Publications by authors named "Annemie P Gijsen"

36 Publications

Exercise Plus Presleep Protein Ingestion Increases Overnight Muscle Connective Tissue Protein Synthesis Rates in Healthy Older Men.

Int J Sport Nutr Exerc Metab 2021 Feb 14;31(3):217-226. Epub 2021 Feb 14.

Maastricht University Medical Centre.

Protein ingestion and exercise stimulate myofibrillar protein synthesis rates. When combined, exercise further increases the postprandial rise in myofibrillar protein synthesis rates. It remains unclear whether protein ingestion with or without exercise also stimulates muscle connective tissue protein synthesis rates. The authors assessed the impact of presleep protein ingestion on overnight muscle connective tissue protein synthesis rates at rest and during recovery from resistance-type exercise in older men. Thirty-six healthy, older men were randomly assigned to ingest 40 g intrinsically L-[1-13C]-phenylalanine and L-[1-13C]-leucine-labeled casein protein (PRO, n = 12) or a nonprotein placebo (PLA, n = 12) before going to sleep. A third group performed a single bout of resistance-type exercise in the evening before ingesting 40 g intrinsically-labeled casein protein prior to sleep (EX+PRO, n = 12). Continuous intravenous infusions of L-[ring-2H5]-phenylalanine and L-[1-13C]-leucine were applied with blood and muscle tissue samples collected throughout overnight sleep. Presleep protein ingestion did not increase muscle connective tissue protein synthesis rates (0.049 ± 0.013 vs. 0.060 ± 0.024%/hr in PLA and PRO, respectively; p = .73). Exercise plus protein ingestion resulted in greater overnight muscle connective tissue protein synthesis rates (0.095 ± 0.022%/hr) when compared with PLA and PRO (p < .01). Exercise increased the incorporation of dietary protein-derived amino acids into muscle connective tissue protein (0.036 ± 0.013 vs. 0.054 ± 0.009 mole percent excess in PRO vs. EX+PRO, respectively; p < .01). In conclusion, resistance-type exercise plus presleep protein ingestion increases overnight muscle connective tissue protein synthesis rates in older men. Exercise enhances the utilization of dietary protein-derived amino acids as precursors for de novo muscle connective tissue protein synthesis during overnight sleep.
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http://dx.doi.org/10.1123/ijsnem.2020-0222DOI Listing
February 2021

Dose-response effects of dietary protein on muscle protein synthesis during recovery from endurance exercise in young men: a double-blind randomized trial.

Am J Clin Nutr 2020 08;112(2):303-317

NUTRIM School of Nutrition and Translational Research in Metabolism, Department of Human Biology, Maastricht University Medical Center+, Maastricht, Netherlands.

Background: Protein ingestion increases skeletal muscle protein synthesis rates during recovery from endurance exercise.

Objectives: We aimed to determine the effect of graded doses of dietary protein co-ingested with carbohydrate on whole-body protein metabolism, and skeletal muscle myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis rates during recovery from endurance exercise.

Methods: In a randomized, double-blind, parallel-group design, 48 healthy, young, endurance-trained men (mean ± SEM age: 27 ± 1 y) received a primed continuous infusion of l-[ring-2H5]-phenylalanine, l-[ring-3,5-2H2]-tyrosine, and l-[1-13C]-leucine and ingested 45 g carbohydrate with either 0 (0 g PRO), 15 (15 g PRO), 30 (30 g PRO), or 45 (45 g PRO) g intrinsically l-[1-13C]-phenylalanine and l-[1-13C]-leucine labeled milk protein after endurance exercise. Blood and muscle biopsy samples were collected over 360 min of postexercise recovery to assess whole-body protein metabolism and both MyoPS and MitoPS rates.

Results: Protein intake resulted in ∼70%-74% of the ingested protein-derived phenylalanine appearing in the circulation. Whole-body net protein balance increased dose-dependently after ingestion of 0, 15, 30, or 45 g protein (mean ± SEM: -0.31± 0.16, 5.08 ± 0.21, 10.04 ± 0.30, and 13.49 ± 0.55 μmol phenylalanine · kg-1 · h-1, respectively; P < 0.001). 30 g PRO stimulated a ∼46% increase in MyoPS rates (%/h) compared with 0 g PRO and was sufficient to maximize MyoPS rates after endurance exercise. MitoPS rates were not increased after protein ingestion; however, incorporation of dietary protein-derived l-[1-13C]-phenylalanine into de novo mitochondrial protein increased dose-dependently after ingestion of 15, 30, and 45 g protein at 360 min postexercise (0.018 ± 0.002, 0.034 ± 0.002, and 0.046 ± 0.003 mole percentage excess, respectively; P < 0.001).

Conclusions: Protein ingested after endurance exercise is efficiently digested and absorbed into the circulation. Whole-body net protein balance and dietary protein-derived amino acid incorporation into mitochondrial protein respond to increasing protein intake in a dose-dependent manner. Ingestion of 30 g protein is sufficient to maximize MyoPS rates during recovery from a single bout of endurance exercise.This trial was registered at trialregister.nl as NTR5111.
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http://dx.doi.org/10.1093/ajcn/nqaa073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398777PMC
August 2020

Casein Ingestion Does Not Increase Muscle Connective Tissue Protein Synthesis Rates.

Med Sci Sports Exerc 2020 09;52(9):1983-1991

NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, THE NETHERLANDS.

Purpose: This study aimed to assess the effect of dietary protein ingestion on intramuscular connective tissue protein synthesis rates during overnight recovery from a single bout of resistance exercise.

Methods: Thirty-six healthy, young males were randomly assigned to one of three treatments. One group ingested 30 g intrinsically L-[1-C]-phenylalanine-labeled casein protein before sleep (PRO, n = 12). The other two groups performed a bout of resistance exercise in the evening and ingested either placebo (EX, n = 12) or 30 g intrinsically L-[1-C]-phenylalanine-labeled casein protein before sleep (EX + PRO, n = 12). Continuous intravenous infusions of L-[ring-H5]-phenylalanine and L-[1-C]-leucine were applied, and blood and muscle tissue samples were collected to assess connective tissue protein synthesis rates and dietary protein-derived amino acid incorporation in the connective tissue protein fraction.

Results: Resistance exercise resulted in higher connective tissue protein synthesis rates when compared with rest (0.086 ± 0.017%·h [EX] and 0.080 ± 0.019%·h [EX + PRO] vs 0.059 ± 0.016%·h [PRO]; P < 0.05). Postexercise casein protein ingestion did not result in higher connective tissue protein synthesis rates when compared with postexercise placebo ingestion (P = 1.00). Dietary protein-derived amino acids were incorporated into the connective tissue protein fraction at rest, and to a greater extent during recovery from exercise (P = 0.002).

Conclusion: Resistance exercise increases intramuscular connective tissue protein synthesis rates during overnight sleep, with no further effect of postexercise protein ingestion. However, dietary protein-derived amino acids are being used as precursors to support de novo connective tissue protein synthesis.
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http://dx.doi.org/10.1249/MSS.0000000000002337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431152PMC
September 2020

Endurance-Type Exercise Increases Bulk and Individual Mitochondrial Protein Synthesis Rates in Rats.

Int J Sport Nutr Exerc Metab 2020 Feb 7:1-12. Epub 2020 Feb 7.

Maastricht University.

