Muscle Protein Synthesis Rates Research Articles

Postexercise cooling impairs muscle protein synthesis rates in recreational athletes.

Key points Protein ingestion and cooling are strategies employed by athletes to improve postexercise recovery and, as such, to facilitate muscle conditioning. However, whether cooling affects postprandial protein handling and subsequent muscle protein synthesis rates during recovery from exercise has not been assessed.We investigated the effect of postexercise cooling on the incorporation of dietary protein‐derived amino acids into muscle protein and acute postprandial (hourly) as well as prolonged (daily) myofibrillar protein synthesis rates during recovery from resistance‐type exercise over 2 weeks.Cold‐water immersion during recovery from resistance‐type exercise lowers the capacity of the muscle to take up and/or direct dietary protein‐derived amino acids towards de novo myofibrillar protein accretion. In addition, cold‐water immersion during recovery from resistance‐type exercise lowers myofibrillar protein synthesis rates during prolonged resistance‐type exercise training.Individuals aiming to improve skeletal muscle conditioning should reconsider applying cooling as a part of their postexercise recovery strategy. We measured the impact of postexercise cooling on acute postprandial (hourly) as well as prolonged (daily) myofibrillar protein synthesis rates during adaptation to resistance‐type exercise over 2 weeks. Twelve healthy males (aged 21 ± 2 years) performed a single resistance‐type exercise session followed by water immersion of both legs for 20 min. One leg was immersed in cold water (8°C: CWI), whereas the other leg was immersed in thermoneutral water (30°C: CON). After water immersion, a beverage was ingested containing 20 g of intrinsically (l‐[1‐13C]‐phenylalanine and l‐[1‐13C]‐leucine) labelled 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. In addition, deuterated water (2H2O) was applied with the collection of saliva, blood and muscle biopsies over 2 weeks to assess the effects of postexercise cooling with protein intake on myofibrillar protein synthesis rates during more prolonged resistance‐type exercise training (thereby reflecting short‐term training adaptation). Incorporation of dietary protein‐derived l‐[1‐13C]‐phenylalanine into myofibrillar protein was significantly lower in CWI compared to CON (0.016 ± 0.006 vs. 0.021 ± 0.007 MPE; P = 0.016). Postexercise myofibrillar protein synthesis rates were lower in CWI compared to CON based upon l‐[1‐13C]‐leucine (0.058 ± 0.011 vs. 0.072 ± 0.017% h−1, respectively; P = 0.024) and l‐[ring‐2H5]‐phenylalanine (0.042 ± 0.009 vs. 0.053 ± 0.013% h−1, respectively; P = 0.025). Daily myofibrillar protein synthesis rates assessed over 2 weeks were significantly lower in CWI compared to CON (1.48 ± 0.17 vs. 1.67 ± 0.36% day−1, respectively; P = 0.042). Cold‐water immersion during recovery from resistance‐type exercise reduces myofibrillar protein synthesis rates and, as such, probably impairs muscle conditioning.

Effects of fish protein hydrolysate ingestion on postexercise aminoacidemia compared with whey protein hydrolysate in young individuals.

The aminoacidemia resulting from food protein digestion in response to exercise plays an underlying role in the rate of muscle protein synthesis. Whey protein hydrolysate (WPH) has been demonstrated to cause more pronounced postexercise aminoacidemia compared with casein and soy. Although fish protein has been demonstrated to be a great source of amino acids, there is no data available providing information about the postexercise aminoacidemia after fish protein hydrolysate (FPH) intake. The present study investigated the characteristic patterns of postexercise aminoacidemia after WPH and FPH intake in nine physically active subjects (six males and three females). In a crossover, double-blind, and randomized design, all participants received oral doses of either 0.25 g/kg of FPH or WPH or placebo (PLA) immediately after a resistance exercise bout. Blood samples were taken before and at 30, 60, 90, 120 and 180min after supplementation. There was a significant increase in plasma total amino acids (TAA), essential amino acids (EAA), branched-chain amino acids (BCAA), and leucine concentrations at 30 and 60min after FPH supplementation, and at 30, 60, 90, and 120min after WPH as compared to PLA. No significant differences were observed in plasma TAA, EAA, BCAA, and leucine concentrations between FPH and WPH at any time point, and there were no significant difference observed in the area under the curve for TAA, EAA, BCAA, and leucine between FPH and WPH. In conclusion, both FPH and WPH showed a rapid and pronounced postexercise aminoacidemia. FPH presented itself to be an alternative food source of rapidly digested proteins to be used after resistance exercise. PRACTICAL APPLICATION: Fish protein hydrolysate (FPH) demonstrated a rapid and pronounced postexercise aminoacidemia. Whey protein hydrolysate showed similar effects. FPH is presented as an alternative food source of rapidly digested proteins to be consumed by the population, especially physically active individuals.

