Muscle Protein Synthesis Rates Research Articles

Safety of soy-derived phosphatidic acid supplementation in healthy young males

Background The mammalian target of rapamycin (mTOR) has been shown to regulate rates of muscle protein synthesis, and one novel nutritional activator of mTOR is the phospholipid Phosphatidic Acid (PA). We have recently found that PA supplementation over 8 weeks of resistance training augmented responses in skeletal muscle hypertrophy and strength. However, we are unaware of research investigating the safety of PA in human subjects. Therefore the purpose of this study was to investigate the effects of 8 weeks of 750 mg per day of PA supplementation on safety parameters in healthy college aged males.

Effect of oral administration of soy-derived phosphatidic acid on concentrations of phosphatidic acid and lyso-phosphatidic acid molecular species in human plasma

Background The glycerophospholipid Phosphatidic acid (PA) has been identified as a potential nutritional treatment for gastrointestinal disorders. Dietary food sources rich in PA include cabbage and radish leaves as well as Mallotus japonicas, a Japanese edible herb historically used for the treatment of stomach ulcers. The mammalian target of rapamycin (mTOR) has been shown to regulate rates of muscle protein synthesis and a mechanical stimulus (resistance exercise) has been shown to activate mTOR with PA playing a key role. Supplementation with soy-derived PA significantly increases responses in skeletal muscle hypertrophy, lean body mass, and maximal strength to resistance exercise. PA accounts for less than 0.1% of the total glycerophospholipid concentration of 201 mg/dl in the human plasma. 15 of the more than 600 distinct molecular lipid species quantified in human plasma are PA, 6 are lysophosphatidic acid (LPA). Orally administered PA can be metabolized to LPA and glycerophosphate by pancreatic phospholipases A1 and A2, which hydrolyze the fatty acid at the sn-1 position and the sn-2 position, respectively. Lysophospholipids are absorbed by the mucosal cells of the gastrointestinal tract and are rapidly re-acylated with fatty acids of the body pool resulting in a newly-formed phospholipid-molecule whose fatty acid composition is determined by the physiological and nutritional status and not by its source. This study sought to assess the effect of soy-derived PA supplementation on concentrations LPA and PA molecular species in human plasma. Methods After a 12 hour overnight fast one subject (20 years of age, bodyweight of 82 kg, and height of 178 cm) was assigned to receive 1.5 grams of soy-derived PA (Mediator, Chemi Nutra, White Bear Lake, MN). Blood draws were taken immediately prior to, and at 30 min, 1, 2, 3, and 7 hours following supplementation. The samples were analyzed by an ultra-performance liquid chromatograph with triple quadrupole mass spectrometry (LC/MS/MS) using 17:1-LPA and 37:4-PA as internal standards to determine the concentration of LPA and PA molecular species in human plasma. Results At baseline, 19 PA (highest concentrations: C34:2 (15%), C40:4 (11%), and C36:4 (10%)) and 5 LPA (16:0 (45%), 18:2 (19%), 20:4 (17%), 14:0 (11%) and 18:1 (8%)) molecular species could be quantified with total concentrations of PA of 2.66 nmol/ml, and LPA of 0.11 nmol/ml. Plasma concentrations of PA peaked at 3 hours (+32%) after ingestion and stayed elevated even after 7h ours (+18%). LPA showed a bimodal absorption kinetic with peaks after 1 hour (+500%) and 3 hours (+264%), after almost dropping back to baseline levels after 2 hours. On an individual fatty acid level, most prominent was a 23-fold increase in 20:4-LPA after 1 hour compared to baseline. The increase in 20:4-LPA does not result from the administration of PA, since soy-derived PA does not contain any arachidonic acid (fatty acids distribution of soy-PA: 18:2 (66.1%), 18:1 (12.6%), 16:0 (11.7%), 18:3 (6.1%) and 18:0 (3.4%)). Absorption of soy-derived PA must yield glycerophosphate which is re-acylated with arachidonic acid.

