Omega-3 fatty acid supplementation attenuates skeletal muscle disuse atrophy during two weeks of unilateral leg immobilization in healthy young women.

Omega-3 (n-3) fatty acid supplementation enhances muscle protein synthesis and muscle size. Whether n-3 fatty acid supplementation attenuates human muscle disuse atrophy is unknown. We determined the influence of n-3 fatty acid supplementation on muscle size, mass, and integrated rates of myofibrillar protein synthesis (MyoPS) following 2 wk of muscle disuse and recovery in women. Twenty women (BMI = 23.0 ± 2.3 kg/m2, age = 22 ± 3 yr) underwent 2 wk of unilateral limb immobilization followed by 2 wk of return to normal activity. Starting 4 wk prior to immobilization, participants consumed either 5 g/d of n-3 fatty acid or an isoenergetic quantity of sunflower oil (control). Muscle size and mass were measured pre- and postimmobilization, and after recovery. Serial muscle biopsies were obtained to measure integrated (daily) MyoPS. Following immobilization, the decline in muscle volume was greater in the control group compared to the n-3 fatty acid group (14 vs. 8%, P < 0.05) and was not different from preimmobilization at recovery in the n-3 fatty acid group; however, it was still lower in the control group ( P < 0.05). Muscle mass was reduced in the control group only ( P < 0.05). MyoPS was higher in the n-3 group compared with the control group at all times ( P < 0.05). We conclude that n-3 fatty acid supplementation attenuates skeletal muscle disuse atrophy in young women, which may be mediated by higher rates of MyoPS.-McGlory, C., Gorissen, S. H. M., Kamal, M., Bahniwal, R., Hector, A. J., Baker, S. K., Chabowski, A., Phillips, S. M. Omega-3 fatty acid supplementation attenuates skeletal muscle disuse atrophy during two weeks of unilateral leg immobilization in healthy young women.

Resistance training in young men induces muscle transcriptome-wide changes associated with muscle structure and metabolism refining the response to exercise-induced stress.

BACKGROUND: Gene expression is an important process underpinning the acute and chronic adaptive response to resistance exercise (RE) training. PURPOSE: To investigate the effect of training status on vastus lateralis muscle global transcriptome at rest and following acute RE. METHODS: Muscle biopsies of nine young men (age: 26(2) years; body mass: 69(9) kg; height 172(6) cm) who undertook RE training for 10 weeks were collected pre and 24 h post-RE in the untrained (W1) and trained (W10) states and analysed using microarray. Tests of differential expression were conducted for rested and after RE contrasts in both training states. To control for false discovery rate (FDR), multiple testing correction was performed at a cut-off of FDR < 0.05. RESULTS: Unaccustomed RE (at W1) upregulated muscle gene transcripts related to stress (e.g., heat shock proteins), damage and inflammation, structural remodelling, protein turnover and increased translational capacity. Trained muscles (at W10) showed changes in the transcriptome signature regarding the regulation of energy metabolism, favouring a more oxidative one, upregulated antioxidant- and immune-related genes/terms, and gene transcripts related to the cytoskeleton and extracellular matrix, muscle contraction, development and growth. CONCLUSIONS: These results highlight that chronic repetition of RE changes muscle transcriptome response towards a more refined response to RE-induced stress.

Recent Perspectives Regarding the Role of Dietary Protein for the Promotion of Muscle Hypertrophy with Resistance Exercise Training.

Skeletal muscle supports locomotion and serves as the largest site of postprandial glucose disposal; thus it is a critical organ for physical and metabolic health. Skeletal muscle mass is regulated by the processes of muscle protein synthesis (MPS) and muscle protein breakdown (MPB), both of which are sensitive to external loading and aminoacidemia. Hyperaminoacidemia results in a robust but transient increase in rates of MPS and a mild suppression of MPB. Resistance exercise potentiates the aminoacidemia-induced rise in MPS that, when repeated over time, results in gradual radial growth of skeletal muscle (i.e., hypertrophy). Factors that affect MPS include both quantity and composition of the amino acid source. Specifically, MPS is stimulated in a dose-responsive manner and the primary amino acid agonist of this process is leucine. MPB also appears to be regulated in part by protein intake, which can exert a suppressive effect on MPB. At high protein doses the suppression of MPB may interfere with skeletal muscle adaptation following resistance exercise. In this review, we examine recent advancements in our understanding of how protein ingestion impacts skeletal muscle growth following resistance exercise in young adults during energy balance and energy restriction. We also provide practical recommendations for exercisers who wish to maximize the hypertrophic response of skeletal muscle during resistance exercise training.

