Sarcopenia, a loss of skeletal muscle mass and function, is prevalent in older people and associated with functional decline and mortality. Protein supplementation is necessary to maintain skeletal muscle mass and whey protein hydrolysates have the best nutrient quality among food proteins. In the first study, C57BL/6 mice were subjected to immobilization for 1 week to induce muscle atrophy. Then, mice were administered with four different whey protein hydrolysates for 2 weeks with continuous immobilization. Among them, soluble whey protein hydrolysate (WP-S) had the greatest increase in grip strength, muscle weight, and cross-sectional area of muscle fiber than other whey protein hydrolysates. To investigate the molecular mechanism, we conducted another experiment with the same experimental design. WP-S significantly promoted the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway and inhibited the PI3K/Akt/forkhead box O (FoxO) pathway. In addition, it increased myosin heavy chain (MyHC) expression in both the soleus and quadriceps and changed MyHC isoform expressions. In conclusion, WP-S attenuated muscle atrophy induced by immobilization by enhancing the net protein content regulating muscle protein synthesis and degradation. Thus, it is a necessary and probable candidate for developing functional food to prevent sarcopenia. Full article

Childhood growth and its sensitivity to dietary protein is reviewed within a Protein-Stat model of growth regulation. The coordination of growth of muscle and stature is a combination of genetic programming, and of two-way mechanical interactions involving the mechanotransduction of muscle growth through stretching by bone length growth, the core Protein-Stat feature, and the strengthening of bone through muscle contraction via the mechanostat. Thus, growth in bone length is the initiating event and this is always observed. Endocrine and cellular mechanisms of growth in stature are reviewed in terms of the growth hormone-insulin like growth factor-1 (GH-IGF-1) and thyroid axes and the sex hormones, which together mediate endochondral ossification in the growth plate and bone lengthening. Cellular mechanisms of muscle growth during development are then reviewed identifying (a) the difficulties posed by the need to maintain its ultrastructure during myofibre hypertrophy within the extracellular matrix and the concept of muscle as concentric “bags” allowing growth to be conceived as bag enlargement and filling, (b) the cellular and molecular mechanisms involved in the mechanotransduction of satellite and mesenchymal stromal cells, to enable both connective tissue remodelling and provision of new myonuclei to aid myofibre hypertrophy and (c) the implications of myofibre hypertrophy for protein turnover within the myonuclear domain. Experimental data from rodent and avian animal models illustrate likely changes in DNA domain size and protein turnover during developmental and stretch-induced muscle growth and between different muscle fibre types. Growth of muscle in male rats during adulthood suggests that “bag enlargement” is achieved mainly through the action of mesenchymal stromal cells. Current understanding of the nutritional regulation of protein deposition in muscle, deriving from experimental studies in animals and human adults, is reviewed, identifying regulation by amino acids, insulin and myofibre volume changes acting to increase both ribosomal capacity and efficiency of muscle protein synthesis via the mechanistic target of rapamycin complex 1 (mTORC1) and the phenomenon of a “bag-full” inhibitory signal has been identified in human skeletal muscle. The final section deals with the nutritional sensitivity of growth of muscle and stature to dietary protein in children. Growth in length/height as a function of dietary protein intake is described in the context of the breastfed child as the normative growth model, and the “Early Protein Hypothesis” linking high protein intakes in infancy to later adiposity. The extensive paediatric studies on serum IGF-1 and child growth are reviewed but their clinical relevance is of limited value for understanding growth regulation; a role in energy metabolism and homeostasis, acting with insulin to mediate adiposity, is probably more important. Information on the influence of dietary protein on muscle mass per se as opposed to lean body mass is limited but suggests that increased protein intake in children is unable to promote muscle growth in excess of that linked to genotypic growth in length/height. One possible exception is milk protein intake, which cohort and cross-cultural studies suggest can increase height and associated muscle growth, although such effects have yet to be demonstrated by randomised controlled trials. Full article

