L-Ornithine salts as somatotropic axis modulators for the correction of sarcopenia in chronic liver disease

Sarcopenia is a syndrome characterized by a progressive and generalized loss of skeletal muscle mass, strength, and function, that exists in a primary and a secondary form. Secondary sarcopenia complicates chronic liver disease with a prevalence ranging from 30 to 100% depending on the nature of disease, its severity, and compensation status. The presence of sarcopenia limits normal daily activity, reduces work capacity, diminishes quality of life, may lead to disability, and increases all-cause mortality risk. Despite the evident medical and social burden of this condition, as of today, no agents for its treatment have proven to be both effective and safe. Significant attention of the scientific community has recently been drawn to molecules that improve and normalize the somatotropic axis function, which is found to be impaired in all types of sarcopenia. L-ornithine and its salts (L-aspartate, α-ketoglutarate) are not only capable of direct hepatoprotection and facilitation of ammonia clearance, but also modulate the somatotropic axis as well as have a number of pleiotropic metabolic effects. Preclinical studies have found L-ornithine to act as an indirect growth hormone secretagogue and enhance the activity of its main effector molecule, insulin-like growth factor 1. In clinical trials, course treatment with L-ornithine L-aspartate as an add-on to standard therapy increased the levels of circulating growth hormone, promoted arm muscle growth, improved handgrip strength and standing balance. L-ornithine α-ketoglutarate increased appetite and skeletal muscle gain in malnourished older adults, mitigated glutamine loss by skeletal muscle following major surgery, and improved quality of life in elderly convalescent subjects. The available data suggest potential effectiveness of L-ornithine formulations for the treatment of sarcopenia associated with chronic liver disease, and highlight this indication as an important field for future research.