356 Meal feeding compared with continuous feeding enhances insulin and amino acid signaling to translation initiation in skeletal muscle of pigs

Abstract Objectives: Meal feeding enhances skeletal muscle protein synthesis and lean growth more than continuous feeding in piglets. This enhanced muscle protein synthesis with meal feeding is associated with increased activation of mTORC1-dependent translation initiation. The mechanism underlying this response is unknown. We aimed to identify insulin and amino acid signaling components involved in the enhanced lean growth that results from meal feeding vs. continuous feeding in term-born pigs. Methods: Newborn piglets were fed for 21 d an equal amount of sow milk replacer (12.8 g protein and 155 kcal/(kg BW.d)) by gastrostomy tube either as intermittent bolus meals every 4 h (MEAL) or by continuous infusion (CON). After 21 d, gastrocnemius muscle was collected from CON, and before (MEAL-0) or 60 min after a meal (MEAL-60). Components of the insulin and amino acid signaling pathways up- and downstream of mTORC1 that regulate protein translation were measured. Results: Phosphorylation of AKT and TCS2 was greater in MEAL-60 than in MEAL-0 and CON (P < 0.05). The association of Sestrin2 with GATOR2 was similar in CON and MEAL-0 but was lower in MEAL-60 (P < 0.05). The abundances of RagA-mTOR, RagC-mTOR, and Rheb-mTOR, but not CASTOR1-GATOR2, complexes were higher in MEAL-60 than in CON and MEAL-0 (P < 0.05). The phosphorylation of S6K1 and 4EBP1 was higher in MEAL-60 than CON and MEAL-0 (P < 0.05). The abundances of Sestrin2, GATOR2, CASTOR1, RagA, RagC, and Rheb and the phosphorylation of eIF2alpha, eEF2, ERK1/2 and AMPK were unaffected by treatments. Conclusions: Our results demonstrate that the enhanced rate of skeletal muscle protein synthesis and lean growth with meal feeding compared with continuous feeding are due to the enhanced activation of both insulin and amino acid signaling pathways that result in the greater stimulation of translation initiation. Support: NIH HD085573, USDA CRIS 6250-51000-055, NIH HD072891, USDA NIFA 2013-67015-20438.

Effects of whey protein hydrolysate ingestion on post-exercise muscle protein synthesis compared with intact whey protein in rats

BackgroundIt is well known that ingestion of protein sources can stimulate muscle protein synthesis (MPS). The intake of whey protein is highly effective especially for accelerating MPS. Whey protein hydrolysate (WPH) can raise postprandial plasma concentration of amino acids, which impact stimulation of MPS more rapidly and highly than intact whey protein. However, it is unclear which is more effective for stimulating MPS, WPH or intact whey protein. The aim of the present study was to compare the effects of the WPH and whey protein on MPS in rats after exercise.MethodsRats were first subjected to a 2 h. swimming protocol. After this, in experiment 1, we evaluated time-dependent changes in the fractional synthetic rate (FSR) of the triceps muscle in Male Sprague-Dawley rats after ingestion of intact whey protein (30, 60, 90 or 120 min after ingestion). Then in experiment 2, at the time point that the results of Experiment 1 revealed postprandial FSR was highest (60 min after ingestion), we measured the FSR after ingestion of the WPH or whey protein at two different doses (0.5 or 2.0 g protein/kg body weight), or with deionized water (control), again after exercise. Plasma components and mammalian target of rapamycin (mTOR) signaling were also measured.ResultsIn experiment 1, postprandial FSR was highest 60 min after whey protein was administered. In experiment 2, the FSR 60 min after ingestion of the WPH was higher than that of whey protein (significant treatment main effect). Moreover, at a lower dose, only the WPH ingestion caused greater MPS and phosphorylated 4E-binding protein 1 (4E-BP1) levels compared with the control group.ConclusionThese results indicate that ingestion of the WPH was associated with greater post-exercise MPS compared with intact whey protein, especially at lower doses.