Physical activity increases muscle protein synthesis rates. However, the impact of exercise on the coordinated up- and/or downregulation of individual protein synthesis rates in skeletal muscle tissue remains unclear. The authors assessed the impact of exercise on mixed muscle, myofibrillar, and mitochondrial protein synthesis rates as well as individual protein synthesis rates in vivo in rats. Adult Lewis rats either remained sedentary (n = 3) or had access to a running wheel (n = 3) for the last 2 weeks of a 3-week experimental period. Deuterated water was injected and subsequently administered in drinking water over the experimental period. Blood and soleus muscle were collected and used to assess bulk mixed muscle, myofibrillar, and mitochondrial protein synthesis rates using gas chromatography-mass spectrometry and individual muscle protein synthesis rates using liquid chromatography-mass spectrometry (i.e., dynamic proteomic profiling). Wheel running resulted in greater myofibrillar (3.94 ± 0.26 vs. 3.03 ± 0.15%/day; p < .01) and mitochondrial (4.64 ± 0.24 vs. 3.97 ± 0.26%/day; p < .05), but not mixed muscle (2.64 ± 0.96 vs. 2.38 ± 0.62%/day; p = .71) protein synthesis rates, when compared with the sedentary condition. Exercise impacted the synthesis rates of 80 proteins, with the difference from the sedentary condition ranging between -64% and +420%. Significantly greater synthesis rates were detected for F1-ATP synthase, ATP synthase subunit alpha, hemoglobin, myosin light chain-6, and synaptopodin-2 (p < .05). The skeletal muscle protein adaptive response to endurance-type exercise involves upregulation of mitochondrial protein synthesis rates, but it is highly coordinated as reflected by the up- and downregulation of various individual proteins across different bulk subcellular protein fractions.
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http://dx.doi.org/10.1123/ijsnem.2019-0281DOI Listing
February 2020

Short-term muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates.

Am J Physiol Endocrinol Metab 2020 02 19;318(2):E117-E130. Epub 2019 Nov 19.

Department of Sport and Health Sciences, College of Life and Environmental Science, University of Exeter, Exeter, United Kingdom.

Short-term muscle disuse has been reported to lower both postabsorptive and postprandial myofibrillar protein synthesis rates. This study assessed the impact of disuse on daily myofibrillar protein synthesis rates following short-term (2 and 7 days) muscle disuse under free living conditions. Thirteen healthy young men (age: 20 ± 1 yr; BMI: 23 ± 1 kg/m) underwent 7 days of unilateral leg immobilization via a knee brace, with the nonimmobilized leg acting as a control. Four days before immobilization participants ingested 400 mL of 70% deuterated water, with 50-mL doses consumed daily thereafter. Upper leg bilateral MRI scans and muscle biopsies were collected before and after 2 and 7 days of immobilization to determine quadriceps volume and daily myofibrillar protein synthesis rates. Immobilization reduced quadriceps volume in the immobilized leg by 1.7 ± 0.3 and 6.7 ± 0.6% after 2 and 7 days, respectively, with no changes in the control leg. Over the 1-wk immobilization period, myofibrillar protein synthesis rates were 36 ± 4% lower in the immobilized (0.81 ± 0.04%/day) compared with the control (1.26 ± 0.04%/day) leg ( < 0.001). Myofibrillar protein synthesis rates in the control leg did not change over time ( = 0.775), but in the immobilized leg they were numerically lower during the 0- to 2-day period (16 ± 6%, 1.11 ± 0.09%/day, = 0.153) and were significantly lower during the 2- to 7-day period (44 ± 5%, 0.70 ± 0.06%/day, < 0.001) when compared with the control leg. We conclude that 1 wk of muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates in healthy young men.
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http://dx.doi.org/10.1152/ajpendo.00360.2019DOI Listing
February 2020

Protein synthesis rates of muscle, tendon, ligament, cartilage, and bone tissue in vivo in humans.

PLoS One 2019 7;14(11):e0224745. Epub 2019 Nov 7.

Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Skeletal muscle plasticity is reflected by a dynamic balance between protein synthesis and breakdown, with basal muscle tissue protein synthesis rates ranging between 0.02 and 0.09%/h. Though it is evident that other musculoskeletal tissues should also express some level of plasticity, data on protein synthesis rates of most of these tissues in vivo in humans is limited. Six otherwise healthy patients (62±3 y), scheduled to undergo unilateral total knee arthroplasty, were subjected to primed continuous intravenous infusions with L-[ring-13C6]-Phenylalanine throughout the surgical procedure. Tissue samples obtained during surgery included muscle, tendon, cruciate ligaments, cartilage, bone, menisci, fat, and synovium. Tissue-specific fractional protein synthesis rates (%/h) were assessed by measuring the incorporation of L-[ring-13C6]-Phenylalanine in tissue protein and were compared with muscle tissue protein synthesis rates using a paired t test. Tendon, bone, cartilage, Hoffa's fat pad, anterior and posterior cruciate ligament, and menisci tissue protein synthesis rates averaged 0.06±0.01, 0.03±0.01, 0.04±0.01, 0.11±0.03, 0.07±0.02, 0.04±0.01, and 0.04±0.01%/h, respectively, and did not significantly differ from skeletal muscle protein synthesis rates (0.04±0.01%/h; P>0.05). Synovium derived protein (0.13±0.03%/h) and intercondylar notch bone tissue protein synthesis rates (0.03±0.01%/h) were respectively higher and lower compared to skeletal muscle protein synthesis rates (P<0.05 and P<0.01, respectively). Basal protein synthesis rates in various musculoskeletal tissues are within the same range of skeletal muscle protein synthesis rates, with fractional muscle, tendon, bone, cartilage, ligament, menisci, fat, and synovium protein synthesis rates ranging between 0.02 and 0.13% per hour in vivo in humans. Clinical trial registration: NTR5147.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224745PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837426PMC
March 2020

Branched-chain amino acid and branched-chain ketoacid ingestion increases muscle protein synthesis rates in vivo in older adults: a double-blind, randomized trial.

Am J Clin Nutr 2019 10;110(4):862-872

Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, Netherlands.

Background: Protein ingestion increases muscle protein synthesis rates. However, limited data are currently available on the effects of branched-chain amino acid (BCAA) and branched-chain ketoacid (BCKA) ingestion on postprandial muscle protein synthesis rates.

Objective: The aim of this study was to compare the impact of ingesting 6 g BCAA, 6 g BCKA, and 30 g milk protein (MILK) on the postprandial rise in circulating amino acid concentrations and subsequent myofibrillar protein synthesis rates in older males.

Methods: In a parallel design, 45 older males (age: 71 ± 1 y; BMI: 25.4 ± 0.8 kg/m2) were randomly assigned to ingest a drink containing 6 g BCAA, 6 g BCKA, or 30 g MILK. Basal and postprandial myofibrillar protein synthesis rates were assessed by primed continuous l-[ring-13C6]phenylalanine infusions with the collection of blood samples and muscle biopsies.

Results: Plasma BCAA concentrations increased following test drink ingestion in all groups, with greater increases in the BCAA and MILK groups compared with the BCKA group (P < 0.05). Plasma BCKA concentrations increased following test drink ingestion in all groups, with greater increases in the BCKA group compared with the BCAA and MILK groups (P < 0.05). Ingestion of MILK, BCAA, and BCKA significantly increased early myofibrillar protein synthesis rates (0-2 h) above basal rates (from 0.020 ± 0.002%/h to 0.042 ± 0.004%/h, 0.022 ± 0.002%/h to 0.044 ± 0.004%/h, and 0.023 ± 0.003%/h to 0.044 ± 0.004%/h, respectively; P < 0.001), with no differences between groups (P > 0.05). Myofibrillar protein synthesis rates during the late postprandial phase (2-5 h) remained elevated in the MILK group (0.039 ± 0.004%/h; P < 0.001), but returned to baseline values following BCAA and BCKA ingestion (0.024 ± 0.005%/h and 0.024 ± 0.005%/h, respectively; P > 0.05).

Conclusions: Ingestion of 6 g BCAA, 6 g BCKA, and 30 g MILK increases myofibrillar protein synthesis rates during the early postprandial phase (0-2 h) in vivo in healthy older males. The postprandial increase following the ingestion of 6 g BCAA and BCKA is short-lived, with higher myofibrillar protein synthesis rates only being maintained following the ingestion of an equivalent amount of intact milk protein. This trial was registered at Nederlands Trial Register (www.trialregister.nl) as NTR6047.
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http://dx.doi.org/10.1093/ajcn/nqz120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766442PMC
October 2019

Blood Flow Restriction Only Increases Myofibrillar Protein Synthesis with Exercise.