Disuse Impairs the Muscle Protein Synthetic Response to Protein Ingestion in Healthy Men

Disuse leads to rapid skeletal muscle atrophy, which brings about numerous negative health consequences. Muscle disuse atrophy is, at least in part, attributed to a decline in basal (postabsorptive) muscle protein synthesis rates. However, it remains to be determined whether muscle disuse also impairs the muscle protein synthetic response to dietary protein ingestion. We assessed muscle protein synthesis rates after protein ingestion before and after a period of disuse in humans. Twelve healthy young (24 ± 1 year) men underwent a 14-day period of one-legged knee immobilization by way of a full leg cast. Before and after the immobilization period, quadriceps cross-sectional area, muscle strength, skeletal muscle protein synthesis rates, and associated im (intramuscular) molecular signaling were assessed. Continuous infusions of l-[ring-²H₅]phenylalanine were applied to assess mixed-muscle protein fractional synthetic rates after the ingestion of 20 g dietary protein. Immobilization led to an 8.4% ± 2.8% (P < .001) and 22.9% ± 2.6% (P < .001) decrease in quadriceps muscle cross-sectional area and strength, respectively. Immobilization resulted in a 31% ± 12% reduction in postprandial muscle protein synthesis rates (from 0.046% ± 0.004% to 0.032% ± 0.006% per hour; P < .05). These findings were observed without any discernible changes in the skeletal muscle phosphorylation status of mammalian target of rapamycin or p70 ribosomal protein S6 kinase. A short period of muscle disuse impairs the muscle protein synthetic response to dietary protein intake in vivo in healthy young men. Thus, anabolic resistance to protein ingestion contributes significantly to the loss of muscle mass that is observed during disuse.

Phosphatidic acid supplementation increases skeletal muscle hypertrophy and strength

The accretion of skeletal muscle tissue can be critical for a varied population including athletes and elderly. Skeletal muscle hypertrophy is largely mediated through increased muscle protein synthesis. The mammalian target of rapamycin (mTOR) has been shown to regulate rates of muscle protein synthesis and a mechanical stimulus (resistance exercise) has been shown to activate mTOR with the phospholipid Phosphatidic Acid (PA) playing a key role. A first pilot study found that oral supplementation with soy-derived PA in athletes undergoing progressive resistance training very likely resulted in greater increases in squat strength and lean mass over the placebo. However, this pilot study was likely underpowered, the workout was not supervised and no direct measures of skeletal muscle hypertrophy were taken. Therefore, the purpose of this study was to investigate the effects of PA on body composition, strength, power and muscular hypertrophy.

Effects of advanced age on whole-body protein synthesis and skeletal muscle mechanistic target of rapamycin signaling in horses

To determine the effects of advanced age on whole-body protein synthesis and activation of the mechanistic target of rapamycin (mTOR) signaling pathway in skeletal muscle of horses. Six 22- to 26-year-old (aged) and six 7- to 14-year-old (mature) horses. Whole-body protein synthesis was measured with a 2-hour primed constant infusion of (13)C sodium bicarbonate, followed by a 4-hour primed constant infusion of 1-(13)C phenylalanine. After the infusions, a biopsy specimen was obtained from a gluteus medius muscle and activation of protein kinase B (Akt), p70 riboprotein S6 kinase (S6K1), riboprotein S6 (rpS6), and eukaryotic initiation factor 4E binding protein 1 (4EBP1) was determined with western immunoblot analysis. For all horses, inflammatory cytokine expression in muscle and blood samples was measured with quantitative real-time PCR analysis. Advanced age had no effect on whole-body protein synthesis or the phosphorylation of Akt, rpS6, and 4EBP1; however, muscle specimens of aged horses had 42% lower phosphorylation of S6K1 than did those of mature horses. Aged and mature horses had similar inflammatory cytokine expression in muscle and blood samples. The lower S6K1 activation for aged horses, compared with that for mature horses, could be indicative of low rates of muscle protein synthesis in aged horses. However, advanced age had no effect on any other indicators of whole-body or muscle protein synthesis or on measures of systemic or muscle inflammation, which suggested that protein metabolism and subsequently requirements may not differ between healthy mature and aged horses.

