Context Lean body mass is essential for health, yet consensus regarding the effectiveness of protein interventions in increasing lean body mass is lacking. Objective The aim of this systematic review was to evaluate the dose–response relationship of the effects of protein intake on lean body mass. Data Sources The PubMed and Ichushi-Web databases were searched electronically, and reference lists of the literature included here and in other meta-analyses were searched manually. Study Selection Randomized controlled trials evaluating the effects of protein intake on lean body mass were included. Data Extraction Two authors independently screened the abstracts; 5 reviewed the full texts. Results A total of 5402 study participants from 105 articles were included. In the multivariate spline model, the mean increase in lean body mass associated with an increase in protein intake of 0.1 g/kg of body weight per day was 0.39 kg (95%CI, 0.36–0.41) and 0.12 kg (95%CI, 0.11–0.14) below and above the total protein intake of 1.3 g/kg/d, respectively. Conclusions These findings suggest that slightly increasing current protein intake for several months by 0.1 g/kg/d in a dose-dependent manner over a range of doses from 0.5 to 3.5 g/kg/d may increase or maintain lean body mass. Systematic Review Registration UMIN registration number UMIN000039285.

Whey protein (WP) is characterized as a “fast” protein and caseinate (CA) as a “slow” protein according to their digestion and absorption rates. We hypothesized that co-ingestion of milk proteins (WP and CA) may be effective for prolonging the muscle protein synthesis response compared to either protein alone. We therefore compared the effect of ingesting milk protein (MP) to either WP or CA alone on muscle protein synthesis after exercise in rats. We also compared the effects of these milk-derived proteins to a control, soy protein (SP). Male Sprague-Dawley rats swam for two hours. Immediately after exercise, one of the following four solutions was administered: WP, CA, MP, or SP. Individual rats were euthanized at designated postprandial time points and triceps muscle samples collected for measurement of the protein fractional synthesis rate (FSR). FSR tended to increase in all groups post-ingestion, although the initial peaks of FSR occurred at different times (WP, peak time = 60 min, FSR = 7.76%/day; MP, peak time = 90 min, FSR = 8.34%/day; CA, peak time = 120 min, FSR = 7.85%/day). Milk-derived proteins caused significantly greater increases (p < 0.05) in FSR compared with SP at different times (WP, 60 min; MP, 90 and 120 min; CA, 120 min). Although statistical analysis could not be performed, the calculated the area under the curve (AUC) values for FSR following this trend were: MP, 534.61; CA, 498.22; WP, 473.46; and SP, 406.18. We conclude that ingestion of MP, CA or WP causes the initial peak time in muscle protein synthesis to occur at different times (WP, fast; MP, intermediate; CA, slow) and the dairy proteins have a superior effect on muscle protein synthesis after exercise compared with SP.

Background Muscle protein synthesis (MPS) can be stimulated by ingestion of protein sources, such as whey, casein, or soy. Protein supplementation can enhance muscle protein synthesis after exercise and may preserve skeletal muscle mass and function in aging adults. Therefore, identifying protein sources with higher anabolic potency is of high significance. Objective The aim of this study was to determine the anabolic potency and efficacy of a novel whey protein hydrolysate mixture (WPH) on mechanistic target of rapamycin complex 1 (mTORC1) signaling and skeletal MPS in healthy young subjects. Methods Ten young men (aged 28.7 ± 3.6 y, 25.2 ± 2.9 kg/m2 body mass index [BMI]) were recruited into a double-blind two-way crossover trial. Subjects were randomized to receive either 0.08 g/kg of body weight (BW) of WPH or an intact whey protein (WHEY) mixture during stable isotope infusion experiments. Fractional synthetic rate, leucine and phenylalanine kinetics, and markers of amino acid sensing were assessed as primary outcomes before and 1–3 h after protein ingestion using a repeated measures mixed model. Results Blood leucine concentration, delivery of leucine to muscle, transport of leucine from blood into muscle and intracellular muscle leucine concentration significantly increased to a similar extent 1 h after ingestion of both mixtures (P &lt; 0.05). Phosphorylation of S6K1 (i.e. a marker of mTORC1 activation) increased equally by ∼20% 1-h postingestion (P &lt; 0.05). Ingestion of WPH and WHEY increased mixed MPS similarly in both groups by ∼43% (P &lt; 0.05); however, phenylalanine utilization for synthesis increased in both treatments 1-h postingestion but remained elevated 3-h postingestion only in the WPH group (P &lt; 0.05). Conclusions We conclude that a small dose of WPH effectively increases leucine transport into muscle, activating mTORC1 and stimulating MPS in young men. WPH anabolic potency and efficacy for promoting overall muscle protein anabolism is similar to WHEY, an intact protein source. This trial was registered at clinicaltrials.gov as NCT03313830.

It is well known that ingestion of a protein source is effective in stimulating muscle protein synthesis after exercise. In addition, there are numerous reports on the impact of leucine and leucine-rich whey protein on muscle protein synthesis and mammalian target of rapamycin (mTOR) signalling. However, there is only limited information on the effects of whey protein hydrolysates (WPH) on muscle protein synthesis and mTOR signalling. The aim of the present study was to compare the effects of WPH and amino acids on muscle protein synthesis and the initiation of translation in skeletal muscle during the post-exercise phase. Male Sprague -Dawley rats swam for 2 h to depress muscle protein synthesis. Immediately after exercise, the animals were administered either carbohydrate (CHO), CHO plus an amino acid mixture (AA) or CHO plus WPH. At 1 h after exercise, the supplements containing whey-based protein (AA and WPH) caused a significant increase in the fractional rate of protein synthesis (FSR) compared with CHO. WPH also caused a significant increase in FSR compared with AA. Post-exercise ingestion of WPH caused a significant increase in the phosphorylation of mTOR levels compared with AA or CHO. In addition, WPH caused greater phosphorylation of ribosomal protein S6 kinase and eukaryotic initiation factor 4E-binding protein 1 than AA and CHO. In contrast, there was no difference in plasma amino acid levels following supplementation with either AA or WPH. These results indicate that WPH may include active components that are superior to amino acids for stimulating muscle protein synthesis and initiating translation.

Purpose The purpose of this study was to examine whether long-term ingestion of low-dose milk protein supplementation causes a greater increase in muscle mass and strength of older adults during low-to-moderate intensity exercise training intervention than isocaloric carbohydrate. Methods In a randomized, double-blind, and placebo-controlled design, 122 healthy older adults (60–84 year) received either an acidified milk protein drink containing 10 g of milk protein (MILK; n = 61) or an isocaloric placebo drink (PLA; n = 61) daily throughout 6 months of body weight and medicine ball exercise training. Measurements before and after the intervention included body composition, physical performance and blood biochemistry. Results Lean body mass significantly increased in the MILK group (+ 0.54 kg, p < 0.001), but did not change in the PLA group (− 0.10 kg, p = 0.534). The increases in the MILK group were significantly greater than in the PLA group (p = 0.004). Fat mass (− 0.77 kg) and plasma uric acid levels (− 0.3 mg/dL) significantly decreased only in the MILK group (p < 0.001), with a significant group difference (p = 0.002 and p < 0.001, respectively). Most of the physical performance tests significantly improved in both groups, but no group differences were found. Conclusion We conclude that low-dose milk protein supplementation (10 g of protein/day) combined with low-to-moderate intensity exercise training is associated with increased muscle mass, but not improved physical performance compared to carbohydrate combined with exercise in healthy older adults. This study was registered in the UMIN Clinical Trials Registry (UMIN000032189).