Mechanism-based nutritional approaches in cancer cachexia

PURPOSE OF REVIEW: Cancer cachexia is a complex multiorgan wasting syndrome that negatively impacts on cancer patient's survival and quality of life. Standard nutritional support is considered insufficient to counteract cachexia, and no approved nutritional approach or standard of care for cachexia exists so far. This review highlights recent reports focused on nutrition, aimed at sparing skeletal muscle and targeting molecular pathways underlying cachexia with specific supplements. RECENT FINDINGS: In animal models of cancer cachexia, branched-chain amino acids (BCAAs) help restore skeletal muscle proteostasis. In combination with the alanine dipeptide, with strong proteinogenic potential, BCAAs enhance anabolic signaling and suppress proteolysis via mTOR. α-ketoisocaproate exerts additional protective effects against muscle loss by targeting the Akt/FoxO3a and myostatin signaling. Methionine and the derivative SAM improve muscle status via epigenetic control and REDD1 suppression. L-carnitine shows multitarget functions, including muscle proteostasis control, inflammation attenuation, and reduced muscle fibrosis. Omega-3 polyunsaturated fatty acids show anti-inflammatory properties, improve the nutritional status, and prevent adipose tissue browning. SUMMARY: Overall, recent findings in preclinical and partly in clinical studies indicate that nutrient-based interventions target complementary cancer cachexia alterations. It is likely that combinatorial approaches, integrating several specific nutrients, will provide an effective base for managing cancer patients during the long journey of the disease, building future interventions against cancer cachexia.