Ingestion of a Pre-bedtime Protein Containing Beverage Prevents Overnight Induced Negative Whole Body Protein Balance in Healthy Middle-Aged Men: A Randomized Trial

Age related muscle wasting leads to overall reductions of lean body mass, reduced muscle strength, and muscle function resulting in compromised quality of life. Utilizing novel nutritional strategies to attenuate such losses is of great importance in elderly individuals. We aimed to test if a complete dietary supplement containing 25 g of milk proteins and ingested in the evening before bed would improve protein metabolism in terms of whole body protein balance over a 10 h overnight period following ingestion of the test drink in healthy middle-aged male subjects. In addition we also assessed the rates of muscle protein synthesis during the second half of the night in order to see if previously reported extended amino acidemia during sleep results in increased rates of muscle protein synthesis. Seventeen healthy middle-aged male subjects (59.4 ± 3.2 year) consumed a dietary supplement drink at 21:00 containing either 25 g milk protein concentrate, 25 g maltodextrin, 7.75 g canola oil (treatment group), or an isocaloric protein void drink (placebo group). Muscle protein synthesis was assessed from a muscle biopsy following the continuous intravenous infusion of 13C-phenylalanine for 5 h (from 03:00 to 08:00). Whole body protein balance was greater in the treatment group (−0.13 ± 11.30 g prot/10 h) compared to placebo (−12.22 ± 6.91 g prot/10 h) (P ≤ 0.01). In contrast, no changes were observed on rates of muscle protein synthesis during the second half of the night. Ingestion of a dietary supplement containing 25 g of milk proteins significantly reduced the negative protein balance observed during the night. Therefore, pre-bedtime protein ingestion may attenuate overnight losses of lean tissue in healthy elderly men. Despite increases in aminoacidemia during the second part of the night, no changes were observed in the rates of muscle protein synthesis during this time.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02041143.

Time-dependent regulation of postprandial muscle protein synthesis rates after milk protein ingestion in young men.

The anabolic action of "fast" whey protein on the regulation of postprandial muscle protein synthesis has been established to be short-lived in healthy young adults. We assessed the time course of anabolic signaling activation and stimulation of myofibrillar protein synthesis rates (MPS) after ingestion of a food source that represents a more typical meal-induced pattern of aminoacidemia. Seven young men (age: 22 ± 1 y) underwent repeated blood and biopsy sampling during primed, continuous l-[ring-2H5]phenylalanine and l-[1-13C]leucine tracer infusions and ingested 38 g of l-[1-13C]phenylalanine- and l-[1-13C]leucine-labeled milk protein concentrate. A total of ∼27 ± 4 (∼10 g) and ∼31 ± 1% (∼12 g) of dietary protein-derived amino acids were released in circulation between 0 and 120 min and 120-300 min, respectively, of the postprandial period. l-[ring-2H5]phenylalanine-based MPS increased above basal (0.025 ± 0.008%/h) by ∼75% (0.043 ± 0.009%/h; P = 0.05) between 0 and 120 min and by ∼86% (0.046 ± 0.004%/h; P = 0.02) between 120 and 300 min, respectively. l-[1-13C]leucine-based MPS increased above basal (0.027 ± 0.002%/h) by ∼72% (0.051 ± 0.016%/h; P = 0.10) between 0 and 120 min and by ∼62% (0.047 ± 0.004%/h; P = 0.001) between 120 and 300 min, respectively. Myofibrillar protein-bound l-[1-13C]phenylalanine increased over time (P < 0.001) and equaled 0.004 ± 0.001, 0.008 ± 0.002, 0.017 ± 0.004, and 0.020 ± 0.003 mole percent excess at 60, 120, 180, and 300 min, respectively, of the postprandial period. Milk protein ingestion increased mTORC1 phosphorylation at 120, 180, and 300 min of the postprandial period (all P < 0.05). Our results show that ingestion of 38 g of milk protein results in sustained increases in MPS throughout a 5-h postprandial period in healthy young men.NEW & NOTEWORTHY The stimulation of muscle protein synthesis after whey protein ingestion is short-lived due to its transient systemic appearance of amino acids. Our study characterized the muscle anabolic response to a protein source that results in a more gradual release of amino acids into circulation. Our work demonstrates that a sustained increase in postprandial plasma amino acid availability after milk protein ingestion results in a prolonged stimulation of muscle protein synthesis rates in healthy young men.

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

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

Is N-Carbamoyl Putrescine, the Decarboxylation Derivative of Citrulline, a Regulator of Muscle Protein Metabolism in Rats?