Epinephrine depletion exacerbates the fasting-induced protein breakdown in fast-twitch skeletal muscles

The physiological role of epinephrine in the regulation of skeletal muscle protein metabolism under fasting is unknown. We examined the effects of plasma epinephrine depletion, induced by adrenodemedullation (ADMX), on muscle protein metabolism in fed and 2-day-fasted rats. In fed rats, ADMX for 10 days reduced muscle mass, the cross-sectional area of extensor digitorum longus (EDL) muscle fibers, and the phosphorylation levels of Akt. In addition, ADMX led to a compensatory increase in muscle sympathetic activity, as estimated by the rate of norepinephrine turnover; this increase was accompanied by high rates of muscle protein synthesis. In fasted rats, ADMX exacerbated fasting-induced proteolysis in EDL but did not affect the low rates of protein synthesis. Accordingly, ADMX activated lysosomal proteolysis and further increased the activity of the ubiquitin (Ub)-proteasome system (UPS). Moreover, expression of the atrophy-related Ub ligases atrogin-1 and MuRF1 and the autophagy-related genes LC3b and GABARAPl1 were upregulated in EDL muscles from ADMX-fasted rats compared with sham-fasted rats, and ADMX reduced cAMP levels and increased fasting-induced Akt dephosphorylation. Unlike that observed for EDL muscles, soleus muscle proteolysis and Akt phosphorylation levels were not affected by ADMX. In isolated EDL, epinephrine reduced the basal UPS activity and suppressed overall proteolysis and atrogin-1 and MuRF1 induction following fasting. These data suggest that epinephrine released from the adrenal medulla inhibits fasting-induced protein breakdown in fast-twitch skeletal muscles, and these antiproteolytic effects on the UPS and lysosomal system are apparently mediated through a cAMP-Akt-dependent pathway, which suppresses ubiquitination and autophagy.

Protein Redistribution From Skeletal Muscle to Splanchnic Tissue on Fasting and Refeeding in Young and Older Healthy Individuals

During aging, a shift of protein metabolism from muscle to splanchnic tissue contributes to increased muscle protein loss after a period of metabolic stress (eg, fasting). To study the adaptation of protein metabolism in the whole body and tissue (ie, skeletal muscle and splanchnic area) to metabolic stress, such as short-term fasting and refeeding, in aged people. We studied splanchnic and muscle protein metabolism after 38 hours of fasting and refeeding in 7 young (5 men/2 women, 24.4 ± 2.0 years) and 8 elderly individuals (6 men/2 women, 70.6 ± 3.1 years). We used intravenous (IV) L-[(13)C6]phenylalanine, IV L-[(2)H3]leucine, and oral L-[(13)C1]leucine to obtain (1) whole-body protein kinetics, (2) muscle and albumin fractional synthesis rate (FSR, %/d; (13)C6-Phe, and (13)C1-Leu), and (3) splanchnic extraction during fasting and refeeding (%, (2)H3- and (13)C1-Leu). Whole-body protein breakdown was activated during fasting in young and older individuals (P<.01 vs fasted state). Muscle FSR remained unchanged in both groups and not stimulated by refeeding in either group with either IV (13)C Phe or oral (13)C Leu, probably because of high plasma levels of essential amino acids (EAAs) and branched-chain amino acids (BCAAs). Splanchnic extraction of leucine was 42% higher in the elderly individuals (P= .03 vs young) and was associated with an increased albumin synthesis rate in elderly individuals in the fed state (P < .05 vs young). Splanchnic protein metabolism is modified by age, but this metabolic change is not associated with a lower synthesis rate of muscle protein, provided high plasma levels of essential EAAs are maintained. Our data also suggest that splanchnic protein synthesis is a metabolic priority during recovery after metabolic stress in healthy elderly persons and that it might be even more affected in polymedicated older individuals having chronic diseases.

PP253-SUN CYSTINE SUPPRESSES INFLAMMATORY REACTION INDUCED BY LPS THROUGH AUGMENTATION OF INTERLEUKIN-10 PRODUCTION

(p = 0.049). No interaction between treatment and exercise was observed (p = 0.519). Higher postprandial concentrations of essential amino acids and leucine are possible mediating factors for the FSR response. Conclusion: Ingestion of a high whey protein, leucineenriched supplement resulted in a higher overall postprandial muscle protein synthesis rate in healthy older subjects compared with a conventional dairy product.

