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OBJECTIVE: Dietary protein and physical activity interventions are increasingly implemented during hemodialysis to support muscle maintenance in patients with end-stage renal disease (ESRD). Although muscle maintenance is important, adequate removal of uremic toxins throughout hemodialysis is the primary concern for patients. It remains to be established whether intradialytic protein ingestion and/or exercise modulate uremic toxin removal during hemodialysis. METHODS: We recruited 10 patients with ESRD (age: 65 ± 16 y, BMI: 24.2 ± 4.8 kg/m2) on chronic hemodialysis treatment to participate in this randomized cross-over trial. During hemodialysis, patients were assigned to ingest 40 g protein or a nonprotein placebo both at rest (protein [PRO] and placebo [PLA], respectively) and following 30 min of exercise (PRO + exercise [EX] and PLA + EX, respectively). Blood and spent dialysate samples were collected throughout hemodialysis to assess reduction ratios and removal of urea, creatinine, phosphate, cystatin C, and indoxyl sulfate. RESULTS: The reduction ratios of urea and indoxyl sulfate were higher during PLA (76 ± 6% and 46 ± 9%, respectively) and PLA + EX interventions (77 ± 5% and 45 ± 10%, respectively) when compared to PRO (72 ± 4% and 40 ± 8%, respectively) and PRO + EX interventions (73 ± 4% and 43 ± 7%, respectively; protein effect: P = .001 and P = .023, respectively; exercise effect: P = .25 and P = .52, respectively). Nonetheless, protein ingestion resulted in greater urea removal (P = .046) during hemodialysis. Reduction ratios and removal of creatinine, phosphate, and cystatin C during hemodialysis did not differ following intradialytic protein ingestion or exercise (protein effect: P > .05; exercise effect: P>.05). Urea, creatinine, and phosphate removal were greater throughout the period with intradialytic exercise during PLA + EX and PRO + EX interventions when compared to the same period during PLA and PRO interventions (exercise effect: P = .034, P = .039, and P = .022, respectively). CONCLUSION: The removal of uremic toxins is not compromised by protein feeding and/or exercise implementation during hemodialysis in patients with ESRD.

Purpose To determine the effects of dietary sugar or carbohydrate restriction on physical activity energy expenditure, energy intake, and physiological outcomes across 24 h. Methods In a randomized, open-label crossover design, twenty-five healthy men (n = 10) and women (n = 15) consumed three diets over a 24-h period: moderate carbohydrate and sugar content (MODSUG = 50% carbohydrate [20% sugars], 15% protein, 35% fat); low sugar content (LOWSUG = 50% carbohydrate [ Results The MODSUG, LOWSUG and LOWCHO diets resulted in similar mean [95%CI] rates of both physical activity energy expenditure (771 [624, 919] vs. 677 [565, 789] vs. 802 [614, 991] kcal·d−1; p = 0.29] and energy intake (2071 [1794, 2347] vs. 2195 [1918, 2473] vs. 2194 [1890, 2498] kcal·d−1; P = 0.34), respectively. The LOWCHO condition elicited the lowest glycaemic and insulinaemic responses to breakfast (P P p Conclusion When energy density is controlled for, restricting either sugar or total dietary carbohydrate does not modulate physical activity level or energy intake over a 24-h period (~ 19-h free-living) despite substantial metabolic changes. Clinical trials registration ID NCT03509610, https://clinicaltrials.gov/show/NCT03509610

OBJECTIVE: This study aimed to assess the impact of time-restricted eating (TRE) on integrated skeletal muscle myofibrillar protein synthesis (MyoPS) rates in males with overweight/obesity.METHODS: A total of 18 healthy males (age 46 ± 5 years; BMI: 30 ± 2 kg/m2 ) completed this exploratory, parallel, randomized dietary intervention after a 3-day lead-in diet. Participants then consumed an isoenergetic diet (protein: ~1.0 g/kg body mass per day) following either TRE (10:00 a.m. to 6:00 p.m.) or an extended eating control (CON; 8:00 a.m. to 8:00 p.m.) protocol for 10 days. Integrated MyoPS rates were measured using deuterated water administration with repeated saliva, blood, and muscle sampling. Secondary measures included continuous glucose monitoring and body composition (dual-energy x-ray absorptiometry).RESULTS: There were no differences in daily integrated MyoPS rates (TRE: 1.28% ± 0.18% per day, CON: 1.26% ± 0.22% per day; p = 0.82) between groups. From continuous glucose monitoring, 24-hour total area under the curve was reduced following TRE (-578 ± 271 vs. CON: 12 ± 272 mmol/L × 24 hours; p = 0.001). Total body mass declined (TRE: -1.6 ± 0.9 and CON: -1.1 ± 0.7 kg; p CONCLUSION: Consuming food within an 8-hour time-restricted period does not lower daily MyoPS rates when compared with an isoenergetic diet consumed over 12 hours. Future research should investigate whether these results translate to free-living TRE.

ObjectivesTo assess the adverse impact of the first 5 months of androgen deprivation therapy on body composition, physical performance, cardiometabolic health and health-related quality-of-life in prostate cancer patients.Materials and MethodsThirty-four prostate cancer patients (70 +/- 7 years) were assessed shortly after initiation of androgen deprivation therapy and again 5 months thereafter. Measurements consisted of whole-body dual-energy x-ray absorptiometry (body composition), computed tomography scanning of the upper leg (muscle mass), one-repetition maximum leg press (muscle strength), cardiopulmonary exercise testing (aerobic capacity), blood draws (metabolic parameters), accelerometry (habitual physical activity) and questionnaires (health-related quality-of-life). Data were analyzed with Student's paired t-tests.ResultsOver time, whole-body fat mass (from 26.2 +/- 7.7 to 28.4 +/- 8.3 kg, p < 0.001) and fasting insulin (from 9.5 +/- 5.8 to 11.3 +/- 6.9 mU/L, p < 0.001) increased. Declines were observed for quadriceps cross-sectional area (from 66.3 +/- 9.1 to 65.0 +/- 8.5 cm(2), p < 0.01), one-repetition maximum leg press (from 107 +/- 27 to 100 +/- 27 kg, p < 0.01), peak oxygen uptake (from 23.2 +/- 3.7 to 20.3 +/- 3.4 mL/min/kg body weight, p < 0.001), step count (from 7,048 +/- 2,277 to 5,842 +/- 1,749 steps/day, p < 0.01) and health-related quality-of-life (from 84.6 +/- 13.5 to 77.0 +/- 14.6, p < 0.001).ConclusionsAndrogen deprivation therapy induces adverse changes in body composition, muscle strength, cardiometabolic health and health-related quality-of-life already within 5 months after the start of treatment, possibly largely contributed by diminished habitual physical activity. Prostate cancer patients should, therefore, be stimulated to increase their habitual physical activity immediately after initiation of androgen deprivation therapy, to limit adverse side-effects and to improve health-related quality-of-life.

