Publications by authors named "Janneau van Kranenburg"

38 Publications

Ingestion of Free Amino Acids Compared with an Equivalent Amount of Intact Protein Results in More Rapid Amino Acid Absorption and Greater Postprandial Plasma Amino Acid Availability Without Affecting Muscle Protein Synthesis Rates in Young Adults in a Double-Blind Randomized Trial.

J Nutr 2021 Oct 12. Epub 2021 Oct 12.

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

Background: The rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and modulates postprandial muscle protein synthesis rates.

Objective: We sought to compare protein digestion, amino acid absorption kinetics, and the postprandial muscle protein synthetic response following ingestion of intact milk protein or an equivalent amount of free amino acids.

Methods: Twenty-four healthy, young participants (mean ± SD age: 22 ± 3 y and BMI 23 ± 2 kg/m2; sex: 12 male and 12 female participants) received a primed continuous infusion of l-[ring-2H5]-phenylalanine and l-[ring-3,5-2H2]-tyrosine, after which they ingested either 30 g intrinsically l-[1-13C]-phenylalanine-labeled milk protein or an equivalent amount of free amino acids labeled with l-[1-13C]-phenylalanine. Blood samples and muscle biopsies were obtained to assess protein digestion and amino acid absorption kinetics (secondary outcome), whole-body protein net balance (secondary outcome), and mixed muscle protein synthesis rates (primary outcome) throughout the 6-h postprandial period.

Results: Postprandial plasma amino acid concentrations increased after ingestion of intact milk protein and free amino acids (both P < 0.001), with a greater increase following ingestion of the free amino acids than following ingestion of intact milk protein (P-time × treatment < 0.001). Exogenous phenylalanine release into plasma, assessed over the 6-h postprandial period, was greater with free amino acid ingestion (76 ± 9%) than with milk protein treatment (59 ± 10%; P < 0.001). Ingestion of free amino acids and intact milk protein increased mixed muscle protein synthesis rates (P-time < 0.001), with no differences between treatments (from 0.037 ± 0.015%/h to 0.053 ± 0.014%/h and 0.039 ± 0.016%/h to 0.051 ± 0.010%/h, respectively; P-time × treatment = 0.629).

Conclusions: Ingestion of a bolus of free amino acids leads to more rapid amino acid absorption and greater postprandial plasma amino acid availability than ingestion of an equivalent amount of intact milk protein. Ingestion of free amino acids may be preferred over ingestion of intact protein in conditions where protein digestion and amino acid absorption are compromised.
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http://dx.doi.org/10.1093/jn/nxab305DOI Listing
October 2021

Amino acid removal during hemodialysis can be compensated for by protein ingestion and is not compromised by intradialytic exercise: a randomized controlled crossover trial.

Am J Clin Nutr 2021 Sep 12. Epub 2021 Sep 12.

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

Background: Patients with end-stage renal disease (ESRD) undergoing hemodialysis experience a rapid decline in skeletal muscle mass and strength. Hemodialysis removes amino acids (AAs) from the circulation, thereby lowering plasma AA concentrations and stimulating proteolysis.

Objectives: In the present study, we evaluate the impact of intradialytic protein ingestion at rest and following exercise on AA removal and plasma AA availability in patients with ESRD.

Methods: Ten patients (age: 65 ± 16 y, male/female: 8/2, BMI: 24.2 ± 4.8 kg/m2, serum albumin: 3.4 ± 0.3 g/dL) with ESRD undergoing hemodialysis participated in this randomized controlled crossover trial. During 4 hemodialysis sessions, patients were assigned to ingest 40 g protein or a placebo 60 min after initiation, both at rest (PRO and PLA, respectively) and following exercise (PRO + EX and PLA + EX, respectively). Spent dialysate and blood samples were collected every 30 min throughout hemodialysis to assess AA removal and plasma AA availability.

Results: Plasma AA concentrations declined by 26.1 ± 4.5% within 30 min after hemodialysis initiation during all interventions (P < 0.001, η2p > 0.79). Protein ingestion, but not intradialytic exercise, increased AA removal throughout hemodialysis (9.8 ± 2.0, 10.2 ± 1.6, 16.7 ± 2.2, and 17.3 ± 2.3 g during PLA, PLA + EX, PRO, and PRO + EX interventions, respectively; protein effect P < 0.001, η2p = 0.97; exercise effect P = 0.32, η2p = 0.11). Protein ingestion increased plasma AA concentrations until the end of hemodialysis, whereas placebo ingestion resulted in decreased plasma AA concentrations (time effect P < 0.001, η2p > 0.84). Plasma AA availability (incremental AUC) was greater during PRO and PRO + EX interventions (49 ± 87 and 70 ± 34 mmol/L/240 min, respectively) compared with PLA and PLA + EX interventions (-227 ± 54 and -208 ± 68 mmol/L/240 min, respectively; protein effect P < 0.001, η2p = 0.98; exercise effect P = 0.21, η2p = 0.16).

Conclusions: Protein ingestion during hemodialysis compensates for AA removal and increases plasma AA availability both at rest and during recovery from intradialytic exercise. Intradialytic exercise does not compromise AA removal or reduce plasma AA availability during hemodialysis in a postabsorptive or postprandial state.
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http://dx.doi.org/10.1093/ajcn/nqab274DOI Listing
September 2021

No differences in muscle protein synthesis rates following ingestion of wheat protein, milk protein, and their protein blend in healthy, young males.

Br J Nutr 2021 Feb 18:1-11. Epub 2021 Feb 18.

TiFN, Wageningen, The Netherlands.

