Effect of 1-year daily protein supplementation and physical exercise on muscle protein synthesis rate and muscle metabolome in healthy older Danes: a randomized controlled trial.

BACKGROUND: The skeletal muscle mass decreases with age and the responsiveness of aging muscles' protein synthesis rate (MPS) to protein intake seems to deteriorate. OBJECTIVE: This study investigated the impact of 12 months of protein supplementation with or without physical exercise training on the basal and postprandial MPS and the skeletal muscle metabolome of healthy older Danes (> 65 years, 29 females/37 males). METHODS: Subjects were randomized to follow one of five intervention groups: (1) carbohydrate, (2) collagen protein, (3) whey protein, (4) home-based light resistance training with whey protein, and (5) center-based heavy-load resistance training with whey protein. Before and after the intervention, a tracer infusion trial was conducted to measure basal and postprandial MPS in response to intake of a cocktail consisting of 20 g whey hydrolysate + 10 g glucose. In addition, the skeletal muscle metabolome was measured using gas chromatography-mass spectrometry (GC-MS) at basal state and 4 h after the intake of the cocktail. RESULTS: One year of daily protein or carbohydrate supplementation did not alter the basal and protein-stimulated postprandial muscle protein synthesis rate or the muscle metabolome of healthy older Danes. Basal MPS (%/h) at baseline for all subjects were 0.0034 ± 0,011 (mean ± SD). In contrast to previous studies, no difference was observed in basal MPS between males and females (p = 0.75). With the developed untargeted GC-MS methodology, it was possible to detect and tentatively annotate > 70 metabolites from the human skeletal muscle samples. CONCLUSION: One year of protein supplementation in comparison to an isocaloric-control supplement seems to affect neither the MPS at basal or postprandial state nor the skeletal muscle metabolome. CLINICAL TRIAL REGISTRY: Number: NCT02115698, clinicaltrials.gov/ct2/show/NCT02115698.

Changes in Muscle Mass and Strength During Follow-Up After One-Year Resistance Training Interventions in Older Adults.

ABSTRACT: Mertz, KH, Reitelseder, S, Rasmussen, MA, Bülow, J, Højfeldt, G, Jensen, M, Hjulmand, M, Lindberg, J, Kramer, MU, Bechshøft, R, and Holm, L. Changes in muscle mass and strength during follow-up after one-year resistance training interventions in older adults. J Strength Cond Res 37(10): 2064-2070, 2023-The aim of this study was to investigate if home-based resistance training compared with center-based resistance training was associated with better preservation of muscle mass and strength in older individuals, 6 months after the interventions ended. One hundred four healthy older individuals (>65 years) who had completed 1 year of either home-based light-intensity training with daily whey protein supplementation (LITW), center-based heavy resistance training with whey protein supplementation (HRTW), or daily whey protein supplementation alone (WHEY) returned for follow-up measurement 6 months after the interventions. Measures of muscle mass, strength, and power were assessed at the end of intervention as well as at follow-up. Furthermore, we compared changes in these parameters between subjects who continued resistance training (≥1 weekly training session) during follow-up (CONT) with those who stopped (STOP). Resistance training continuation during follow-up did not differ between HRTW and LITW (41 vs. 41%, P = 1.0) but was higher for both groups compared with WHEY (18%, P = 0.04-0.05). However, no between-group differences were observed between LITW/HRTW/WHEY in changes in muscle mass, strength, or power during follow-up. STOP was associated with a poorer preservation of quadriceps cross-sectional area compared with CONT (-1.7 cm 2 [-0.4 to -3.0], P = 0.01, effect size: 0.79). No effect of training continuation was observed on changes in muscle strength and power. In conclusion, maintenance of muscle mass and strength is not superior after home-based resistance training compared with center-based training. However, training continuation seems crucial for the maintenance of muscle mass, irrespective of the training intervention.

Postprandial Nutrient Handling and Gastrointestinal Hormone Secretion After Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy.