Rationale: Dietary protein may attenuate the muscle atrophy experienced by patients in the ICU, yet protein handling is poorly understood. Objectives: To quantify protein digestion and amino acid absorption and fasting and postprandial myofibrillar protein synthesis during critical illness. Methods: Fifteen mechanically ventilated adults (12 male; aged 50 ± 17 yr; body mass index, 27 ± 5 kg⋅m-2) and 10 healthy control subjects (6 male; 54 ± 23 yr; body mass index, 27 ± 4 kg⋅m-2) received a primed intravenous L-[ring-2H5]-phenylalanine, L-[3,5-2H2]-tyrosine, and L-[1-13C]-leucine infusion over 9.5 hours and a duodenal bolus of intrinsically labeled (L-[1-13C]-phenylalanine and L-[1-13C]-leucine) intact milk protein (20 g protein) over 60 minutes. Arterial blood and muscle samples were taken at baseline (fasting) and for 6 hours following duodenal protein administration. Data are mean ± SD, analyzed with two-way repeated measures ANOVA and independent samples t test. Measurements and Main Results: Fasting myofibrillar protein synthesis rates did not differ between ICU patients and healthy control subjects (0.023 ± 0.013% h-1 vs. 0.034 ± 0.016% h-1; P = 0.077). After protein administration, plasma amino acid availability did not differ between groups (ICU patients, 54.2 ± 9.1%, vs. healthy control subjects, 61.8 ± 13.1%; P = 0.12), and myofibrillar protein synthesis rates increased in both groups (0.028 ± 0.010% h-1 vs. 0.043 ± 0.018% h-1; main time effect P = 0.046; P-interaction = 0.584) with lower rates in ICU patients than in healthy control subjects (main group effect P = 0.001). Incorporation of protein-derived phenylalanine into myofibrillar protein was ∼60% lower in ICU patients (0.007 ± 0.007 mol percent excess vs. 0.017 ± 0.009 mol percent excess; P = 0.007). Conclusions: The capacity for critically ill patients to use ingested protein for muscle protein synthesis is markedly blunted despite relatively normal protein digestion and amino acid absorption.

Context Androgen deprivation therapy (ADT) forms the cornerstone in prostate cancer (PCa) treatment. However, ADT also lowers skeletal muscle mass. Objective To identify the impact of ADT with and without resistance exercise training on muscle fiber characteristics in PCa patients. Methods Twenty-one PCa patients (72 ± 6 years) starting ADT were included. Tissue samples from the vastus lateralis muscle were assessed at baseline and after 20 weeks of usual care (n = 11) or resistance exercise training (n = 10). Type I and II muscle fiber distribution, fiber size, and myonuclear and capillary contents were determined by immunohistochemistry. Results Significant decreases in type I (from 7401 ± 1183 to 6489 ± 1293 μm2, P < .05) and type II (from 6225 ± 1503 to 5014 ± 714 μm2, P < .05) muscle fiber size were observed in the usual care group. In addition, type I and type II individual capillary-to-fiber ratio (C/Fi) declined (−12% ± 12% and −20% ± 21%, respectively, P < .05). In contrast, significant increases in type I (from 6700 ± 1464 to 7772 ± 1319 μm2, P < .05) and type II (from 5248 ± 892 to 6302 ± 1385 μm2, P < .05) muscle fiber size were observed in the training group, accompanied by an increase in type I and type II muscle fiber myonuclear contents (+24% ± 33% and +21% ± 23%, respectively, P < .05) and type I C/Fi (+18% ± 14%, P < .05). Conclusion The onset of ADT is followed by a decline in both type I and type II muscle fiber size and capillarization in PCa patients. Resistance exercise training offsets the negative impact of ADT and increases type I and II muscle fiber size and type I muscle fiber capillarization in these patients.

Consumers are increasingly encouraged to consume more plant-based foods and lower their consumption of foods from animal origin. Concurrently, older adults are recommended to consume an adequate amount of high-quality dietary protein for the prevention of age-related muscle loss. In the current Perspective article, we discuss why it may not be preferred to consume a vegan diet at an older age. Our perspective is based on the proposed lower bioavailability and functionality of proteins in a vegan diet due to the matrix of the whole-food protein sources, the lower essential amino acid (EAA) content, and specific EAA deficiencies in proteins derived from plant-based foods. We propose that a vegan diet increases the risk of an inadequate protein intake at an older age and that current strategies to improve the anabolic properties of plant-based foods are not feasible for many older adults. We provide recommendations for further research to substantiate the remaining knowledge gaps regarding the consequences of a vegan diet on skeletal muscle mass and strength at an older age.Statement of Significance: To our knowledge, this is the first article that provides an evidence-based perspective regarding the potential impact of a vegan diet on muscle mass and strength in older adults. The current perspective is highly relevant considering the envisaged shifts towards sustainable dietary guidelines.

Background Protein ingestion increases muscle protein synthesis rates. The food matrix in which protein is provided can strongly modulate the postprandial muscle protein synthetic response. So far, the muscle protein synthetic response to the ingestion of whole foods remains largely unexplored. Objectives To compare the impact of ingesting 30 g protein provided as milk protein or cheese on postprandial plasma amino acid concentrations and muscle protein synthesis rates at rest and during recovery from exercise in vivo in young males. Methods In this randomized, parallel-group intervention trial, 20 healthy males aged 18-35 y ingested 30 g protein provided as cheese or milk protein concentrate following a single-legged resistance-type exercise session consisting of 12 sets of leg press and leg extension exercises. Primed, continuous intravenous L-[ring-C-13(6)]-phenylalanine infusions were combined with the collection of blood and muscle tissue samples to assess postabsorptive and 4-h postprandial muscle protein synthesis rates at rest and during recovery from exercise. Data were analyzed using repeated measures Time x Group (x Leg) ANOVA. Results Plasma total amino acid concentrations increased after protein ingestion (Time: P < 0.001), with 38% higher peak concentrations following milk protein than cheese ingestion (Time x Group: P < 0.001). Muscle protein synthesis rates increased following both cheese and milk protein ingestion from 0.037 +/- 0.014 to 0.055 +/- 0.018%center dot h(-1) and 0.034 +/- 0.008 to 0.056 +/- 0.010%center dot h(-1) at rest and even more following exercise from 0.031 +/- 0.010 to 0.067 +/- 0.013%center dot h(-1) and 0.030 +/- 0.008 to 0.063 +/- 0.010%center dot h(-1), respectively (Time: all P < 0.05; Time x Leg: P = 0.002), with no differences between cheese and milk protein ingestion (Time x Group: both P > 0.05). Conclusion Cheese ingestion increases muscle protein synthesis rates both at rest and during recovery from exercise. The postprandial muscle protein synthetic response to the ingestion of cheese or milk protein does not differ when 30 g protein is ingested at rest or during recovery from exercise in healthy, young males.