Effect of citrulline on muscle functions during moderate dietary restriction in healthy adult rats

Low calorie diets are designed to reduce body weight and fat mass, but they also lead to a detrimental loss of lean body mass, which is an important problem for overweight people trying to lose weight. In this context, a specific dietary intervention that preserves muscle mass in people following a slimming regime would be of great benefit. Leucine (LEU) and Citrulline (CIT) are known to stimulate muscle protein synthesis (MPS) in post-prandial and post-absorptive state, respectively. This makes them interesting bioactive components to test in the context of dietary restriction. We tested the concept of combining LEU and CIT in adult female rats. We postulated that the sequential administration of LEU (mixed in chow) and CIT (given in drinking water before a rest period) could be beneficial for preservation of muscle function during food restriction. Sixty female rats (22 weeks old) were randomized into six groups: one group fed ad libitum with a standard diet (C) and five food-restricted groups (60 % of spontaneous intake for 2 weeks) receiving a standard diet (R group), a CIT-supplemented diet (0.2 or 1 g/kg/day, CIT0.2 group and CIT1 group, respectively), a LEU-supplemented diet (1.0 g/kg/day) or a CIT + LEU-supplemented diet (CIT + LEU 1.0 g/kg/day each). At the end of the experiment, body composition, muscle contractile properties and muscle protein synthesis (MPS) rate were studied in the tibialis anterior muscle. Dietary restriction tended to decrease MPS (R: 2.5 ± 0.2 vs. C: 3.4 ± 0.4 %/day, p = 0.06) and decrease muscle strength (R: 3,045 ± 663 vs. C: 5,650 ± 661 A.U., p = 0.03). Only CIT administration (1 g/kg) was able to restore MPS (CIT1: 3.4 ± 0.3 vs. R: 2.5 ± 0.2 %/day, p = 0.05) and increase muscle maximum tetanic force (CIT1: 441 ± 15 vs. R: 392 ± 22 g, p = 0.05) and muscle strength (CIT1: 4,259 ± 478 vs. R: 3,045 ± 663 A.U., p = 0.05). LEU had no effect and CIT + LEU supplementation had few effects, limited to adipose mass and fatigue force. The results of this study highlight the ability of CIT alone to preserve muscle function during dietary restriction. Surprisingly, LEU antagonized some effects of CIT. The mechanisms involved in this antagonistic effect warrant further study.

Minced beef is more rapidly digested and absorbed than beef steak, resulting in greater postprandial protein retention in older men

Older individuals generally experience a reduced food-chewing efficiency. As a consequence, food texture may represent an important factor that modulates dietary protein digestion and absorption kinetics and the subsequent postprandial protein balance. We assessed the effect of meat texture on the dietary protein digestion rate, amino acid availability, and subsequent postprandial protein balance in vivo in older men. Ten older men (mean ± SEM age: 74 ± 2 y) were randomly assigned to a crossover experiment that involved 2 treatments in which they consumed 135 g of specifically produced intrinsically L-[1-(13)C]phenylalanine-labeled beef, which was provided as beef steak or minced beef. Meat consumption was combined with continuous intravenous L-[ring-(2)H5]phenylalanine and L-[ring-(2)H2]tyrosine infusion to assess beef protein digestion and absorption kinetics as well as whole-body protein balance and skeletal muscle protein synthesis rates. Meat protein-derived phenylalanine appeared more rapidly in the circulation after minced beef than after beef steak consumption (P < 0.05). Also, its availability in the circulation during the 6-h postprandial period was greater after minced beef than after beef steak consumption (61 ± 3% compared with 49 ± 3%, respectively; P < 0.01). The whole-body protein balance was more positive after minced beef than after beef steak consumption (29 ± 2 compared with 19 ± 3 μmol phenylalanine/kg, respectively; P < 0.01). Skeletal muscle protein synthesis rates did not differ between treatments when assessed over a 6-h postprandial period. Minced beef is more rapidly digested and absorbed than beef steak, which results in increased amino acid availability and greater postprandial protein retention. However, this does not result in greater postprandial muscle protein synthesis rates. This trial was registered at clinicaltrials.gov as NCT01145131.

