Alcohol-Mediated Skeletal Muscle Adaptations and Their Impact on Comorbidities.

At-risk alcohol use has significant adverse effects on multiple tissue and organ systems, including the skeletal muscle. The pathophysiological mechanisms underlying alcohol-induced dysfunctional skeletal muscle (SKM) mass are multifactorial, involving decreased protein synthesis, increased protein degradation, impaired glucose homeostasis, bioenergetic dysregulation, aberrant extracellular matrix remodeling, impaired satellite cell function, circadian rhythm disruption, and epigenomic adaptations. This review provides a brief overview of these major alcohol-induced mechanisms of SKM dysfunction. Additionally, the review examines the current literature on alcohol-mediated SKM maladaptations in the context of comorbidities such as aging, alcohol-related liver disease, systemic and diet-induced metabolic dysregulation, cancer cachexia, and musculoskeletal pain. Although alcohol-induced skeletal muscle alterations may function as both the cause and consequence of these comorbid conditions, critical research gaps remain, particularly in the need for systematic clinical studies complemented by preclinical mechanistic research. Notably, 40% to 60% of people with at-risk alcohol use exhibit skeletal muscle maladaptations, yet data on associated healthcare or productivity loss costs are lacking. A comprehensive understanding of alcohol-induced SKM dysfunction is warranted for developing targeted interventions to reduce healthcare costs and improve quality of life in this population.