# The Role of Ketogenic Diet and β-Hydroxybutyrate in the Prevention of Muscle Catabolism and Sarcopenia in Aging Populations: Mechanisms, Evidence, and Clinical Perspectives

## TL;DR

This paper explores how ketogenic diets and β-hydroxybutyrate may help prevent muscle loss in aging by acting as energy sources and signaling molecules.

## Contribution

The paper provides a novel integrative framework on the potential of ketogenic diets as an adjunct strategy for sarcopenia prevention.

## Key findings

- Ketogenic diets may preserve muscle mass and mitochondrial function in aging models.
- β-hydroxybutyrate influences muscle health through histone deacetylase inhibition and anti-inflammatory effects.
- Protein-adequate ketogenic diets combined with exercise may improve functional outcomes in sarcopenic individuals.

## Abstract

Sarcopenia, characterized by the progressive loss of skeletal muscle mass, strength, and function, represents a growing public health challenge in aging populations. Emerging mechanistic evidence suggests that ketogenic diets (KDs) and elevated circulating β-hydroxybutyrate (βOHB) levels may offer selective and context-dependent nutritional strategies to support muscle health during aging. This review summarizes current evidence on the effects of ketogenic diets and ketone body metabolism on muscle mass and function, with a focus on underlying molecular mechanisms and clinical relevance in older adults. βOHB acts not only as an alternative energy substrate but also as a signaling molecule, notably through histone deacetylase inhibition and modulation of inflammatory pathways. Nutritional ketosis in humans typically results in circulating βOHB concentrations of approximately 0.5–3.0 mM, which may be sufficient to engage some of these signaling pathways, although the extent of these effects in human tissues remains incompletely defined. Preclinical studies indicate that long-term ketogenic diets preserve muscle mass, strength, and mitochondrial function in aging models. Limited clinical evidence, largely derived from populations with sarcopenic obesity or metabolic comorbidities, suggests that protein-adequate ketogenic diets, when implemented as an adjunct to physical exercise, may help preserve fat-free mass and improve functional outcomes, while exogenous ketones show potential to augment post-exercise anabolic signaling. Overall, the integration of mechanistic and preliminary clinical data provides a supplementary and exploratory framework suggesting that ketogenic diets may represent a promising adjunctive strategy for sarcopenia prevention, although well-designed long-term randomized controlled trials are required to define their efficacy, safety, and optimal clinical application.