Refining dietary protein recommendations for the athlete

Refining dietary protein recommendations for the athlete

Amino Acid-carbohydrate intake combined with multiple bouts of resistance exercise increases resting energy expenditure.

Increasing the rate of muscle protein synthesis is an energy consuming process that explains the acute elevations in resting energy expenditure (REE) observed 12 to 72 hours after a resistance exercise session. We hypothesized that multiple sessions of resistance exercise combined with the intake of amino acids would increase REE and alter the nonprotein respiratory exchange ratio (RER). Ten male participants completed two separate seven-day trials where REE and RER were measured on each morning via indirect calorimetry. On four consecutive days within each seven-day trial, acute resistance exercise was performed, and nutritional intake was manipulated by providing (1) amino acids and carbohydrate (AA-RT) or (2) nonnitrogenous, isoenergetic carbohydrate (CHO-RT) before and during each resistance exercise session. Average REE within the training period was 3.61% greater in AA-RT (7897 ± 252 kJ) compared to CHO-RT (7622 ± 289 kJ; P = 0.02). RER declined (P < 0.0001) from baseline after each resistance exercise was initiated in both AA-RT (0.82 ± 0.01 to 0.77 ± 0.01) and CHO-RT (0.82 ± 0.02 to 0.77 ± 0.02). We conclude the provision of amino acids with multiple bouts of resistance exercise enhances energy expenditure at rest without altering the utilization of lipid.

Mammalian target of rapamycin-independent S6K1 and 4E-BP1 phosphorylation during contraction in rat skeletal muscle

Muscle protein synthesis rates decrease during contraction/exercise, but rapidly increase post-exercise. Previous studies mainly focused on signaling pathways that control protein synthesis during post-exercise recovery, such as mTOR and its downstream targets S6K1 and 4E-BP1. In this study, we investigated the effect of high-frequency electrical stimulation on the phosphorylation state of signaling components controlling protein synthesis in rat skeletal muscle. Electrical stimulation increased S6K1 Thr389 phosphorylation, which was unaffected by Torin1, a selective mTOR inhibitor, suggesting that S6K1 phosphorylation by contraction was mTOR-independent. Phosphorylation of eIF4B Ser422 was also increased during electrical stimulation, which was abrogated by inhibition of MEK/ERK/RSK1 activation. Moreover, although phosphorylation of conventional mTOR sites in 4E-BP1 decreased during contraction, mTOR-independent phosphorylation was also apparent, which was associated with the release of 4E-BP1 from eIF4E. The results indicate mTOR-independent phosphorylation of S6K1 and 4E-BP1 and suggest MEK/ERK/RSK1-dependent phosphorylation of eIF4B during skeletal muscle contraction. These phosphorylation events would keep the translation initiation machinery “primed” in an active state so that protein synthesis could quickly resume post-exercise.

Role of protein and amino acids in promoting lean mass accretion with resistance exercise and attenuating lean mass loss during energy deficit in humans

Amino acids are major nutrient regulators of muscle protein turnover. After protein ingestion, hyperaminoacidemia stimulates increased rates of skeletal muscle protein synthesis, suppresses muscle protein breakdown, and promotes net muscle protein accretion for several hours. These acute observations form the basis for strategized protein intake to promote lean mass accretion, or prevent lean mass loss over the long term. However, factors such as protein dose, protein source, and timing of intake are important in mediating the anabolic effects of amino acids on skeletal muscle and must be considered within the context of evaluating the reported efficacy of long-term studies investigating protein supplementation as part of a dietary strategy to promote lean mass accretion and/or prevent lean mass loss. Current research suggests that dietary protein supplementation can augment resistance exercise-mediated gains in skeletal muscle mass and strength and can preserve skeletal muscle mass during periods of diet-induced energy restriction. Perhaps less appreciated, protein supplementation can augment resistance training-mediated gains in skeletal muscle mass even in individuals habitually consuming 'adequate' (i.e., >0.8 g kg⁻¹ day⁻¹) protein. Additionally, overfeeding energy with moderate to high-protein intake (15-25 % protein or 1.8-3.0 g kg⁻¹ day⁻¹) is associated with lean, but not fat mass accretion, when compared to overfeeding energy with low protein intake (5 % protein or ~0.68 g kg⁻¹ day⁻¹). Amino acids represent primary nutrient regulators of skeletal muscle anabolism, capable of enhancing lean mass accretion with resistance exercise and attenuating the loss of lean mass during periods of energy deficit, although factors such as protein dose, protein source, and timing of intake are likely important in mediating these effects.