N-carbamoyl putrescine (NCP), the decarboxylation derivative of citrulline, metabolically related to polyamines, may exert biological effects in mammals. The aim of this study was (i) to evaluate the nutritional properties of NCP in healthy rats and (ii) to determine the effect of NCP administration on muscle metabolism in malnourished old rats. The nutritional properties of NCP were first evaluated in 20 8-week-old male rats randomized to receive for two weeks a standard diet either alone (C group) or supplemented with NCP, 5 or 50 mg/kg/d. In a second study, 29 malnourished 18-month-old male rats were studied either before or after a 4-day refeeding with a standard diet either alone (REN group) or supplemented with NCP, 1 or 10 mg/kg/d. NCP had no effect on weight gain and body composition in either of the two studies. In healthy rats, muscle protein content was significantly increased in the soleus with NCP 5 mg/kg/d. A decrease in plasma glutamine and kidney spermine was observed at the 50 mg/kg/d dose; otherwise, no significant changes in plasma chemistry and tissue polyamines were observed. In malnutrition-induced sarcopenic old rats, refeeding with NCP 10 mg/kg/d was associated with higher tibialis weight and a trend for increased protein content in extensor digitorum longus (EDL). While the muscle protein synthesis rate was similar between groups, ribosomal protein S6 kinase was increased in tibialis and higher in the EDL in NCP-treated rats. The muscle RING-finger protein-1 expression was decreased in tibialis and urinary 3-methyl-histidine to creatinine ratio slightly lower with the supply of NCP. However, this initial period of refeeding was also associated with elevated fasted plasma triglycerides and glucose, significant in NCP groups, suggesting glucose intolerance and possibly insulin resistance. NCP was well-tolerated in healthy young-adults and in malnourished old rats. In healthy adults, NCP at 5 mg/kg/d induced a significant increase in protein content in the soleus, a type I fiber-rich muscle. In malnourished old rats, NCP supply during refeeding, may help to preserve lean mass by limiting protein breakdown; however, these effects may be limited in our model by a possible immediate refeeding-associated glucose intolerance.

The Phenylalanine Requirement of Elderly Men and Women Measured by Direct 13C Carbon Oxidation Method Is Similar to That of Young Adults

The phenylalanine requirement of the elderly is not known. Current recommendations are based on studies in young adults and are derived from a combined estimate of the total aromatic amino acids, phenylalanine, and tyrosine. The purpose of this study was to determine the dietary phenylalanine requirement of adults aged >65 y, using the direct amino acid oxidation method, by measuring the oxidation of l-[1-13C]phenylalanine to 13CO2 in response to graded phenylalanine intakes in the presence of excess tyrosine. Twelve subjects (6 men, 6 women), aged 73.8±6.7 y (mean±SD) and with a BMI (in kg/m2) of 26.4±4.8 and 25.2±4.4 for men and women, respectively, were randomized to phenylalanine intakes ranging from 7.20 to 40.0 mg .kg-1 .d-1 for a total of 66 studies. Study diets were isocaloric and isonitrogenous, providing protein and energy at 1.0 g .kg-1 .d-1 and 1.5 × resting energy expenditure (REE), respectively. Protein was provided as an amino acid mixture patterned after egg protein, with an excess of tyrosine and alanine to balance the nitrogen as phenylalanine intakes were varied. Two days prior to the study day, subjects were adapted to a milkshake diet providing protein at 1.0 g.kg-1 .d-1 and energy at 1.7 × REE. The mean phenylalanine requirement was determined using biphase linear regression analysis, which identified a breakpoint in the F13CO2 in response to graded phenylalanine intakes. The mean and upper 95% CIs (approximating the recommended dietary allowance) of phenylalanine requirements were estimated to be 9.03 and 15.9 mg.kg-1 .d-1, respectively. These results are similar to previously derived estimates of 9.1 and 13.6 mg.kg-1 .d-1 in young adult men and suggest that higher protein needs of the elderly to stimulate similar muscle protein synthesis rates as young adults are not driven by an increased requirement for phenylalanine. This trial was registered at clinicaltrials.gov as NCT02971059.

Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men.

