Application of novel deuterium oxide tracer techniques to determine the effects of ß-hydroxy ß-methylbutyrate (HMB) supplementation and exercise in ageing: a randomized placebo controlled trial

Background: Skeletal muscles are crucial in our interaction with the environment considering the fact that they play vital role in our movement, maintenance of posture and regulation of metabolic milieu of our body. Almost 40 % of the body is comprised of skeletal muscle. Adequate skeletal muscle functioning is commensurate upon a dynamic equilibrium in protein turnover whereby a balance in synthesis and breakdown maintains muscle mass. Old age is associated with an imbalance in this dynamic equilibrium and, hence, strategies are needed to mitigate it. Sarcopenia is a progressive and multifactorial process resulting in age-related deterioration in skeletal muscle mass and strength; characterized by decreases of 1-2%/year in muscle mass beyond the age of 50. Exercise, resistance (weight) training in particular, especially when combined with optimal nutritional interventions, has been shown to be an effective counter measure, arresting decline and substantially improving the physical strength and function. Advanced sarcopenia is synonymous with physical frailty, leading previously asymptomatic individuals to experience injurious events and acute/temporary disability. Given the high clinical costs of this insidious process; an in-depth understanding of aging muscle and protein metabolism is acutely needed. Considering the established anabolic role of leucine and its metabolites in the stimulation of protein synthesis and inhibition of protein degradation; we hypothesized that exercise coupled to supplementation of the leucine metabolite ß-hydroxy ß-methylbutyrate (HMB) would positively impact the skeletal muscle protein synthesis (MPS) leading to increased muscle mass and better functional capabilities in older individuals. Objectives: To determine the chronic effects (6 weeks) of ß-hydroxy ß-methylbutyrate (HMB) supplementation and exercise on muscle protein metabolism in older men. Design: This study was conducted in 16 healthy volunteers: Older men were randomly assigned to two groups (Treatment group; n=8, Age 67.8±1.1y, Height 1.76±0.02 m, BMI 28±1.2 kg.m-2: Placebo group; n=8, Age 68.5±1.1y, Height 1.74±0.02 m, BMI 27±0.9 kg.m-2) and asked to perform unilateral resistance exercise training regime (RET) of 6x8 repetitions at 75% 1RM for a period of 6 weeks. A randomised double-blinded placebo controlled trial was carried out and one group received ß-hydroxy ß-methylbutyrate (HMB) to ascertain the effects of supplementation on muscle protein synthesis. Results: Over a period of 6 weeks, RET increased 1-RM strength in both groups i.e. from a baseline of 398±22N to 499±30N in treatment group and 396±29N to 510±43N in placebo group. MVC increased from a baseline of 185±10Nm to 217±11Nm in placebo group (P<0.05) and 179±12Nm to 203±12Nm (P<0.05) in treatment group. Thigh lean mass assessed by DXA increased significantly over 6 weeks only in treatment group to 5734±245g p=0.015 vs 5644±323g p=0.06 in placebo group. VL thickness measured by ultrasound showed significant increases over 6 weeks in exercise legs of both groups, Placebo group: 20.7±0.6mm to 22.4±0.7mm P