Sex hormones and skeletal muscle weakness

Human ageing is accompanied with deterioration in endocrine functions the most notable and well characterized of which being the decrease in the production of sex hormones. Current research literature suggests that low sex hormone concentration may be among the key mechanism for sarcopenia and muscle weakness. Within the European large scale MYOAGE project, the role of sex hormones, estrogens and testosterone, in causing the aging-related loss of muscle mass and function was further investigated. Hormone replacement therapy (HRT) in women is shown to diminish age-associated muscle loss, loss in fast muscle function (power), and accumulation of fat in skeletal muscle. Further HRT raises the protein synthesis rate in skeletal muscle after resistance training, and has an anabolic effect upon connective tissue in both skeletal muscle and tendon, which influences matrix structure and mechanical properties. HRT influences gene expression in e.g. cytoskeletal and cell-matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal muscle.

Regulation of Skeletal Muscle Plasticity by Glycogen Synthase Kinase-3&amp;beta;: A Potential Target for the Treatment of Muscle Wasting

Muscle wasting is a prevalent and disabling condition in chronic disease and cancer and has been associated with increased mortality and impaired efficacy of surgical and medical interventions. Pharmacological therapies to combat muscle wasting are currently limited but considered as an important unmet medical need. Muscle wasting has been attributed to increased muscle proteolysis, and in particular ubiquitin 26S-proteasome system (UPS)-dependent protein breakdown. However, rates of muscle protein synthesis are also subject to extensive (patho) physiological regulation, and the balance between synthesis and degradation ultimately determines net muscle protein turnover. As multinucleated muscle fibers accommodate threshold changes in muscle protein content by the accretion and loss of muscle nuclei, myonuclear turnover may additionally determine muscle mass. Current insights in the mechanisms dictating muscle mass plasticity not only reveal intricate interactions and crosstalk between these processes, but imply the existence of signaling molecules that act as molecular switchboards, which coordinate and integrate cellular responses upon conditions that evoke changes in muscle mass. These "master regulators" of skeletal muscle mass plasticity are preferred targets for pharmacological modulation of skeletal muscle wasting. In this review Glycogen synthase kinase-3β (GSK-3β) is highlighted as a master regulator of muscle mass plasticity since, in addition to its role in UPS-mediated muscle protein degradation, it also controls protein synthesis, and influences myonuclear accretion and cell death. Moreover, the regulation of GSK-3β activity as well as currently available pharmacological inhibitors are described and discussed in the context of multimodal treatment strategies aimed at the inhibition of GSK-3β, and optimal exploitation of its potential role as a central regulator of skeletal muscle mass plasticity for the treatment of muscle wasting.

Female sex steroid effects on basal muscle protein synthesis rates in postmenopausal women

We recently reported a greater basal, postabsorptive rate of muscle protein synthesis (MPS) in post‐compared with premenopausal women. This finding suggests that ovarian hormones suppress MPS. In the current study, we tested this hypothesis by measuring the basal rate of MPS (by using stable isotope‐labeled tracer methods) in postmenopausal women before and after treatment with either estradiol (Mylan Pharmaceuticals; 0.1 mg/d delivered transdermally; n=6) or progesterone (Endometrin®; 100 mg/d delivered vaginally; n =5). The MPS rate was unaffected by estrogen treatment (0.063±0.006 vs. 0.063±0.010 %/h, before and after treatment respectively; P=0.99) but was markedly increased after progesterone treatment (0.102±0.018 %/h vs. 0.055±0.007; P=0.02). We conclude that the menopause associated decline in ovarian female sex hormone production is not responsible for the age‐associated increase in MPS in old women.Supported by grants from the NIH.

