The RDA for protein describes the quantity that should be consumed daily to meet population needs and to prevent deficiency. Protein consumption in many countries exceeds the RDA; however, intake is often skewed toward the evening meal, whereas breakfast is typically carbohydrate rich and low in protein. We examined the effects of protein distribution on 24-h skeletal muscle protein synthesis in healthy adult men and women (n = 8; age: 36.9 ± 3.1 y; BMI: 25.7 ± 0.8 kg/m2). By using a 7-d crossover feeding design with a 30-d washout period, we measured changes in muscle protein synthesis in response to isoenergetic and isonitrogenous diets with protein at breakfast, lunch, and dinner distributed evenly (EVEN; 31.5 ± 1.3, 29.9 ± 1.6, and 32.7 ± 1.6 g protein, respectively) or skewed (SKEW; 10.7 ± 0.8, 16.0 ± 0.5, and 63.4 ± 3.7 g protein, respectively). Over 24-h periods on days 1 and 7, venous blood samples and vastus lateralis muscle biopsy samples were obtained during primed (2.0 μmol/kg) constant infusion [0.06 μmol/(kg⋅min)] of l-[ring-13C6]phenylalanine. The 24-h mixed muscle protein fractional synthesis rate was 25% higher in the EVEN (0.075 ± 0.006%/h) vs. the SKEW (0.056 ± 0.006%/h) protein distribution groups (P = 0.003). This pattern was maintained after 7 d of habituation to each diet (EVEN vs. SKEW: 0.077 ± 0.006 vs. 0.056 ± 0.006%/h; P = 0.001). The consumption of a moderate amount of protein at each meal stimulated 24-h muscle protein synthesis more effectively than skewing protein intake toward the evening meal.

Bed rest has a profoundly negative effect on muscle metabolism, mass, and function in middle-aged adults. Leucine supplementation may partially protect muscle health during relatively brief periods of physical inactivity. This trial was registered at clinicaltrials.gov as NCT00968344.

An increase in muscle force potentiation may function as a mechanism to prolong muscular endurance.

Reductions in skeletal muscle function occur during the course of healthy aging as well as with bedrest or diverse diseases such as cancer, muscular dystrophy, and heart failure. However, there are no accepted pharmacologic therapies to improve impaired skeletal muscle function. Nitric oxide may influence skeletal muscle function through effects on excitation-contraction coupling, myofibrillar function, perfusion, and metabolism. Here we show that augmentation of nitric oxide-cyclic guanosine monophosphate signaling by short-term daily administration of the phosphodiesterase 5 inhibitor sildenafil increases protein synthesis, alters protein expression and nitrosylation, and reduces fatigue in human skeletal muscle. These findings suggest that phosphodiesterase 5 inhibitors represent viable pharmacologic interventions to improve muscle function.

With muscular training, the central nervous system may regulate motor unit firing rates to sustain force output and delay fatigue. The aims of this study were to investigate motor unit firing rates and patterns of the adductor pollicis (AdP) muscle in young, able-bodied adults throughout a sustained submaximal isometric fatiguing contraction and postactivation potentiation pre-post 4 weeks of muscular endurance training. Fifteen participants (training group: N = 10; control group: N = 5) performed maximal voluntary contractions (MVCs) and a sustained isometric 20 % MVC fatigue task pre-post training. Single-motor-unit potentials were recorded from the AdP during the fatigue task with intramuscular fine-wire electrodes. Twitch force potentiation was measured during single-pulse electrical stimulation of the ulnar nerve before and after MVCs. The training group endurance trained their AdP muscle at 20 % MVC for 4 weeks. Mean motor unit firing rates were calculated every 5 % of endurance time (ET). ET increased by 45.2 ± 8.7 % (p < 0.001) following muscular endurance training. Although ET increased, mean motor unit firing rates during the fatigue task did not change significantly with training. The general motor unit firing pattern consisted of an initial slowing followed by an increase in firing rate late in fatigue and remained consistent pre-post training. Potentiation did not change following training. These data suggest that the ability of the neuromuscular system to sustain motor unit firing rate may serve as a mechanism to augment the duration of submaximal muscle performance and delay muscular fatigue.