Med Sci Sports Exerc 2019 06;51(6):1137-1145

NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, THE NETHERLANDS.

Purpose: Combining blood flow restriction (BFR) with exercise can stimulate skeletal muscle hypertrophy. Recent observations in an animal model suggest that BFR performed without exercise can also induce anabolic effects. We assessed the effect of BFR performed both with and without low-load resistance-type exercise (LLRE) on in vivo myofibrillar protein synthesis rates in young men.

Methods: Twenty healthy young men (age = 24 ± 1 yr, body mass index = 22.9 ± 0.6 kg·m) were randomly assigned to remain in resting condition (REST ± BFR; n = 10) or to perform LLRE (LLRE ± BFR at 20% one-repetition maximum; n = 10), combined with two 5-min cycles of single leg BFR. Myofibrillar protein synthesis rates were assessed during a 5-h post-BFR period by combining a primed continuous L-[ring-C6]phenylalanine infusion with the collection of blood samples, and muscle biopsies from the BFR leg and the contralateral control leg. The phosphorylation status of anabolic signaling (mammalian target of rapamycin pathway) and metabolic stress (acetyl-CoA carboxylase)-related proteins, as well as the mRNA expression of genes associated with skeletal muscle mass regulation, was assessed in the collected muscle samples.

Results: Under resting conditions, no differences in anabolic signaling or myofibrillar protein synthesis rates were observed between REST + BFR and REST (0.044% ± 0.004% vs 0.043% ± 0.004% per hour, respectively; P = 0.683). By contrast, LLRE + BFR increased myofibrillar protein synthesis rates by 10% ± 5% compared with LLRE (0.048% ± 0.005% vs 0.043% ± 0.004% per hour, respectively; P = 0.042). Furthermore, compared with LLRE, LLRE + BFR showed higher phosphorylation status of acetyl-CoA carboxylase and 4E-BP1 as well as the elevated mRNA expression of MuRF1 (all P < 0.05).

Conclusion: BFR does not increase myofibrillar protein synthesis rates in healthy young men under resting conditions. When combined with LLRE, BFR increases postexercise myofibrillar protein synthesis rates in vivo in humans.
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http://dx.doi.org/10.1249/MSS.0000000000001899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553970PMC
June 2019

Dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during short-term bed rest.

Am J Physiol Endocrinol Metab 2019 03 15;316(3):E536-E545. Epub 2019 Jan 15.

Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+ , The Netherlands.

Short periods of bed rest lead to the loss of muscle mass and quality. It has been speculated that dietary feeding pattern may have an impact upon muscle protein synthesis rates and, therefore, modulate the loss of muscle mass and quality. We subjected 20 healthy men (age: 25 ± 1 yr, body mass index: 23.8 ± 0.8 kg/m) to 1 wk of strict bed rest with intermittent (4 meals/day) or continuous (24 h/day) enteral tube feeding. Participants consumed deuterium oxide for 7 days before bed rest and throughout the 7-day bed rest period. Prior to and immediately after bed rest, lean body mass (dual energy X-ray absorptiometry), quadriceps cross-sectional area (CSA; CT), maximal oxygen uptake capacity (V̇o), and whole body insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed. Muscle biopsies were collected 7 days before, 1 day before, and immediately after bed rest to assess muscle tracer incorporation. Bed rest resulted in 0.3 ± 0.3 vs. 0.7 ± 0.4 kg lean tissue loss and a 1.1 ± 0.6 vs. 0.8 ± 0.5% decline in quadriceps CSA in the intermittent vs. continuous feeding group, respectively (both P < 0.05), with no differences between groups (both P > 0.05). Moreover, feeding pattern did not modulate the bed rest-induced decline in insulin sensitivity (-46 ± 3% vs. 39 ± 3%; P < 0.001) or V̇o (-2.5 ± 2.2 vs. -8.6 ± 2.2%; P < 0.010) (both P > 0.05). Myofibrillar protein synthesis rates during bed rest did not differ between the intermittent and continuous feeding group (1.33 ± 0.07 vs. 1.50 ± 0.13%/day, respectively; P > 0.05). In conclusion, dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during 1 wk of bed rest in healthy men.
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http://dx.doi.org/10.1152/ajpendo.00378.2018DOI Listing
March 2019

Protein Supplementation after Exercise and before Sleep Does Not Further Augment Muscle Mass and Strength Gains during Resistance Exercise Training in Active Older Men.

J Nutr 2018 11;148(11):1723-1732

NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands.

Background: The proposed benefits of protein supplementation on the skeletal muscle adaptive response to resistance exercise training in older adults remain unclear.

Objective: The present study assessed whether protein supplementation after exercise and before sleep augments muscle mass and strength gains during resistance exercise training in older individuals.

Methods: Forty-one older men [mean ± SEM age: 70 ± 1 y; body mass index (kg/m2): 25.3 ± 0.4] completed 12 wk of whole-body resistance exercise training (3 sessions/wk) and were randomly assigned to ingest either protein (21 g protein, 3 g total leucine, 9 g carbohydrate, 3 g fat; n = 21) or an energy-matched placebo (0 g protein, 25 g carbohydrate, 6 g fat; n = 20) after exercise and each night before sleep. Maximal strength was assessed by 1-repetition-maximum (1RM) strength testing, and muscle hypertrophy was assessed at the whole-body (dual-energy X-ray absorptiometry), upper leg (computed tomography scan), and muscle fiber (biopsy) levels. Muscle protein synthesis rates were assessed during week 12 of training with the use of deuterated water (2H2O) administration.

Results: Leg-extension 1RM increased in both groups (placebo: 88 ± 3 to 104 ± 4 kg; protein: 85 ± 3 to 102 ± 4 kg; P < 0.001), with no differences between groups. Quadriceps cross-sectional area (placebo: 67.8 ± 1.7 to 73.5 ± 2.0 cm2; protein: 68.4 ± 1.4 to 72.3 ± 1.4 cm2; P < 0.001) increased in both groups, with no differences between groups. Muscle fiber hypertrophy occurred in type II muscle fibers (placebo: 5486 ± 418 to 6492 ± 429 µm2; protein: 5367 ± 301 to 6259 ± 391 µm2; P < 0.001), with no differences between groups. Muscle protein synthesis rates were 1.62% ± 0.06% and 1.57% ± 0.05%/d in the placebo and protein groups, respectively, with no differences between groups.

Conclusion: Protein supplementation after exercise and before sleep does not further augment skeletal muscle mass or strength gains during resistance exercise training in active older men. This study was registered at the Netherlands Trial Registry (www.trialregister.nl) as NTR5082.
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http://dx.doi.org/10.1093/jn/nxy169DOI Listing
November 2018

Muscle Atrophy Due to Nerve Damage Is Accompanied by Elevated Myofibrillar Protein Synthesis Rates.

Front Physiol 2018 31;9:1220. Epub 2018 Aug 31.

Experimental and Clinical Research Center, a Joint Cooperation of Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Berlin, Germany.

Muscle loss is a severe complication of many medical conditions such as cancer, cardiac failure, muscular dystrophies, and nerve damage. The contribution of myofibrillar protein synthesis (MPS) to the loss of muscle mass after nerve damage is not clear. Using deuterium oxide (DO) labeling, we demonstrate that MPS is significantly increased in rat (TA) compared to control (3.23 ± 0.72 [damaged] to 2.09 ± 0.26%day [control]) after 4 weeks of nerve constriction injury. This is the case despite substantial loss of mass of the TA (350 ± 96 mg [damaged] to 946 ± 361 mg [control]). We also show that expression of regulatory proteins involved with MPS (p70s6k1: 2.4 ± 0.3 AU [damaged] to 1.8 ± 0.2 AU [control]) and muscle protein breakdown (MPB) (MAFbx: 5.3 ± 1.2 AU [damaged] to 1.4 ± 0.4 AU [control]) are increased in nerve damaged muscle. Furthermore, the expression of p70s6k1 correlates with MPS rates ( = 0.57). In conclusion, this study shows that severe muscle wasting following nerve damage is accompanied by increased as opposed to decreased MPS.
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http://dx.doi.org/10.3389/fphys.2018.01220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127268PMC
August 2018

Brain tissue plasticity: protein synthesis rates of the human brain.

