Anabolic and anticatabolic actions of ketone bodies on skeletal muscle: potential relevance in the management of skeletal muscle wasting

Purpose of review Skeletal muscle loss is a hallmark of aging, disease, and physical inactivity, with few effective treatments. Ketone bodies are lipid-derived molecules whose endogenous production is substantially amplified under conditions characterized by carbohydrate deprivation (e.g. fasting, a ketogenic diet). Orally ingested ketone supplements are now available that can rapidly induce a pronounced state of ketosis lasting hours without dietary carbohydrate restriction. Historically, ketone bodies have been hypothesized to spare muscle protein during starvation. Recently, their potential anabolic and anticatabolic effects on skeletal muscle have garnered renewed research and clinical interest. This review examines emerging evidence on ketone body administration and its influence on skeletal muscle protein turnover and related signaling, with consideration for therapeutic application in muscle wasting and rehabilitation. Recent findings Oral ketone supplementation has been shown to enhance postprandial muscle protein synthesis (MPS) in healthy young males. Under inflammatory catabolic conditions, ketone bodies may also promote a favorable net protein balance via suppression of muscle protein breakdown (MPB). Summary Ketone body administration may attenuate MPB and stimulate MPS, suggesting potential utility in counteracting muscle wasting. However, further studies are needed to elucidate underlying mechanisms and assess long-term effects on muscle mass and function in clinical settings.