Dietary supplementation with ursolic acid preserves skeletal muscle mass and strength in mouse models of cancer cachexia.

Skeletal muscle atrophy is a devastating and defining feature of cancer cachexia that reduces quality of life, treatment tolerance, and survival, but cannot be prevented or reversed by current management strategies. Ursolic acid is a natural dietary compound that has been shown to inhibit atrophy-associated changes in skeletal muscle mRNA expression in rodents and dogs, leading to beneficial changes in skeletal muscle structure and function. We hypothesized that dietary supplementation with ursolic acid might help support skeletal muscle mass and function during cancer. To test this hypothesis, we investigated ursolic acid's effects in five in vivo mouse models of cancer cachexia that are driven by pancreatic, colon, and lung cancer cells of mouse and human origin. We found that dietary supplementation with ursolic acid has broad-spectrum effects toward cancer-induced skeletal muscle atrophy, significantly preserving muscle mass in all five cancer cachexia models. Ursolic acid's positive effects on muscle mass and muscle fiber size led to significant improvements in grip strength and muscle tetanic force, persisted in the presence of chemotherapy, and were not associated with discernible changes in food intake or tumor growth. Ursolic acid appeared to generate its beneficial effects in skeletal muscle by acting directly on muscle cells, inhibiting catabolic effects of tumor-derived secreted factors, and inhibiting >90% of cancer-induced changes in skeletal muscle mRNA expression. These results strongly nominate ursolic acid as a promising potential nutritional approach for supporting muscle mass and function in individuals with cancer.NEW & NOTEWORTHY Cancer-induced muscle wasting affects many people with cancer, reducing treatment tolerance and survival. We identified a natural dietary compound, ursolic acid, that attenuates muscle atrophy across five preclinical cancer models spanning pancreatic, colon, and lung cancer. Ursolic acid inhibits cancer-induced changes in muscle mRNA expression, preserves muscle strength, and remains protective during chemotherapy, without affecting food intake or tumor burden. These results identify ursolic acid as a promising, translatable dietary supplement for supportive cancer care.