# Nutritional strategies against skeletal muscle wasting in cancer-associated cachexia: the role of β-hydroxybutyrate and polyunsaturated fatty acids

## TL;DR

This paper explores how β-hydroxybutyrate and polyunsaturated fatty acids may help prevent muscle loss in cancer patients.

## Contribution

The study proposes a novel nutritional strategy combining ketone bodies and polyunsaturated fatty acids to combat cancer-related muscle wasting.

## Key findings

- β-hydroxybutyrate and polyunsaturated fatty acids may reduce inflammation and metabolic stress in cancer cachexia.
- These compounds could help preserve skeletal muscle by modulating anabolic and catabolic pathways.
- Dietary supplementation with these nutrients may support muscle integrity in advanced cancer patients.

## Abstract

•Skeletal muscle homeostasis is closely related to the control of protein anabolism and catabolism.•Skeletal muscle wasting is highly prevalent in cancer-associated cachexia.•A combination of ketone bodies and polyunsaturated fatty acids intake may help to preserve skeletal muscle integrity in cancer-associated cachexia.

Skeletal muscle homeostasis is closely related to the control of protein anabolism and catabolism.

Skeletal muscle wasting is highly prevalent in cancer-associated cachexia.

A combination of ketone bodies and polyunsaturated fatty acids intake may help to preserve skeletal muscle integrity in cancer-associated cachexia.

Cachexia is a multifactorial syndrome that occurs in many cancers, particularly in their advanced stages, decreasing the quality of life and lifespan of patients. One of the hallmarks of cancer-associated cachexia is skeletal muscle wasting. Multiple causes include inflammation, metabolic deregulation, energy utilization, endoplasmic reticulum and oxidative stress. Loss of skeletal muscle is characterised by an imbalance in protein homeostasis, with decreased anabolism (regulated by the Akt/GSK3/eIF2α and Akt/mTORC1 pathways) and increased catabolism (regulated by autophagy and the ubiquitin-proteasome system), as well as an impairment in myogenesis. Accumulating evidence suggests that dietary intervention of β-hydroxybutyrate, the major ketone body produced by ketogenesis, and n-3 polyunsaturated fatty acids may mitigate skeletal muscle wasting. Polyunsaturated fatty acids and β-hydroxybutyrate are able to favourably modulate inflammation, insulin resistance, unfolded protein response and stresses (such as metabolic stress and oxidative stress). A well-adapted nutritional strategy may include a “classic” diet supplemented with β-hydroxybutyrate and polyunsaturated fatty acids to maintain skeletal muscle integrity and reduce wasting.

Image, graphical abstract