Plant-derived proteins have been suggested to have less anabolic properties when compared with animal-derived proteins. Whether blends of plant- and animal-derived proteins can compensate for their lesser anabolic potential has not been assessed. The present study compares post-prandial muscle protein synthesis rates following the ingestion of milk protein with wheat protein or a blend of wheat plus milk protein in healthy, young males. In a randomised, double-blind, parallel-group design, 36 males (23 (sd 3) years) received a primed continuous L-[ring-13C6]-phenylalanine infusion after which they ingested 30 g milk protein (MILK), 30 g wheat protein (WHEAT) or a 30 g blend combining 15 g wheat plus 15 g milk protein (WHEAT+MILK). Blood and muscle biopsies were collected frequently for 5 h to assess post-prandial plasma amino acid profiles and subsequent myofibrillar protein synthesis rates. Ingestion of protein increased myofibrillar protein synthesis rates in all treatments (P < 0·001). Post-prandial myofibrillar protein synthesis rates did not differ between MILK v. WHEAT (0·053 (sd 0·013) v. 0·056 (sd 0·012) %·h-1, respectively; t test P = 0·56) or between MILK v. WHEAT+MILK (0·053 (sd 0·013) v. 0·059 (sd 0·025) %·h-1, respectively; t test P = 0·46). In conclusion, ingestion of 30 g milk protein, 30 g wheat protein or a blend of 15 g wheat plus 15 g milk protein increases muscle protein synthesis rates in young males. Furthermore, muscle protein synthesis rates following the ingestion of 30 g milk protein do not differ from rates observed after ingesting 30 g wheat protein or a blend with 15 g milk plus 15 g wheat protein in healthy, young males.
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http://dx.doi.org/10.1017/S0007114521000635DOI Listing
February 2021

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

Casein Protein Processing Strongly Modulates Post-Prandial Plasma Amino Acid Responses In Vivo in Humans.

Nutrients 2020 Jul 31;12(8). Epub 2020 Jul 31.

NUTRIM School of Nutrition and Translation Research in Metabolism, Maastricht University Medical Centre, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

Micellar casein is characterized as a slowly digestible protein source, and its structure can be modulated by various food processing techniques to modify its functional properties. However, little is known about the impact of such modifications on casein protein digestion and amino acid absorption kinetics and the subsequent post-prandial plasma amino acid responses. In the present study, we determined post-prandial aminoacidemia following ingestion of isonitrogenous amounts of casein protein (40 g) provided as micellar casein (Mi-CAS), calcium caseinate (Ca-CAS), or cross-linked sodium caseinate (XL-CAS). Fifteen healthy, young men (age: 26 ± 4 years, BMI: 23 ± 1 kg·m) participated in this randomized cross-over study and ingested 40 g Mi-Cas, Ca-CAS, and XL-CAS protein, with a ~1 week washout between treatments. On each trial day, arterialized blood samples were collected at regular intervals during a 6 h post-prandial period to assess plasma amino acid concentrations using ultra-performance liquid chromatography. Plasma amino acid concentrations were higher following the ingestion of XL-CAS when compared to Mi-CAS and Ca-CAS from t = 15 to 90 min (all < 0.05). Plasma amino acid concentrations were higher following ingestion of Mi-CAS compared to Ca-CAS from t = 30 to 45 min (both < 0.05). Plasma total amino acids iAUC were higher following the ingestion of XL-CAS when compared to Ca-CAS (294 ± 63 vs. 260 ± 75 mmol·L, = 0.006), with intermediate values following Mi-CAS ingestion (270 ± 63 mmol·L, > 0.05). In conclusion, cross-linked sodium caseinate is more rapidly digested when compared to micellar casein and calcium caseinate. Protein processing can strongly modulate the post-prandial rise in plasma amino acid bioavailability in vivo in humans.
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http://dx.doi.org/10.3390/nu12082299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468913PMC
July 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

End-Stage Renal Disease Patients Lose a Substantial Amount of Amino Acids during Hemodialysis.

J Nutr 2020 05;150(5):1160-1166

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

Background: Poor nutritional status is frequently observed in end-stage renal disease patients and associated with adverse clinical outcomes and increased mortality. Loss of amino acids (AAs) during hemodialysis (HD) may contribute to protein malnutrition in these patients.

Objective: We aimed to assess the extent of AA loss during HD in end-stage renal disease patients consuming their habitual diet.

Methods: Ten anuric chronic HD patients (mean ± SD age: 67.9 ± 19.3 y, BMI: 23.2 ± 3.5 kg/m2), undergoing HD 3 times per week, were selected to participate in this study. Spent dialysate was collected continuously and plasma samples were obtained directly before and after a single HD session in each participant. AA profiles in spent dialysate and in pre-HD and post-HD plasma were measured through ultra-performance liquid chromatography to determine AA concentrations and, as such, net loss of AAs. In addition, dietary intake before and throughout HD was assessed using a 24-h food recall questionnaire during HD. Paired-sample t tests were conducted to compare pre-HD and post-HD plasma AA concentrations.

Results: During an HD session, 11.95 ± 0.69 g AAs were lost via the dialysate, of which 8.26 ± 0.46 g were nonessential AAs, 3.69 ± 0.31 g were essential AAs, and 1.64 ± 0.17 g were branched-chain AAs. As a consequence, plasma total and essential AA concentrations declined significantly from 2.88 ± 0.15 and 0.80 ± 0.05 mmol/L to 2.27 ± 0.11 and 0.66 ± 0.05 mmol/L, respectively (P < 0.05). AA profiles of pre-HD plasma and spent dialysate were similar. Moreover, AA concentrations in pre-HD plasma and spent dialysate were strongly correlated (Spearman's ρ = 0.92, P < 0.001).

Conclusions: During a single HD session, ∼12 g AAs are lost into the dialysate, causing a significant decline in plasma AA concentrations. AA loss during HD can contribute substantially to protein malnutrition in end-stage renal disease patients. This study was registered at the Netherlands Trial Registry (NTR7101).
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http://dx.doi.org/10.1093/jn/nxaa010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198312PMC
May 2020

The glycation level of milk protein strongly modulates post-prandial lysine availability in humans.

Br J Nutr 2020 03 15;123(5):545-552. Epub 2019 Nov 15.

Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, 6229 ERMaastricht, the Netherlands.

Industrial heat treatment of milk results in protein glycation. A high protein glycation level has been suggested to compromise the post-prandial rise in plasma amino acid availability following protein ingestion. In the present study, we assessed the impact of glycation level of milk protein on post-prandial plasma amino acid responses in humans. Fifteen healthy, young men (age 26 (SEM 1) years, BMI 24 (SEM 1) kg/m2) participated in this randomised cross-over study and ingested milk protein powder with protein glycation levels of 3, 20 and 50 % blocked lysine. On each trial day, arterialised blood samples were collected at regular intervals during a 6-h post-prandial period to assess plasma amino acid concentrations using ultra-performance liquid chromatography. Plasma essential amino acid (EAA) concentrations increased following milk protein ingestion, with the 20 and 50 % glycated milk proteins showing lower overall EAA responses compared with the 3 % glycated milk protein (161 (SEM 7) and 142 (SEM 7) v. 178 (SEM 9) mmol/l × 6 h, respectively; P ≤ 0·011). The lower post-prandial plasma amino acid responses were fully attributed to an attenuated post-prandial rise in circulating plasma lysine concentrations. Plasma lysine responses (incremental AUC) following ingestion of the 20 and 50 % glycated milk proteins were 35 (SEM 4) and 92 (SEM 2) % lower compared with the 3 % glycated milk protein (21·3 (SEM 1·4) and 2·8 (SEM 0·7) v. 33·3 (SEM 1·7) mmol/l × 6 h, respectively; P < 0·001). Milk protein glycation lowers post-prandial plasma lysine availability in humans. The lower post-prandial availability of lysine following ingestion of proteins with a high glycation level may compromise the anabolic properties of a protein source.
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http://dx.doi.org/10.1017/S0007114519002927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015880PMC
March 2020

Short-term bed rest-induced insulin resistance cannot be explained by increased mitochondrial H O emission.