BACKGROUND & AIMS: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) induce substantial weight loss and improve glycemic control in patients with type 2 diabetes, but it is not clear whether these occur via the same mechanisms. We compared absorption rates of glucose and protein, as well as profiles of gastro-entero-pancreatic hormones, in patients who had undergone SG or RYGB vs controls. METHODS: We performed a cross-sectional study of 12 patients who had undergone sleeve gastrectomy, 12 patients who had undergone RYGB, and 12 individuals who had undergone neither surgery (controls), all in Denmark. Study participants were matched for body mass index, age, sex, and postoperative weight loss, and all had stable weights. They received continuous infusions of stable isotopes of glucose, glycerol, phenylalanine, tyrosine, and urea before and during a mixed meal containing labeled glucose and intrinsically phenylalanine-labeled caseinate. Blood samples were collected for 6 hours, at 10- to 60-minute intervals, and analyzed. RESULTS: The systemic appearance of ingested glucose was faster after RYGB and SG vs controls; the peak glucose appearance rate was 64% higher after RYGB, and 23% higher after SG (both P < .05); the peak phenylalanine appearance rate from ingested casein was 118% higher after RYGB (P < .01), but similar between patients who had undergone SG and controls. Larger, but more transient increases in levels of plasma glucose and amino acids were accompanied by higher secretion of insulin, glucagon-like peptide 1, peptide YY, and cholecystokinin after RYGB, whereas levels of ghrelin were lower after SG, compared with RYGB and controls. Total 6-hour oral recovery of ingested glucose and protein was comparable among groups. CONCLUSIONS: Postprandial glucose and protein absorption and gastro-entero-pancreatic hormone secretions differ after SG and RYGB. RYGB was characterized by accelerated absorption of glucose and amino acids, whereas protein metabolism after SG did not differ significantly from controls, suggesting that different mechanisms explain improved glycemic control and weight loss after these surgical procedures. ClinicalTrials.gov ID NCT03046186.

Even effect of milk protein and carbohydrate intake but no further effect of heavy resistance exercise on myofibrillar protein synthesis in older men.

PURPOSE: The responsiveness of older individuals' skeletal muscle to anabolic strategies may be impaired. However, direct comparisons within the same experimental setting are sparse. The aim of this study was to assess the resting and post-resistance exercise muscle protein synthesis rates in response to two types of milk protein and carbohydrate using a unilateral exercise leg model. METHODS: Twenty-seven older (69 ± 1 year, mean ± SE) men were randomly assigned one of three groups: Whey hydrolysate (WH), caseinate (CAS), or carbohydrate (CHO). By applying stable isotope tracer techniques (L-[15N]phenylalanine), the fasted-rested (basal) myofibrillar fractional synthesis rate (FSR) was measured. Hereafter, FSR was measured in the postprandial phase (0.45 g nutrient/kg LBM) in both legs, one rested (fed-rest) and one exercised (10 × 8 reps at 70% 1RM; fed-exercise). In addition, the activity of p70S6K and venous plasma insulin, phenylalanine, and leucine concentrations were measured. RESULTS: Insulin, phenylalanine, and leucine concentrations differed markedly after intake of the different study drinks. The basal FSR in WH, CAS, and CHO were 0.027 ± 0.003, 0.030 ± 0.003, and 0.030 ± 0.004%/h, the fed-rested FSR were 0.043 ± 0.004, 0.045 ± 0.003, and 0.035 ± 0.004%/h, and the fed-exercised FSR were 0.041 ± 0.004, 0.043 ± 0.004, and 0.034 ± 0.004%/h, respectively. No significant differences were observed at any state between the groups. Fed-rested- and fed-exercised FSR were higher than basal (P < 0.001). 3 h after exercise and feeding, no significant group differences were detected in the activity of p70S6K. CONCLUSIONS: Milk protein and carbohydrate supplementation stimulate myofibrillar protein synthesis in older men, with no further effect of heavy resistance exercise within 0-3 h post exercise.

Influence of between-limb asymmetry in muscle mass, strength, and power on functional capacity in healthy older adults.

