A natural dietary supplement preserved muscle mass and strength in mice, counteracting the effects of a harmful condition called cancer cachexia, UF Health Cancer Institute researchers found.
The compound, ursolic acid, shows promise to be used as a nutritional treatment for the condition in humans, according to the study, published recently in the American Journal of Physiology – Cell Physiology.
“Importantly, ursolic acid appeared to generate its beneficial effects in skeletal muscle by acting directly on muscle cells, which distinguishes it from other emerging therapies that target appetite and food intake,” said senior author Andrew Judge, Ph.D., a professor in the Department of Physical Therapy in the UF College of Public Health and Health Professions. “Ultimately, we believe that multimodal therapies targeting skeletal muscle, appetite and other key mechanisms will provide the greatest opportunity to prevent or reverse cancer cachexia.”
As many as half of all people living with cancer, and up to 80% of people living with advanced cancer, lose significant muscle and body weight. The condition, known as cancer cachexia, impairs physical function and reduces independence in daily living. Cachexia can also lower tolerance to cancer treatments like chemotherapy, radiation and immunotherapy, increase surgical complications, and shorten lifespan.
There are no FDA-approved treatments for cancer cachexia. The American Society of Clinical Oncology recommends dietary counseling for people living with cancer cachexia. It recommends clinicians consider low-dose olanzapine to improve appetite and weight gain in adults with advanced cancer.
The new study built on research by Judge lab collaborators showing ursolic acid decreases muscle atrophy and weakness in preclinical models. Ursolic acid is abundant in apples and other edible herbs and fruits.
“We wanted to find out whether supplementing standard rodent chow with ursolic acid could protect against cancer-induced muscle atrophy and weakness,” Judge said.
The researchers tested the idea in five preclinical models of pancreatic, colon and lung cancer. Supplementation significantly preserved muscle mass in all five cancer cachexia models, the researchers found. Its positive effects on muscle mass and muscle fiber size led to significant improvements in grip strength and muscle force production. Ursolic acid had the same effects even when the mice were receiving chemotherapy.
Ursolic acid supplements have recently become available to improve muscle health in dogs and cats, and Judge’s lab is working to bring them to humans. His lab recently completed a National Institutes of Health grant in collaboration with the pharmaceutical company Emmyon testing a chemical derivative of ursolic acid in preclinical models of cancer cachexia. Those results will serve as a foundation for studies that will lay the groundwork to ultimately test the supplement in humans.
Judge encouraged anyone with cancer or caring for someone with cancer experiencing involuntary weight loss to speak with their healthcare provider. Often, healthcare providers can refer patients to a registered dietician or physical therapist.
“We hope that very soon healthcare providers will also be able to offer nutritional and pharmacological therapeutics that target muscle health and improve physical function in people living with, or recovering from, cancer,” Judge said.
Jeremy Ducharme, Ph.D., the study’s first author, participated in the UF Health Cancer Institute’s NCI-funded Team-based Interdisciplinary Cancer Research Training Program. The study received funding from the U.S. Department of Veterans, Florida Department of Health, National Cancer Institute and UF Health Cancer Institute.
Judge and other co-authors have an interest in Emmyon, which is licensed to make ursolic acid to preserve muscle mass and function.