J Physiol 2020 01 26;598(1):123-137. Epub 2019 Dec 26.

Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.

Key Points: We determined if bed rest increased mitochondrially derived reactive oxygen species and cellular redox stress, contributing to the induction of insulin resistance. Bed rest decreased maximal and submaximal ADP-stimulated mitochondrial respiration. Bed rest did not alter mitochondrial H O emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H O emission to mitochondrial O consumption or markers of oxidative stress The present data suggest strongly that mitochondrial H O does not contribute to bed rest-induced insulin resistance ABSTRACT: Mitochondrial H O has been causally linked to diet-induced insulin resistance, although it remains unclear if muscle disuse similarly increases mitochondrial H O . Therefore, we investigated the potential that an increase in skeletal muscle mitochondrial H O emission, potentially as a result of decreased ADP sensitivity, contributes to cellular redox stress and the induction of insulin resistance during short-term bed rest in 20 healthy males. Bed rest led to a decline in glucose infusion rate during a hyperinsulinaemic-euglycaemic clamp (-42 ± 2%; P < 0.001), and in permeabilized skeletal muscle fibres it decreased OXPHOS protein content (-16 ± 8%) and mitochondrial respiration across a range of ADP concentrations (-13 ± 5%). While bed rest tended to increase maximal mitochondrial H O emission rates (P = 0.053), H O emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H O emission to mitochondrial O consumption, and markers of oxidative stress were not altered following bed rest. Altogether, while bed rest impairs mitochondrial ADP-stimulated respiration, an increase in mitochondrial H O emission does not contribute to the induction of insulin resistance following short-term bed rest.
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http://dx.doi.org/10.1113/JP278920DOI Listing
January 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

Nandrolone decanoate administration does not attenuate muscle atrophy during a short period of disuse.

PLoS One 2019 28;14(1):e0210823. Epub 2019 Jan 28.

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

Background: A few days of bed rest or immobilization following injury, disease, or surgery can lead to considerable loss of skeletal muscle mass and strength. It has been speculated that such short, successive periods of muscle disuse may be largely responsible for the age-related loss of muscle mass throughout the lifespan.

Objective: To assess whether a single intramuscular injection of nandrolone decanoate prior to immobilization can attenuate the loss of muscle mass and strength in vivo in humans.

Design, Setting And Participants: Thirty healthy (22 ± 1 years) men were subjected to 7 days of one-legged knee immobilization by means of a full leg cast with (NAD, n = 15) or without (CON, n = 15) prior intramuscular nandrolone decanoate injection (200 mg).

Measures: Before and immediately after immobilization, quadriceps muscle cross-sectional area (CSA) (by means of single-slice computed tomography (CT) scans of the upper leg) and one-legged knee extension strength (one-repetition maximum [1-RM]) were assessed for both legs. Furthermore, muscle biopsies from the immobilized leg were taken before and after immobilization to assess type I and type II muscle fiber cross-sectional area.

Results: Quadriceps muscle CSA decreased during immobilization in both CON and NAD (-6 ± 1% and -6 ± 1%, respectively; main effect of time P<0.01), with no differences between the groups (time × treatment interaction, P = 0.59). Leg muscle strength declined following immobilization (-6 ± 2% in CON and -7 ± 3% in NAD; main effect of time, P<0.05), with no differences between groups (time × treatment interaction, P = 0.55).

Conclusions: This is the first study to report that nandrolone decanoate administration does not preserve skeletal muscle mass and strength during a short period of leg immobilization in vivo in humans.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210823PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349315PMC
October 2019

The Muscle Protein Synthetic Response to Whey Protein Ingestion Is Greater in Middle-Aged Women Compared With Men.

J Clin Endocrinol Metab 2019 04;104(4):994-1004

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

Rationale: Muscle mass maintenance is largely regulated by the postprandial rise in muscle protein synthesis rates. It remains unclear whether postprandial protein handling differs between women and men.

Methods: Healthy men (43 ± 3 years; body mass index, 23.4 ± 0.4 kg/m2; n = 12) and women (46 ± 2 years; body mass index, 21.3 ± 0.5 kg/m2; n = 12) received primed continuous infusions of l-[ring-2H5]-phenylalanine and l-[ring-3,5-2H2]-tyrosine and ingested 25 g intrinsically l-[1-13C]-phenylalanine-labeled whey protein. Blood samples and muscle biopsies were collected to assess dietary protein digestion and amino acid absorption kinetics as well as basal and postprandial myofibrillar protein synthesis rates.

Results: Plasma phenylalanine and leucine concentrations rapidly increased after protein ingestion (both P < 0.001), with no differences between middle-aged women and men (Time × Sex, P = 0.307 and 0.529, respectively). The fraction of dietary protein-derived phenylalanine that appeared in the circulation over the 5-hour postprandial period averaged 56 ± 1% and 53 ± 1% in women and men, respectively (P = 0.145). Myofibrillar protein synthesis rates increased (Time, P = 0.010) from 0.035 ± 0.004%/h and 0.030 ± 0.002%/h in the postabsorptive state (t test, P = 0.319) to 0.045 ± 0.002%/h and 0.034 ± 0.002%/h in the 5-hour postprandial phase in middle-aged women and men, respectively, with higher postprandial myofibrillar protein synthesis rates in women compared with men (t test, P = 0.005). Middle-aged women showed a greater increase in myofibrillar protein synthesis rates during the early (0 to 2 hours) postprandial period compared with men (Time × Sex, P = 0.001).

Conclusions: There are no differences in postabsorptive myofibrillar protein synthesis rates between middle-aged women and men. The myofibrillar protein synthetic response to the ingestion of 25 g whey protein is greater in women than in men.
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http://dx.doi.org/10.1210/jc.2018-01734DOI Listing
April 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

One Week of Hospitalization Following Elective Hip Surgery Induces Substantial Muscle Atrophy in Older Patients.