Brain 2018 04;141(4):1122-1129

Department of Human Biology and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.

All tissues undergo continuous reconditioning via the complex orchestration of changes in tissue protein synthesis and breakdown rates. Skeletal muscle tissue has been well studied in this regard, and has been shown to turnover at a rate of 1-2% per day in vivo in humans. Few data are available on protein synthesis rates of other tissues. Because of obvious limitations with regard to brain tissue sampling no study has ever measured brain protein synthesis rates in vivo in humans. Here, we applied stable isotope methodology to directly assess protein synthesis rates in neocortex and hippocampus tissue of six patients undergoing temporal lobectomy for drug-resistant temporal lobe epilepsy (Clinical trial registration: NTR5147). Protein synthesis rates of neocortex and hippocampus tissue averaged 0.17 ± 0.01 and 0.13 ± 0.01%/h, respectively. Brain tissue protein synthesis rates were 3-4-fold higher than skeletal muscle tissue protein synthesis rates (0.05 ± 0.01%/h; P < 0.001). In conclusion, the protein turnover rate of the human brain is much higher than previously assumed.
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http://dx.doi.org/10.1093/brain/awy015DOI Listing
April 2018

Daily resistance-type exercise stimulates muscle protein synthesis in vivo in young men.

J Appl Physiol (1985) 2018 01 21;124(1):66-75. Epub 2017 Sep 21.

NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+ (MUMC+) , Maastricht , The Netherlands.

Resistance-type exercise increases muscle protein synthesis rates during acute postexercise recovery. The impact of resistance-type exercise training on (local) muscle protein synthesis rates under free-living conditions on a day-to-day basis remains unclear. We determined the impact of daily unilateral resistance-type exercise on local myofibrillar protein synthesis rates during a 3-day period. Twelve healthy young men (22 ± 1 yr) were recruited to participate in this study where they performed daily, unilateral resistance-type exercise during a 3-day intervention period. Two days before the exercise training subjects ingested 400 ml deuterated water (HO). Additional 50-ml doses of deuterated water were ingested daily during the training period. Saliva and blood samples were collected daily to assess body water and amino acid precursor deuterium enrichments, respectively. Muscle tissue biopsies were collected before and after the 3 days of unilateral resistance-type exercise training from both the exercised and the nonexercised, control leg for the assessment of muscle protein synthesis rates. Deuterated water dosing resulted in a steady-state body water enrichment of 0.70 ± 0.03%. Intramuscular free [H]alanine enrichment increased up to 1.84 ± 0.06 mole percent excess (MPE) before the exercise training and did not change in both the exercised and control leg during the 3 subsequent exercise training days (2.11 ± 0.11 and 2.19 ± 0.12 MPE, respectively; P > 0.05). Muscle protein synthesis rates averaged 1.984 ± 0.118 and 1.642 ± 0.089%/day in the exercised vs. nonexercised, control leg when assessed over the entire 3-day period ( P < 0.05). Daily resistance-type exercise stimulates (local) muscle protein synthesis in vivo in humans. NEW & NOTEWORTHY This study demonstrates that daily resistance-type exercise stimulates muscle protein synthesis rates in vivo in humans over multiple days. Whereas acute studies have shown that resistance-type exercise increases muscle protein synthesis rates by 50-100%, we observed a lower impact of resistance-type exercise under free-living conditions. We also compared precursor tracer selection for the calculation of muscle protein synthesis rates and observed that saliva deuterium enrichment serves as an appropriate and practical choice of precursor.
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http://dx.doi.org/10.1152/japplphysiol.00610.2017DOI Listing
January 2018

Presleep protein ingestion does not compromise the muscle protein synthetic response to protein ingested the following morning.

Am J Physiol Endocrinol Metab 2016 12 25;311(6):E964-E973. Epub 2016 Oct 25.

Department of Human Biology and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands

Protein ingestion before sleep augments postexercise muscle protein synthesis during overnight recovery. It is unknown whether postexercise and presleep protein consumption modulates postprandial protein handling and myofibrillar protein synthetic responses the following morning. Sixteen healthy young (24 ± 1 yr) men performed unilateral resistance-type exercise (contralateral leg acting as a resting control) at 2000. Participants ingested 20 g of protein immediately after exercise plus 60 g of protein presleep (PRO group; n = 8) or equivalent boluses of carbohydrate (CON; n = 8). The subsequent morning participants received primed, continuous infusions of l-[ring-H]phenylalanine and l-[1-C]leucine combined with ingestion of 20 g intrinsically l-[1-C]phenylalanine- and l-[1-C]leucine-labeled protein to assess postprandial protein handling and myofibrillar protein synthesis in the rested and exercised leg in CON and PRO. Exercise increased postabsorptive myofibrillar protein synthesis rates the subsequent day (P < 0.001), with no differences between CON and PRO. Protein ingested in the morning increased myofibrillar protein synthesis in both the exercised and rested leg (P < 0.01), with no differences between treatments. Myofibrillar protein bound l-[1-C]phenylalanine enrichments were greater in the exercised (0.016 ± 0.002 and 0.015 ± 0.002 MPE in CON and PRO, respectively) vs. rested (0.010 ± 0.002 and 0.009 ± 0.002 MPE in CON and PRO, respectively) leg (P < 0.05), with no differences between treatments (P > 0.05). The additive effects of resistance-type exercise and protein ingestion on myofibrillar protein synthesis persist for more than 12 h after exercise and are not modulated by protein consumption during acute postexercise recovery. This work provides evidence of an extended window of opportunity where presleep protein supplementation can be an effective nutrient timing strategy to optimize skeletal muscle reconditioning.
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http://dx.doi.org/10.1152/ajpendo.00325.2016DOI Listing
December 2016

A single session of neuromuscular electrical stimulation does not augment postprandial muscle protein accretion.

Am J Physiol Endocrinol Metab 2016 Jul 7;311(1):E278-85. Epub 2016 Jun 7.

NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands

The loss of muscle mass and strength that occurs with aging, termed sarcopenia, has been (at least partly) attributed to an impaired muscle protein synthetic response to food intake. Previously, we showed that neuromuscular electrical stimulation (NMES) can stimulate fasting muscle protein synthesis rates and prevent muscle atrophy during disuse. We hypothesized that NMES prior to protein ingestion would increase postprandial muscle protein accretion. Eighteen healthy elderly (69 ± 1 yr) males participated in this study. After a 70-min unilateral NMES protocol was performed, subjects ingested 20 g of intrinsically l-[1-(13)C]phenylalanine-labeled casein. Plasma samples and muscle biopsies were collected to assess postprandial mixed muscle and myofibrillar protein accretion as well as associated myocellular signaling during a 4-h postprandial period in both the control (CON) and stimulated (NMES) leg. Protein ingestion resulted in rapid increases in both plasma phenylalanine concentrations and l-[1-(13)C]phenylalanine enrichments, which remained elevated during the entire 4-h postprandial period (P < 0.05). Mixed-muscle protein-bound l-[1-(13)C]phenylalanine enrichments increased significantly over time following protein ingestion, with no differences between the CON (0.0164 ± 0.0019 MPE) and NMES (0.0164 ± 0.0019 MPE) leg (P > 0.05). In agreement, no differences were observed in the postprandial rise in myofibrillar protein bound l-[1-(13)C]phenylalanine enrichments between the CON and NMES legs (0.0115 ± 0.0014 vs. 0.0133 ± 0.0013 MPE, respectively, P > 0.05). Significant increases in mTOR and P70S6K phosphorylation status were observed in the NMES-stimulated leg only (P < 0.05). We conclude that a single session of NMES prior to food intake does not augment postprandial muscle protein accretion in healthy older men.
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http://dx.doi.org/10.1152/ajpendo.00085.2016DOI Listing
July 2016

Co-ingesting milk fat with micellar casein does not affect postprandial protein handling in healthy older men.