PURPOSE: Numerous daily tasks such as walking and rising from a chair involve bilateral lower limb movements. During such tasks, lower extremity function (LEF) may be compromised among older adults. LEF may be further impaired due to high degrees of between-limb asymmetry. The present study investigated the prevalence of between-limb asymmetry in muscle mass, strength, and power in a cohort of healthy older adults and examined the influence of between-limb asymmetry on LEF. METHODS: Two hundred and eight healthy older adults (mean age 70.2 ± 3.9 years) were tested for LEF (400 m walking and 30-seconds chair stand). Furthermore, maximal isometric and dynamic knee extensor strength, leg extensor power, and lower limb lean tissue mass (LTM) were obtained unilaterally. RESULTS: Mean between-limb asymmetry in maximal muscle strength and power ranged between 10% and 13%, whereas LTM asymmetry was 3 ± 2.3%. Asymmetry in dynamic knee extensor strength was larger for women compared with men (15.0 ± 11.8% vs 11.1 ± 9.5%; P = .005) Leg strength and power were positively correlated with LEF (r2  = .43-.46, P < .001). The weakest leg was not a stronger predictor of LEF than the strongest leg. Between-limb asymmetry in LTM and isometric strength was negatively associated with LEF (LTM; r2  = .12, P = .005, isometric peak torque; r2  = 0.40, P = .03.) but dynamic strength and power were not. CONCLUSION: The present study supports the notion that in order to improve or maintain LEF, healthy older adults should participate in training interventions that increase muscle strength and power, whereas the effects of reducing between-limb asymmetry in these parameters might be of less importance.

Beta2 -adrenoceptor agonist salbutamol increases protein turnover rates and alters signalling in skeletal muscle after resistance exercise in young men.

KEY POINTS: Animal models have shown that beta2 -adrenoceptor stimulation increases protein synthesis and attenuates breakdown processes in skeletal muscle. Thus, the beta2 -adrenoceptor is a potential target in the treatment of disuse-, disease- and age-related muscle atrophy. In the present study, we show that a few days of oral treatment with the commonly prescribed beta2 -adrenoceptor agonist, salbutamol, increased skeletal muscle protein synthesis and breakdown during the first 5 h after resistance exercise in young men. Salbutamol also counteracted a negative net protein balance in skeletal muscle after resistance exercise. Changes in protein turnover rates induced by salbutamol were associated with protein kinase A-signalling, activation of Akt2 and modulation of mRNA levels of growth-regulating proteins in skeletal muscle. These findings indicate that protein turnover rates can be augmented by beta2 -adrenoceptor agonist treatment during recovery from resistance exercise in humans. ABSTRACT: The effect of beta2 -adrenoceptor stimulation on skeletal muscle protein turnover and intracellular signalling is insufficiently explored in humans, particularly in association with exercise. In a randomized, placebo-controlled, cross-over study investigating 12 trained men, the effects of beta2 -agonist (6 × 4 mg oral salbutamol) on protein turnover rates, intracellular signalling and mRNA response in skeletal muscle were investigated 0.5-5 h after quadriceps resistance exercise. Each trial was preceded by a 4-day lead-in treatment period. Leg protein turnover rates were assessed by infusion of [13 C6 ]-phenylalanine and sampling of arterial and venous blood, as well as vastus lateralis muscle biopsies 0.5 and 5 h after exercise. Furthermore, myofibrillar fractional synthesis rate, intracellular signalling and mRNA response were measured in muscle biopsies. The mean (95% confidence interval) myofibrillar fractional synthesis rate was higher for salbutamol than placebo [0.079 (95% CI, 0.064 to 0.093) vs. 0.066 (95% CI, 0.056 to 0.075%) × h-1 ] (P < 0.05). Mean net leg phenylalanine balance 0.5-5 h after exercise was higher for salbutamol than placebo [3.6 (95% CI, 1.0 to 6.2 nmol) × min-1  × 100 gLeg Lean Mass-1 ] (P < 0.01). Phosphorylation of Akt2, cAMP response element binding protein and PKA substrate 0.5 and 5 h after exercise, as well as phosphorylation of eEF2 5 h after exercise, was higher (P < 0.05) for salbutamol than placebo. Calpain-1, Forkhead box protein O1, myostatin and Smad3 mRNA content was higher (P < 0.01) for salbutamol than placebo 0.5 h after exercise, as well as Forkhead box protein O1 and myostatin mRNA content 5 h after exercise, whereas ActivinRIIB mRNA content was lower (P < 0.01) for salbutamol 5 h after exercise. These observations suggest that beta2 -agonist increases protein turnover rates in skeletal muscle after resistance exercise in humans, with concomitant cAMP/PKA and Akt2 signalling, as well as modulation of mRNA response of growth-regulating proteins.

The effect of casein, hydrolyzed casein, and whey proteins on urinary and postprandial plasma metabolites in overweight and moderately obese human subjects.