J Am Med Dir Assoc 2019 01 11;20(1):35-42. Epub 2018 Aug 11.

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

Objectives: Short successive periods of skeletal muscle disuse have been suggested to substantially contribute to the observed loss of skeletal muscle mass over the life span. Hospitalization of older individuals due to acute illness, injury, or major surgery generally results in a mean hospital stay of 5 to 7 days, during which the level of physical activity is strongly reduced. We hypothesized that hospitalization following elective total hip arthroplasty is accompanied by substantial leg muscle atrophy in older men and women.

Design And Participants: Twenty-six older patients (75 ± 1 years) undergoing elective total hip arthroplasty participated in this observational study.

Measurements: On hospital admission and on the day of discharge, computed tomographic (CT) scans were performed to assess muscle cross-sectional area (CSA) of both legs. During surgery and on the day of hospital discharge, a skeletal muscle biopsy was taken from the m. vastus lateralis of the operated leg to assess muscle fiber type-specific CSA.

Results: An average of 5.6 ± 0.3 days of hospitalization resulted in a significant decline in quadriceps (-3.4% ± 1.0%) and thigh muscle CSA (-4.2% ± 1.1%) in the nonoperated leg (P < .05). Edema resulted in a 10.3% ± 1.7% increase in leg CSA in the operated leg (P < .05). At hospital admission, muscle fiber CSA was smaller in the type II vs type I fibers (3326 ± 253 μm vs 4075 ± 279 μm, respectively; P < .05). During hospitalization, type I and II muscle fiber CSA tended to increase, likely due to edema in the operated leg (P = .10).

Conclusions: Six days of hospitalization following elective total hip arthroplasty leads to substantial leg muscle atrophy in older patients. Effective intervention strategies are warranted to prevent the loss of muscle mass induced by short periods of muscle disuse during hospitalization.
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http://dx.doi.org/10.1016/j.jamda.2018.06.018DOI Listing
January 2019

Skeletal muscle fiber characteristics in patients with chronic heart failure: impact of disease severity and relation with muscle oxygenation during exercise.

J Appl Physiol (1985) 2018 08 9. Epub 2018 Aug 9.

Cardiology, Máxima Medical Centre, Netherlands.

Introduction: Skeletal muscle function in patients with heart failure and reduced ejection fraction (HFrEF) greatly determines exercise capacity. However, reports on skeletal muscle fiber dimensions, fiber capillarization, and their physiological importance are inconsistent.

Methods: Twenty-five moderately-impaired patients with HFrEF and 25 healthy control (HC) subjects underwent muscle biopsy sampling. Type I and type II muscle fiber characteristics were determined by immunohistochemistry. In patients with HFrEF, enzymatic oxidative capacity was assessed, and pulmonary oxygen uptake (VO) and skeletal muscle oxygenation during maximal and moderate-intensity exercise were measured using near-infrared spectroscopy.

Results: While muscle fiber cross-sectional area (CSA) was not different between patients with HFrEF and HC, percentage of type I fibers was higher in HC (46±15% versus 37±12%, respectively, P=0.041). Fiber type distribution and CSA were not different between patients in New York Heart Association (NYHA) class II and III. Type I muscle fiber capillarization was higher in HFrEF compared with controls (capillary-to-fiber perimeter exchange (CFPE) index: 5.70±0.92 versus 5.05±0.82, respectively, P=0.027). Patients in NYHA class III had slower VO and muscle deoxygenation kinetics during onset of exercise, and lower muscle oxidative capacity than those in class II (P<0.05). Also, fiber capillarization was lower, but not compared with HC. Higher CFPE index was related to faster deoxygenation (r=-0.682, P=0.001), however, not to muscle oxidative capacity (r=-0.282, P=0.216).

Conclusions: Type I muscle fiber capillarization is higher in HFrEF compared with HC, but not in patients with greater exercise impairment. Greater capillarization may positively affect VO kinetics by enhancing muscle oxygen diffusion.
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http://dx.doi.org/10.1152/japplphysiol.00057.2018DOI Listing
August 2018

Leucine Supplementation Does Not Attenuate Skeletal Muscle Loss during Leg Immobilization in Healthy, Young Men.

Nutrients 2018 May 17;10(5). Epub 2018 May 17.

Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, P.O. Box 61 6200 MD Maastricht, The Netherlands.

Background: Short successive periods of physical inactivity occur throughout life and contribute considerably to the age-related loss of skeletal muscle mass. The maintenance of muscle mass during brief periods of disuse is required to prevent functional decline and maintain metabolic health.

Objective: To assess whether daily leucine supplementation during a short period of disuse can attenuate subsequent muscle loss in vivo in humans.

Methods: Thirty healthy (22 ± 1 y) young males were exposed to a 7-day unilateral knee immobilization intervention by means of a full leg cast with (LEU, = 15) or without (CON, = 15) daily leucine supplementation (2.5 g leucine, three times daily). Prior to and directly after immobilization, quadriceps muscle cross-sectional area (computed tomography (CT) scan) and leg strength (one-repetition maximum (1-RM)) were assessed. Furthermore, muscle biopsies were taken in both groups before and after immobilization to assess changes in type I and type II muscle fiber CSA.

Results: Quadriceps muscle cross-sectional area (CSA) declined in the CON and LEU groups ( < 0.01), with no differences between the two groups (from 7712 ± 324 to 7287 ± 305 mm² and from 7643 ± 317 to 7164 ± 328 mm²; = 0.61, respectively). Leg muscle strength decreased from 56 ± 4 to 53 ± 4 kg in the CON group and from 63 ± 3 to 55 ± 2 kg in the LEU group (main effect of time < 0.01), with no differences between the groups ( = 0.052). Type I and II muscle fiber size did not change significantly over time, in both groups ( > 0.05).

Conclusions: Free leucine supplementation with each of the three main meals (7.5 g/d) does not attenuate the decline of muscle mass and strength during a 7-day limb immobilization intervention.
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http://dx.doi.org/10.3390/nu10050635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986514PMC
May 2018

Temporal Response of Angiogenesis and Hypertrophy to Resistance Training in Young Men.

Med Sci Sports Exerc 2018 Jan;50(1):36-45

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

Although endurance exercise training promotes angiogenesis and improves metabolic health, the effect of resistance training on this process is less well defined. We hypothesized that capillarization would increase proportionally, and concurrently, with muscle fiber hypertrophy in response to resistance training in young men.