BackgroundThe andropause is associated with declines in serum testosterone (T), loss of muscle mass (sarcopenia), and frailty. Two major interventions purported to offset sarcopenia are anabolic steroid therapies and resistance exercise training (RET). Nonetheless, the efficacy and physiological and molecular impacts of T therapy adjuvant to short‐term RET remain poorly defined.MethodsEighteen non‐hypogonadal healthy older men, 65–75 years, were assigned in a random double‐blinded fashion to receive, biweekly, either placebo (P, saline, n = 9) or T (Sustanon 250 mg, n = 9) injections over 6 week whole‐body RET (three sets of 8–10 repetitions at 80% one‐repetition maximum). Subjects underwent dual‐energy X‐ray absorptiometry, ultrasound of vastus lateralis (VL) muscle architecture, and knee extensor isometric muscle force tests; VL muscle biopsies were taken to quantify myogenic/anabolic gene expression, anabolic signalling, muscle protein synthesis (D2O), and breakdown (extrapolated).ResultsTestosterone adjuvant to RET augmented total fat‐free mass (P=0.007), legs fat‐free mass (P=0.02), and appendicular fat‐free mass (P=0.001) gains while decreasing total fat mass (P=0.02). Augmentations in VL muscle thickness, fascicle length, and quadriceps cross‐section area with RET occured to a greater extent in T (P < 0.05). Sum strength (P=0.0009) and maximal voluntary contract (e.g. knee extension at 70°) (P=0.002) increased significantly more in the T group. Mechanistically, both muscle protein synthesis rates (T: 2.13 ± 0.21%·day−1 vs. P: 1.34 ± 0.13%·day−1, P=0.0009) and absolute breakdown rates (T: 140.2 ± 15.8 g·day−1 vs. P: 90.2 ± 11.7 g·day−1, P=0.02) were elevated with T therapy, which led to higher net turnover and protein accretion in the T group (T: 8.3 ± 1.4 g·day−1 vs. P: 1.9 ± 1.2 g·day−1, P=0.004). Increases in ribosomal biogenesis (RNA:DNA ratio); mRNA expression relating to T metabolism (androgen receptor: 1.4‐fold; Srd5a1: 1.6‐fold; AKR1C3: 2.1‐fold; and HSD17β3: two‐fold); insulin‐like growth factor (IGF)‐1 signalling [IGF‐1Ea (3.5‐fold) and IGF‐1Ec (three‐fold)] and myogenic regulatory factors; and the activity of anabolic signalling (e.g. mTOR, AKT, and RPS6; P < 0.05) were all up‐regulated with T therapy. Only T up‐regulated mitochondrial citrate synthase activity (P=0.03) and transcription factor A (1.41 ± 0.2‐fold, P=0.0002), in addition to peroxisome proliferator‐activated receptor‐γ co‐activator 1‐α mRNA (1.19 ± 0.21‐fold, P=0.037).ConclusionsAdministration of T adjuvant to RET enhanced skeletal muscle mass and performance, while up‐regulating myogenic gene programming, myocellular translational efficiency and capacity, collectively resulting in higher protein turnover, and net protein accretion. T coupled with RET is an effective short‐term intervention to improve muscle mass/function in older non‐hypogonadal men.

Effect of citrulline on muscle protein turnover in an in vitro model of muscle catabolism.

Muscle net catabolism, as seen after severe trauma or sepsis or in postoperative situations, is mediated by hormones (e.g., cortisol) and proinflammatory cytokines (e.g., tumor necrosis factor alpha [TNF-α]). Specific amino acids may be able to limit this muscle mass loss. Citrulline (CIT) stimulates muscle protein synthesis in various situations, but little data exist on hypercatabolic situations and the effects on protein breakdown are unknown. Our aim was to assess the effect of CIT on protein turnover in an in vitro model of muscle hypercatabolism. Myotubes derived from C2C12 myoblasts were treated with 150 nM dexamethasone (DEX), 10 ng/mL TNF-α, or 0.006% ethanol (as control [CON]) for 24 h. Subsequently, myotubes were incubated with or without 5 mM CIT for 6 h. Muscle protein synthesis rate was evaluated by the surface sensing of translation method and by l-[3,5-3H]tyrosine (Tyr) incorporation. The muscle protein breakdown rate was evaluated from Tyr release into culture medium. CIT action was analyzed by non-parametric Kruskal-Wallis and Mann-Whitney tests. CIT treatment significantly increased protein synthesis rates compared with the DEX or TNF-α group (surface sensing of translation method; DEX + CIT versus DEX; P = 0.03 and TNF-α+CIT versus TNF-α; P = 0.05) and significantly decreased protein breakdown rate in the CON and DEX groups (CON + CIT versus CON; P = 0.05 and DEX + CIT versus DEX; P = 0.05). CIT treatment regulated muscle protein turnover in an in vitro model of muscle net catabolism. Exploring the underlying mechanisms would also be of interest.

Revisiting the roles of protein synthesis during skeletal muscle hypertrophy induced by exercise.

