The Combined Oral Stable Isotope Assessment of Muscle (COSIAM) reveals D-3 creatine derived muscle mass as a standout cross-sectional biomarker of muscle physiology vitality in older age.

Validated diagnostics of skeletal muscle vitality could benefit clinical and basic science in terms of mechanistic insights and in determining the efficacy of interventions, e.g. exercise/pharmaceuticals/nutrients. We recently developed a Combined Oral Assessment of Muscle (COSIAM) that can be used to simultaneously quantify whole-body muscle mass (WBMM), muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Here, we aimed to establish, in a cross-sectional fashion, links between COSIAM parameters and established aspects of muscle function. We recruited 37 healthy older adults (male (M):female (F) (21/16); 72 ± 5 y)) into a 3-day trial. Subjects consumed D3-creatine (D3-Cr dilution to assess WBMM), D2O (MPS by incorporation of alanine) and D3-3-methylhistidine (D3-MH dilution to assess MPB). A biopsy at day 3 was used to determine MPS, and blood/urine samples were collected to determine D3-Cr/D3-MH dilution for WBMM and MPB. Physiological measures of muscle mass (e.g. DXA/ultrasound) and function (e.g. handgrip strength, maximum voluntary contraction (MVC), one-repetition maximum (1-RM)) were ascertained. A stepwise linear regression approach was used to address links between facets of COSIAM (MPS, MPB, WBMM) and muscle physiology. Despite expected differences in muscle mass, there were no significant differences in MPS or MPB between sexes. WBMM as measured using D3-Cr positively correlated with DXA-derived lean body mass (LBM) and appendicular LBM (ABLM). Stepwise linear regression was used to assess which combination of MPS, MPB, D3-Cr and absolute synthesis rate (ASR) best predicted physiological measures of muscle health in these older adults. D3-Cr WBMM alone was the best predictor of handgrip, 1RM and MVC, and outperformed more traditional measures of muscle mass by DXA. The COSIAM approach substantiates D3-Cr as a robust biomarker of multiple muscle physiology health biomarkers. Future work using COSIAM should focus upon how and which parameters it can inform upon in relation to disease progression and the efficacy of interventions.

Combined in vivo muscle mass, muscle protein synthesis and muscle protein breakdown measurement: a 'Combined Oral Stable Isotope Assessment of Muscle (COSIAM)' approach.

Optimising approaches for measuring skeletal muscle mass and turnover that are widely applicable, minimally invasive and cost effective is crucial in furthering research into sarcopenia and cachexia. Traditional approaches for measurement of muscle protein turnover require infusion of expensive, sterile, isotopically labelled tracers which limits the applicability of these approaches in certain populations (e.g. clinical, frail elderly). To concurrently quantify skeletal muscle mass and muscle protein turnover i.e. muscle protein synthesis (MPS) and muscle protein breakdown (MPB), in elderly human volunteers using stable-isotope labelled tracers i.e. Methyl-[D3]-creatine (D3-Cr), deuterium oxide (D2O), and Methyl-[D3]-3-methylhistidine (D3-3MH), to measure muscle mass, MPS and MPB, respectively. We recruited 10 older males (71 ± 4 y, BMI: 25 ± 4 kg.m2, mean ± SD) into a 4-day study, with DXA and consumption of D2O and D3-Cr tracers on day 1. D3-3MH was consumed on day 3, 24 h prior to returning to the lab. From urine, saliva and blood samples, and a single muscle biopsy (vastus lateralis), we determined muscle mass, MPS and MPB. D3-Cr derived muscle mass was positively correlated to appendicular fat-free mass (AFFM) estimated by DXA (r = 0.69, P = 0.027). Rates of cumulative myofibrillar MPS over 3 days were 0.072%/h (95% CI, 0.064 to 0.081%/h). Whole-body MPB over 6 h was 0.052 (95% CI, 0.038 to 0.067). These rates were similar to previous literature. We demonstrate the potential for D3-Cr to be used alongside D2O and D3-3MH for concurrent measurement of muscle mass, MPS, and MPB using a minimally invasive design, applicable for clinical and frail populations.