Methods: In this double-blind, randomized control trial, 36 men (22 ± 1 yr) were randomized to placebo or protein supplementation, and participated in 12 wk of resistance training. Skeletal muscle biopsies were collected before and after 2, 4, 8, and 12 wk of training. Immunohistochemistry assessed fiber type-specific size and capillarization. Western blot and reverse transcription polymerase chain reaction assessed proteins involved in the molecular regulation of angiogenesis.

Results: Resistance training effectively increased Type I (15% ± 4%; P < 0.01) and Type II fiber cross-sectional area (28% ± 5%; P < 0.0001), an effect that tended to be further enhanced with protein supplementation in Type II fibers (P = 0.078). Capillary-to-fiber ratio significantly increased in Type I (P = 0.001) and II (P = 0.015) fibers after 12 wk of resistance exercise training and was evident after only 2 wk. Capillary-to-fiber perimeter exchange index increased in the Type I fibers only (P = 0.054) after 12 wk of training. Training resulted in a reduction in vascular endothelial growth factor mRNA. A (P = 0.008), while vascular endothelial growth factor receptor 2 (P = 0.016), hypoxia-inducible factor 1α (P = 0.016), and endothelial nitric oxide synthase (P = 0.01) increased in both groups. Hypoxia-inducible factor 1α protein content was higher in the protein group (main group effect, P = 0.02), and endothelial nitric oxide synthase content demonstrated a divergent relationship (time-group interaction, P = 0.049).

Conclusions: This study presents novel evidence that microvascular adaptations and the molecular pathways involved are elevated after 2 wk of a 12-wk resistance training program. Increases in muscle fiber cross-sectional area are effectively matched by the changes in the microvasculature, providing further support for resistance training programs to optimize metabolic health.
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http://dx.doi.org/10.1249/MSS.0000000000001409DOI Listing
January 2018

Extensive Type II Muscle Fiber Atrophy in Elderly Female Hip Fracture Patients.

J Gerontol A Biol Sci Med Sci 2017 Oct;72(10):1369-1375

Department of Human Movement Sciences.

Background: Sarcopenia, or the loss of muscle mass and strength, is known to increase the risk for falls and (hip) fractures in older people. The objective of this study was to assess the skeletal muscle fiber characteristics in elderly female hip fracture patients.

Method: Percutaneous needle biopsies were collected from the vastus lateralis muscle in 15 healthy young women (20 ± 0.4 years), 15 healthy elderly women (79 ± 1.7 years), and 15 elderly women with a fall-related hip fracture (82 ± 1.5 years). Immunohistochemical analyses were performed to assess Type I and Type II muscle fiber size, and myonuclear and satellite cell content.

Results: Type II muscle fiber size was significantly different between all groups (p < .05), with smaller Type II muscle fibers in the hip fracture patients (2,609 ± 185 µm2) compared with healthy elderly group (3,723 ± 322 µm2) and the largest Type II muscle fibers in the healthy young group (4,755 ± 335 µm2). Furthermore, Type I muscle fiber size was significantly lower in the hip fracture patients (4,684 ± 211 µm2) compared with the healthy elderly group (5,842 ± 316 µm2, p = .02). The number of myonuclei per Type II muscle fiber was significantly lower in the healthy elderly and hip fracture group compared with the healthy young group (p = .011 and p = .002, respectively). Muscle fiber satellite cell content did not differ between groups.

Conclusion: Elderly female hip fracture patients show extensive Type II muscle fiber atrophy when compared with healthy young or age-matched healthy elderly controls. Type II muscle fiber atrophy is an important hallmark of sarcopenia and may predispose to falls and (hip) fractures in the older population.
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http://dx.doi.org/10.1093/gerona/glw253DOI Listing
October 2017

Increasing Insulin Availability Does Not Augment Postprandial Muscle Protein Synthesis Rates in Healthy Young and Older Men.

J Clin Endocrinol Metab 2016 Nov 19;101(11):3978-3988. Epub 2016 Jul 19.

Top Institute Food and Nutrition (B.B.L.G., A.M.H.H., H.M.H., J.v.K., L.J.C.v.L.), 6709 PG Wageningen, The Netherlands; Departments of Human Biology and Movement Sciences (B.B.L.G., A.M.H.H., H.M.H., L.J.C.v.L.), Radiology (M.d.H.), Clinical Genetics, and Surgery (M.P.), Laboratory Biochemical Genetics (J.B.), and Central Diagnostic Laboratory (W.K.W.H.W.), Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands; and Department of Nutrition and Metabolism (B.B.R.), University of Texas Medical Branch, Galveston, Texas 77550.

Context: Skeletal muscle protein synthesis is highly responsive to food intake. It has been suggested that the postprandial increase in circulating insulin modulates the muscle protein synthetic response to feeding.

Objective: The objective of the study was to investigate whether a greater postprandial rise in circulating insulin level increases amino acid uptake in muscle and augments postprandial muscle protein synthesis rates.

Participants And Design: Forty-eight healthy young (age 22 ± 1 y; body mass index 22.0 ± 0.3 kg/m) and older males (age 68 ± 1 y; body mass index 26.3 ± 0.4 kg/m) ingested 20 g intrinsically L-[1-C]-leucine- and L-[1-C]-phenylalanine-labeled casein protein with or without local insulin infusion. Primed continuous infusions of L-[1-C]-leucine and L-[ring-H]-phenylalanine were applied, with arterial and venous blood samples and muscle biopsies being collected during a 5-hour postprandial period.

Results: Insulin administration did not increase overall leg blood flow (P = .509) but increased amino acid uptake over the leg in both young and older subjects (P = .003). The greater amino acid uptake over the leg did not further increase postprandial muscle protein synthesis rates (0.050% ± 0.006% and 0.037% ± 0.004% per hour vs 0.044% ± 0.004% and 0.037% ± 0.002% per hour in the insulin-stimulated vs control condition in the young and older groups, respectively; P = .804) and did not affect postprandial deposition of dietary protein-derived amino acids in de novo muscle protein (P = .872).

Conclusion: Greater postprandial plasma insulin availability stimulates amino acid uptake over the leg but does not further augment postprandial muscle protein synthesis rates or stimulate the postprandial deposition of protein derived amino acids into de novo muscle protein in healthy young and older men.
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http://dx.doi.org/10.1210/jc.2016-1436DOI Listing
November 2016

Neuromuscular electrical stimulation prior to presleep protein feeding stimulates the use of protein-derived amino acids for overnight muscle protein synthesis.