Clin Nutr 2017 04 24;36(2):429-437. Epub 2015 Dec 24.

NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands; Top Institute Food & Nutrition (TIFN), Wageningen, The Netherlands. Electronic address:

Background & Aim: Dietary protein digestion and absorption plays an important role in modulating postprandial muscle protein synthesis. The impact of co-ingesting other macronutrients with dietary protein on protein digestion and absorption and the subsequent muscle protein synthetic response remains largely unexplored. This study investigated the impact of co-ingesting milk fat with micellar casein on dietary protein-derived amino acid appearance in the circulation and the subsequent postprandial muscle protein synthetic response in healthy older men.

Methods: Twenty-four healthy, older males (age: 65 ± 1 y, BMI: 25.7 ± 0.5 kg/m) received a primed continuous infusion of L-[ring-H]-phenylalanine and L-[1-C]-leucine and ingested 20 g intrinsically L-[1-C]-phenylalanine and L-[1-C]-leucine-labeled casein with (PRO + FAT; n = 12) or without (PRO; n = 12) 26.7 g milk fat. Plasma samples and muscle biopsies were collected in both the postabsorptive and postprandial state.

Results: Release of dietary protein-derived phenylalanine into the circulation increased following protein ingestion (P < 0.001) and tended to be higher in PRO compared with PRO + FAT (Time × Treatment P = 0.076). No differences were observed in dietary protein-derived plasma phenylalanine availability (52 ± 2 vs 52 ± 3% in PRO vs PRO + FAT, respectively; P = 0.868). Myofibrillar protein synthesis rates did not differ between treatments, calculated using either the L-[ring-H]-phenylalanine (0.036 ± 0.003 vs 0.036 ± 0.004 %/h after PRO vs PRO + FAT, respectively; P = 0.933) or L-[1-C]-leucine (0.051 ± 0.004 vs 0.046 ± 0.004 %/h, respectively; P = 0.480) tracer. In accordance, no differences were observed in myofibrillar protein-bound L-[1-C]-phenylalanine enrichments between treatments (0.018 ± 0.002 vs 0.014 ± 0.001 MPE, respectively; P = 0.173).

Conclusion: Co-ingesting milk fat with micellar casein does not impair protein-derived phenylalanine appearance in the circulation and does not modulate postprandial myofibrillar protein synthesis rates.

Clinical Trial Registration Number: NCT01680146 (http://www.clinicaltrials.gov/).
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http://dx.doi.org/10.1016/j.clnu.2015.12.011DOI Listing
April 2017

The use of doubly labeled milk protein to measure postprandial muscle protein synthesis rates in vivo in humans.

J Appl Physiol (1985) 2014 Dec 2;117(11):1363-70. Epub 2014 Oct 2.

NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands

We aimed to determine the impact of precursor pool dilution on the assessment of postprandial myofibrillar protein synthesis rates (MPS). A Holstein dairy cow was infused with large amounts of L-[1-(13)C]phenylalanine and L-[1-(13)C]leucine, and the milk was collected and fractionated. The enrichment levels in the casein were 38.7 and 9.3 mole percent excess, respectively. In a subsequent human experiment, 11 older men (age: 71 ± 1 y, body mass index: 26 ± 0.1 kg·m(-2)) received a primed constant infusion of L-[ring-(2)H5]phenylalanine and L-[1-(13)C]leucine. Blood and muscle samples were collected before and after the ingestion of 20-g doubly labeled casein to assess postprandial MPS based on the 1) constant tracer infusion of L-[ring-(2)H5]phenylalanine, 2) ingestion of intrinsically L-[1-(13)C]phenylalanine-labeled casein, and 3) constant infusion of L-[1-(13)C]leucine in combination with the ingestion of intrinsically L-[1-(13)C]leucine-labeled casein. Postprandial MPS was increased (P < 0.05) after protein ingestion (∼70% above postabsorptive values) based on the L-[1-(13)C]leucine tracer. There was no significant stimulation of postprandial MPS (∼27% above postabsorptive values) when the calculated fractional synthesis rate was based on the L-[ring-(2)H5]phenylalanine (P = 0.2). Comparisons of postprandial MPS based on the primed continuous infusion of L-[1-(13)C]leucine or the ingestion of intrinsically L-[1-(13)C]phenylalanine-labeled casein protein demonstrated differences compared with the primed continuous infusion of L-[ring-(2)H5]phenylalanine (P > 0.05). Our findings confirm that the postprandial MPS assessed using the primed continuous tracer infusion approach may differ if tracer steady-state conditions in the precursor pools are perturbed. The use of intrinsically doubly labeled protein provides a method to study the metabolic fate of the ingested protein and the subsequent postprandial MPS response.
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http://dx.doi.org/10.1152/japplphysiol.00411.2014DOI Listing
December 2014

Carbohydrate coingestion delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion.

J Clin Endocrinol Metab 2014 Jun 14;99(6):2250-8. Epub 2014 Mar 14.

Top Institute Food and Nutrition (S.H.M.G., N.A.B., H.M.H., L.J.C.v.L.), 6709 PA Wageningen, The Netherlands; Department of Human Movement Sciences (S.H.M.G., N.A.B., H.M.H., B.B.G., L.J.C.v.L.), NUTRIM School for Nutrition, Toxicology, and Metabolism, and Department of Human Biology (A.P.G.), NUTRIM, Maastricht University Medical Centre+, 6200 MD Maastricht, The Netherlands.

Background: Dietary protein digestion and absorption is an important factor modulating muscle protein accretion. However, there are few data available on the effects of coingesting other macronutrients with protein on digestion and absorption kinetics and the subsequent muscle protein synthetic response.

Objective: The objective of the study was to determine the impact of carbohydrate coingestion with protein on dietary protein digestion and absorption and muscle protein accretion in healthy young and older men.

Design: Twenty-four healthy young (aged 21± 1 y, body mass index 21.8 ±0.5 kg/m(2)) and 25 older (aged 75 ± 1 y, body mass index 25.4 ± 0.6 kg/m(2)) men received a primed continuous L-[ring-(2)H5]-phenylalanine and L-[ring-3,5-(2)H2]-tyrosine infusion and ingested 20 g intrinsically L-[1-(13)C]-phenylalanine-labeled protein with (Pro+CHO) or without (Pro) 60 g carbohydrate. Plasma samples and muscle biopsies were collected in a postabsorptive and postprandial state.

Results: Carbohydrate coingestion delayed the appearance of exogenous phenylalanine in the circulation (P = .001). Dietary protein-derived phenylalanine availability over the 5-hour postprandial period was lower in the older (62 ± 2%) when compared with the young subjects (74 ± 2%; P = .007), with no differences between conditions (P = .20). Carbohydrate coingestion did not modulate postprandial muscle protein synthesis rates (0.035 ± 0.003 vs 0.043 ± 0.004 and 0.033 ± 0.002 vs 0.035 ± 0.003%/h after Pro vs Pro+CHO in the young and older group, respectively). In accordance, no differences in muscle protein-bound L-[1-(13)C]-phenylalanine enrichments were observed between conditions (0.020 ± 0.002 vs 0.020 ± 0.002 and 0.019 ± 0.003 vs 0.022 ± 0.004 mole percent excess after Pro vs Pro+CHO in the young and older subjects, respectively).

Conclusion: Carbohydrate coingestion with protein delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion in healthy young or older men.
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http://dx.doi.org/10.1210/jc.2013-3970DOI Listing
June 2014

Disuse impairs the muscle protein synthetic response to protein ingestion in healthy men.

J Clin Endocrinol Metab 2013 Dec 9;98(12):4872-81. Epub 2013 Oct 9.

PhD, Department of Human Movement Sciences, Maastricht University Medical Center, Maastricht 6200 MD, The Netherlands.

Background: Disuse leads to rapid skeletal muscle atrophy, which brings about numerous negative health consequences. Muscle disuse atrophy is, at least in part, attributed to a decline in basal (postabsorptive) muscle protein synthesis rates. However, it remains to be determined whether muscle disuse also impairs the muscle protein synthetic response to dietary protein ingestion.

