Can Supplemental Leucine Offset Disuse-induced Muscle Atrophy?

It is well established that skeletal muscle mass progressively declines with healthy ageing, a phenomenon commonly termed sarcopenia. Overtime, this leads to a loss in functional independence and provides an increased risk of developing a co-morbidity. Recent estimates suggest that 30% of those aged 75-84 years suffer from sarcopenia. As the 85-and-over population are rapidly expanding, sarcopenia places a considerable socio-economic burden to healthcare services. From a physiological perspective, the maintenance of muscle mass is dependent on a fine balance between muscle protein synthesis (MPS) and breakdown (MPB) rates. In old age, the MPS response to nutrition is impaired (termed 'anabolic resistance'), leaving muscle in a chronic catabolic state and ultimately underpinning the progression of sarcopenia.

Age-associated muscle anabolic resistance may stem from an accumulation of periods of inactivity/disuse, which are strongly associated with a decline in muscle mass (atrophy) in both the young and old. In fact, the associated loss of muscle mass is the most rapid at the onset of muscle disuse, with significant declines in muscle mass occurring after just 5 days of disuse. This is of particular importance since the average length of hospitalization in older individuals in 5-6 days. Disuse-induced muscle deconditioning is attributed to declines in MPS in response to nutrition, and potentially an elevated MPB. Therefore, an accumulation of these periods of disuse over a lifetime may lead to an acceleration in the trajectory of sarcopenia that is commonly seen with ageing. Consequently, nutritional strategies to maximize healthy musculoskeletal ageing should focus on alleviating muscle metabolic dysregulation during short-term disuse.

One approach to counteract muscle deterioration during short-term disuse is to increase dietary protein consumption. In fact, adequate protein intake is a necessity for muscle to remain in a positive net protein balance, with the importance of this nutritional intervention increasing during periods of disuse. However, this approach is not always feasible as activity levels are more limited during periods of disuse and individuals are thus less likely to consume adequate nutritional intake. A more feasible approach may be to enhance the anabolic potency of sub-optimal protein doses through supplementation with the amino acid, leucine. Leucine is unique in its ability to increase the protein balance more so than any other amino acid through stimulation of MPS and suppression of MPB. Leucine provides a strong anti-catabolic effect during hind limb immobilization in rats, which has yet to be examined in humans. Therefore, it is clear that leucine represents a viable strategy to offset the dysregulation of MPS and MPB and preserve musculoskeletal health during short-term disuse in both young and old individuals and thus warrants further investigation.

Participants:

Twenty-four healthy (non-obese, non-diabetic, non-smokers) males aged 18-35 years will be recruited to participate in the study. The current study will be a placebo controlled double-blind study with two intervention groups, in which, participants will be randomly assigned to receive supplemental leucine (LEU; n=12) or placebo (PLA; n=12) during 7 days of unilateral leg immobilization. Participants will be active, but athletically untrained (i.e. exercise ≤3x/week). All study procedures will be clearly explained and participants will provide written informed consent prior to obtaining baseline measures.