J Appl Physiol (1985) 2017 01 27;122(1):20-27. Epub 2016 Oct 27.

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

Short periods of muscle disuse result in substantial skeletal muscle atrophy. Recently, we showed that both neuromuscular electrical stimulation (NMES) as well as presleep dietary protein ingestion represent effective strategies to stimulate muscle protein synthesis rates. In this study, we test our hypothesis that NMES can augment the use of presleep protein-derived amino acids for overnight muscle protein synthesis in older men. Twenty healthy, older [69 ± 1 (SE) yr] men were subjected to 24 h of bed rest, starting at 8:00 AM. In the evening, volunteers were subjected to 70-min 1-legged NMES, while the other leg served as nonstimulated control (CON). Immediately following NMES, 40 g of intrinsically l-[1-C]-phenylalanine labeled protein was ingested prior to sleep. Blood samples were taken throughout the night, and muscle biopsies were obtained from both legs in the evening and the following morning (8 h after protein ingestion) to assess dietary protein-derived l-[1-C]-phenylalanine enrichments in myofibrillar protein. Plasma phenylalanine concentrations and plasma l-[1-C]-phenylalanine enrichments increased significantly following protein ingestion and remained elevated for up to 6 h after protein ingestion (P < 0.05). During overnight sleep, myofibrillar protein-bound l-[1-C]-phenylalanine enrichments (MPE) increased to a greater extent in the stimulated compared with the control leg (0.0344 ± 0.0019 vs. 0.0297 ± 0.0016 MPE, respectively; P < 0.01), representing 18 ± 6% greater incorporation of presleep protein-derived amino acids in the NMES compared with CON leg. In conclusion, application of NMES prior to presleep protein feeding stimulates the use of dietary protein-derived amino acids for overnight muscle protein synthesis in older men.

New & Noteworthy: Neuromuscular electrical stimulation (NMES) as well as presleep dietary protein ingestion represent effective strategies to stimulate muscle protein synthesis rates. Here we demonstrate that in older men after a day of bed rest, the application of NMES prior to presleep protein feeding stimulates the use of dietary protein-derived amino acids for overnight muscle protein synthesis by 18% compared with presleep protein feeding only.
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http://dx.doi.org/10.1152/japplphysiol.00331.2016DOI Listing
January 2017

Resistance Training Increases Skeletal Muscle Capillarization in Healthy Older Men.

Med Sci Sports Exerc 2016 11;48(11):2157-2164

1NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, THE NETHERLANDS; and 2Department of Kinesiology and Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON, CANADA.

Purpose: Skeletal muscle capillarization plays a key role in oxygen and nutrient delivery to muscle. The loss of muscle mass with aging and the concept of anabolic resistance have been, at least partly, attributed to changes in skeletal muscle capillary structure and function. We aimed to compare skeletal muscle capillarization between young and older men and evaluate whether resistance-type exercise training increases muscle capillarization in older men.

Methods: Muscle biopsies were obtained from the vastus lateralis of healthy young (n = 14, 26 ± 2 yr) and older (n = 16, 72 ± 1 yr) adult men, with biopsies before and after 12 wk of resistance-type exercise training in the older subjects. Immunohistochemistry was used to assess skeletal muscle fiber size, capillary contacts (CC) per muscle fiber, and the capillary-to-fiber perimeter exchange (CFPE) index in type I and II muscle fibers.

Results: Type II muscle fibers were smaller in old versus young (4507 ± 268 vs 6084 ± 497 μm, respectively, P = 0.007). Type I and type II muscle fiber CC and CFPE index were smaller in old compared with young muscle (CC type I: 3.8 ± 0.2 vs 5.0 ± 0.3; CC type II: 3.2 ± 0.2 vs 4.2 ± 0.2, respectively; both P < 0.001). Resistance-type exercise training increased type II muscle fiber size only. In addition, CC and CFPE index increased in both the type I (26% ± 9% and 27% ± 8%) and type II muscle fibers (33% ± 7% and 24% ± 6%, respectively; all P ≤ 0.001) after 12 wk resistance training in older men.

Conclusions: We conclude that resistance-type exercise training can effectively augment skeletal muscle fiber capillarization in older men. The greater capillary supply may be an important prerequisite to reverse anabolic resistance and support muscle hypertrophy during lifestyle interventions aiming to support healthy aging.
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http://dx.doi.org/10.1249/MSS.0000000000001019DOI Listing
November 2016

Both basal and post-prandial muscle protein synthesis rates, following the ingestion of a leucine-enriched whey protein supplement, are not impaired in sarcopenic older males.

Clin Nutr 2017 10 29;36(5):1440-1449. Epub 2016 Sep 29.

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

Background: Studying the muscle protein synthetic response to food intake in elderly is important, as it aids the development of interventions to combat sarcopenia. Although sarcopenic elderly are the target group for many of these nutritional interventions, no studies have assessed basal or post-prandial muscle protein synthesis rates in this population.

Objective: To assess the basal and post-prandial muscle protein synthesis rates between healthy and sarcopenic older men.

Design: A total of 15 healthy (69 ± 1 y) and 15 sarcopenic (81 ± 1 y) older men ingested a leucine-enriched whey protein nutritional supplement containing 21 g of protein, 9 g of carbohydrate, and 3 g of fat. Stable isotope methodology combined with frequent collection of blood and muscle samples was applied to assess basal and post-prandial muscle protein fractional synthetic rates. Handgrip strength, muscle mass, and gait speed were assessed to identify sarcopenia, according to international criteria.

Results: Basal mixed muscle protein fractional synthetic rates (FSR) averaged 0.040 ± 0.005 and 0.032 ± 0.003%/h (mean ± SEM) in the sarcopenic and healthy group, respectively (P = 0.14). Following protein ingestion, FSR increased significantly to 0.055 ± 0.004 and 0.053 ± 0.004%/h in the post-prandial period in the sarcopenic (P = 0.003) and healthy groups (P < 0.001), respectively, with no differences between groups (P = 0.45). Furthermore, no differences were observed between groups in muscle protein synthesis rates during the early (0.058 ± 0.007 vs 0.060 ± 0.008%/h, sarcopenic vs healthy, respectively) and late (0.052 ± 0.004 vs 0.048 ± 0.003%/h) stages of the post-prandial period (P = 0.93 and P = 0.34, respectively).

