Stable isotope approaches to study muscle mass outcomes in clinical populations

This is the final version. Available on open access from Elsevier via the DOI in this recordBoth low muscle mass and muscle loss are associated with reduced physical function, mobility, independence, and quality of life, and are characteristic of a number of clinical conditions including diabetes, cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), and critical illness. The accurate measurement of muscle mass is critical to assess the efficacy of an intervention or therapy. Stable isotope amino acid approaches can be used to quantify specific aspects of whole-body and muscle protein turnover, including synthesis and breakdown, which play distinctive roles in muscle mass maintenance in direct response to therapies. This review aims to elucidate whether acute responses measured using stable isotope amino acid tracers relate to changes in muscle mass in vulnerable clinical populations. Experimental studies quantifying whole-body protein synthesis and breakdown rates in clinical populations have been conducted to determine the response to nutritional interventions or to compare disease with health; however, these studies show limited potential to translate to expected muscle mass outcomes. In addition, clinical studies that have assessed both muscle mass and acute changes in whole-body or muscle protein turnover are lacking. We argue that the assessment of both muscle protein synthesis and breakdown rates, or simply limb net balance, obtains the most complete picture in relation to muscle-specific outcomes. While stable isotope amino acid tracer experiments provide meaningful mechanistic insight into the acute response to clinical interventions, they should be combined with, and/or followed-up by, longer-term studies incorporating measurements of muscle mass to ascertain the impact of an intervention on muscle mass maintenance in clinical populations

Intermittent versus continuous enteral nutrition attenuates increases in insulin and leptin during short-term bed rest

This is the final version. Available on open access from Springer via the DOI in this recordPurpose: To compare endocrine responses to intermittent vs continuous enteral nutrition provision during short-term bed rest. Methods: Twenty healthy men underwent 7 days of bed rest, during which they were randomized to receive enteral nutrition (47%E as carbohydrate, 34%E as fat, 16%E as protein and 3%E as fibre) in a continuous (CONTINUOUS; n = 10; 24 h day−1 at a constant rate) or intermittent (INTERMITTENT; n = 10; as 4 meals per day separated by 5 h) pattern. Daily plasma samples were taken every morning to assess metabolite/hormone concentrations. Results: During bed rest, plasma leptin concentrations were elevated to a lesser extent with INTERMITTENT vs CONTINUOUS (iAUC: 0.42 ± 0.38 vs 0.95 ± 0.48 nmol L−1, respectively; P = 0.014) as were insulin concentrations (interaction effect, P < 0.001) which reached a peak of 369 ± 225 pmol L−1 in CONTINUOUS, compared to 94 ± 38 pmol L−1 in INTERMITTENT (P = 0.001). Changes in glucose infusion rate were positively correlated with changes in fasting plasma GLP-1 concentrations (r = 0.44, P = 0.049). Conclusion: Intermittent enteral nutrition attenuates the progressive rise in plasma leptin and insulinemia seen with continuous feeding during bed rest, suggesting that continuous feeding increases insulin requirements to maintain euglycemia. This raises the possibility that hepatic insulin sensitivity is impaired to a greater extent with continuous versus intermittent feeding during bed rest. To attenuate endocrine and metabolic changes with enteral feeding, an intermittent feeding strategy may, therefore, be preferable to continuous provision of nutrition. This trial was registered on clinicaltrials.gov as NCT02521025.University of Bat

Dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during short-term bed rest

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this record.Short periods of bed rest lead to the loss of muscle mass and quality. It has been speculated that dietary feeding pattern may impact upon muscle protein synthesis rates and, therefore, modulate the loss of muscle mass and quality. We subjected 20 healthy men (age: 25±1 y, BMI: 23.8±0.8 kg·m-2) to one week of strict bed rest with intermittent (4 meals/day) or continuous (24 h/day) enteral tube feeding. Participants consumed deuterium oxide for 7 days prior to bed rest and throughout the 7-day bed rest period. Prior to and immediately after bed rest, lean body mass (DXA), quadriceps cross-sectional area (CSA; CT), maximal oxygen uptake capacity (VO2peak), and whole-body insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) were assessed. Muscle biopsies were collected 7 days prior to, 1 day prior to, and immediately after bed rest to assess muscle tracer incorporation. Bed rest resulted in 0.3±0.3 vs 0.7±0.4 kg lean tissue loss and a 1.1±0.6 vs 0.8±0.5% decline in quadriceps CSA in the intermittent vs continuous feeding group, respectively (both P0.05). Moreover, feeding pattern did not modulate the bed rest-induced decline in insulin sensitivity (-46±3% vs 39±3%; P0.05). Myofibrillar protein synthesis rates during bed rest did not differ between the intermittent and continuous feeding group (1.33±0.07 vs 1.50±0.13%·d−1, respectively; P>0.05). In conclusion, dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during one week of bed rest in healthy men