Background Casein protein ingestion prior to sleep has been shown to increase myofibrillar protein synthesis rates during overnight sleep. It remains to be assessed whether pre-sleep protein ingestion can also increase mitochondrial protein synthesis rates. Though it has been suggested that casein protein may be preferred as a pre-sleep protein source, no study has compared the impact of pre-sleep whey versus casein ingestion on overnight muscle protein synthesis rates. Objective We aimed to assess the impact of casein and whey protein ingestion prior to sleep on mitochondrial and myofibrillar protein synthesis rates during overnight recovery from a bout of endurance-type exercise. Methods Thirty-six healthy young men performed a single bout of endurance-type exercise in the evening (19:45 h). Thirty minutes prior to sleep (23:30 h), participants ingested 45 g of casein protein, 45 g of whey protein, or a non-caloric placebo. Continuous intravenous l-[ring-13C6]-phenylalanine infusions were applied, with blood and muscle tissue samples being collected to assess overnight mitochondrial and myofibrillar protein synthesis rates. Results Pooled protein ingestion resulted in greater mitochondrial (0.087 ± 0.020 vs 0.067 ± 0.016%·h−1, p = 0.005) and myofibrillar (0.060 ± 0.014 vs 0.047 ± 0.011%·h−1, p = 0.012) protein synthesis rates when compared with placebo. Casein and whey protein ingestion did not differ in their capacity to stimulate mitochondrial (0.082 ± 0.019 vs 0.092 ± 0.020%·h−1, p = 0.690) and myofibrillar (0.056 ± 0.009 vs 0.064 ± 0.018%·h−1, p = 0.440) protein synthesis rates. Conclusions Protein ingestion prior to sleep increases both mitochondrial and myofibrillar protein synthesis rates during overnight recovery from exercise. The overnight muscle protein synthetic response to whey and casein protein does not differ. Clinical Trial Registration NTR7251.

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.

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/m(2), 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, eta(2)(p) > 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, eta(2)(p) = 0.97; exercise effect P = 0.32, eta(2)(p) = 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, eta(2)(p) > 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, eta(2)(p) = 0.98; exercise effect P = 0.21, eta(2)(p) = 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.

Skeletal muscle is maintained and repaired by sub-laminar, Pax7-expressing satellite cells. However, recent mouse investigations have described a second myogenic progenitor population that resides within the myofiber interstitium and expresses the transcription factor Twist2. Twist2-expressing cells exclusively repair and maintain type IIx/b muscle fibers. Currently, it is unknown if Twist2-expressing cells are present in human skeletal muscle and if they function as myogenic progenitors. Here, we perform a combination of single-cell RNA sequencing analysis and immunofluorescence staining to demonstrate the identity and localization of Twist2-expressing cells in human skeletal muscle. Twist2-expressing cells were identified to be anatomically and transcriptionally comparable to fibro-adipogenic progenitors (FAPs) and lack expression of typical satellite cell markers such as Pax7. Comparative analysis revealed that human and mouse Twist2-expressing cells were highly transcriptionally analogous and resided within the same anatomical structures in vivo. Examination of young and aged skeletal muscle biopsy samples revealed that Twist2-positive cells are more prevalent in aged muscle and increase following 12-weeks of resistance exercise training (RET) in humans. However, the quantity of Twist2-positive cells was not correlated with indices of muscle mass or muscle fiber cross-sectional area (CSA) in young or older muscle, and their abundance was surprisingly, negatively correlated with CSA and myonuclear domain size following RET. Taken together, we have identified cells expressing Twist2 in human skeletal muscle which are responsive to aging and exercise. Further examination of their myogenic potential is warranted.

Skeletal muscle mass losses with age are associated with negative health consequences, including an increased risk of developing metabolic disease and the loss of independence. Athletes adopt numerous nutritional strategies to maximize the benefits of exercise training and enhance recovery in pursuit of improving skeletal muscle quality, mass, or function. Importantly, many of the principles applied to enhance skeletal muscle health in athletes may be applicable to support active aging and prevent sarcopenia in the healthy (non-clinical) aging population. Here, we discuss the anabolic properties of protein supplementation in addition to ingredients that may enhance the anabolic effects of protein (e.g. omega 3 s, creatine, inorganic nitrate) in older persons. We conclude that nutritional strategies used in pursuit of performance enhancement in athletes are often applicable to improve skeletal muscle health in the healthy older population when implemented as part of a healthy active lifestyle. Further research is required to elucidate the mechanisms by which these nutrients may induce favourable changes in skeletal muscle and to determine the appropriate dosing and timing of nutrient intakes to support active aging.

Patients infected with SARS-CoV-2 who have been admitted to the intensive care unit (ICU) often face months of physical disability after discharge. To optimize recovery, it is important to understand the role of musculoskeletal alterations in critically ill patients infected with SARS-CoV-2. The main aim of the present study was to describe the presence and morphology of nemaline bodies found in skeletal muscle tissue from critically ill patients infected with SARS-CoV-2. In n=7 patients infected with SARS-CoV-2, ultrastructural characteristics of vastus lateralis muscle obtained on days 1-3 (T0) and days 5-8 (T1) following ICU admission were investigated in more detail with electron microscopy. Those muscle biopsies consistently showed variable degrees of myofiber necrosis and myofibrillar disorganisation. In 4/7 (57%) patients at T1, the Z-line material accumulated into nemaline bodies with a typical lattice-like appearance at higher magnification, similar to that found in nemaline myopathy. This study is the first to describe the disintegration of myofibrils and accumulation of Z-line material into nemaline bodies in skeletal muscle tissue obtained from critically ill COVID-19 patients following ICU admission, which should be interpreted primarily as a non-specific pathological response of extreme myofibrillar disintegration associated with myofiber necrosis. Mini abstract This study describes the presence and morphology of typical nemaline bodies in skeletal muscle ti0ssue from critically ill patients infected with SARS-CoV-2, which should be interpreted primarily as a non-specific pathological response of extreme myofibrillar disintegration associated with myofiber necrosis.