Conclusions: Basal muscle protein synthesis rates are not lower in sarcopenic older men compared to healthy older men. The ingestion of 21 g of a leucine-enriched whey protein effectively increases muscle protein synthesis rates in both sarcopenic and healthy older men. Public trial registry number: NTR3047.
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http://dx.doi.org/10.1016/j.clnu.2016.09.023DOI Listing
October 2017

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

Post-Prandial Protein Handling: You Are What You Just Ate.

PLoS One 2015 10;10(11):e0141582. Epub 2015 Nov 10.

Top Institute Food and Nutrition, Wageningen, The Netherlands.

Background: Protein turnover in skeletal muscle tissue is highly responsive to nutrient intake in healthy adults.

Objective: To provide a comprehensive overview of post-prandial protein handling, ranging from dietary protein digestion and amino acid absorption, the uptake of dietary protein derived amino acids over the leg, the post-prandial stimulation of muscle protein synthesis rates, to the incorporation of dietary protein derived amino acids in de novo muscle protein.

Design: 12 healthy young males ingested 20 g intrinsically [1-13C]-phenylalanine labeled protein. In addition, primed continuous L-[ring-2H5]-phenylalanine, L-[ring-2H2]-tyrosine, and L-[1-13C]-leucine infusions were applied, with frequent collection of arterial and venous blood samples, and muscle biopsies throughout a 5 h post-prandial period. Dietary protein digestion, amino acid absorption, splanchnic amino acid extraction, amino acid uptake over the leg, and subsequent muscle protein synthesis were measured within a single in vivo human experiment.

Results: 55.3±2.7% of the protein-derived phenylalanine was released in the circulation during the 5 h post-prandial period. The post-prandial rise in plasma essential amino acid availability improved leg muscle protein balance (from -291±72 to 103±66 μM·min-1·100 mL leg volume-1; P<0.001). Muscle protein synthesis rates increased significantly following protein ingestion (0.029±0.002 vs 0.044±0.004%·h-1 based upon the muscle protein bound L-[ring-2H5]-phenylalanine enrichments (P<0.01)), with substantial incorporation of dietary protein derived L-[1-13C]-phenylalanine into de novo muscle protein (from 0 to 0.0201±0.0025 MPE).

Conclusion: Ingestion of a single meal-like amount of protein allows ~55% of the protein derived amino acids to become available in the circulation, thereby improving whole-body and leg protein balance. About 20% of the dietary protein derived amino acids released in the circulation are taken up in skeletal muscle tissue following protein ingestion, thereby stimulating muscle protein synthesis rates and providing precursors for de novo muscle protein synthesis.

Trial Registration: trialregister.nl 3638.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0141582PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640549PMC
June 2016

Impact of the Macronutrient Composition of a Nutritional Supplement on Muscle Protein Synthesis Rates in Older Men: A Randomized, Double Blind, Controlled Trial.

J Clin Endocrinol Metab 2015 Nov 26;100(11):4124-32. Epub 2015 Aug 26.

NUTRIM School for Nutrition and Translational Research in Metabolism (I.F.K., L.B.V., H.M.H., I.W.K.K., J.M.S., J.v.K., A.P.G., M.P., L.J.C.v.L.), Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands; Nutricia Research (S.V., Y.L.), Nutricia Advanced Medical Nutrition, 3584 CT Utrecht, The Netherlands; and Department of Surgery (I.F.K., M.P.), Division of Trauma Surgery, Maastricht University Medical Centre, 6200MD Maastricht, The Netherlands.

Context: An impaired muscle protein synthetic response to feeding likely contributes to muscle loss with aging. There are few data available on the effect of the macronutrient composition of clinical supplements on the postprandial muscle protein synthetic response in older subjects.

Objective: The objective of the study was to determine the impact of the macronutrient composition of a nutritional supplement on the postprandial muscle protein synthetic response in older men.

Methods: A total of 45 nonsarcopenic older men (aged 69 ± 1 y; body mass index 25.7 ± 0.3 kg/m(2)) were randomly assigned to ingest 21 g of leucine-enriched whey protein with carbohydrate (9 g) and fat (3 g) (Pro-En), an isonitrogenous amount of 21 g of leucine-enriched whey protein without carbohydrate and fat (Pro), or an isocaloric mixture (628 kJ) containing carbohydrate and fat only (En). Stable isotope tracer methodology was applied to assess the basal as well as the postprandial muscle protein synthesis rates in the three groups.

Results: Ingestion of protein in the Pro-En and Pro groups significantly increased muscle protein synthesis rates when compared with the basal rates (from 0.032 ± 0.003%/h to 0.05%/h 3 ± 0.004%/h and 0.040%/h ± 0.003%/h to 0.049%/h ± 0.003%/h, respectively; P < .05), whereas ingestion of carbohydrate and fat did not increase muscle protein synthesis rates in the En group (from 0.039%/h ± 0.004%/h to 0.040%/h ± 0.003%/h; P = .60). Despite the greater postprandial rise in circulating insulin concentration in the Pro-En group, no significant differences were observed in postprandial muscle protein synthesis rates between the Pro-En and Pro groups (P = .32). Postprandial muscle protein synthesis rates were higher in the Pro-En vs En group (P = .01).

Conclusion: The ingestion of a nutritional supplement containing 21 g of leucine-enriched whey protein significantly raises muscle protein synthesis rates in nonsarcopenic older men, but coingestion of carbohydrate and fat does not modulate the postprandial muscle protein synthetic response to protein ingestion in older men.
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http://dx.doi.org/10.1210/jc.2015-2352DOI Listing
November 2015

Postprandial Protein Handling Is Not Impaired in Type 2 Diabetes Patients When Compared With Normoglycemic Controls.

J Clin Endocrinol Metab 2015 Aug 2;100(8):3103-11. Epub 2015 Jun 2.

NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands.

Context: The progressive loss of muscle mass with aging is accelerated in type 2 diabetes patients. It has been suggested that this is attributed to a blunted muscle protein synthetic response to food intake.

Objective: The objective of the study was to test the hypothesis that the muscle protein synthetic response to protein ingestion is impaired in older type 2 diabetes patients when compared with healthy, normoglycemic controls.

Design: A clinical intervention study with two parallel groups was conducted between August 2011 and July 2012.