Purpose: We assessed muscle protein synthesis rates after protein ingestion before and after a period of disuse in humans.

Methods: Twelve healthy young (24 ± 1 year) men underwent a 14-day period of one-legged knee immobilization by way of a full leg cast. Before and after the immobilization period, quadriceps cross-sectional area, muscle strength, skeletal muscle protein synthesis rates, and associated im (intramuscular) molecular signaling were assessed. Continuous infusions of l-[ring-²H₅]phenylalanine were applied to assess mixed-muscle protein fractional synthetic rates after the ingestion of 20 g dietary protein.

Results: Immobilization led to an 8.4% ± 2.8% (P < .001) and 22.9% ± 2.6% (P < .001) decrease in quadriceps muscle cross-sectional area and strength, respectively. Immobilization resulted in a 31% ± 12% reduction in postprandial muscle protein synthesis rates (from 0.046% ± 0.004% to 0.032% ± 0.006% per hour; P < .05). These findings were observed without any discernible changes in the skeletal muscle phosphorylation status of mammalian target of rapamycin or p70 ribosomal protein S6 kinase.

Conclusions: A short period of muscle disuse impairs the muscle protein synthetic response to dietary protein intake in vivo in healthy young men. Thus, anabolic resistance to protein ingestion contributes significantly to the loss of muscle mass that is observed during disuse.
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http://dx.doi.org/10.1210/jc.2013-2098DOI Listing
December 2013

Substantial Differences between Organ and Muscle Specific Tracer Incorporation Rates in a Lactating Dairy Cow.

PLoS One 2013 27;8(6):e68109. Epub 2013 Jun 27.

Top Institute Food and Nutrition (TIFN), Wageningen, The Netherlands ; Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands.

We aimed to produce intrinsically L-[1-(13)C]phenylalanine labeled milk and beef for subsequent use in human nutrition research. The collection of the various organ tissues after slaughter allowed for us to gain insight into the dynamics of tissue protein turnover in vivo in a lactating dairy cow. One lactating dairy cow received a constant infusion of L-[1-(13)C]phenylalanine (450 µmol/min) for 96 h. Plasma and milk were collected prior to, during, and after the stable isotope infusion. Twenty-four hours after cessation of the infusion the cow was slaughtered. The meat and samples of the various organ tissues (liver, heart, lung, udder, kidney, rumen, small intestine, and colon) were collected and stored. Approximately 210 kg of intrinsically labeled beef (bone and fat free) with an average L-[1-(13)C]phenylalanine enrichment of 1.8±0.1 mole percent excess (MPE) was obtained. The various organ tissues differed substantially in L-[1-(13)C]phenylalanine enrichments in the tissue protein bound pool, the highest enrichment levels were achieved in the kidney (11.7 MPE) and the lowest enrichment levels in the skeletal muscle tissue protein of the cow (between 1.5-2.4 MPE). The estimated protein synthesis rates of the various organ tissues should be regarded as underestimates, particularly for the organs with the higher turnover rates and high secretory activity, due to the lengthened (96 h) measurement period necessary for the production of the intrinsically labeled beef. Our data demonstrates that there are relatively small differences in L-[1-(13)C]phenylalanine enrichments between the various meat cuts, but substantial higher enrichment values are observed in the various organ tissues. We conclude that protein turnover rates of various organs are much higher when compared to skeletal muscle protein turnover rates in large lactating ruminants.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0068109PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694909PMC
October 2017

Carbohydrate co-ingestion with protein does not further augment post-prandial muscle protein accretion in older men.

Nutr Metab (Lond) 2013 Jan 25;10(1):15. Epub 2013 Jan 25.

Department of Human Movement Sciences, Maastricht University Medical Centre, PO Box 616, Maastricht, MD, 6200, The Netherlands.

Background: A blunted muscle protein synthetic response to protein ingestion may contribute to the age related loss of muscle tissue. We hypothesized that the greater endogenous insulin release following co-ingestion of carbohydrate facilitates post-prandial muscle protein accretion after ingesting a meal-like bolus of protein in older males.

Methods: Twenty-four healthy older men (75±1 y) were randomly assigned to ingest 20 g intrinsically L-[1-13C] phenylalanine-labeled casein protein with (PRO-CHO) or without (PRO) 40 g carbohydrate. Ingestion of specifically produced intrinsically L-[1-13C] phenylalanine labeled protein allowed us to assess post-prandial incorporation of dietary protein derived amino acids into muscle protein. Blood samples were collected at regular intervals, with muscle biopsies being obtained prior to and 2 and 6 h after protein ingestion.

Results: Plasma glucose and insulin concentrations showed a greater increase in PRO-CHO compared with PRO (P<0.001). Muscle protein-bound L-[1-13C] phenylalanine enrichments tended to increase to a greater extent in PRO-CHO compared with PRO during the first 2 h after protein ingestion (0.0072±0.0013 vs 0.0046±0.010 MPE, respectively; P=0.13). However, 6 h after protein ingestion, differences in muscle protein-bound L-[1-13C] phenylalanine enrichments were no longer observed between experiments (0.0213±0.0024 vs 0.0185±0.0010 MPE, respectively; P=0.30).

Conclusions: This study shows that carbohydrate ingestion may accelerate, but does not further augment post-prandial incorporation of dietary protein derived amino acids into muscle protein in healthy elderly men.
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http://dx.doi.org/10.1186/1743-7075-10-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585863PMC
January 2013

Leucine co-ingestion improves post-prandial muscle protein accretion in elderly men.

Clin Nutr 2013 Jun 20;32(3):412-9. Epub 2012 Sep 20.

Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 616, Maastricht, 6200 MD, The Netherlands.

Background & Aims: It has been speculated that the amount of leucine in a meal largely determines the post-prandial muscle protein synthetic response to food intake. The present study investigates the impact of leucine co-ingestion on subsequent post-prandial muscle protein accretion following the ingestion of a single bolus of dietary protein in elderly males.

Methods: Twenty-four elderly men (74.3±1.0 y) were randomly assigned to ingest 20 g intrinsically L-[1-(13)C]phenylalanine-labeled casein protein with (PRO+LEU) or without (PRO) 2.5 g crystalline leucine. Ingestion of specifically produced intrinsically labeled protein allowed us to create a plasma phenylalanine enrichment pattern similar to the absorption pattern of phenylalanine from the ingested protein and assess the subsequent post-prandial incorporation of L-[1-(13)C] phenylalanine into muscle protein.

Results: Plasma amino acid concentrations increased rapidly following protein ingestion in both groups, with higher leucine concentrations observed in the PRO+LEU compared with the PRO group (P<0.01). Plasma L-[1-(13)C]phenylalanine enrichments increased rapidly and to a similar extent in both groups following protein ingestion. Muscle protein-bound L-[1-(13)C]phenylalanine enrichments were significantly greater after PRO+LEU when compared with PRO at 2 h (72%; 0.0078±0.0010 vs. 0.0046±0.00100 MPE, respectively; P<0.05) and 6 h (25%; 0.0232±0.0015 vs. 0.0185±0.0010 MPE, respectively; P<0.05) following protein ingestion. The latter translated into a greater muscle protein synthetic rate following PRO+LEU compared with PRO over the entire 6 h post-prandial period (22%; 0.049±0.003 vs. 0.040±0.003% h(-1), respectively; P<0.05).

Conclusion: Leucine co-ingestion with a bolus of pure dietary protein further stimulates post-prandial muscle protein synthesis rates in elderly men.
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http://dx.doi.org/10.1016/j.clnu.2012.09.002DOI Listing
June 2013

The single biopsy approach is reliable for the measurement of muscle protein synthesis rates in vivo in older men.

J Appl Physiol (1985) 2012 Sep 19;113(6):896-902. Epub 2012 Jul 19.

Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre (MUMC Maastricht, the Netherlands.