BACKGROUND: Casein and whey proteins differ in amino acid composition and absorption rate; however, the absorption rate of casein can be increased to mimic that of whey proteins by exogenous hydrolysis. In view of these compositional differences, we studied the metabolic responses to intake of casein, hydrolyzed casein, and whey proteins in overweight and moderately obese men and women by investigating select urinary and blood plasma metabolites. RESULTS: A total of 21 urinary and 23 plasma metabolites were identified by nuclear magnetic resonance spectroscopy. The postprandial plasma metabolites revealed a significant diet-time interaction for isoleucine (P = 0.001) and tyrosine (P = 0.001). The level of isoleucine and tyrosine peaked 90 min postprandially with a 1.4-fold difference following intake of whey proteins compared with either casein or hydrolyzed casein. A 1.2-fold higher urinary level of lactate was observed after intake of whey proteins compared with intake of intact casein (P < 0.01). CONCLUSION: The plasma metabolites revealed different amino acid profiles reflecting the amino acid composition of casein and whey proteins. Furthermore, the results support that casein hydrolysates neither affect the postprandial amino acid absorption rate nor the amino acid level compared with that of intact casein. The urinary lactate increases following whey protein intake might indicate a higher metabolism of glucogenic amino acids. © 2018 Society of Chemical Industry.

Light-load resistance exercise increases muscle protein synthesis and hypertrophy signaling in elderly men.

The present study investigated whether well-tolerated light-load resistance exercise (LL-RE) affects skeletal muscle fractional synthetic rate (FSR) and anabolic intracellular signaling as a way to counteract age-related loss of muscle mass. Untrained healthy elderly (>65-yr-old) men were subjected to 13 h of supine rest. After 2.5 h of rest, unilateral LL-RE, consisting of leg extensions (10 sets, 36 repetitions) at 16% of 1 repetition maximum (RM), was conducted. Subsequently, the subjects were randomized to oral intake of 4 g of whey protein per hour (PULSE, n = 10), 28 g of whey protein at 0 h and 12 g of whey protein at 7 h postexercise (BOLUS, n = 10), or 4 g of maltodextrin per hour (placebo, n = 10). Quadriceps muscle biopsies were taken at 0, 3, 7, and 10 h postexercise from the resting and the exercised leg of each subject. Myofibrillar FSR and activity of select targets from the mechanistic target of rapamycin complex 1-signaling cascade were analyzed from the biopsies. LL-RE increased myofibrillar FSR compared with the resting leg throughout the 10-h postexercise period. Phosphorylated (T308) AKT expression increased in the exercised leg immediately after exercise. This increase persisted in the placebo group only. Levels of phosphorylated (T37/46) eukaryotic translation initiation factor 4E-binding protein 1 increased throughout the postexercise period in the exercised leg in the placebo and BOLUS groups and peaked at 7 h. In all three groups, phosphorylated (T56) eukaryotic elongation factor 2 decreased in response to LL-RE. We conclude that resistance exercise at only 16% of 1 RM increased myofibrillar FSR, irrespective of nutrient type and feeding pattern, which indicates an anabolic effect of LL-RE in elderly individuals. This finding was supported by increased signaling for translation initiation and translation elongation in response to LL-RE.

Whey protein stories - An experiment in writing a multidisciplinary biography.

This is an experimental, dual-purpose article about whey protein and how to conduct interdisciplinary analyses and writings. On the one hand, this article is a multidisciplinary commodity biography, which consists of five descriptions of whey protein written by the five different research groups involved in the interdisciplinary research project CALM(Counteracting Age-related loss of Skeletal Muscle Mass). On the other hand, it is a meta-analysis, which aims to uncover and highlight examples of how the five descriptions contribute to each other with insights into the contextualisation of knowledge, contrasts between the descriptions and the new dimensions they bring to established fields of interest. The meta-analysis also contains a discussion of interdisciplinary study objects and the usefulness of the multidisciplinary commodity biography as a format for interdisciplinary publications. The article contributes to the field of food studies with a multidisciplinary biography of whey protein - including its sensory qualities and challenges, insights into its cultural history, its nutritional value and effects on the human body and an analysis of how it is perceived by people who consume it. The biography thereby expands upon existing understandings of whey protein while discussing the usefulness of employing the commodity biography format in interdisciplinary writing. Moreover, the article contributes to the field of interdisciplinary research by providing a practical example of a joint publication and reflections upon the existence, interaction and possibilities of monodisciplinary knowledge structures within interdisciplinary studies and publications.

