interface. In this ...