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Background Aging appears to attenuate the response of skeletal muscle protein synthesis (MPS) to anabolic stimuli such as protein ingestion (and the ensuing hyperaminoacidemia) and resistance exercise (RE). Objectives The purpose of this study was to determine the effects of protein quality on feeding- and feeding plus RE–induced increases of acute and longer-term MPS after ingestion of whey protein (WP) and collagen protein (CP). Methods In a double-blind parallel-group design, 22 healthy older women (mean ± SD age: 69 ± 3 y, n  = 11/group) were randomly assigned to consume a 30-g supplement of either WP or CP twice daily for 6 d. Participants performed unilateral RE twice during the 6-d period to determine the acute (via [13C6]-phenylalanine infusion) and longer-term (ingestion of deuterated water) MPS responses, the primary outcome measures. Results Acutely, WP increased MPS by a mean ± SD 0.017 ± 0.008%/h in the feeding-only leg (Rest) and 0.032 ± 0.012%/h in the feeding plus exercise leg (Exercise) (both P  < 0.01), whereas CP increased MPS only in Exercise (0.012 ± 0.013%/h) (P  < 0.01) and MPS was greater in WP than CP in both the Rest and Exercise legs (P  = 0.02). Longer-term MPS increased by 0.063 ± 0.059%/d in Rest and 0.173 ± 0.104%/d in Exercise (P  < 0.0001) with WP; however, MPS was not significantly elevated above baseline in Rest (0.011 ± 0.042%/d) or Exercise (0.020 ± 0.034%/d) with CP. Longer-term MPS was greater in WP than in CP in both Rest and Exercise (P  < 0.001). Conclusions Supplementation with WP elicited greater increases in both acute and longer-term MPS than CP supplementation, which is suggestive that WP is a more effective supplement to support skeletal muscle retention in older women than CP. This trial was registered at clinicaltrials.gov as NCT03281434. [ABSTRACT FROM AUTHOR]

Background: In older persons, muscle loss is accelerated during physical inactivity and hypoenergetic states, both of which are features of hospitalization. Protein supplementation may represent a strategy to offset the loss of muscle during inactivity, and enhance recovery on resumption of activity. Objective: We aimed to determine if protein supplementation, with proteins of substantially different quality, would alleviate the loss of lean mass by augmenting muscle protein synthesis (MPS) while inactive during a hypoenergetic state. Design: Participants (16 men, mean ± SD age: 69 ± 3 y; 15 women, mean ± SD age: 68 ± 4 y) consumed a diet containing 1.6 g protein · kg-1 · d-1, with 55% ± 9% of protein from foods and 45% ± 9% from supplements, namely, whey protein (WP) or collagen peptides (CP): 30 g each, consumed 2 times/d. Participants were in energy balance (EB) for 1 wk, then began a period of energy restriction (ER; -500 kcal/d) for 1 wk, followed by ER with step reduction (ER+SR; <750 steps/d) for 2 wk, before a return to habitual activity in recovery (RC) for 1 wk. Results: There were significant reductions in leg lean mass (LLM) from EB to ER, and from ER to ER + SR in both groups (P < 0.001) with no differences between WP and CP or when comparing the change from phase to phase. During RC, LLM increased from ER + SR, but in the WP group only. Rates of integrated muscle protein synthesis decreased during ER and ER + SR in both groups (P < 0.01), but increased during RC only in the WP group (P = 0.05). Conclusions: Protein supplementation did not confer a benefit in protecting LLM, but only supplemental WP augmented LLM and muscle protein synthesis during recovery from inactivity and a hypoenergetic state. This trial was registered at clinicaltrials.gov as NCT03285737. [ABSTRACT FROM AUTHOR]