We aimed to assess the reliability of the single biopsy approach for calculating muscle protein synthesis rates compared with the well described sequential muscle biopsy approach following a primed continuous infusion of L-[ring-(2)H(5)]phenylalanine and GC-MS analysis in older men. Two separate experimental infusion protocols, with differing stable isotope amino acid incorporation times, were employed consisting of n = 27 (experiment 1) or n = 9 (experiment 2). Specifically, mixed muscle protein FSR were calculated from baseline plasma protein enrichments and muscle protein enrichments obtained at 90 min or 50 min (1BX SHORT), 210 min or 170 min (1BX LONG), and between the muscle protein enrichments obtained at 90 and 210 min or 50 min and 170 min (2BX) of the infusion for experiments 1 and 2, respectively. In experiment 2, we also assessed the error that is introduced to the single muscle biopsy approach when nontracer naive subjects are recruited for participation in a primed continuous infusion of isotope-labeled amino acids. In experiment 1, applying the individual plasma protein enrichment values to the single muscle biopsy approach resulted in no differences in muscle protein FSR between the 1BX SHORT (0.031 ± 0.003%·h(-1)), 1BX LONG (0.032 ± 0.002%·h(-1)), or the 2BX approach (0.034 ± 0.002%·h(-1)). A significant correlation in muscle protein FSR was observed only between the 1BX LONG and 2BX approach (r = 0.8; P < 0.001). Similar results were observed in experiment 2. In addition, using the single biopsy approach in nontracer naïve state results in a muscle protein FSR that is negative for both the 1BX SHORT (-0.67 ± 0.051%·h(-1)) and 1BX LONG (-0.19 ± 0.051%·h(-1)) approaches. This is the first study to demonstrate that the single biopsy approach, coupled with the background enrichment of L-[ring-(2)H(5)]-phenylalanine of mixed plasma proteins, generates data that are similar to using the sequential muscle biopsy approach in the elderly population.
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http://dx.doi.org/10.1152/japplphysiol.00513.2012DOI Listing
September 2012

Amino acid absorption and subsequent muscle protein accretion following graded intakes of whey protein in elderly men.

Am J Physiol Endocrinol Metab 2012 Apr 14;302(8):E992-9. Epub 2012 Feb 14.

Top Institute Food & Nutrition, Wageningen, The Netherlands.

Whey protein ingestion has been shown to effectively stimulate postprandial muscle protein accretion in older adults. However, the impact of the amount of whey protein ingested on protein digestion and absorption kinetics, whole body protein balance, and postprandial muscle protein accretion remains to be established. We aimed to fill this gap by including 33 healthy, older men (73 ± 2 yr) who were randomly assigned to ingest 10, 20, or 35 g of intrinsically l-[1-¹³C]phenylalanine-labeled whey protein (n = 11/treatment). Ingestion of labeled whey protein was combined with continuous intravenous l-[ring-²H₅]phenylalanine and l-[ring-²H₂]tyrosine infusion to assess the metabolic fate of whey protein-derived amino acids. Dietary protein digestion and absorption rapidly increased following ingestion of 10, 20, and 35 g whey protein, with the lowest and highest (peak) values observed following 10 and 35 g, respectively (P < 0.05). Whole body net protein balance was positive in all groups (19 ± 1, 37 ± 2, and 58 ± 2 μmol/kg), with the lowest and highest values observed following ingestion of 10 and 35 g, respectively (P < 0.05). Postprandial muscle protein accretion, assessed by l-[1-¹³C]phenylalanine incorporation in muscle protein, was higher following ingestion of 35 g when compared with 10 (P < 0.01) or 20 (P < 0.05) g. We conclude that ingestion of 35 g whey protein results in greater amino acid absorption and subsequent stimulation of de novo muscle protein synthesis compared with the ingestion of 10 or 20 g whey protein in healthy, older men.
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http://dx.doi.org/10.1152/ajpendo.00517.2011DOI Listing
April 2012

Protein ingestion before sleep improves postexercise overnight recovery.

Med Sci Sports Exerc 2012 Aug;44(8):1560-9

Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Introduction: The role of nutrition in modulating postexercise overnight recovery remains to be elucidated. We assessed the effect of protein ingestion immediately before sleep on digestion and absorption kinetics and protein metabolism during overnight recovery from a single bout of resistance-type exercise.

Methods: Sixteen healthy young males performed a single bout of resistance-type exercise in the evening (2000 h) after a full day of dietary standardization. All subjects were provided with appropriate recovery nutrition (20 g of protein, 60 g of CHO) immediately after exercise (2100 h). Thereafter, 30 min before sleep (2330 h), subjects ingested a beverage with (PRO) or without (PLA) 40 g of specifically produced intrinsically [1-C]phenylalanine-labeled casein protein. Continuous intravenous infusions with [ring-H5]phenylalanine and [ring-H2]tyrosine were applied with blood and muscle samples collected to assess protein digestion and absorption kinetics, whole-body protein balance and mixed muscle protein synthesis rates throughout the night (7.5 h).

Results: During sleep, casein protein was effectively digested and absorbed resulting in a rapid rise in circulating amino acid levels, which were sustained throughout the remainder of the night. Protein ingestion before sleep increased whole-body protein synthesis rates (311 ± 8 vs 246 ± 9 μmol·kg per 7.5 h) and improved net protein balance (61 ± 5 vs -11 ± 6 μmol·kg per 7.5 h) in the PRO vs the PLA experiment (P < 0.01). Mixed muscle protein synthesis rates were ∼22% higher in the PRO vs the PLA experiment, which reached borderline significance (0.059%·h ± 0.005%·h vs 0.048%·h ± 0.004%·h, P = 0.05).

Conclusions: This is the first study to show that protein ingested immediately before sleep is effectively digested and absorbed, thereby stimulating muscle protein synthesis and improving whole-body protein balance during postexercise overnight recovery.
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http://dx.doi.org/10.1249/MSS.0b013e31824cc363DOI Listing
August 2012

The reliability of using the single-biopsy approach to assess basal muscle protein synthesis rates in vivo in humans.

Metabolism 2012 Jul 29;61(7):931-6. Epub 2011 Dec 29.

Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+(MUMC+), PO Box 616, 6200 MD, Maastricht, The Netherlands.

It has recently been proposed that basal muscle protein synthesis can be effectively assessed by measuring the background enrichment in total plasma protein, thereby omitting the initial biopsy, and determining the difference in enrichment from a single muscle biopsy obtained during a primed continuous infusion of isotope-labeled amino acids. We determined the reliability of calculating basal mixed muscle protein fractional synthetic rates (FSRs) from mixed plasma proteins and a single muscle biopsy compared against the sequential muscle biopsy approach. Ten men (age, 23 ± 1 years; body mass index, 22 ± 1 kg∙m(-2)) received muscle biopsies of the vastus lateralis after 2 and 4 hours of a primed continuous infusion of l-[ring-(13)C(6)]phenylalanine. Mixed muscle protein FSR was calculated from baseline plasma enrichments and muscle protein enrichments determined from the biopsy at 2 hours (1BX SHORT) or 4 hours (1BX LONG), or between muscle protein enrichments at 2 and 4 hours (2BX) of the infusion. No differences (P = .50) were observed in mixed muscle protein FSR, using plasma [ring-(13)C(6)]phenylalanine enrichments as the precursor, between the 1BX SHORT (0.031% ± 0.010%∙h(-1)), 1BX LONG (0.032% ± 0.007%∙h(-1)), or 2BX (0.035% ± 0.011%∙h(-1)) approach. A significant correlation was observed between the calculated muscle protein FSR assessed using the 1BX LONG and 2BX approach (r = 0.7, P = .02). Our data demonstrate that the single-biopsy approach, irrespective of whether the biopsy is obtained at 2 or 4 hours, can be used as a surrogate for the sequential-biopsy approach to determine basal muscle protein synthesis in a group.
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http://dx.doi.org/10.1016/j.metabol.2011.11.004DOI Listing
July 2012

Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men.

Am J Clin Nutr 2011 May 2;93(5):997-1005. Epub 2011 Mar 2.

