Creatine is widely known as a supplement used by athletes and bodybuilders to improve strength and performance. Now, new research from UCLA suggests it may have another surprising role: helping the immune system mount a stronger attack against cancer.
The study, published in iSciencediscovered that creatine increases the activity of dendritic cells, specialized immune cells that detect tumors and activate killer T cells responsible for destroying cancer. The findings, based on experiments in mice and human cells, are based on previous research from the same lab that shows creatine also improves the function of cancer-fighting T cells.
Creatine May Strengthen Cancer Immunotherapy
Many of the current cancer immunotherapies are designed to activate killer T cells, but only 20% to 40% of patients experience significant benefits. The UCLA team believes that improving the function of dendritic cells, which coordinate and direct those T cells, could make immunotherapy effective for more people.
“Immunotherapy has shown great promise, but it only works for a subset of patients,” said Lili Yang, senior author of the study, professor of microbiology, immunology and molecular genetics and member of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA. “What this study shows is that creatine not only helps T cells fight cancer, but also energizes the entire infrastructure that supports and guides them. That makes creatine a promising supplement to comprehensively support the immune response that modern immunotherapies depend on.”
Scientists discover creatine’s role in dendritic cells
To understand how creatine influences the immune system, the researchers first examined the activity of metabolic genes in dendritic cells that had entered tumors in mice. They found that the gene responsible for producing the creatine transporter, a protein that transports creatine into cells, was much more active in tumor-infiltrated dendritic cells than in dendritic cells found in healthy tissue.
The team then engineered dendritic cells that lacked the creatine transporter. Without the ability to take up creatine, the cells survived less effectively, became less active, and were much less able to prime T cells to recognize and attack tumors. When these creatine-deficient dendritic cells were cultured alongside T cells in laboratory experiments, the T cells multiplied less and produced fewer signaling molecules needed to mount an effective anti-cancer response.
Creatine slowed tumor growth in mice
The researchers also tested whether increasing creatine levels could produce the opposite effect.
Daily injections of creatine in mouse models of melanoma significantly slowed tumor growth while simultaneously increasing both the number and activity of dendritic cells that had entered the tumors. The treated dendritic cells also released higher levels of chemical signals that attracted additional immune cells to the tumor environment.
Using metabolomic analysis, the scientists found that creatine supplementation increased intracellular ATP levels in dendritic cells. ATP serves as the primary energy source that powers almost all cellular processes. By increasing these energy stores, creatine helped maintain inflammatory signaling pathways necessary for dendritic cell activation.
The researchers compared creatine’s role to that of a rechargeable battery, allowing dendritic cells to store and release energy as needed, even as they compete with fast-growing tumor cells for limited nutrients.
Potential benefits of cancer vaccines
The team also explored the effects of creatine on human immune cells.
In laboratory experiments, creatine enhanced the activation of human monocyte-derived dendritic cells, which are commonly used to develop vaccines against dendritic cell cancer. It also improved the ability of those cells to stimulate human T cells against a target associated with cancer.
The findings suggest that adding creatine during the production of dendritic cell vaccines could make those therapies more effective.
“The potential we see here is that creatine could be used in two complementary ways: as a supplement to enhance the immune response of patients already receiving immunotherapy, and as a tool to improve the quality of dendritic cell-based vaccines before they are administered,” said James Elsten-Brown, co-senior author and graduate student in Yang’s lab.
Overall, the results suggest that creatine could strengthen the immune system’s anti-cancer defenses at multiple stages, starting with the cells that detect cancer and initiate the body’s response.
“Understanding how to metabolically support dendritic cells involves supporting the entire antitumor response, not just the killer T cells at the end,” said Elliot Kang, co-first author of the study and former undergraduate student researcher in Yang’s lab.
Human trials still needed
Despite the encouraging findings, the researchers caution that the work is still in an early stage. The experiments were performed on mice and human cells grown in the lab, not on cancer patients, so the results should not be interpreted as evidence that creatine supplements improve cancer treatment in people.
Although creatine monohydrate has been widely used for decades and is generally considered safe when taken at recommended doses, researchers emphasize that anyone receiving cancer treatment should consult their doctor before adding any supplements to their routine.
The next step will be prospective clinical trials to determine whether creatine supplementation can improve outcomes for patients undergoing cancer immunotherapy.
The experimental approaches described in the study have not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in people.
Funding for the research was provided by a Rose Hills Foundation Innovator Grant from the UCLA Broad Stem Cell Research Center; the UCLA Health Jonsson Comprehensive Cancer Center and the UCLA Broad Stem Cell Research Center Ablon Scholars Program; and a Principal Investigator Grant from the Magnolia Council and a grant from the Tower Cancer Research Foundation.
The potential therapeutic strategy identified in the study is also the subject of a patent application filed by the UCLA Technology Development Group on behalf of the Regents of the University of California.