Background In vivo muscle protein synthesis rates are typically assessed by measuring the incorporation rate of stable isotope labelled amino acids in skeletal muscle tissue collected from vastus lateralis muscle. It remains to be established whether muscle protein synthesis rates in the vastus lateralis are representative of muscle protein synthesis rates of other muscle groups. We hypothesized that post-absorptive muscle protein synthesis rates differ between vastus lateralis and rectus abdominis, pectoralis major, or temporalis muscle in vivo in humans.Methods Twenty-four patients (62 +/- 3 years, 42% female), scheduled to undergo surgery, participated in this study and underwent primed continuous intravenous infusions with l-[ring-C-13(6)]-phenylalanine. During the surgical procedures, serum samples were collected, and muscle tissue was obtained from the vastus lateralis as well as from the rectus abdominis, pectoralis major, or temporalis muscle. Fractional mixed muscle protein synthesis rates (%/h) were assessed by measuring the incorporation of l-[ring-C-13(6)]-phenylalanine into muscle tissue protein.Results Serum l-[ring-C-13(6)]-phenylalanine enrichments did not change throughout the infusion period. Post-absorptive muscle protein synthesis rates calculated based upon serum l-[ring-C-13(6)]-phenylalanine enrichments did not differ between vastus lateralis and rectus abdominis (0.032 +/- 0.004 vs. 0.038 +/- 0.003%/h), vastus lateralis and pectoralis major, (0.025 +/- 0.003 vs. 0.022 +/- 0.005%/h) or vastus lateralis and temporalis (0.047 +/- 0.005 vs. 0.043 +/- 0.005%/h) muscle, respectively (P > 0.05). When fractional muscle protein synthesis rates were calculated based upon tissue-free l-[ring-C-13(6)]-phenylalanine enrichments as the preferred precursor pool, muscle protein synthesis rates were significantly higher in rectus abdominis (0.089 +/- 0.008%/h) compared with vastus lateralis (0.054 +/- 0.005%/h) muscle (P < 0.01). No differences were observed between fractional muscle protein synthesis rates in vastus lateralis and pectoralis major (0.046 +/- 0.003 vs. 0.041 +/- 0.008%/h) or vastus lateralis and temporalis (0.073 +/- 0.008 vs. 0.083 +/- 0.011%/h) muscle, respectively.Conclusions Post-absorptive muscle protein synthesis rates are higher in rectus abdominis when compared with vastus lateralis muscle. Post-absorptive muscle protein synthesis rates do not differ between vastus lateralis and pectoralis major or temporalis muscle. Protein synthesis rates in muscle tissue samples obtained during surgery do not necessarily represent a good proxy for appendicular skeletal muscle protein synthesis rates.

Sports nutrition supplements have previously been reported to contain undeclared doping substances. The use of such supplements can lead to general health risks and may give rise to unintentional doping violations in elite sports. To assess the prevalence of doping substances in a range of high-risk sports nutrition supplements available from Dutch web shops. A total of 66 sports nutrition supplements - identified as potentially high-risk products claiming to modulate hormone regulation, stimulate muscle mass gain, increase fat loss, and/or boost energy - were selected from 21 different brands and purchased from 17 web shops. All products were analyzed for doping substances by the UK life sciences testing company LGC, formerly known as the Laboratory of the Government Chemist, using an extended version of their ISO17025 accredited nutritional supplement screen. A total of 25 out of the 66 products (38%) contained undeclared doping substances, which included high levels of the stimulants oxilofrine, beta-methylphenethylamine (BMPEA) and N,beta-dimethylphenethylamine (NBDMPEA), the stimulant 4-methylhexan-2-amine (methylhexaneamine, 1,3-dimethylamylamine, DMAA), the anabolic steroids boldione (1,4-androstadiene-3,17-dione) and 5-androstene-3 beta,17 alpha-diol (17 alpha-AED), the beta-2 agonist higenamine and the beta-blocker bisoprolol. Based upon the recommended dose and the potential variability of analyte concentration, the ingestion of some products identified within this study could pose a significant risk of unintentional doping violations. In addition to inadvertent doping risks, the prescribed use of 3 products (4.5%) could likely impose general health risks.

The impact of resistance exercise frequency on muscle protein synthesis rates remains unknown. The aim of this study was to compare daily myofibrillar protein synthesis rates over a 7-day period of low-frequency (LF) versus high-frequency (HF) resistance exercise training. Nine young men (21 ± 2 years) completed a 7-day period of habitual physical activity (BASAL). This was followed by a 7-day exercise period of volume-matched, LF (10 × 10 repetitions at 70% one-repetition maximum, once per week) or HF (2 × 10 repetitions at ∼70% one-repetition maximum, five times per week) resistance exercise training. The participants had one leg randomly allocated to LF and the other to HF. Skeletal muscle biopsies and daily saliva samples were collected to determine myofibrillar protein synthesis rates using 2H2O, with intracellular signaling determined using Western blotting. The myofibrillar protein synthesis rates did not differ between the LF (1.46 ± 0.26%/day) and HF (1.48 ± 0.33%/day) conditions over the 7-day exercise training period (p > .05). There were no significant differences between the LF and HF conditions over the first 2 days (1.45 ± 0.41%/day vs. 1.25 ± 0.46%/day) or last 5 days (1.47 ± 0.30%/day vs. 1.50 ± 0.41%/day) of the exercise training period (p > .05). Daily myofibrillar protein synthesis rates were not different from BASAL at any time point during LF or HF (p > .05). The phosphorylation status and total protein content of selected proteins implicated in skeletal muscle ribosomal biogenesis were not different between conditions (p > .05). Under the conditions of the present study, resistance exercise training frequency did not modulate daily myofibrillar protein synthesis rates in young men.

All human tissues are in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates. It has been well-established that protein ingestion stimulates skeletal muscle and whole-body protein synthesis. Stable isotope-labelled amino acid methodologies are commonly applied to assess the various aspects of protein metabolism in vivo in human subjects. However, to achieve a more comprehensive assessment of post-prandial protein handling in vivo in human subjects, intravenous stable isotope-labelled amino acid infusions can be combined with the ingestion of intrinsically labelled protein and the collection of blood and muscle tissue samples. The combined application of ingesting intrinsically labelled protein with continuous intravenous stable isotope-labelled amino acid infusion allows the simultaneous assessment of protein digestion and amino acid absorption kinetics (e.g. release of dietary protein-derived amino acids into the circulation), whole-body protein metabolism (whole-body protein synthesis, breakdown and oxidation rates and net protein balance) and skeletal muscle metabolism (muscle protein fractional synthesis rates and dietary protein-derived amino acid incorporation into muscle protein). The purpose of this review is to provide an overview of the various aspects of post-prandial protein handling and metabolism with a focus on insights obtained from studies that have applied intrinsically labelled protein under a variety of conditions in different populations.

