Emerging treatments

Drugs that affect the myostatin-activin pathway

The first in-human study investigating ACE-083 (a locally acting follistatin-based therapeutic that binds myostatin and other muscle regulators) in healthy postmenopausal women showed peak volume increases of 14.5% and 8.9% in the rectus femoris and tibialis anterior muscles (compared with placebo), respectively, but without changes in strength.[86] Subsequently, two clinical trials reported significant changes in various components of body composition, with a very mild effect on muscle function and strength, with LY2495655 (a monoclonal antibody that binds and neutralizes myostatin) and bimagrumab (a monoclonal antibody that binds to and inhibits activin receptor type 2B).[87][88] These drugs are still considered investigational, and further research is required.

Omega-3 fatty acids

Omega-3 fatty acids have the potential to enhance skeletal muscle anabolism and may reduce the impact of periods of limb immobilization on muscle mass atrophy.[89]

Leucine and hydroxymethylbutyrate (HMB)

Leucine, an essential amino acid, has the potential to activate the anabolic pathway leading to protein synthesis.[90] It has been suggested that supplementation of leucine can enhance and promote higher muscle mass and improve functional capacity in the long term.[91] HMB is a metabolite of the oxidation of leucine; around 5% of ingested leucine is converted to HMB.[92] HMB plays a role in preserving muscle mass through slowing muscle protein breakdown.[93] A study of young resistance-trained athletes receiving HMB for 12 weeks showed comparable effects to leucine supplementation on muscle hypertrophy.[94] An open-label randomized controlled trial in healthy older women concluded that HMB showed promising results in strength, although it had no significant effects on Short Physical Performance Battery score.[95] However, the role of HMB in older adults is still under debate.[96] The task force of the International Conference on Sarcopenia and Frailty Research (ICSFR) considered the benefits of supplementation with leucine and HMB in the management of sarcopenia, but it found the evidence base to be very limited for older adults with sarcopenia and was uncertain that any effect could be established.[2]

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