Setting: The study was conducted at the research unit of Maastricht University, The Netherlands. Intervention, Participants, and Main Outcome Measures: Eleven older type 2 diabetes males [diabetes; age 71 ± 1 y, body mass index (BMI) 26.2 ± 0.5 kg/m(2)] and 12 age- and BMI-matched normoglycemic controls (control; age 74 ± 1 y, BMI 24.8 ± 1.1 kg/m(2)) participated in an experiment in which they ingested 20 g intrinsically L-[1-(13)C]phenylalanine-labeled protein. Continuous iv L-[ring-(2)H5]phenylalanine infusion was applied, and blood and muscle samples were obtained to assess amino acid kinetics and muscle protein synthesis rates in the postabsorptive and postprandial state.

Results: Plasma insulin concentrations increased after protein ingestion in both groups, with a greater rise in the diabetes group. Postabsorptive and postprandial muscle protein synthesis rates did not differ between groups and averaged 0.029 ± 0.003 vs 0.029 ± 0.003%/h(1) and 0.031 ± 0.002 vs 0.033 ± 0.002%/h(1) in the diabetes versus control group, respectively. Postprandial L-[1-(13)C]phenylalanine incorporation into muscle protein did not differ between groups (0.018 ± 0.001 vs 0.019 ± 0.002 mole percent excess, respectively).

Conclusions: Postabsorptive muscle protein synthesis and postprandial protein handling is not impaired in older individuals with type 2 diabetes when compared with age-matched, normoglycemic controls.
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http://dx.doi.org/10.1210/jc.2015-1234DOI Listing
August 2015

Ingestion of Casein in a Milk Matrix Modulates Dietary Protein Digestion and Absorption Kinetics but Does Not Modulate Postprandial Muscle Protein Synthesis in Older Men.

J Nutr 2015 Jul 27;145(7):1438-45. Epub 2015 May 27.

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

Background: The slow digestion and amino acid absorption kinetics of isolated micellar casein have been held responsible for its relatively lower postprandial muscle protein synthetic response compared with rapidly digested proteins such as isolated whey. However, casein is normally consumed within a milk matrix. We hypothesized that protein digestion and absorption kinetics and the subsequent muscle protein synthetic response after micellar casein ingestion are modulated by the milk matrix.

Objective: The aim of this study was to determine the impact of a milk matrix on casein protein digestion and absorption kinetics and postprandial muscle protein synthesis in older men.

Methods: In a parallel-group design, 32 healthy older men (aged 71 ± 1 y) received a primed continuous infusion of L-[ring-(2)H5]-phenylalanine, L-[ring-3,5-(2)H2]-tyrosine, and L-[1-(13)C]-leucine, and ingested 25 g intrinsically L-[1-(13)C]-phenylalanine and L-[1-(13)C]-leucine labeled casein dissolved in bovine milk serum (Cas+Serum) or water (Cas). Plasma samples and muscle biopsies were collected in the postabsorptive state and for 300 min in the postprandial period to examine whole-body and skeletal muscle protein metabolism.

Results: Casein ingestion increased plasma leucine and phenylalanine concentrations and L-[1-(13)C]-phenylalanine enrichments, with a more rapid rise after Cas vs. Cas+Serum. Nonetheless, dietary protein-derived phenylalanine availability did not differ between Cas+Serum (47 ± 2%, mean ± SEM) and Cas (46 ± 3%) when assessed over the 300-min postprandial period (P = 0.80). The milk matrix did not modulate postprandial myofibrillar protein synthesis rates from 0 to 120 min (0.038 ± 0.005 vs. 0.031 ± 0.007%/h) or from 120 to 300 min (0.052 ± 0.004 vs. 0.067 ± 0.005%/h) after Cas+Serum vs. Cas. Similarly, no treatment differences in muscle protein-bound L-[1-(13)C]-phenylalanine enrichments were observed at 120 min (0.003 ± 0.001 vs. 0.002 ± 0.001) or 300 min (0.015 ± 0.002 vs. 0.016 ± 0.002 mole percent excess) after Cas+Serum vs. Cas.

Conclusions: Casein ingestion in a milk matrix delays protein digestion and absorption but does not modulate postprandial muscle protein synthesis when compared to the ingestion of micellar casein only in healthy older men. This trial was registered at Nederlands Trial Register as NTR4429.
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http://dx.doi.org/10.3945/jn.115.213710DOI Listing
July 2015

Protein Ingestion before Sleep Increases Muscle Mass and Strength Gains during Prolonged Resistance-Type Exercise Training in Healthy Young Men.

J Nutr 2015 Jun 29;145(6):1178-84. Epub 2015 Apr 29.

Department of Human Movement Sciences, Faculty of Health, Medicine, and Life Sciences, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands; Department of Human Movement Sciences, Faculty of Health, Medicine, and Life Sciences, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands;

Background: It has been demonstrated that protein ingestion before sleep increases muscle protein synthesis rates during overnight recovery from an exercise bout. However, it remains to be established whether dietary protein ingestion before sleep can effectively augment the muscle adaptive response to resistance-type exercise training.

Objective: Here we assessed the impact of dietary protein supplementation before sleep on muscle mass and strength gains during resistance-type exercise training.

Methods: Forty-four young men (22 ± 1 y) were randomly assigned to a progressive, 12-wk resistance exercise training program. One group consumed a protein supplement containing 27.5 g of protein, 15 g of carbohydrate, and 0.1 g of fat every night before sleep. The other group received a noncaloric placebo. Muscle hypertrophy was assessed on a whole-body (dual-energy X-ray absorptiometry), limb (computed tomography scan), and muscle fiber (muscle biopsy specimen) level before and after exercise training. Strength was assessed regularly by 1-repetition maximum strength testing.

Results: Muscle strength increased after resistance exercise training to a significantly greater extent in the protein-supplemented (PRO) group than in the placebo-supplemented (PLA) group (+164 ± 11 kg and +130 ± 9 kg, respectively; P < 0.001). In addition, quadriceps muscle cross-sectional area increased in both groups over time (P < 0.001), with a greater increase in the PRO group than in the PLA group (+8.4 ± 1.1 cm(2) vs. +4.8 ± 0.8 cm(2), respectively; P < 0.05). Both type I and type II muscle fiber size increased after exercise training (P < 0.001), with a greater increase in type II muscle fiber size in the PRO group (+2319 ± 368 μm(2)) than in the PLA group (+1017 ± 353 μm(2); P < 0.05).

Conclusion: Protein ingestion before sleep represents an effective dietary strategy to augment muscle mass and strength gains during resistance exercise training in young men. This trial was registered at clinicaltrials.gov as NCT02222415.
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http://dx.doi.org/10.3945/jn.114.208371DOI Listing
June 2015
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