Background: Older adults show a blunted muscle protein synthesis (MPS) response to postprandial hyperaminoacidemia relative to younger adults. Evidence suggests that this anabolic resistance can be overcome by consuming greater quantities of leucine.Objective: The purpose of this trial was to determine whether the addition of leucine to a smaller dose (10 g) of milk proteins would, when compared with a larger dose (25 g) of whey protein isolate (WPI), result in similar increases in acute (hourly) and integrated (daily) myofibrillar protein synthesis (myoPS).Methods: Healthy older (mean ± SD age: 69 ± 1 y) women (n = 11/group) were randomly assigned with the use of a single-blind, parallel-group design to twice-daily consumption of either WPI [25 g WPI (3 g l-leucine)] or leucine (LEU; 10 g milk protein with 3 g total l-leucine) for 6 d. Participants performed unilateral resistance exercise to allow assessment of the impact of the supplement alone and with resistance exercise. We determined acute (13C6-phenylanine) and integrated [using deuterated water (D2O)] rates of myoPS in the fasting (acute), basal (integrated), nonexercised, and exercised states.Results: Acute myoPS increased in both legs in response to LEU (fed: 45%; fed+exercise: 71%; P < 0.001) and WPI (fed: 29%; fed+exercise: 47%; P < 0.001) compared with fasting; the increase was greater with LEU than with WPI in the exercised leg (46%; P = 0.04) but not in the rested leg (P = 0.07). The acute myoPS response was greater in the exercised leg than in the rested leg for both WPI (63%) and LEU (58%) (P < 0.001). Integrated myoPS increased with WPI and LEU in the exercised leg (both 9%; P < 0.001) during supplementation, and with WPI (3%; P = 0.02) but not LEU (2%, P = 0.1) in the rested leg compared with the basal state.Conclusions: A lower-protein (10 compared with 25 g/dose), leucine-matched beverage induced similar increases in acute and integrated myoPS in healthy older women. Lower-protein supplements with added leucine may represent an advantageous approach in older adults to maintain skeletal muscle anabolic sensitivity and attenuate muscle loss; however, further work is needed using longer-term interventions to substantiate these findings. This trial was registered at www.clinicaltrials.gov as NCT02282566. [ABSTRACT FROM AUTHOR]

Background: Older women may not be consuming enough protein to maintain muscle mass. Augmentation of protein intake with leucine may enhance the muscle protein synthetic response in older women to aid in maintaining muscle mass. Objective: We measured the acute (hourly) and integrated (daily) myofibrillar protein synthesis (myoPS) response to consumption of a high-quality mixed protein beverage compared with an isonitrogenous protein beverage with added leucine. Design: In a parallel design, free-living, healthy older women (aged 65-75 y, n = 11/group) consumed a fixed, weight-maintaining diet with protein at 1.0 g · kg-1 · d-1 and were randomly assigned to twice-daily consumption of either 15 g milk protein beverage containing 4.2 g leucine (LEU) or 15 g mixed protein (milk and soy) beverage containing 1.3 g leucine (CON). Unilateral leg resistance exercise allowed a determination of acute ([13C6]-phenylalanine infusion, hourly rate) and integrated (deuterated water ingestion, daily rate) exercised and rested myoPS responses. Results: Acute myoPS increased in response to feeding in the rested (CON: 13% ± 4%; LEU: 53% ± 5%) and exercised (CON: 30% ± 4%; LEU: 87%±7%) leg in both groups, but the increasewas greater in LEU (P < 0.001). Integrated myoPS increased during the supplementation period in both legs (rested: 9% ±1%; exercised: 17% ± 2%; P < 0.001) in LEU, but in the exercised leg only (7% ± 2%; P < 0.001) in CON. Conclusions: A 15-g protein-containing beverage with ~4 g leucine induced greater increases in acute and integrated myoPS than did an isonitrogenous, isoenergetic mixed-protein beverage. Declines in muscle mass in older women may be attenuated with habitual twicedaily consumption of a protein beverage providing 15 g protein and higher (4.2 g/serving) amounts of leucine. This trial was registered at clinicaltrials.gov as NCT02282566. [ABSTRACT FROM AUTHOR]