Protein synthesis is deemed the underpinning mechanism enhancing protein balance required for skeletal muscle hypertrophy in response to resistance exercise. The current model of skeletal muscle hypertrophy induced by resistance training states that the acute increase in the rates of protein synthesis after each bout of resistance exercise is the basis for muscle growth. Within this paradigm, each resistance exercise session would add a specific amount of muscle mass; therefore, muscle hypertrophy could be defined as the result of intermittent and short-lived increases in muscle protein synthesis rates following each resistance exercise session. Although a substantial amount of data has accumulated in the last decades regarding the acute changes in protein synthesis (or translational efficiency) following resistance exercise, considerable gaps on the mechanism of muscle growth still exist. Ribosome biogenesis and translational capacity have emerged as important mediators of skeletal muscle hypertrophy. Recent advances in the field have demonstrated that skeletal muscle hypertrophy is associated with markers of translational capacity and long-term changes in protein synthesis under resting conditions. This review will discuss the caveats of the current model of skeletal muscle hypertrophy induced by resistance training while proposing a working model that takes into consideration the novel data generated by independent laboratories utilizing different methodologies. It is argued, herein, that the role of protein synthesis in the current model of muscle hypertrophy warrants revisiting.

Maximizing Post-exercise Anabolism: The Case for Relative Protein Intakes.

Maximizing the post-exercise increase in muscle protein synthesis, especially of the contractile myofibrillar protein fraction, is essential to facilitate effective muscle remodeling, and enhance hypertrophic gains with resistance training. MPS is the primary regulated variable influencing muscle net balance with dietary amino acid ingestion representing the single most important nutritional variable enhancing post-exercise rates of muscle protein synthesis. Dose-response studies in average (i.e., ~80 kg) males have reported an absolute 20 g dose of high quality, rapidly digested protein maximizes mixed, and myofibrillar protein synthetic rates. However, it is unclear if these absolute protein intakes can be viewed in a “one size fits all” solution. Re-analysis of published literature in young adults suggests a relative single meal intake of ~0.31 g/kg of rapidly digested, high quality protein (i.e., whey) should be considered as a nutritional guideline for individuals of average body composition aiming to maximize post-exercise myofibrillar protein synthesis while minimizing irreversible amino acid oxidative catabolism that occurs with excessive intakes of this macronutrient. This muscle-specific bolus intake is lower than that reported to maximize whole body anabolism (i.e., ≥0.5 g/kg). Review of the available literature suggests that potential confounders such as the co-ingestion of carbohydrate, sex, and amount of active muscle mass do not represent significant barriers to the translation of this objectively determined relative protein intake. Additional research is warranted to elucidate the effective dose for proteins with suboptimal amino acid compositions (e.g., plant-based), and/or slower digestion rates as well as whether recommendations are appreciably affected by other physiological conditions such endurance exercise, high habitual daily protein ingestion, aging, obesity, and/or periods of chronic negative energy balance.

The Influence of Omega-3 Fatty Acids on Skeletal Muscle Protein Turnover in Health, Disuse, and Disease.

Ingestion of omega-3 fatty acids is known to exert favorable health effects on a number of biological processes such as improved immune profile, enhanced cognition, and optimized neuromuscular function. Recently, data have emerged demonstrating a positive influence of omega-3 fatty acid intake on skeletal muscle. For instance, there are reports of clinically-relevant gains in muscle size and strength in healthy older persons with omega-3 fatty acid intake as well as evidence that omega-3 fatty acid ingestion alleviates the loss of muscle mass and prevents decrements in mitochondrial respiration during periods of muscle-disuse. Cancer cachexia that is characterized by a rapid involuntary loss of lean mass may also be attenuated by omega-3 fatty acid provision. The primary means by which omega-3 fatty acids positively impact skeletal muscle mass is via incorporation of eicosapentaenoic acid (EPA; 20:5n−3) and docosahexaenoic acid (DHA; 22:6n−3) into membrane phospholipids of the sarcolemma and intracellular organelles. Enrichment of EPA and DHA in these membrane phospholipids is linked to enhanced rates of muscle protein synthesis, decreased expression of factors that regulate muscle protein breakdown, and improved mitochondrial respiration kinetics. However, exactly how incorporation of EPA and DHA into phospholipid membranes alters these processes remains unknown. In this review, we discuss the interaction between omega-3 fatty acid ingestion and skeletal muscle protein turnover in response to nutrient provision in younger and older adults. Additionally, we examine the role of omega-3 fatty acid supplementation in protecting muscle loss during muscle-disuse and in cancer cachexia, and critically evaluate the molecular mechanisms that underpin the phenotypic changes observed in skeletal muscle with omega-3 fatty acid intake.