A low protein diet (LPD) has historically been used to delay uremic symptoms and decrease nitrogen (N)-derived catabolic products in patients with chronic kidney disease (CKD). In recent years it has become evident that nutritional intervention is a necessary approach to prevent wasting and reduce CKD complications and disease progression. While a 0.6 g/kg, high biological value protein-based LPD has been used for years, recent observational studies suggest that plant-derived LPDs are a better approach to nutritional treatment of CKD. However, plant proteins are less anabolic than animal proteins and amino acids contained in plant proteins may be in part oxidized; thus, they may not completely be used for protein synthesis. In this review, we evaluate the role of LPDs and plant-based LPDs on maintaining skeletal muscle mass in patients with CKD and examine different nutritional approaches for improving the anabolic properties of plant proteins when used in protein-restricted diets. Full article

Nutrition is a cornerstone in the management of chronic kidney disease (CKD). To limit urea generation and accumulation, a global reduction in protein intake is routinely proposed. However, recent evidence has accumulated on the benefits of plant-based diets and plant-derived proteins without a clear understanding of underlying mechanisms. Particularly the roles of some amino acids (AAs) appear to be either deleterious or beneficial on the progression of CKD and its complications. This review outlines recent data on the role of a low protein intake, the plant nature of proteins, and some specific AAs actions on kidney function and metabolic disorders. We will focus on renal hemodynamics, intestinal microbiota, and the production of uremic toxins. Overall, these mechanistic effects are still poorly understood but deserve special attention to understand why low-protein diets provide clinical benefits and to find potential new therapeutic targets in CKD. Full article

Low-protein diets (LPDs) are the main treatment for urea cycle disorders (UCDs) and organic acidemias (OAs). In most cases, LPDs start in childhood and must be continued into adulthood. The improved life expectancy of patients with UCDs and OAs raises the question of their consequences on nutritional status in adult subjects. As this topic has so far received little attention, we conducted a review of scientific studies that investigated the nutrient intake and nutritional status in adult patients with UCDs and branched chain organic acidemias (BCOAs) on LPD. Methods: The literature search was conducted in PubMed/MEDLINE, Scopus, EMBASE and Google Scholar from 1 January 2000 to 31 May 2020, focusing on nutrient intake and nutritional status in UCD and OA adult patients. Results: Despite protein restriction is recommended as the main treatment for UCDs and OAs, in these patients, protein intake ranges widely, with many patients who do not reach safety levels. When evaluated, micronutrient intake resulted below recommended values in some patients. Lean body mass resulted in most cases lower than normal range while fat body mass (FM) was often found normal or higher than the controls or reference values. Protein intake correlated inversely with FM both in adult and pediatric UCD patients. Conclusions: The clinical management of adult patients with UCDs and BCOAs should include an accurate assessment of the nutritional status and body composition. However, as little data is still available on this topic, further studies are needed to better clarify the effects of LPDs on nutritional status in adult UCD and BCOA patients. Full article

Deterioration of muscle strength during cancer results in functional limitation, poor quality of life and reduced survival. The indirect effects on muscle strength of nutritional interventions based on protein and amino acid derivatives targeted at improving muscle mass are poorly documented. A scoping review was performed to examine the available evidence on the effects of proteins, amino acids and their derivatives on muscle strength in adult cancer patients. Pubmed and Scopus databases were searched to identify research articles published in the last 10 years. Fourteen studies met the inclusion criteria, showing that changes in muscle strength following protein or amino acid supplementation are generally concordant with those in muscle mass in cancer patients. Administration of both energy and proteins in the presence of reduced oral intakes results in more robust effects on both muscle strength and mass. It is not clear whether this is due to the correction of the energy deficit or to an interaction between proteins and other macronutrients. The optimal mixture, type, and dose of amino acid/protein supplementation alone or in combination with other anabolic strategies should be determined to provide the best nutritional approach in cancer. Full article