Impact of prolonged mechanical ventilation on diaphragmatic protein synthesis

Mechanical ventilation (MV) is a life‐saving intervention in patients suffering from respiratory failure. Unfortunately, prolonged MV promotes the rapid development of diaphragmatic atrophy due to increased proteolysis and decreased protein synthesis. These experiments investigated the influence of two different modes of MV on rat diaphragm protein synthesis. Specifically, we examined the mixed protein synthesis rate of diaphragm muscle proteins during controlled MV (CMV) which causes complete diaphragmatic inactivity and pressure support MV (PSV) which permits partial activity of the diaphragm. Our results reveal that compared to spontaneously breathing animals, diaphragm protein synthesis rates are not depressed during the first 6‐hours of PSV but are significantly decreased in animals exposed to CMV. However, the rates of diaphragm protein synthesis are depressed at similar levels in both CMV and PSV animals during 6–12 hours of MV. We conclude that while PSV can initially delay the MV‐induced decreases in diaphragm protein synthesis, this protective effect is rapidly lost after the first 6 hours of MV. NIH RO1 HL087839 (SKP)

Carbohydrate co‐ingestion with protein delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion

We determined the impact of carbohydrate co‐ingestion with protein on dietary protein digestion and absorption kinetics and postprandial muscle protein accretion in healthy men. Twenty‐four young (age: 21±1 y, BMI: 21.8±0.5 kg/m2) and 24 older (age: 75±1 y, BMI: 25.4±0.6 kg/m2) men received a primed continuous L‐[ring‐2H5]‐phenylalanine infusion and ingested 20 g L‐[1‐13C]‐ phenylalanine‐labeled protein with (PRO+CHO) or without (PRO) 60 g carbohydrate. Biopsies were collected from the vastus lateralis. Carbohydrate co‐ingestion delayed the rise in exogenous phenylalanine appearance rate (P&lt;0.05). Dietary protein‐derived phenylalanine availability over the postprandial period was lower in the old (60±2%) when compared with the young (72±2%; P&lt;0.05), with no differences between the PRO and PRO+CHO condition (P=0.42). Carbohydrate co‐ingestion did not modulate postprandial muscle protein synthesis rates (0.035±0.003 vs 0.043±0.004 and 0.033±0.002 vs 0.035±0.003 %/h following PRO vs PRO+CHO in the young and old, respectively). In accordance, no differences in muscle protein‐bound L‐[1‐13C]‐phenylalanine enrichments were observed between groups (0.020±0.003 vs 0.018±0.003 and 0.017±0.003 vs 0.022±0.004 MPE following PRO vs PRO+CHO in the young and old, respectively). We conclude that carbohydrate co‐ingestion does not modulate postprandial muscle protein accretion in young or older men.

Nutritional strategies to attenuate muscle disuse atrophy

Situations such as recovery from injury or illness require otherwise healthy humans to undergo periods of disuse, which lead to considerable losses of skeletal muscle mass and, subsequently, numerous negative health consequences. It has been established that prolonged disuse (>10 days) leads to a decline in basal and postprandial rates of muscle protein synthesis, without an apparent change in muscle protein breakdown. It also seems, however, that an early and transient (1-5 days) increase in basal muscle protein breakdown may also contribute to disuse atrophy. A period of disuse reduces energy requirements and appetite. Consequently, food intake generally declines, resulting in an inadequate dietary protein consumption to allow proper muscle mass maintenance. Evidence suggests that maintaining protein intake during a period of disuse attenuates disuse atrophy. Furthermore, supplementation with dietary protein and/or essential amino acids can be applied to further aid in muscle mass preservation during disuse. Such strategies are of particular relevance to the older patient at risk of developing sarcopenia. More work is required to elucidate the impact of disuse on basal and postprandial rates of muscle protein synthesis and breakdown. Such information will provide novel targets for nutritional interventions to further attenuate muscle disuse atrophy and, as such, support healthy aging.