Background: Leucine co-ingestion with lower-protein (LP)-containing meals may overcome the blunted muscle protein synthetic response to food intake in the elderly but may be effective only in individuals who consume LP diets. Objective: We examined the impact of leucine co-ingestion with mixed macronutrient meals on integrated 3-d rates of myofibrillar protein synthesis (MyoPS) in free-living older men who consumed higher protein (HP) (1.2 g ⋅ kg-1 ⋅ d-1) or LP (0.8 g ⋅ kg-1 ⋅ d-1) in rested and resistance exercise (REX) conditions. Design: In a crossover design, 20 healthy older men [aged 65-85 y] were randomly assigned to receive LP or HP diets while ingesting a placebo (days 0-2) and Leu supplement (5 g leucine/meal; days 3-5) with their 3 main daily meals. A bout of unilateral REX was performed during the placebo and Leu treatments. Ingested ²H2O and skeletal muscle biopsies were used to measure the 3-d integrated rate of MyoPS during the placebo and Leu treatments in the rested and REX legs. Results: Leucinemia was higher with Leu treatment than with placebo treatment (P < 0.001). MyoPS was similar in LP and HP during both treatments (P = 0.39) but was higher with Leu treatment than with placebo treatment in the rested (pooled mean ± SD: Leu, 1.57% ± 0.11%/d; placebo, 1.48% ± 0.08%/d; main effect of treatment: P < 0.001) and REX (pooled mean: Leu, 1.87% ± 0.09%/d; placebo, 1.71 ± 0.10%/d; main effect of treatment: P < 0.001) legs. Conclusions: Leu co-ingestion with daily meals enhances integrated MyoPS in free-living older men in rested and REX conditions and is equally effective in older men who consume daily protein intakes greater than or equal to the RDA. This trial was registered at clinicaltrials.gov as NCT02371278. [ABSTRACT FROM AUTHOR]

Background: Higher dietary energy as protein during weight loss results in a greater loss of fat mass and retention of muscle mass; however, the impact of protein quality on the rates of myofibrillar protein synthesis (MPS) and lipolysis, processes that are important in the maintenance of muscle and loss of fat, respectively, are unknown. Objective: We aimed to determine how the consumption of different sources of proteins (soy or whey) during a controlled short-term (14-d) hypoenergetic diet affected MPS and lipolysis. Methods: Men (n = 19) and women (n = 21) (age 35-65 y; body mass index 28-50 kg/m²) completed a 14-d controlled hypoenergetic diet (2750 kcal/d). Participants were randomly assigned, double blind, to receive twice-daily supplements of isolated whey (27 g/supplement) or soy (26g/supplement), providing a total protein intake of 1.3 ± 0.1 g/(kg ⋅ d), or isoenergetic carbohydrate (25 g maltodextrin/supplement) resulting in a total protein intake of 0.76 0.1 g/(kg ⋅ d). Before and after the dietary intervention, primed continuous infusions of L-[ring-13C6] phenylalanine and [²H5]-glycerol were used to measure postabsorptive and postprandial rates of MPS and lipolysis. Results: Preintervention, MPS was stimulated more (P < 0.05) with ingestion of whey than with soy or carbohydrate. Postintervention, postabsorptive MPS decreased similarly in all groups (all P < 0.05). Postprandial MPS was reduced by 9 ± 1% in the whey group, which was less (P < 0.05) than the reduction in soy and carbohydrate groups (28 ± 5% and 31 ± 5%, respectively; both P < 0.05) after the intervention. Lipolysis was suppressed during the postprandial period (P < 0.05), but more so with ingestion of carbohydrate (P < 0.05) than soy or whey. Conclusion: We conclude that whey protein supplementation attenuated the decline in postprandial rates of MPS after weight loss, which may be of importance in the preservation of lean mass during longer-term weight loss interventions. This trial was registered at clinicaltrials.gov as NCT01530646. [ABSTRACT FROM AUTHOR]