The single-biopsy approach in determining protein synthesis in human slow-turning-over tissue: use of flood-primed, continuous infusion of amino acid tracers.

Muscle protein synthesis (MPS) rate is determined conventionally by obtaining two or more tissue biopsies during a primed, continuous infusion of a stable isotopically labeled amino acid. The purpose of the present study was to test whether tracer priming given as a flooding dose, thereby securing an instantaneous labeling of the tissue pools of free tracee amino acids, followed by a continuous infusion of the same tracer to maintain tracer isotopic steady state, could be used to determine the MPS rate over a prolonged period of time by obtaining only a single tissue biopsy. We showed that the tracer from the flood prime appeared immediately in the muscle free pool of amino acids and that this abundance could be kept constant by a subsequent continuous infusion of the tracer. When using phenylalanine as tracer, the flood-primed, continuous infusion protocol does not stimulate the MPS rate per se. In conclusion, the flood-primed, continuous infusion protocol using phenylalanine as tracer can validly be used to measure the protein synthesis rate in human in vivo experiments by obtaining only a single tissue biopsy after a prolonged infusion period.

Effects of hydrolysed casein, intact casein and intact whey protein on energy expenditure and appetite regulation: a randomised, controlled, cross-over study.

Casein and whey differ in amino acid composition and in the rate of absorption; however, the absorption rate of casein can be increased to mimic that of whey by exogenous hydrolysis. The objective of the present study was to compare the effects of hydrolysed casein (HC), intact casein (IC) and intact whey (IW) on energy expenditure (EE) and appetite regulation, and thereby to investigate the influence of amino acid composition and the rate of absorption. In the present randomised cross-over study, twenty-four overweight and moderately obese young men and women consumed three isoenergetic dietary treatments that varied in protein source. The study was conducted in a respiration chamber, where EE, substrate oxidation and subjective appetite were measured over 24 h at three independent visits. Moreover, blood and urine samples were collected from the participants. The results showed no differences in 24 h and postprandial EE or appetite regulation. However, lipid oxidation, estimated from the respiratory quotient (RQ), was found to be higher after consumption of IW than after consumption of HC during daytime (P= 0·014) as well as during the time after the breakfast meal (P= 0·008) when the food was provided. Likewise, NEFA concentrations were found to be higher after consumption of IW than after consumption of HC and IC (P< 0·01). However, there was no overall difference in the concentration of insulin or glucagon-like peptide 1. In conclusion, dietary treatments when served as high-protein mixed meals induced similar effects on EE and appetite regulation, except for lipid oxidation, where RQ values suggest that it is higher after consumption of IW than after consumption of HC.

Positive muscle protein net balance and differential regulation of atrogene expression after resistance exercise and milk protein supplementation.

PURPOSE: Resistance exercise and amino acid availability are positive regulators of muscle protein net balance (NB). However, anabolic responses to resistance exercise and protein supplementation deserve further elucidation. The purpose was to compare intakes of whey, caseinate (both: 0.30 g/kg lean body mass), or a non-caloric control after heavy resistance exercise on protein turnover and mRNA expressions of forkhead homeobox type O (FOXO) isoforms, muscle RING finger 1 (MuRF1), and Atrogin1 in young healthy males. METHODS: Protein turnover was determined by stable isotope-labeled leucine and femoral arteriovenous blood samples at rest and during 6-h recovery. Muscle biopsies were collected at -60 min (rest) and at 60, 210, and 360 min in the recovery period. RESULTS: During recovery, leucine NB was significantly higher in the protein groups compared to control (P < 0.001). Differences in leucine NB, rate of disappearance, and oxidation were observed in the early recovery period between whey and caseinate. FOXO1A and MuRF1 were upregulated at 60 and 210 min, and, in contrast, FOXO3 and Atrogin1 were downregulated at 210 and 360 min. For leucine rate of appearance and all FOXO and atrogene mRNA expressions, no differences were observed between groups. CONCLUSIONS: Whey and caseinate were equally superior to control in the 6-h recovery period and displayed temporal differences with whey having a fast and superior effect in the early part of the recovery period. Effects on mRNA expressions indicate different regulatory mechanisms on the ubiquitin ligases MuRF1 and Atrogin1 in recovery from heavy resistance exercise.