Pronounced energy restriction with elevated protein intake results in no change in proteolysis and reductions in skeletal muscle protein synthesis that are mitigated by resistance exercise.

Preservation of lean body mass (LBM) may be important during dietary energy restriction (ER) and requires equal rates of muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Currently, the relative contribution of MPS and MPB to the loss of LBM during ER in humans is unknown. We aimed to determine the impact of dietary protein intake and resistance exercise on MPS and MPB during a controlled short-term energy deficit. Adult men (body mass index, 28.6 ± 0.6 kg/m2; age 22 ± 1 yr) underwent 10 d of 40%-reduced energy intake while performing unilateral resistance exercise and consuming lower protein (1.2 g/kg/d, n = 12) or higher protein (2.4 g/kg/d, n = 12). Pre- and postintervention testing included dual-energy X-ray absorptiometry, primed constant infusion of ring-[13C6]phenylalanine, and 15[N]phenylalanine to measure acute postabsorptive MPS and MPB; D2O to measure integrated MPS; and gene and protein expression. There was a decrease in acute MPS after ER (higher protein, 0.059 ± 0.006 to 0.051 ± 0.009%/h; lower protein, 0.061 ± 0.005 to 0.045 ± 0.006%/h; P < 0.05) that was attenuated with resistance exercise (higher protein, 0.067 ± 0.01%/h; lower protein, 0.061 ± 0.006%/h), and integrated MPS followed a similar pattern. There was no change in MPB (energy balance, 0.080 ± 0.01%/hr; ER rested legs, 0.078 ± 0.008%/hr; ER exercised legs, 0.079 ± 0.006%/hr). We conclude that a reduction in MPS is the main mechanism that underpins LBM loss early in ER in adult men.-Hector, A. J., McGlory, C., Damas, F., Mazara, N., Baker, S. K., Phillips, S. M. Pronounced energy restriction with elevated protein intake results in no change in proteolysis and reductions in skeletal muscle protein synthesis that are mitigated by resistance exercise.

Protein Recommendations for Weight Loss in Elite Athletes: A Focus on Body Composition and Performance.

There exists a large body of scientific evidence to support protein intakes in excess of the recommended dietary allowance (RDA) (0.8 g protein/kg/day) to promote the retention of skeletal muscle and loss of adipose tissue during dietary energy restriction. Diet-induced weight loss with as low as possible ratio of skeletal muscle to fat mass loss is a situation we refer to as high-quality weight loss. We propose that high-quality weight loss is often of importance to elite athletes in order to maintain their muscle (engine) and shed unwanted fat mass, potentially improving athletic performance. Current recommendations for protein intakes during weight loss in athletes are set at 1.6-2.4 g protein/kg/day. However, the severity of the caloric deficit and type and intensity of training performed by the athlete will influence at what end of this range athletes choose to be. Other considerations regarding protein intake that may help elite athletes achieve weight loss goals include the quality of protein consumed, and the timing and distribution of protein intake throughout the day. This review highlights the scientific evidence used to support protein recommendations for high-quality weight loss and preservation of performance in athletes. Additionally, the current knowledge surrounding the use of protein supplements, branched chain amino acids (BCAA), ß-hydroxy ß-methylbutyrate (HMB), and other dietary supplements with weight loss claims will be discussed.

Failed Recovery of Glycemic Control and Myofibrillar Protein Synthesis With 2 wk of Physical Inactivity in Overweight, Prediabetic Older Adults.