Summary Dietary amino acid absorption kinetics are an important determinant of protein quality. The term "amino acid digestibility" is commonly used to refer to the amount of ingested amino acids that become available following absorption. However, one should differentiate between the subsequent processes of converting protein into smaller constituents (protein digestion) and luminal amino acid uptake (amino acid absorption). Amino acid "absorbability" or "bioavailability" is assessed by quantifying the disappearance of amino acids across (part of) the gastrointestinal tract. The assessment of fecal, apparent ileal (AID), standardized ileal (SID), and true ileal disappearance (TID), reflect amino acid absorbability with increasing accuracy, due to correction for microbial metabolism in the large intestine, basal gut endogenous amino acid losses, and total gut endogenous amino acids losses, respectively. A substantial amount of absorbed amino acids undergo first-pass splanchnic extraction, but the majority is immediately released in the circulation and becomes available for peripheral tissues. The assessment of amino acid "bioavailability" or "absorbability" is used in protein quality ranking systems such as the Digestible Indispensable Amino Acid Score (DIAAS). However, such scores neglect that the rate of absorption is also an important determinant of postprandial metabolism. In addition, amino acid absorption and/or its rate are highly dependent on factors such as the duration of the postprandial assessment period. Therefore, amino acid absorption kinetics should be assessed under the relevant experimental conditions. To this end, an oral-intravenous dual tracer approach can be applied to assess dietary protein derived amino acid release into the circulation and allows the assessment of the subsequent impact on postprandial whole-body protein metabolism.

Previous studies have used supplements to increase dietary nitrate intake in clinical populations. Little is known about whether effects can also be induced through vegetable consumption. Therefore, the aim of this study was to assess the impact of dietary nitrate, through nitrate-rich vegetables (NRV) and beetroot juice (BRJ) supplementation, on plasma nitrate and nitrite concentrations, exercise tolerance, muscle oxygenation, and cardiovascular function in patients with peripheral arterial disease. In a randomized crossover design, 18 patients with peripheral arterial disease (age: 73 ± 8 years) followed a nitrate intake protocol (∼6.5 mmol) through the consumption of NRV, BRJ, and nitrate-depleted BRJ (placebo). Blood samples were taken, blood pressure and arterial stiffness were measured in fasted state and 150 min after intervention. Each intervention was followed by a maximal walking exercise test to determine claudication onset time and peak walking time. Gastrocnemius oxygenation was measured by near-infrared spectroscopy. Blood samples were taken and blood pressure was measured 10 min after exercise. Mean plasma nitrate and nitrite concentrations increased (nitrate; Time × Intervention interaction; p p p = .762 and p = .165, respectively). Gastrocnemius oxygenation, blood pressure, and arterial stiffness were not affected by the intervention. NRV and BRJ intake markedly increase plasma nitrate and nitrite, but this does not translate to improved exercise tolerance, muscle oxygenation, and/or cardiovascular function.

Maintaining good glycemic control to prevent complications is crucial in people with type 2 diabetes and in people with prediabetes and in the general population. Different strategies to improve glycemic control involve the prescription of blood glucose-lowering drugs and the modulation of physical activity and diet. Interestingly, lifestyle intervention may be more effective in lowering hyperglycemia than pharmaceutical intervention. Regulation of postprandial glycemia is complex, but specific nutritional strategies can be applied to attenuate postprandial hyperglycemia. These strategies include reducing total carbohydrate intake, consuming carbohydrates with a lower glycemic index, the addition of or substitution by sweeteners and fibers, using food compounds which delay or inhibit gastric emptying or carbohydrate digestion, and using food compounds which inhibit intestinal glucose absorption. Nevertheless, it must be noted that every individual may respond differently to certain nutritional interventions. Therefore, a personalized approach is of importance to choose the optimal nutritional strategy to improve postprandial glycemia for each individual, but this requires a better understanding of the mechanisms explaining the differential responses between individuals.

Collagen is the central structural component of extracellular connective tissue, which provides elastic qualities to tissues. For skeletal muscle, extracellular connective tissue transmits contractile force to the tendons and bones. Connective tissue proteins are in a constant state of remodeling and have been shown to express a high level of plasticity. Dietary-protein ingestion increases muscle protein synthesis rates. High-quality, rapidly digestible proteins are generally considered the preferred protein source to maximally stimulate myofibrillar (contractile) protein synthesis rates. In contrast, recent evidence demonstrates that protein ingestion does not increase muscle connective tissue protein synthesis. The absence of an increase in muscle connective tissue protein synthesis after protein ingestion may be explained by insufficient provision of glycine and/or proline. Dietary collagen contains large amounts of glycine and proline and, therefore, has been proposed to provide the precursors required to facilitate connective tissue protein synthesis. This literature review provides a comprehensive evaluation of the current knowledge on the proposed benefits of dietary collagen consumption to stimulate connective tissue remodeling to improve health and functional performance.

Accumulating evidence suggests that most elite cyclists have lower bone mineral density (BMD) values when compared with their nonelite counterparts (1) or sedentary young males (2, 3). This raises the question whether these ostensibly healthy athletes have a higher acute bone fracture risk and a higher risk of osteoporosis and associated comorbidities later in life. Although treatment of low BMD seems warranted in elite cyclists, the benefits of treatment for health and performance in this population remain to be established. In this viewpoint, we describe the etiology and consequences of impaired bone health in elite cyclists and discuss the need for interventions to optimize bone health in this unique population.

Key pointsKetone bodies are proposed to represent an alternative fuel source driving energy production, particularly during exercise. Biologically, the extent to which mitochondria utilize ketone bodies compared to other substrates remains unknown. We demonstratein vitrothat maximal mitochondrial respiration supported by ketone bodies is low when compared to carbohydrate-derived substrates in the left ventricle and red gastrocnemius muscle from rodents, and in human skeletal muscle. When considering intramuscular concentrations of ketone bodies and the presence of other carbohydrate and lipid substrates, biological rates of mitochondrial respiration supported by ketone bodies are predicted to be minimal. At the mitochondrial level, it is therefore unlikely that ketone bodies are an important source for energy production in cardiac and skeletal muscle, particularly when other substrates are readily available. Ketone bodies (KB) have recently gained popularity as an alternative fuel source to support mitochondrial oxidative phosphorylation and enhance exercise performance. However, given the low activity of ketolytic enzymes and potential inhibition from carbohydrate oxidation, it remains unknown if KBs can contribute to energy production. We therefore determined the ability of KBs (sodiumdl-beta-hydroxybutyrate, beta-HB; lithium acetoacetate, AcAc) to stimulatein vitromitochondrial respiration in the left ventricle (LV) and red gastrocnemius (RG) of rats, and in human vastus lateralis. Compared to pyruvate, the ability of KBs to maximally drive respiration was low in isolated mitochondria and permeabilized fibres (PmFb) from the LV (similar to 30-35% of pyruvate), RG (similar to 10-30%), and human vastus lateralis (similar to 2-10%). In PmFb, the concentration of KBs required to half-maximally drive respiration (LV: 889 mu m beta-HB, 801 mu mAcAc; RG: 782 mu m beta-HB, 267 mu mAcAc) were greater than KB content representative of the muscle microenvironment (similar to 100 mu m). This would predict low rates (similar to 1-4% of pyruvate) of biological KB-supported respiration in the LV (8-14 pmol s(-1) mg(-1)) and RG (3-6 pmol s(-1) mg(-1)) at rest and following exercise. Moreover, KBs did not increase respiration in the presence of saturating pyruvate, submaximal pyruvate (100 mu m) reduced the ability of physiological beta-HB to drive respiration, and addition of other intracellular substrates (succinate + palmitoylcarnitine) decreased maximal KB-supported respiration. As a result, product inhibition is likely to limit KB oxidation. Altogether, the ability of KBs to drive mitochondrial respiration is minimal and they are likely to be outcompeted by other substrates, compromising their use as an important energy source.

