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 tested, improving grip strength and muscle tetanic force, persisting in the presence of chemotherapy, and without discernible changes in food intake or tumor growth.
Key Findings
Results
Dietary supplementation with ursolic acid significantly preserved skeletal muscle mass in all five mouse models of cancer cachexia tested.
Five distinct in vivo mouse models were used, driven by pancreatic, colon, and lung cancer cells of both mouse and human origin.
Ursolic acid demonstrated 'broad-spectrum effects toward cancer-induced skeletal muscle atrophy' across all models tested.
Models spanned multiple cancer types, suggesting a generalizable rather than cancer-type-specific effect.
Preservation of muscle mass was observed consistently regardless of the cancer cell line driving cachexia.
Results
Ursolic acid supplementation led to significant improvements in grip strength and muscle tetanic force in cancer cachexia models.
Both grip strength (a functional measure of whole-body muscle force) and tetanic force (a direct measure of isolated muscle contractile function) were significantly improved.
Improvements in muscle function were associated with preservation of muscle mass and muscle fiber size.
These functional improvements were observed across the cancer cachexia models studied.
Results
The protective effects of ursolic acid on skeletal muscle persisted in the presence of chemotherapy.
Ursolic acid's positive effects on muscle mass and strength were maintained when chemotherapy was co-administered.
This finding suggests ursolic acid may be compatible with standard cancer treatment regimens.
Chemotherapy is itself a known contributor to muscle wasting, making this finding particularly relevant to clinical translation.
Results
Ursolic acid's beneficial effects on muscle were not associated with discernible changes in food intake or tumor growth.
Food intake did not differ detectably between ursolic acid-supplemented and control animals, ruling out hyperphagia as a mechanism.
Tumor growth was not measurably affected by ursolic acid supplementation, indicating the muscle-protective effects are independent of effects on tumor burden.
This dissociation from tumor growth is important for establishing safety of ursolic acid in a cancer context.
Results
Ursolic acid inhibited greater than 90% of cancer-induced changes in skeletal muscle mRNA expression.
Ursolic acid inhibited >90% of cancer-induced changes in skeletal muscle mRNA expression.
This broad transcriptional effect suggests ursolic acid acts on fundamental regulatory pathways governing muscle catabolism.
Inhibition of atrophy-associated changes in skeletal muscle mRNA expression had previously been shown in rodents and dogs, and this study extends those findings to cancer cachexia models.
Results
Ursolic acid appeared to act directly on muscle cells by inhibiting catabolic effects of tumor-derived secreted factors.
Mechanistic evidence suggested ursolic acid acts directly on muscle cells rather than exclusively through systemic or tumor-mediated pathways.
Ursolic acid inhibited catabolic effects of tumor-derived secreted factors on muscle cells.
This direct muscle cell action is consistent with prior reports of ursolic acid inhibiting atrophy-associated mRNA changes in muscle.
Results
Ursolic acid preserved muscle fiber size in addition to whole-muscle mass in cancer cachexia models.
Positive effects were observed at the level of individual muscle fiber size, not only whole-muscle mass.
Preservation of muscle fiber size contributed to the functional improvements in grip strength and tetanic force.
Muscle fiber-level preservation suggests ursolic acid acts on the structural components of the muscle atrophy process.
What This Means
This research suggests that a natural compound called ursolic acid, found in foods like apple peels, rosemary, and holy basil, may help prevent the severe muscle loss (called cachexia) that commonly occurs in people with cancer. The study tested ursolic acid as a dietary supplement in five different mouse models of cancer, covering pancreatic, colon, and lung cancers. In every model tested, mice receiving ursolic acid maintained significantly more muscle mass and strength compared to untreated mice with cancer. Importantly, these benefits occurred without affecting how much the animals ate or how fast their tumors grew, and the protective effects continued even when chemotherapy was given at the same time.
The researchers also investigated how ursolic acid works at the molecular level. They found it blocked more than 90% of the gene expression changes that cancer normally causes in muscle tissue, and that it appeared to act directly on muscle cells to counteract harmful signals released by tumors. This suggests ursolic acid is targeting the core biological processes that drive cancer-related muscle wasting, rather than working through indirect or non-specific effects.
This research matters because cancer-related muscle loss is a major problem that reduces patients' ability to tolerate treatment, lowers quality of life, and shortens survival — and there are currently no approved treatments to prevent or reverse it. The fact that ursolic acid is a naturally occurring dietary compound that showed consistent protective effects across multiple cancer types, worked alongside chemotherapy, and did not promote tumor growth makes it a potentially attractive candidate for further study as a nutritional supplement for people undergoing cancer treatment. Human clinical trials would be needed to confirm whether these findings translate to people.
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Ducharme J, Ebert S, Cameron M, Schonk M, Callaway C, D'Lugos A, et al.. (2026). Dietary supplementation with ursolic acid preserves skeletal muscle mass and strength in mouse models of cancer cachexia.. American journal of physiology. Cell physiology. https://doi.org/10.1152/ajpcell.00159.2026