Top Institute Food & Nutrition, Wageningen, Netherlands.

Background: Sarcopenia has been attributed to a diminished muscle protein synthetic response to food intake. Differences in digestion and absorption kinetics of dietary protein, its amino acid composition, or both have been suggested to modulate postprandial muscle protein accretion.

Objective: The objective was to compare protein digestion and absorption kinetics and subsequent postprandial muscle protein accretion after ingestion of whey, casein, and casein hydrolysate in healthy older adults.

Design: A total of 48 older men aged 74 ± 1 y (mean ± SEM) were randomly assigned to ingest a meal-like amount (20 g) of intrinsically l-[1-(13)C]phenylalanine-labeled whey, casein, or casein hydrolysate. Protein ingestion was combined with continuous intravenous l-[ring-(2)H(5)]phenylalanine infusion to assess in vivo digestion and absorption kinetics of dietary protein. Postprandial mixed muscle protein fractional synthetic rates (FSRs) were calculated from the ingested tracer.

Results: The peak appearance rate of dietary protein-derived phenylalanine in the circulation was greater with whey and casein hydrolysate than with casein (P < 0.05). FSR values were higher after whey (0.15 ± 0.02%/h) than after casein (0.08 ± 0.01%/h; P < 0.01) and casein hydrolysate (0.10 ± 0.01%/h; P < 0.05) ingestion. A strong positive correlation (r = 0.66, P < 0.01) was observed between peak plasma leucine concentrations and postprandial FSR values.

Conclusions: Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men. This effect is attributed to a combination of whey's faster digestion and absorption kinetics and higher leucine content. This trial was registered at clinicaltrials.gov as NCT00557388.
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http://dx.doi.org/10.3945/ajcn.110.008102DOI Listing
May 2011

Post-exercise protein synthesis rates are only marginally higher in type I compared with type II muscle fibres following resistance-type exercise.

Eur J Appl Physiol 2011 Aug 14;111(8):1871-8. Epub 2011 Jan 14.

Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 616, 6200 MD, Maastricht, The Netherlands.

We examined the effect of an acute bout of resistance exercise on fractional muscle protein synthesis rates in human type I and type II muscle fibres. After a standardised breakfast (31 ± 1 kJ kg(-1) body weight, consisting of 52 Energy% (En%) carbohydrate, 34 En% protein and 14 En% fat), 9 untrained men completed a lower-limb resistance exercise bout (8 sets of 10 repetitions leg press and leg extension at 70% 1RM). A primed, continuous infusion of L: -[ring-(13)C(6)]phenylalanine was combined with muscle biopsies collected from both legs immediately after exercise and after 6 h of post-exercise recovery. Single muscle fibres were dissected from freeze-dried biopsies and stained for ATPase activity with pre-incubation at a pH of 4.3. Type I and II fibres were separated under a light microscope and analysed for protein-bound L: -[ring-(13)C(6)]phenylalanine labelling. Baseline (post-exercise) L: -[ring-(13)C(6)]phenylalanine muscle tissue labelling, expressed as (∂(13)C/(12)C), averaged -32.09 ± 0.28, -32.53 ± 0.10 and -32.02 ± 0.16 in the type I and II muscle fibres and mixed muscle, respectively (P = 0.14). During post-exercise recovery, muscle protein synthesis rates were marginally (8 ± 2%) higher in the type I than type II muscle fibres, at 0.100 ± 0.005 versus 0.094 ± 0.005%/h, respectively (P < 0.05), whereby rates of mixed muscle protein were 0.091 ± 0.005%/h. Muscle protein synthesis rates following resistance-type exercise are only marginally higher in type I compared with type II muscle fibres.
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http://dx.doi.org/10.1007/s00421-010-1808-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156941PMC
August 2011

Dietary protein digestion and absorption rates and the subsequent postprandial muscle protein synthetic response do not differ between young and elderly men.

J Nutr 2009 Sep 22;139(9):1707-13. Epub 2009 Jul 22.

Department of Human Movement Sciences, Maastricht University, Maastricht 6200 MD, The Netherlands.

Impaired digestion and/or absorption of dietary protein lowers postprandial plasma amino acid availability and, as such, could reduce the postprandial muscle protein synthetic response in the elderly. We aimed to compare in vivo dietary protein digestion and absorption and the subsequent postprandial muscle protein synthetic response between young and elderly men. Ten elderly (64 +/- 1 y) and 10 young (23 +/- 1 y) healthy males consumed a single bolus of 35 g specifically produced, intrinsically l-[1-(13)C]phenylalanine-labeled micellar casein (CAS) protein. Furthermore, primed continuous infusions with l-[ring-(2)H(5)]phenylalanine, l-[1-(13)C]leucine, and l-[ring-(2)H(2)]tyrosine were applied and blood and muscle tissue samples were collected to assess the appearance rate of dietary protein-derived phenylalanine in the circulation and the subsequent muscle protein fractional synthetic rate over a 6-h postprandial period. Protein ingestion resulted in a rapid increase in exogenous phenylalanine appearance in both the young and elderly men. Total exogenous phenylalanine appearance rates (expressed as area under the curve) were 39 +/- 3 mumol.6 h.kg(-1) in the young men and 38 +/- 2 mumol.6 h.kg(-1) in the elderly men (P = 0.73). In accordance, splanchnic amino acid extraction did not differ between young (72 +/- 2%) and elderly (73 +/- 1%) volunteers (P = 0.74). Muscle protein synthesis rates, calculated from the oral tracer, were 0.063 +/- 0.006 and 0.054 +/- 0.004%/h in the young and elderly men, respectively, and did not differ between groups (P = 0.27). We conclude that protein digestion and absorption kinetics and the subsequent muscle protein synthetic response following the ingestion of a large bolus of intact CAS are not substantially impaired in healthy, elderly men.
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http://dx.doi.org/10.3945/jn.109.109173DOI Listing
September 2009

Ingestion of a protein hydrolysate is accompanied by an accelerated in vivo digestion and absorption rate when compared with its intact protein.

Am J Clin Nutr 2009 Jul 27;90(1):106-15. Epub 2009 May 27.

Department of Human Movement Sciences, Nutrition and Toxicology Research Institute Maastricht, Maastricht, Netherlands.

Background: It has been suggested that a protein hydrolysate, as opposed to its intact protein, is more easily digested and absorbed from the gut, which results in greater plasma amino acid availability and a greater muscle protein synthetic response.

Objective: We aimed to compare dietary protein digestion and absorption kinetics and the subsequent muscle protein synthetic response to the ingestion of a single bolus of protein hydrolysate compared with its intact protein in vivo in humans.

Design: Ten elderly men (mean +/- SEM age: 64 +/- 1 y) were randomly assigned to a crossover experiment that involved 2 treatments in which the subjects consumed a 35-g bolus of specifically produced L-[1-(13)C]phenylalanine-labeled intact casein (CAS) or hydrolyzed casein (CASH). Blood and muscle-tissue samples were collected to assess the appearance rate of dietary protein-derived phenylalanine in the circulation and subsequent muscle protein fractional synthetic rate over a 6-h postprandial period.

Results: The mean (+/-SEM) exogenous phenylalanine appearance rate was 27 +/- 6% higher after ingestion of CASH than after ingestion of CAS (P < 0.001). Splanchnic extraction was significantly lower in CASH compared with CAS treatment (P < 0.01). Plasma amino acid concentrations increased to a greater extent (25-50%) after the ingestion of CASH than after the ingestion of CAS (P < 0.01). Muscle protein synthesis rates averaged 0.054 +/- 0.004% and 0.068 +/- 0.006%/h in the CAS and CASH treatments, respectively (P = 0.10).

Conclusions: Ingestion of a protein hydrolysate, as opposed to its intact protein, accelerates protein digestion and absorption from the gut, augments postprandial amino acid availability, and tends to increase the incorporation rate of dietary amino acids into skeletal muscle protein.
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http://dx.doi.org/10.3945/ajcn.2009.27474DOI Listing
July 2009
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