Background: Physical inactivity impairs insulin sensitivity, which is exacerbated with aging. We examined the impact of 2 wk of acute inactivity and recovery on glycemic control, and integrated rates of muscle protein synthesis in older men and women. Methods: Twenty-two overweight, prediabetic older adults (12 men, 10 women, 69 ± 4 y) undertook 7 d of habitual activity (baseline; BL), step reduction (SR; <1,000 steps.d-1 for 14 d), followed by 14 d of recovery (RC). An oral glucose tolerance test was used to assess glycemic control and deuterated water ingestion to measure integrated rates of muscle protein synthesis. Results: Daily step count was reduced (all p < .05) from BL at SR (7362 ± 3294 to 991 ± 97) and returned to BL levels at RC (7117 ± 3819). Homeostasis model assessment-insulin resistance increased from BL to SR and Matsuda insulin sensitivity index decreased and did not return to BL in RC. Glucose and insulin area under the curve were elevated from BL to SR and did not recover in RC. Integrated muscle protein synthesis was reduced during SR and did not return to BL in RC. Conclusions: Our findings demonstrate that 2 wk of SR leads to lowered rates of muscle protein synthesis and a worsening of glycemic control that unlike younger adults is not recovered during return to normal activity in overweight, prediabetic elderly humans. Clinical Trials Registration: ClinicalTrials.gov identifier: NCT03039556.

Whey protein supplementation preserves postprandial myofibrillar protein synthesis during short-term energy restriction in overweight and obese adults.

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/m(2)) completed a 14-d controlled hypoenergetic diet (-750 kcal/d). Participants were randomly assigned, double blind, to receive twice-daily supplements of isolated whey (27 g/supplement) or soy (26 g/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 0.7 ± 0.1 g/(kg · d). Before and after the dietary intervention, primed continuous infusions of L-[ring-(13)C6] phenylalanine and [(2)H5]-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.

Considerations for protein intake in managing weight loss in athletes.

A large body of evidence now shows that higher protein intakes (2-3 times the protein Recommended Dietary Allowance (RDA) of 0.8 g/kg/d) during periods of energy restriction can enhance fat-free mass (FFM) preservation, particularly when combined with exercise. The mechanisms underpinning the FFM-sparing effect of higher protein diets remain to be fully elucidated but may relate to the maintenance of the anabolic sensitivity of skeletal muscle to protein ingestion. From a practical point of view, athletes aiming to reduce fat mass and preserve FFM should be advised to consume protein intakes in the range of ∼1.8-2.7 g kg(-1) d(-1) (or ∼2.3-3.1 g kg(-1) FFM) in combination with a moderate energy deficit (-500 kcal) and the performance of some form of resistance exercise. The target level of protein intake within this recommended range requires consideration of a number of case-specific factors including the athlete's body composition, habitual protein intake and broader nutrition goals. Athletes should focus on consuming high-quality protein sources, aiming to consume protein feedings evenly spaced throughout the day. Post-exercise consumption of 0.25-0.3 g protein meal(-1) from protein sources with high leucine content and rapid digestion kinetics (i.e. whey protein) is recommended to optimise exercise-induced muscle protein synthesis. When protein is consumed as part of a mixed macronutrient meal and/or before bed slightly higher protein doses may be optimal.

Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial.

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.

Dose-dependent responses of myofibrillar protein synthesis with beef ingestion are enhanced with resistance exercise in middle-aged men.

Aging impairs the sensitivity of skeletal muscle to anabolic stimuli, such as amino acids and resistance exercise. Beef is a nutrient-rich source of dietary protein capable of stimulating muscle protein synthesis (MPS) rates in older men at rest. To date, the dose-response of myofibrillar protein synthesis to graded ingestion of protein-rich foods, such as beef, has not been determined. We aimed to determine the dose-response of MPS with and without resistance exercise to graded doses of beef ingestion. Thirty-five middle-aged men (59 ± 2 years) ingested 0 g, 57 g (2 oz; 12 g protein), 113 g (4 oz; 24 g protein), or 170 g (6 oz; 36 g protein) of (15% fat) ground beef (n = 7 per group). Subjects performed a bout of unilateral resistance exercise to allow measurement of the fed state and the fed plus resistance exercise state within each dose. A primed constant infusion of l-[1-(13)C]leucine was initiated to measure leucine oxidation and of l-[ring-(13)C(6)]phenylalanine was initiated to measure myofibrillar MPS. Myofibrillar MPS was increased with ingestion of 170 g of beef to a greater extent than all other doses at rest and after resistance exercise. There was more leucine oxidation with ingestion of 113 g of beef than with 0 g and 57 g, and it increased further after ingestion of 170 g of beef (all p < 0.05). Ingestion of 170 g of beef protein is required to stimulate a rise in myofibrillar MPS over and above that seen with lower doses. An isolated bout of resistance exercise was potent in stimulating myofibrillar MPS, and acted additively with feeding.

Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men.

Feeding stimulates robust increases in muscle protein synthesis (MPS); however, ageing may alter the anabolic response to protein ingestion and the subsequent aminoacidaemia. With this as background, we aimed to determine in the present study the dose-response of MPS with the ingestion of isolated whey protein, with and without prior resistance exercise, in the elderly. For the purpose of this study, thirty-seven elderly men (age 71 (sd 4) years) completed a bout of unilateral leg-based resistance exercise before ingesting 0, 10, 20 or 40 g of whey protein isolate (W0-W40, respectively). Infusion of l-[1-13C]leucine and l-[ring-13C6]phenylalanine with bilateral vastus lateralis muscle biopsies were used to ascertain whole-body leucine oxidation and 4 h post-protein consumption of MPS in the fed-state of non-exercised and exercised leg muscles. It was determined that whole-body leucine oxidation increased in a stepwise, dose-dependent manner. MPS increased above basal, fasting values by approximately 65 and 90 % for W20 and W40, respectively (P < 0·05), but not with lower doses of whey. While resistance exercise was generally effective at stimulating MPS, W20 and W40 ingestion post-exercise increased MPS above W0 and W10 exercised values (P < 0·05) and W40 was greater than W20 (P < 0·05). Based on the study, the following conclusions were drawn. At rest, the optimal whey protein dose for non-frail older adults to consume, to increase myofibrillar MPS above fasting rates, was 20 g. Resistance exercise increases MPS in the elderly at all protein doses, but to a greater extent with 40 g of whey ingestion. These data suggest that, in contrast to younger adults, in whom post-exercise rates of MPS are saturated with 20 g of protein, exercised muscles of older adults respond to higher protein doses.

Muscle time under tension during resistance exercise stimulates differential muscle protein sub-fractional synthetic responses in men.

We aimed to determine if the time that muscle is under loaded tension during low intensity resistance exercise affects the synthesis of specific muscle protein fractions or phosphorylation of anabolic signalling proteins. Eight men (24 ± 1 years (sem), BMI = 26.5 ± 1.0 kg m(-2)) performed three sets of unilateral knee extension exercise at 30% of one-repetition maximum strength involving concentric and eccentric actions that were 6 s in duration to failure (SLOW) or a work-matched bout that consisted of concentric and eccentric actions that were 1 s in duration (CTL). Participants ingested 20 g of whey protein immediately after exercise and again at 24 h recovery. Needle biopsies (vastus lateralis) were obtained while fasted at rest and after 6, 24 and 30 h post-exercise in the fed-state following a primed, constant infusion of l-[ring-(13)C(6)]phenylalanine. Myofibrillar protein synthetic rate was higher in the SLOW condition versus CTL after 24-30 h recovery (P < 0.001) and correlated to p70S6K phosphorylation (r = 0.42, P = 0.02). Exercise-induced rates of mitochondrial and sarcoplasmic protein synthesis were elevated by 114% and 77%, respectively, above rest at 0-6 h post-exercise only in the SLOW condition (both P < 0.05). Mitochondrial protein synthesis rates were elevated above rest during 24-30 h recovery in the SLOW (175%) and CTL (126%) conditions (both P < 0.05). Lastly, muscle PGC-1α expression was increased at 6 h post-exercise compared to rest with no difference between conditions (main effect for time, P < 0.001). These data show that greater muscle time under tension increased the acute amplitude of mitochondrial and sarcoplasmic protein synthesis and also resulted in a robust, but delayed stimulation of myofibrillar protein synthesis 24-30 h after resistance exercise.