Myogenic, matrix, and growth factor mRNA expression in human skeletal muscle: effect of contraction intensity and feeding.

INTRODUCTION: We examined short-term (3-hour) and long-term (12-week) training effects after heavy load [HL; 70% 1RM] and light load (LL; 16% 1RM) exercise. METHODS: mRNA expression of genes involved in skeletal muscle remodeling were analyzed and muscle activity (EMG measurements) was measured. RESULTS: Relative muscle activity differed between HL and LL resistance exercise, whereas median power frequency was even, suggesting an equal muscle-fiber-type recruitment distribution. mRNA expression of Myf6, myogenin, and p21 was mostly increased, and myostatin was mostly depressed by HL resistance exercise. No major differences were seen in atrophy-related genes between HL and LL resistance exercise. No changes were seen over 12-week training for any of the targets. CONCLUSIONS: Resistance exercise at LL and HL elevated the expression of genes involved in skeletal muscle hypertrophy, although the greatest response was from HL. However, no long-term effect from either LL or HL resistance exercise was seen on basal levels of the mRNA targets.

Whey and casein labeled with L-[1-13C]leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion.

Muscle protein turnover following resistance exercise and amino acid availability are relatively well described. By contrast, the beneficial effects of different sources of intact proteins in relation to exercise need further investigation. Our objective was to compare muscle anabolic responses to a single bolus intake of whey or casein after performance of heavy resistance exercise. Young male individuals were randomly assigned to participate in two protein trials (n = 9) or one control trial (n = 8). Infusion of l-[1-(13)C]leucine was carried out, and either whey, casein (0.3 g/kg lean body mass), or a noncaloric control drink was ingested immediately after exercise. l-[1-(13)C]leucine-labeled whey and casein were used while muscle protein synthesis (MPS) was assessed. Blood and muscle tissue samples were collected to measure systemic hormone and amino acid concentrations, tracer enrichments, and myofibrillar protein synthesis. Western blots were used to investigate the Akt signaling pathway. Plasma insulin and branched-chain amino acid concentrations increased to a greater extent after ingestion of whey compared with casein. Myofibrillar protein synthesis was equally increased 1-6 h postexercise after whey and casein intake, both of which were higher compared with control (P < 0.05). Phosphorylation of Akt and p70(S6K) was increased after exercise and protein intake (P < 0.05), but no differences were observed between the types of protein except for total 4E-BP1, which was higher after whey intake than after casein intake (P < 0.05). In conclusion, whey and casein intake immediately after resistance exercise results in an overall equal MPS response despite temporal differences in insulin and amino acid concentrations and 4E-BP1.

Divergent Anabolic Response to Exercise in Young and Older Adult Men-Dependency on Time Frame of Measurement.

Older adults' skeletal muscle has shown to be less responsive to anabolic stimuli as compared to young both in vitro, in short and controlled in vivo settings and in long-term training studies. However, to translate controlled mechanistic findings to long-term adaptations intermediate measures allowing daily life routines with regard to activity and diet would be useful to evaluate physiological interventions. The purpose of this study was to investigate the exercise effect in young and older adults with 2 independent methods to measure muscle protein synthesis rate. Healthy young and old men were recruited to the study protocol where myofibrillar fractional synthesis rate was measured during 2 days allowing normal activities of daily living with D2O-labeled alanine and during 4 hours in the overnight fasted state with [13C6]phenylalanine infusion. During this period 1 leg completed an exercise session every day (exercise leg) while the contralateral leg was kept inactive (normal leg). Both legs were used for activities of daily living. Two-day myofibrillar fractional synthesis rate was significantly higher in the exercise leg in both young and old as compared to normal leg with no age difference. The 4-hour overnight fasted myofibrillar fractional synthesis rate showed that only young exercise leg was significantly higher than normal leg. The present findings support the notion that anabolic resistance exists in the skeletal muscle of healthy older men when evaluated in controlled settings. However, this response is not as clear when measured during daily life where variance is greater, which calls for further investigations in larger cohorts.

ß2-Adrenergic agonist salbutamol augments hypertrophy in MHCIIa fibers and sprint mean power output but not muscle force during 11 weeks of resistance training in young men.