Background: Leucine is a key amino acid involved in the regulation of skeletal muscle protein synthesis. Objective: We assessed the effect of the supplementation of a lower-protein mixed macronutrient beverage with varying doses of leucine or a mixture of branched chain amino acids (BCAAs) on myofibrillar protein synthesis (MPS) at rest and after exercise. Design: In a parallel group design, 40 men (21 ± 1 y) completed unilateral knee-extensor resistance exercise before the ingestion of 25 g whey protein (W25) (3.0 g leucine), 6.25 g whey protein (W6) (0.75g leucine), 6.25 g whey protein supplemented with leucine to 3.0 g total leucine (W6+Low-Leu), 6.25 g whey protein supplemented with leucine to 5.0 g total leucine (W6+High-Leu), or 6.25 g whey protein supplemented with leucine, isoleucine, and valine to 5.0 g total leucine. A primed continuous infusion of L-[ring-13 C6] phenylalanine with serial muscle biopsies was used to measure MPS under baseline fasted and postprandial conditions in both a rested (response to feeding) and exercised (response to combined feeding and resistance exercise) leg. Results: The area under the blood leucine curve was greatest for the W6+High-Leu group compared with the W6 and W6+Low-Leu groups (P, 0.001). In the postprandial period, rates of MPS were increased above baseline over 0-1.5 h in all treatments. Over 1.5-4.5 h, MPS remained increased above baseline after all treatments but was greatest after W25 (~267%) and W6+High-Leu (~220%) treatments (P=0.002). Conclusions: A low-protein (6.25 g) mixed macronutrient beverage can be as effective as a high-protein dose (25 g) at stimulating increased MPS rates when supplemented with a high (5.0 g total leucine) amount of leucine. These results have important implications for formulations of protein beverages designed to enhance muscle anabolism. This trial was registered at clinicaltrials.gov as NCT 1530646. [ABSTRACT FROM AUTHOR]

Background: Ingestion of whey or casein yields divergent patterns of aminoacidemia that influence whole-body and skeletal muscle myofibrillar protein synthesis (MPS) after exercise. Direct comparisons of the effects of contrasting absorption rates exhibited by these proteins are confounded by their differing amino acid contents. Objective: Our objective was to determine the effect of divergent aminoacidemia by manipulating ingestion patterns of whey protein alone on MPS and anabolic signaling after resistance exercise. Design: In separate trials, 8 healthy men consumed whey protein either as a single bolus (BOLUS; 25-g dose) or as repeated, small, "pulsed" drinks (PULSE; ten 2.5-g drinks every 20 min) to mimic a more slowly digested protein. MPS and phosphorylation of signaling proteins involved in protein synthesis were measured at rest and after resistance exercise. Results: BOLUS increased blood essential amino acid (EAA) concentrations above those of PULSE (162% compared with 53%, P < 0.001) 60 min after exercise, whereas PULSE resulted in a smaller but sustained increase in aminoacidemia that remained elevated above BOLUS amounts later (180-220 min after exercise, P < 0.05). Despite an identical net area under the EAA curve, MPS was elevated to a greater extent after BOLUS than after PULSE early (1-3 h: 95% compared with 42%) and later (3-5 h: 193% compared with 121%) (both P < 0.05). There were greater changes in the phosphorylation of the Akt-mammalian target of rapamycin pathway after BOLUS than after PULSE. Conclusions: Rapid aminoacidemia in the postexercise period enhances MPS and anabolic signaling to a greater extent than an identical amount of protein fed in small pulses that mimic a more slowly digested protein. A pronounced peak aminoacidemia after exercise enhances protein synthesis. [ABSTRACT FROM AUTHOR]

We aimed to determine whether an exercise-mediated enhancement of muscle protein synthesis to feeding persisted 24 h after resistance exercise. We also determined the impact of different exercise intensities (90% or 30% maximal strength) or contraction volume (work-matched or to failure) on the response at 24 h of recovery Fifteen men (21 ± 1 y, BMI 24.1 ± 0.8 kg . m2( received a primed, constant infusion of L-Lr,ng-13C6]phenylalanine to measure muscle protein synthesis after protein feeding at rest (FED; 15 g whey protein) and 24 h after resistance exercise (EX-FED). Participants performed unilateral leg exercises: 1) 4 sets at 90% of maximal strength to failure )90FAIL); 2) 30% work-matched to 9OFAIL (3OWM); or 3) 30% to failure )30FAIL). Regardless of condition, rates of mixed muscle protein and sarcoplasmic prot4n synthesis were similarly stimulated at FED and EX-FED. In contrast, protein ingestion stimulated rates of myofibrillar protein synthesis above fasting rates by 0.016 ± 0.002%/h and the response was enhanced 24 h after resistance exercise, but only in the 9OFAIL and 3OFAIL conditions, by 0.038 ± 0.012 and 0.041 ± 0.010, respectively. Phoskhorylation of protein kinase B on Ser473 was greater than FED at EX-FED only in 9OFA(L, whereas phosphorylation of mbmmalian target of rapamycin on Ser2448 was significantly increased at EX-FED above FED only in the 3OFAIL condkion. Our results suggest that resistance exercise performed until failure confers a sensitizing effect on human skeletaI muscle for at least 24 h that is specific to the myofibrillar protein fraction. [ABSTRACT FROM AUTHOR]