Basal and Postprandial Myofibrillar Protein Synthesis Rates Do Not Differ between Lean and Obese Middle-Aged Men

ABSTRACTBackgroundExcess lipid availability has been associated with the development of anabolic resistance. As such, obesity may be accompanied by impairments in muscle protein metabolism.ObjectiveWe hypothesized that basal and postprandial muscle protein synthesis rates are lower in obese than in lean men.MethodsTwelve obese men [mean ± SEM age: 48 ± 2 y; BMI (in kg/m2): 37.0 ± 1.5; body fat: 32 ± 2%] and 12 age-matched lean controls (age: 43 ± 3 y; BMI: 23.4 ± 0.4; body fat: 21 ± 1%) received primed continuous L-[ring-2H5]-phenylalanine and L-[ring-3,5-2H2]-tyrosine infusions and ingested 25 g intrinsically L-[1-13C]-phenylalanine labeled whey protein. Repeated blood and muscle samples were obtained to assess protein digestion and amino acid absorption kinetics, and basal and postprandial myofibrillar protein synthesis rates.ResultsExogenous phenylalanine appearance rates increased after protein ingestion in both groups (P < 0.001), with a total of 53 ± 1% and 53 ± 2% of dietary protein–derived phenylalanine appearing in the circulation over the 5-h postprandial period in lean and obese men, respectively (P = 0.82). After protein ingestion, whole-body protein synthesis and oxidation rates increased to a greater extent in lean men than in the obese (P-interaction < 0.05), resulting in a higher whole-body protein net balance in the lean than in the obese (7.1 ± 0.2 and 4.6 ± 0.4 µmol phenylalanine · h−1 · kg−1, respectively; P-interaction < 0.001). Myofibrillar protein synthesis rates increased from 0.030 ± 0.002 and 0.028 ± 0.003%/h in the postabsorptive period to 0.034 ± 0.002 and 0.035 ± 0.003%.h−1 in the 5-h postprandial period (P = 0.03) in lean and obese men, respectively, with no differences between groups (P-interaction = 0.58).ConclusionsBasal, postabsorptive myofibrillar protein synthesis rates do not differ between lean and obese middle-aged men. Postprandial protein handling, including protein digestion and amino acid absorption, and the postprandial muscle protein synthetic response after the ingestion of 25 g whey protein are not impaired in obese men. This trial was registered at www.trialregister.nl as NTR4060.

Nutritional Strategies to Combat Type 2 Diabetes in Aging Adults: The Importance of Protein.

The prevalence of pre-diabetes (PD) and type II diabetes (T2D) has risen dramatically in recent years affecting an estimated 422 million adults worldwide. The risk of T2D increases with age, with the sharpest rise in diagnosis occurring after age 40. With age, there is also a progressive decline in muscle mass starting after the age of 30. The decline in muscle mass and function due to aging is termed sarcopenia and immediately precedes the sharp rise in T2D. The purpose of the current review is to discuss the role of protein to attenuate declines in muscle mass and insulin sensitivity to prevent T2D and sarcopenia in aging adults. The current recommended dietary allowance for protein consumption is set at 0.8 g/kg/day and is based on dated studies on young healthy men and may not be sufficient for older adults. Protein consumption upwards of 1.0–1.5 g/kg/day in older adults is able to induce improvements in glycemic control and muscle mass. Obesity, particularly central or visceral obesity is a major risk factor in the development of PD and T2D. However, the tissue composition of weight loss in older adults includes both lean body mass and fat mass and therefore may have adverse metabolic consequences in older adults who are already at a high risk of lean body mass loss. High protein diets have the ability to increase weight loss while preserving lean body mass therefore inducing “high-quality weight loss,” which provides favorable metabolic changes in older adults. High protein diets also induce beneficial outcomes on glycemic markers due to satiety, lowered post-prandial glucose response, increased thermogenesis, and the ability to decrease rates of muscle protein breakdown (MPB). The consumption of dairy specific protein consumption has also been shown to improve insulin sensitivity by improving body composition, enhancing insulin release, accelerating fat oxidation, and stimulating rates of muscle protein synthesis (MPS) in older adults. Exercise, specifically resistance training, also works synergistically to attenuate the progression of PD and T2D by further stimulating rates of MPS thereby increasing muscle mass and inducing favorable changes in glycemic control independent of lean body mass increases.