In this study, we examined the effect of ß2-agonist salbutamol at oral doses during a period of resistance training on sprint performance, quadriceps contractile function, skeletal muscle hypertrophy, fiber type composition, maximal activity of enzymes of importance for anaerobic energy turnover, and sarcoplasmic reticulum Ca2+ handling in young men. Twenty-six men (23 ± 2 yr; means ± SD) were randomized to daily intake of oral salbutamol (16 mg/day; RES+SAL) or placebo (RES) during 11 wk of full-body resistance training 3 times/wk. Mean power output during 10-s maximal cycling increased more (P = 0.027) in RES+SAL (+12%) than in RES (+7%), whereas peak power output increased similarly (RES+SAL: +8%; RES: +7%; P = 0.400). Quadriceps dynamic peak torque and maximal voluntary isometric torque increased by 13 and 14% (P ≤ 0.001) in RES+SAL and 13 and 13% (P ≤ 0.001) in RES, respectively. Myosin heavy-chain (MHC) isoform distribution transitioned from MHCI and MHCIIx toward MHCIIa in RES+SAL (P = 0.002), but not in RES (P = 0.323). MHCIIa cross-sectional-area increased more (P = 0.040) in RES+SAL (+35%) than RES (+21%). Sarcoplasmic reticulum Ca2+ release rate increased in both groups (RES+SAL: +9%, P = 0.048; RES: +13%, P = 0.008), whereas Ca2+-uptake rate increased only in RES (+12%, P = 0.022) but was not different from the nonsignificant change in RES+SAL (+2%, P = 0.484). Maximal activity of lactate dehydrogenase increased only in RES+SAL (+13%, P = 0.008). Muscle content of the dihydropyridine receptor, ryanodine receptor 1, and sarcoplasmic reticulum Ca2+-ATPase isoform 1 and 2 did not change with the intervention in either group (P ≥ 0.100). These observations indicate that the enhancement of sprint mean power output induced by salbutamol is at least partly attributed to greater hypertrophy of MHCIIa fibers and transition toward the MHCIIa isoform.NEW & NOTEWORTHY Here, we show that daily oral treatment with selective ß2-agonist salbutamol induces muscle fiber isoform transition from myosin-heavy-chain (MHC)-I toward MHCIIa and augments hypertrophy of MHCIIa fibers during a period of resistance training. Compared with placebo, salbutamol enhanced sprint mean power output, whereas peak power output and measures of muscle strength increased similarly during the resistance training period despite augmented hypertrophy with salbutamol. Thus, salbutamol is a muscle anabolic drug that can enhance sprint ability adaptations to resistance training.

Human Fecal Metabolome Reflects Differences in Body Mass Index, Physical Fitness, and Blood Lipoproteins in Healthy Older Adults.

This study investigated how body mass index (BMI), physical fitness, and blood plasma lipoprotein levels are related to the fecal metabolome in older adults. The fecal metabolome data were acquired using proton nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry on 163 healthy older adults (65-80 years old, 80 females and 83 males). Overweight and obese subjects (BMI ≥ 27) showed higher levels of fecal amino acids (AAs) (valine, alanine, and phenylalanine) compared to normal-weight subjects (BMI ≤ 23.5). Adults classified in the high-fitness group displayed slightly lower concentrations of fecal short-chain fatty acids, propionic acid, and AAs (methionine, leucine, glutamic acid, and threonine) compared to the low-fitness group. Subjects with lower levels of cholesterol in low-density lipoprotein particles (LDLchol, ≤2.6 mmol/L) displayed higher fecal levels of valine, glutamic acid, phenylalanine, and lactic acid, while subjects with a higher level of cholesterol in high-density lipoprotein particles (HDLchol, ≥2.1 mmol/L) showed lower fecal concentration of isovaleric acid. The results from this study suggest that the human fecal metabolome, which primarily represents undigested food waste and metabolites produced by the gut microbiome, carries important information about human health and should be closely integrated to other omics data for a better understanding of the role of the gut microbiome and diet on human health and metabolism.

The effect of daily protein supplementation, with or without resistance training for 1 year, on muscle size, strength, and function in healthy older adults: A randomized controlled trial.