Abstract: Baker SK. Isolated spinal accessory mononeuropathy associated with neurogenic muscle hypertrophy: restricted neuralgic amyotrophy or stretch-palsy? A case report. A 55-year-old man developed transient bi-brachial paresthesias followed by severe pain over his left shoulder ridge and periscapular region within 8 hours of rigorous hand-over-hand hoisting of a 33.8-kg (75-lb) object. He experienced weakness in shoulder abduction followed several weeks later by focal hypertrophy of the left trapezius. Electrophysiologic studies showed significant spontaneous motor activity in the form of denervation potentials, fasciculations, and complex repetitive discharges. The 2 major diagnostic considerations were restricted neuralgic amyotrophy versus stretch palsy of the spinal accessory nerve. The clinical similarities and differences between restricted forms of neuralgic amyotrophy and stretch palsies are discussed. [Copyright &y& Elsevier]

Loading of skeletal muscle changes the tissue phenotype reflecting altered metabolic and functional demands. In humans, heterogeneous adaptation to loading complicates the identification of the underpinning molecular regulators. A within-person differential loading and analysis strategy reduces heterogeneity for changes in muscle mass by ∼40% and uses a genome-wide transcriptome method that models each mRNA from coding exons and 3′ and 5′ untranslated regions (UTRs). Our strategy detects ∼3–4 times more regulated genes than similarly sized studies, including substantial UTR-selective regulation undetected by other methods. We discover a core of 141 genes correlated to muscle growth, which we validate from newly analyzed independent samples (n = 100). Further validating these identified genes via RNAi in primary muscle cells, we demonstrate that members of the core genes were regulators of protein synthesis. Using proteome-constrained networks and pathway analysis reveals notable relationships with the molecular characteristics of human muscle aging and insulin sensitivity, as well as potential drug therapies. • Muscle loading and unloading regulate the untranslated regions of mRNA • Regulated genes form functional networks central to muscle plasticity • 141 genes correlate with muscle growth in 3 independent validation cohorts • Several growth-correlated network genes directly regulate myocyte protein synthesis Stokes et al. identify and validate a core set of genes that are regulated in proportion to the magnitude of muscle protein turnover with loading. Several of these genes correlate with muscle growth only at their 3′ or 5′ untranslated region, and a subset directly influences protein synthesis in vitro. [ABSTRACT FROM AUTHOR]

Abstract: The National Lipid Association's Muscle Safety Expert Panel was charged with the duty of examining the definitions for statin-associated muscle adverse events, development of a clinical index to assess myalgia, and the use of diagnostic neuromuscular studies to investigate muscle adverse events. We provide guidance as to when a patient should be considered for referral to neuromuscular specialists and indications for the performance of a skeletal muscle biopsy. Based on this review of evidence, we developed an algorithm for the evaluation and treatment of patients who may be intolerant to statins as the result of adverse muscle events. The panel was composed of clinical cardiologists, clinical lipidologists, an exercise physiologist, and a neuromuscular specialist. [Copyright &y& Elsevier]

• CMT2 is an autosomal dominant highly variable peripheral neuropathy. • A novel VCP mutation is identified in this CMT2 family with phenotypic variability. • This novel phenotype reflects a combined ALS-like and CMT2-like phenomena. Charcot-Marie-Tooth (CMT) disease, a hereditary motor and sensory neuropathy, has subtypes with varied inheritance patterns and phenotypic presentation. Subtypes additionally vary by genetic variants in a number of genes. Pathogenic variants in the VCP gene have newly been associated with CMT type 2. We present a family with CMT type 2 with a novel heterozygous VCP variant and phenotypic variability between the proband, his brother, and father. [ABSTRACT FROM AUTHOR]