We reported, using a unilateral resistance training (RT) model, that training with high or low loads (mass per repetition) resulted in similar muscle hypertrophy and strength improvements in RT-naïve subjects. Here we aimed to determine whether the same was true in men with previous RT experience using a whole-body RT program and whether postexercise systemic hormone concentrations were related to changes in hypertrophy and strength. Forty-nine resistance-trained men (23 ± 1 yr, mean ± SE) performed 12 wk of whole-body RT. Subjects were randomly allocated into a higher-repetition (HR) group who lifted loads of ∼30-50% of their maximal strength (1RM) for 20–25 repetitions/set (n = 24) or a lower-repetition (LR) group (∼75–90% 1RM, 8–12 repetitions/set, n = 25), with all sets being performed to volitional failure. Skeletal muscle biopsies, strength testing, dual-energy X-ray absorptiometry scans, and acute changes in systemic hormone concentrations were examined pretraining and posttraining. In response to RT, 1RM strength increased for all exercises in both groups (P < 0.01), with only the change in bench press being significantly different between groups (HR, 9 ± 1, vs. LR, 14 ± 1 kg, P = 0.012). Fat- and bone-free (lean) body mass and type I and type II muscle fiber cross-sectional area increased following training (P < 0.01) with no significant differences between groups. No significant correlations between the acute postexercise rise in any purported anabolic hormone and the change in strength or hypertrophy were found. In congruence with our previous work, acute postexercise systemic hormonal rises are not related to or in any way indicative of RT-mediated gains in muscle mass or strength. Our data show that in resistance-trained individuals, load, when exercises are performed to volitional failure, does not dictate hypertrophy or, for the most part, strength gains.

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.

Skeletal muscle mass is regulated by a balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). In healthy humans, MPS is more sensitive (varying 4-5 times more than MPB) to changes in protein feeding and loading indicating that it is the primary locus determining gains in muscle mass. Performing resistance exercise (RE) followed by the consumption of protein results in an augmentation of MPS and, over time, can lead to muscle hypertrophy. The magnitude of the RE-induced increase in MPS (and potentially subsequent hypertrophy) is dictated by a variety of factors including: the dose of protein, source of protein, and possibly the distribution and timing of post-exercise protein ingestion. In addition, RE variables such as frequency of sessions, time under tension, volume, and training status play roles in regulating MPS. This review provides a brief overview of our current understanding of how RE and protein ingestion can influence gains in skeletal muscle mass in young, healthy individuals. It is the goal of this review to provide nutritional recommendations for optimal skeletal muscle adaptation. Specifically, we will focus on how the manipulation of protein intake during the recovery period following RE augments the adaptive response.

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.

The currently accepted amount of protein required to achieve maximal stimulation of myofibrillar protein synthesis (MPS) following resistance exercise is 20–25 g. However, the influence of lean body mass (LBM) on the response of MPS to protein ingestion is unclear. Our aim was to assess the influence of LBM, both total and the amount activated during exercise, on the maximal response of MPS to ingestion of 20 or 40 g of whey protein following a bout of whole‐body resistance exercise. Resistance‐trained males were assigned to a group with lower LBM (≤65 kg; LLBM n = 15) or higher LBM (≥70 kg; HLBM n = 15) and participated in two trials in random order. MPS was measured with the infusion of ¹³C_6‐phenylalanine tracer and collection of muscle biopsies following ingestion of either 20 or 40 g protein during recovery from a single bout of whole‐body resistance exercise. A similar response of MPS during exercise recovery was observed between LBM groups following protein ingestion (20 g – LLBM: 0.048 ± 0.018%·h⁻¹; HLBM: 0.051 ± 0.014%·h⁻¹; 40 g – LLBM: 0.059 ± 0.021%·h⁻¹; HLBM: 0.059 ± 0.012%·h⁻¹). Overall (groups combined), MPS was stimulated to a greater extent following ingestion of 40 g (0.059 ± 0.020%·h⁻¹) compared with 20 g (0.049 ± 0.020%·h⁻¹; P = 0.005) of protein. Our data indicate that ingestion of 40 g whey protein following whole‐body resistance exercise stimulates a greater MPS response than 20 g in young resistance‐trained men. However, with the current doses, the total amount of LBM does not seem to influence the response.

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/m ² , 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. FASEB J. 33, 4586–4597 (2019). www.fasebj.org