The current double blind, randomized, placebo-controlled trial with two parallel groups aimed to assess the impact of whey protein supplementation on recovery of muscle function and muscle soreness following eccentric exercise. During a 9-day period, forty recreationally active males received twice daily supplementation with either whey protein (PRO; 60 g/day) or an iso-energetic amount of carbohydrate (CON). Muscle function and soreness were assessed before, and 0, 3, 24, 48, and 72 h after performing 100 drop jumps. Recovery of isometric maximal voluntary contraction (MVC) did not significantly differ between groups (timextreatment,P= 0.56). In contrast, the recovery of isokinetic MVC at 90 degrees center dot s(-1)was faster in CON as opposed to PRO (timextreatment interaction,P= 0.044). Recovery of isokinetic MVC at 180 degrees center dot s(-1)was also faster in CON as opposed to PRO (timextreatment interaction,P= 0.011). Recovery of countermovement jump performance did not differ between groups (timextreatment interaction,P= 0.52). Muscle soreness, CK and CRP showed a transient increase over time (P

The purpose of this current opinion paper is to describe the journey of ingested carbohydrate from ‘mouth to mitochondria’ culminating in energy production in skeletal muscles during exercise. This journey is conveniently described as primary, secondary, and tertiary events. The primary stage is detection of ingested carbohydrate by receptors in the oral cavity and on the tongue that activate reward and other centers in the brain leading to insulin secretion. After digestion, the secondary stage is the transport of monosaccharides from the small intestine into the systemic circulation. The passage of these monosaccharides is facilitated by the presence of various transport proteins. The intestinal mucosa has carbohydrate sensors that stimulate the release of two ‘incretin’ hormones (GIP and GLP-1) whose actions range from the secretion of insulin to appetite regulation. Most of the ingested carbohydrate is taken up by the liver resulting in a transient inhibition of hepatic glucose release in a dose-dependent manner. Nonetheless, the subsequent increased hepatic glucose (and lactate) output can increase exogenous carbohydrate oxidation rates by 40–50%. The recognition and successful distribution of carbohydrate to the brain and skeletal muscles to maintain carbohydrate oxidation as well as prevent hypoglycaemia underpins the mechanisms to improve exercise performance.

Background: Protein ingestion increases skeletal muscle protein synthesis rates during recovery from endurance exercise.Objectives: We aimed to determine the effect of graded doses of dietary protein co-ingested with carbohydrate on whole-body protein metabolism, and skeletal muscle myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis rates during recovery from endurance exercise.Methods: In a randomized, double-blind, parallel-group design, 48 healthy, young, endurance-trained men (mean +/- SEM age: 27 +/- 1 y) received a primed continuous infusion of L-[ring-H-2(5)]phenylalanine, L-[ring-3,5-H-2(2)]-tyrosine, and L-[1-C-13]-leucine and ingested 45 g carbohydrate with either 0 (0 g PRO), 15 (15 g PRO), 30 (30 g PRO), or 45 (45 g PRO) g intrinsically L-[1-C-13]-phenylalanine and L-[1-C-13]-leucine labeled milk protein after endurance exercise. Blood and muscle biopsy samples were collected over 360 min of postexercise recovery to assess whole-body protein metabolism and both MyoPS and MitoPS rates.Results: Protein intake resulted in similar to 70%-74% of the ingested protein-derived phenylalanine appearing in the circulation. Whole-body net protein balance increased dose-dependently after ingestion of 0, 15, 30, or 45 g protein (mean +/- SEM: -0.31 +/- 0.16, 5.08 +/- 0.21, 10.04 +/- 0.30, and 13.49 +/- 0.55 mu mol phenylalanine . kg(-1) . h(-1), respectively; P Conclusions: Protein ingested after endurance exercise is efficiently digested and absorbed into the circulation. Whole-body net protein balance and dietary protein-derived amino acid incorporation into mitochondrial protein respond to increasing protein intake in a dose-dependent manner. Ingestion of 30 g protein is sufficient to maximize MyoPS rates during recovery from a single bout of endurance exercise.

Extensive research performed over the past 10 years has resulted in dietary nitrate being considered a nutritional supplement that can improve exercise performance. However, there is still limited insight in the metabolic fate of dietary nitrate following the appearance of nitrate and nitrite in the circulation. Recent observations in humans suggest the storage of nitrate in skeletal muscle tissue. This short review discusses the possibility of nitrate being stored and utilized in human skeletal muscle tissue, and why confirming this may increase our understanding of how the nitrate -nitrite -NO pathway improves exercise performance. Further insight in skeletal muscle nitrate storage and metabolism may provide answers to current gaps in knowledge, such as the ergogenic benefit of acute vs multiday dietary nitrate supplementation, as well as the suggested muscle fiber -type specific effects on exercise performance. In this mini -review, specific questions that need further exploration are also discussed.

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).