SUN-LB670: Branched-Chain Amino Acid and Branched-Chain Ketoacid Ingestion Increase Muscle Protein Synthesis Rates in Vivo in Older Adults

SUN-LB670: Branched-Chain Amino Acid and Branched-Chain Ketoacid Ingestion Increase Muscle Protein Synthesis Rates in Vivo in Older Adults

Aerobic Plus Resistance Exercise in Obese Older Adults Improves Muscle Protein Synthesis and Preserves Myocellular Quality Despite Weight Loss

Anabolic resistance and impaired myocellular quality contribute to age-related sarcopenia, which exacerbates with obesity. Diet-induced muscle mass loss is attenuated by resistance or aerobic plus resistance exercise compared to aerobic exercise in obese elderly. We assessed chronic effects of weight loss plus different exercise modalities on muscle protein synthesis response to feeding and myocellular quality. Obese older adults were randomized to a weight-management program plus aerobic, resistance, or combined aerobic and resistance exercise or to control. Participants underwent vastus lateralis biopsies at baseline and 6months. Muscle protein synthesis rate increased more in resistance and combined than in control. Autophagy mediators' expression decreased more in combined than in aerobic, which experienced a higher increase in inflammation and mitochondrial regulators' expression. In obese elderly, combined aerobic and resistance exercise is superior to either mode independently for improving muscle protein synthesis and myocellular quality, thereby maintaining muscle mass during weight-loss therapy.

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

ABSTRACTBackgroundProtein ingestion increases muscle protein synthesis rates. However, limited data are currently available on the effects of branched-chain amino acid (BCAA) and branched-chain ketoacid (BCKA) ingestion on postprandial muscle protein synthesis rates.ObjectiveThe aim of this study was to compare the impact of ingesting 6 g BCAA, 6 g BCKA, and 30 g milk protein (MILK) on the postprandial rise in circulating amino acid concentrations and subsequent myofibrillar protein synthesis rates in older males.MethodsIn a parallel design, 45 older males (age: 71 ± 1 y; BMI: 25.4 ± 0.8 kg/m2) were randomly assigned to ingest a drink containing 6 g BCAA, 6 g BCKA, or 30 g MILK. Basal and postprandial myofibrillar protein synthesis rates were assessed by primed continuous l-[ring-13C6]phenylalanine infusions with the collection of blood samples and muscle biopsies.ResultsPlasma BCAA concentrations increased following test drink ingestion in all groups, with greater increases in the BCAA and MILK groups compared with the BCKA group (P < 0.05). Plasma BCKA concentrations increased following test drink ingestion in all groups, with greater increases in the BCKA group compared with the BCAA and MILK groups (P < 0.05). Ingestion of MILK, BCAA, and BCKA significantly increased early myofibrillar protein synthesis rates (0–2 h) above basal rates (from 0.020 ± 0.002%/h to 0.042 ± 0.004%/h, 0.022 ± 0.002%/h to 0.044 ± 0.004%/h, and 0.023 ± 0.003%/h to 0.044 ± 0.004%/h, respectively; P < 0.001), with no differences between groups (P > 0.05). Myofibrillar protein synthesis rates during the late postprandial phase (2–5 h) remained elevated in the MILK group (0.039 ± 0.004%/h; P < 0.001), but returned to baseline values following BCAA and BCKA ingestion (0.024 ± 0.005%/h and 0.024 ± 0.005%/h, respectively; P > 0.05).ConclusionsIngestion of 6 g BCAA, 6 g BCKA, and 30 g MILK increases myofibrillar protein synthesis rates during the early postprandial phase (0–2 h) in vivo in healthy older males. The postprandial increase following the ingestion of 6 g BCAA and BCKA is short-lived, with higher myofibrillar protein synthesis rates only being maintained following the ingestion of an equivalent amount of intact milk protein. This trial was registered at Nederlands Trial Register (www.trialregister.nl) as NTR6047.

The Effects of Alcohol Consumption on Recovery Following Resistance Exercise: A Systematic Review.

Background: The aim of this manuscript was to describe the effects of alcohol ingestion on recovery following resistance exercise. Methods: A literature search was performed using the following database: Web of Science, NLM Pubmed, and Scopus. Studies regarding alcohol consumption after resistance exercise evaluating recovery were considered for investigation. The main outcomes took into account biological, physical and cognitive measures. Multiple trained researchers independently screened eligible studies according to the eligibility criteria, extracted data and assessed risk of bias. Results: A total of 12 studies were considered eligible and included in the quantitative synthesis: 10 included at least one measure of biological function, 10 included at least one measure of physical function and one included measures of cognitive function. Conclusions: Alcohol consumption following resistance exercise doesn’t seem to be a modulating factor for creatine kinase, heart rate, lactate, blood glucose, estradiol, sexual hormone binding globulin, leukocytes and cytokines, C-reactive protein and calcium. Force, power, muscular endurance, soreness and rate of perceived exertion are also unmodified following alcohol consumption during recovery. Cortisol levels seemed to be increased while testosterone, plasma amino acids, and rates of muscle protein synthesis decreased.