β-Hydroxy-β-Methylbutyrate as a Countermeasure for Cancer Cachexia: A Cellular and Molecular Rationale
Andy V. Khamoui,
Won Jun Lee.
Cancer cachexia is a life-threatening condition characterized by involuntary body weight loss and skeletal muscle wasting. In
addition to being associated with poor prognosis and reduced survival, patients with cachexia exhibit a critical loss of physical function
that impinges upon their ability to perform basic activities of daily living. Consequently, there is a loss of independence and a drastically
reduced quality of life. Despite being a major unmet medical need of patients, very few treatment options exist. Maintaining muscle mass
represents an important objective in the cancer patient trajectory not only because it relates to one’s capacity to perform activities of daily
living, but also because muscle preservation may be a critical determinant of survival while in a tumor-bearing state. In this regard,
research has been directed towards identifying countermeasures effective in preserving muscle. With respect to nutritional approaches,
administration of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) could be a viable component in multi-modal therapies
targeting cancer cachexia. Evidence suggests that HMB treatment promotes regenerative events (i.e. myogenic program), suppresses
protein degradation, and activates signaling pathways preceding protein synthesis and skeletal muscle growth. HMB therefore, could
conceivably act on key regulatory events driving cancer cachexia, thereby favoring muscle growth/preservation. In this review, we take a
mechanistic approach in making a case for the use of HMB provision as a possible therapeutic strategy for cancer cachexia by
highlighting the cellular and molecular aspects of HMB function.
Keywords: HMB, atrophy, skeletal muscle, protein turnover, regeneration, signaling.
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