The purpose of this study was to assess the impact of postexercise hot-water immersion on postprandial myofibrillar protein synthesis rates during recovery from a single bout of resistance-type exercise in healthy, young men. Twelve healthy, adult men (age: 23 ± 1 y) performed a single bout of resistance-type exercise followed by 20 min of water immersion of both legs. One leg was immersed in hot water [46°C: hot-water immersion (HWI)], while the other leg was immersed in thermoneutral water (30°C: CON). After water immersion, a beverage was ingested containing 20 g intrinsically L-[1-13C]-phenylalanine and L-[1-13C]-leucine labeled milk protein with 45 g of carbohydrates. In addition, primed continuous L-[ ring-2H5]-phenylalanine and L-[1-13C]-leucine infusions were applied, with frequent collection of blood and muscle samples to assess myofibrillar protein synthesis rates in vivo over a 5-h recovery period. Muscle temperature immediately after water immersion was higher in the HWI compared with the CON leg (37.5 ± 0.1 vs. 35.2 ± 0.2°C; P < 0.001). Incorporation of dietary protein-derived L-[1-13C]-phenylalanine into myofibrillar protein did not differ between the HWI and CON leg during the 5-h recovery period (0.025 ± 0.003 vs. 0.024 ± 0.002 MPE; P = 0.953). Postexercise myofibrillar protein synthesis rates did not differ between the HWI and CON leg based upon L-[1-13C]-leucine (0.050 ± 0.005 vs. 0.049 ± 0.002%/h; P = 0.815) and L-[ ring-2H5]-phenylalanine (0.048 ± 0.002 vs. 0.047 ± 0.003%/h; P = 0.877), respectively. Hot-water immersion during recovery from resistance-type exercise does not increase the postprandial rise in myofibrillar protein synthesis rates. In addition, postexercise hot-water immersion does not increase the capacity of the muscle to incorporate dietary protein-derived amino acids in muscle tissue protein during subsequent recovery. NEW & NOTEWORTHY This is the first study to assess the effect of postexercise hot-water immersion on postprandial myofibrillar protein synthesis rates and the incorporation of dietary protein-derived amino acids into muscle protein. We observed that hot-water immersion during recovery from a single bout of resistance-type exercise does not further increase myofibrillar protein synthesis rates or augment the postprandial incorporation of dietary protein-derived amino acids in muscle throughout 5 h of postexercise recovery.

BACKGROUND/OBJECTIVES: Increased risk of type 2 diabetes mellitus (T2DM) is linked to impaired muscle mitochondrial function and reduced mitochondrial DNA copy number (mtDNAnum). However, studies have failed to control for habitual physical activity levels, which directly influences both mtDNA copy number and insulin sensitivity. We, therefore, examined whether physical conditioning status (maximal oxygen uptake, V̇O2max) was associated with skeletal muscle mitochondrial volume and mtDNAnum, and was predictive of T2DM in overweight, middle-aged men.METHODS: Whole-body physiological (ISI-insulin sensitivity index, HOMA-IR, V̇O2max) and muscle biochemical/molecular (vastus lateralis; mtDNAnum, mitochondrial and glycolytic enzymes activity, lipid content and markers of lipid peroxidation) measurements were performed in three groups of overweight, middle-aged male volunteers (n = 10 per group): sedentary T2DM (ST2DM); sedentary control (SC) and non-sedentary control (NSC), who differed in aerobic capacity (ST2DM RESULTS: mtDNAnum was greater in NSC versus SC and ST2DM (P CONCLUSIONS: Body composition and indices of muscle mitochondrial volume/function were similar between SC and ST2DM. However, mtDNAnum differed and was positively associated with ISI, HOMA-IR and V̇O2max across all groups. Collectively, the findings support the contention that habitual physical activity is a key component of T2DM development, possibly by influencing mtDNAnum.

IntroductionThis study examines the role of nutritional status during exercise training in patients with type 2 diabetes mellitus by investigating the effect of endurance-type exercise training in the fasted versus the fed state on clinical outcome measures, glycemic control, and skeletal muscle characteristics in male type 2 diabetes patients. MethodsTwenty-five male patients (glycated hemoglobin (HbA1(c)), 57 +/- 3 mmol center dot mol(-1) (7.4% +/- 0.3%)) participated in a randomized 12-wk supervised endurance-type exercise intervention, with exercise being performed in an overnight-fasted state (n = 13) or after consuming breakfast (n = 12). Patients were evaluated for glycemic control, blood lipid profiles, body composition and physical fitness, and skeletal muscle gene expression. ResultsExercise training was well tolerated without any incident of hypoglycemia. Exercise training significantly decreased whole-body fat mass (-1.6 kg) and increased high-density lipoprotein concentrations (+2 mg center dot dL(-1)), physical fitness (+1.7 mL center dot min(-1)center dot kg(-1)), and fat oxidation during exercise in both groups (P-TIME 0.05). HbA1(c) concentrations significantly decreased after exercise training (P-TIME Endurance-type exercise training in the fasted or fed state do not differ in their efficacy to reduce fat mass, increase fat oxidation capacity, and increase cardiorespiratory fitness and high-density lipoprotein concentrations or their risk of hypoglycemia in male patients with type 2 diabetes. HbA1(c) seems to be improved more with exercise performed in the postprandial compared with the postabsorptive state.

Muscle anabolic resistance to dietary protein is associated with obesity and insulin resistance. However, the contribution of excess consumption of fat to anabolic resistance is not well studied. The aim of these studies was to test the hypothesis that acute and short-term dietary fat overload will impair the skeletal muscle protein synthetic response to dietary protein ingestion. Eight overweight/obese men [46.4 ± 1.4 yr, body mass index (BMI) 32.3 ± 5.4 kg/m2] participated in the acute feeding study, which consisted of two randomized crossover trials. On each occasion, subjects ingested an oral meal (with and without fat emulsion), 4 h before the coingestion of milk protein, intrinsically labeled with [1-13C]phenylalanine, and dextrose. Nine overweight/obese men (44.0 ± 1.7 yr, BMI 30.1 ± 1.1 kg/m2) participated in the chronic study, which consisted of a baseline, 1-wk isocaloric diet, followed by a 2-wk high-fat diet (+25% energy excess). Acutely, incorporation of dietary amino acids into the skeletal muscle was twofold higher ( P < 0.05) in the lipid trial compared with control. There was no effect of prior lipid ingestion on indices of insulin sensitivity (muscle glucose uptake, pyruvate dehydrogenase complex activity, and Akt phosphorylation) in response to the protein/dextrose drink. Fat overfeeding had no effect on muscle protein synthesis or glucose disposal in response to whey protein ingestion, despite increased muscle diacylglycerol C16:0 ( P = 0.06) and ceramide C16:0 ( P < 0.01) levels. Neither acute nor short-term dietary fat overload has a detrimental effect on the skeletal muscle protein synthetic response to dietary protein ingestion in overweight/obese men, suggesting that dietary-induced accumulation of intramuscular lipids per se is not associated with anabolic resistance.