BACKGROUND: Protein supplementation alone or combined with resistance training has been proposed to be effective in counteracting age-related losses of muscle mass and strength. OBJECTIVES: To investigate the effect of protein supplementation alone or combined with light-intensity or heavy-load resistance exercise on muscle size, strength, and function in older adults. METHODS: In a 1-y randomized controlled trial, 208 healthy older adults (>65 y) were randomly assigned to 1 of 5 interventions: 1) carbohydrate supplementation (CARB); 2) collagen protein supplementation (COLL); 3) whey protein supplementation (WHEY); 4) light-intensity resistance training 3-5 times/wk with whey protein supplementation (LITW); and 5) heavy resistance training 3 times weekly with whey protein supplementation (HRTW). Protein supplements contained 20 g protein + 10 g carbohydrate, whereas CARB contained 30 g of carbohydrates. All intervention groups received the supplement twice daily. The primary outcome was change in the quadriceps cross-sectional area (qCSA). Secondary outcomes included measures of lower extremity strength and power, functional capabilities, and body composition. RESULTS: There were 184 participants who completed the study. COLL and WHEY did not affect any measured parameter compared to CARB. Compared to WHEY, HRTW improved the qCSA size (between-group difference, +1.68 cm2; 95% CI, +0.41 to +2.95 cm2; P = 0.03), as well as dynamic (+18.4 Nm; 95% CI, +10.1 to +26.6 Nm; P < 10-4) and isometric knee extensor strength (+23.9 Nm; 95% CI, +14.2 to +33.6 Nm; P < 10-5). LITW did not improve the qCSA size, but increased dynamic knee extensor strength compared to WHEY (+13.7 Nm; 95% CI, +5.3 and +22.1 Nm; P = 0.01). CONCLUSIONS: Recommending protein supplementation as a stand-alone intervention for healthy older individuals seems ineffective in improving muscle mass and strength. Only HRTW was effective in both preserving muscle mass and increasing strength. Thus, we recommend that future studies investigate strategies to increase long-term compliance to heavy resistance exercise in healthy older adults. This trial was registered at clinicaltrials.gov as NCT02034760.

Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis.

In skeletal muscle and tendon the extracellular matrix confers important tensile properties and is crucially important for tissue regeneration after injury. Musculoskeletal tissue adaptation is influenced by mechanical loading, which modulates the availability of growth factors, including growth hormone (GH) and insulin-like growth factor-I (IGF-I), which may be of key importance. To test the hypothesis that GH promotes matrix collagen synthesis in musculotendinous tissue, we investigated the effects of 14 day administration of 33-50 microg kg(-1) day(-1) recombinant human GH (rhGH) in healthy young individuals. rhGH administration caused an increase in serum GH, serum IGF-I, and IGF-I mRNA expression in tendon and muscle. Tendon collagen I mRNA expression and tendon collagen protein synthesis increased by 3.9-fold and 1.3-fold, respectively (P < 0.01 and P = 0.02), and muscle collagen I mRNA expression and muscle collagen protein synthesis increased by 2.3-fold and 5.8-fold, respectively (P < 0.01 and P = 0.06). Myofibrillar protein synthesis was unaffected by elevation of GH and IGF-I. Moderate exercise did not enhance the effects of GH manipulation. Thus, increased GH availability stimulates matrix collagen synthesis in skeletal muscle and tendon, but without any effect upon myofibrillar protein synthesis. The results suggest that GH is more important in strengthening the matrix tissue than for muscle cell hypertrophy in adult human musculotendinous tissue.

Daily Protein and Energy Intake Are Not Associated with Muscle Mass and Physical Function in Healthy Older Individuals-A Cross-Sectional Study.

Dietary protein has a pivotal role in muscle mass maintenance with advancing age. However, an optimal dose and distribution of protein intake across the day as well as the interaction with energy intake for the maintenance of muscle mass and physical function in healthy older adults remain to be fully elucidated. The purpose of this study was to examine the association between muscle mass, strength, and physical function, and the total amount and distribution of protein and energy intake across the day in healthy older individuals. The research question was addressed in a cross-sectional study including 184 Danish men and woman (age: 70.2 ± 3.9 years, body mass: 74.9 ± 12.1 kg, Body Mass Index (BMI): 25.4 ± 3.7 kg/m2) where a 3-day dietary registration, muscle mass, strength, and functional measurements were collected. We found that neither daily total protein intake nor distribution throughout the day were associated with muscle mass, strength, or physical function. Consequently, we do not provide an incentive for healthy older Danish individuals who already adhere to the current internationally accepted recommended dietary protein intake (0.83 g/kg/day) to change dietary protein intake or its distribution pattern throughout the day.