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

To determine the effects of dietary sugar or carbohydrate restriction on physical activity energy expenditure, energy intake, and physiological outcomes across 24 h.In a randomized, open-label crossover design, twenty-five healthy men (n = 10) and women (n = 15) consumed three diets over a 24-h period: moderate carbohydrate and sugar content (MODSUG = 50% carbohydrate [20% sugars], 15% protein, 35% fat); low sugar content (LOWSUG = 50% carbohydrate [ 5% sugars], 15% protein, 35% fat); and low carbohydrate content (LOWCHO = 8% carbohydrate [ 5% sugars], 15% protein, 77% fat). Postprandial metabolic responses to a prescribed breakfast (20% EI) were monitored under laboratory conditions before an ad libitum test lunch, with subsequent diet and physical activity monitoring under free-living conditions until blood sample collection the following morning.The MODSUG, LOWSUG and LOWCHO diets resulted in similar mean [95%CI] rates of both physical activity energy expenditure (771 [624, 919] vs. 677 [565, 789] vs. 802 [614, 991] kcal·dWhen energy density is controlled for, restricting either sugar or total dietary carbohydrate does not modulate physical activity level or energy intake over a 24-h period (~ 19-h free-living) despite substantial metabolic changes.NCT03509610, https://clinicaltrials.gov/show/NCT03509610.

PURPOSE: This study aimed to assess the prevalence of low bone mineral density (BMD) in male and female elite cyclists at different stages of a professional cycling career and to identify potential risk factors of low BMD. METHODS: In this cross-sectional study, 93 male and female early career, advanced career, and postcareer elite cyclists completed dual-energy x-ray absorptiometry at the hip, femoral neck, lumbar spine, and total body; blood sampling; assessment of training history and injuries; and the bone-specific physical activity questionnaire. Backward stepwise multiple regression analyses were conducted to explore associations between BMD and its potential predictors in early and advanced career (i.e., active career) cyclists. RESULTS: With a mean Z -score of -0.3 ± 0.8, -1.5 ± 1.0, and -1.0 ± 0.9, low BMD ( Z -score < -1) at the lumbar spine was present in 27%, 64%, and 50% of the early, advanced, and postcareer elite male cyclists, respectively. Lumbar spine Z -scores of -0.9 ± 1.0, -1.0 ± 1.0, and0.2 ± 1.4 in early, advanced, and postcareer elite female cyclists, respectively, indicated low BMD in 45%, 45%, and 20% of these female subpopulations. Regression analyses identified body mass index, fracture incidence, bone-specific physical activity, and triiodothyronine as the main factors associated with BMD. CONCLUSIONS: Low BMD is highly prevalent in elite cyclists, especially in early career females and advanced career males and females. These low BMD values may not fully recover after the professional cycling career, given the substantial prevalence of low BMD in retired elite cyclists. Exploratory analyses indicated that low BMD is associated with low body mass index, fracture incidence, lack of bone-specific physical activity, and low energy availability in active career elite cyclists.

Background: Handheld dynamometry (HHD) is a practical alternative to traditional testing of lower extremity strength. However, its reliability and validity across different populations and settings are not clear. Hypothesis: We hypothesize that HHD is a valid and reliable device to assess lower extremity strength in a population of older adults. Study Design: Cross-sectional/cohort. Level of Evidence: Level 3. Methods: This study included 258 older adults (≥65 years). Isometric knee extension and flexion force were measured by 1 examiner, using an HHD (n = 222), including 3 repetitions to calculate within-day intrarater reliability. These measurements were repeated by the examiner in a subgroup (n = 23) to analyze intrarater reliability over a test-retest period of on average 8 weeks. In addition, HHD force measures were performed by a second examiner (n = 29) to analyze interrater reliability. In another subgroup (n = 77), isometric knee extension and flexion torque were measured by 1 examiner using both the HHD and Biodex System 4 to assess relative validity. Results: HHD and Biodex measurements were highly correlated and showed excellent concurrent validity. HHD systematically overestimated torque as compared with Biodex by 8 N·m on average. Same-day intrarater intraclass correlation coefficients (ICCs) ranged from 0.97 to 0.98. Interrater reliability ICCs ranged from 0.83 to 0.95. Conclusion: HHD represents a reliable and valid alternative to Biodex to rank individuals on leg strength, or to assess within-person changes in leg strength over time, because of the high validity and reliability. The HHD is less suited for absolute strength assessment because of significant systematic overestimations. Clinical Relevance: Clinicians are encouraged to use HHD to rank older adults on leg strength, or to assess within-person changes in leg strength over time, but not to compare readings with cut-offs or normative values.

Addressing skeletal muscle mass loss is an important focus in oncology research to improve clinical outcomes, including cancer treatment tolerability and survival. Exercise is likely a necessary component of muscle-mass-preserving interventions for people with cancer. However, randomized controlled trials with exercise that include people with cancer with increased susceptibility to more rapid and severe muscle mass loss are limited. The aim of the current review is to highlight features of cancer-related skeletal muscle mass loss, discuss the impact in patients most at risk, and describe the possible role of exercise as a management strategy. We present current gaps within the exercise oncology literature and offer several recommendations for future studies to support research translation, including (1) utilizing accurate and reliable body composition techniques to assess changes in skeletal muscle mass, (2) incorporating comprehensive assessments of patient health status to allow personalized exercise prescription, (3) coupling exercise with robust nutritional recommendations to maximize the impact on skeletal muscle outcomes, and (4) considering key exercise intervention features that may improve exercise efficacy and adherence. Ultimately, the driving forces behind skeletal muscle mass loss are complex and may impede exercise tolerability and efficacy. Our recommendations are intended to foster the design of high-quality patient-centred research studies to determine whether exercise can counteract muscle mass loss in people with cancer and, as such, improve knowledge on this topic.

BACKGROUND: Magnesium plays a key role in bone health and may, therefore, represent an interesting nutrient for the prevention of bone loss and osteoporosis. The aim of this systematic review and meta-analysis was to investigate the impact of magnesium intake from any source on bone mineral density (BMD), bone mineral content (BMC), bone turnover markers, and fracture risk in older adults. METHODS: A systematic search was conducted using Embase, Medline Ovid and Cochrane Central from database inception to October 2020. All studies that related magnesium intake with bone health outcomes among adults aged ≥60 years were included. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias assessments. Authors were contacted for missing data. RESULTS: Once 787 records were screened, six cohort studies, one case-control study and five cross-sectional studies were included. Qualitative evaluation demonstrated a positive trend between higher magnesium intake and higher hip and femoral neck BMD. Meta-analysis of four studies showed a significant positive association between magnesium intake and hip BMD (pooled beta: 0.03, 95% CI: 0.01-0.06, p < 0.05). CONCLUSIONS: This systematic review indicates that a higher magnesium intake may support an increase in hip and femoral neck BMD. Due to limited research no associations with BMD at other sites or fractures were found. There is a need for properly designed cohort studies to determine the association between magnesium intake and bone health in older adults. Next, large and long-term randomized controlled trials in older adults are needed to determine whether an increase in magnesium (supplementation) intake can improve bone health. The combination of several bone nutrients (calcium, vitamin D, protein, magnesium and potentially more) may be needed for the most optimal effect on bone health and to delay or prevent the development of osteoporosis.