Creatine is widely known as a supplement used by athletes and bodybuilders to improve strength and performance. Now, new UCLA research suggests it may have another surprising role: helping the immune system mount a powerful attack against cancer.
This study isciencefound that creatine increases the activity of dendritic cells, specialized immune cells that detect tumors and activate killer T cells responsible for destroying cancer. The finding, based on experiments in mouse and human cells, builds on previous work from the same lab that showed creatine also strengthens the function of cancer-fighting T cells.
Creatine may enhance cancer immunotherapy
Many of today’s cancer immunotherapies are designed to activate killer T cells, but only about 20% to 40% of patients experience meaningful effects. The UCLA team believes that improving the function of dendritic cells, which regulate and direct T cells, could make immunotherapy more effective for more people.
“Immunotherapies have shown remarkable promise, but they are only effective in some patients,” said study lead author Lili Yang, professor of microbiology, immunology, and molecular genetics, and member of UCLA’s Eli Edith Broad Center for Regenerative Medicine and Stem Cell Research. “What this study shows is that creatine not only helps cancer-fighting T cells, but also energizes the entire infrastructure that supports and guides them. This makes creatine a promising supplement to holistically support the immune response that modern immunotherapies rely on.”
Scientists uncover creatine’s role in dendritic cells
To understand how creatine affects the immune system, the researchers first examined the activity of metabolic genes in dendritic cells that had invaded tumors in mice. They found that the gene responsible for producing creatine transporter, a protein that carries creatine into cells, was much more active in tumor-infiltrating dendritic cells than in dendritic cells found in healthy tissue.
The team then created dendritic cells that lacked the creatine transporter. Without the ability to take up creatine, cells survive less efficiently, become less active, and have a significantly reduced ability to prime T cells to recognize and attack tumors. When these creatine-deficient dendritic cells were grown in parallel with T cells in laboratory experiments, the T cells proliferated 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 had the opposite effect.
Daily injections of creatine into a mouse model of melanoma significantly slowed tumor growth while simultaneously increasing both the number and activity of dendritic cells that had invaded the tumors. The treated dendritic cells also released high levels of chemical signals that attracted additional immune cells to the tumor environment.
Using metabolomics analysis, scientists found that creatine supplementation increased intracellular ATP levels in dendritic cells. ATP serves as the primary energy source that powers nearly all cellular processes. By increasing these energy stores, creatine helped maintain the inflammatory signaling pathways required for dendritic cell activation.
The researchers compared creatine’s role to that of a rechargeable battery that allows dendritic cells to store and release energy as needed while competing with rapidly growing tumor cells for limited nutrients.
Potential benefits of cancer vaccines
The research team also investigated the effects of creatine on human immune cells.
In laboratory experiments, creatine promoted the activation of human monocyte-derived dendritic cells, which are commonly used in the development of dendritic cell cancer vaccines. It also improved the ability of these cells to stimulate human T cells against cancer-related targets.
The findings suggest that adding creatine during the production of dendritic cell vaccines could make those treatments more effective.
“The potential we see here is that creatine can be used in two complementary ways: as a supplement to boost the immune response in patients already receiving immunotherapy, and as a tool to improve the quality of dendritic cell-based vaccines before administering them,” said co-first author James Elsten Brown, a graduate student in Yang’s lab.
Overall, the results suggest that creatine may strengthen the immune system’s anti-cancer defenses at multiple stages, starting with the cells that detect cancer and mount the body’s response.
“Understanding how to support dendritic cells metabolically can help support the entire anti-tumor response, not just the killer T cells at the end of the anti-tumor response,” said Elliot Kang, co-first author of the study and a former undergraduate researcher in Yang’s lab.
Human clinical trials still needed
Despite the encouraging findings, researchers caution that the study is still in its early stages. Because this experiment was conducted using lab-grown mouse and human cells, rather than cancer patients, the results should not be interpreted as evidence that creatine supplements improve cancer treatment in humans.
Although creatine monohydrate has been widely used for decades and is generally considered safe when taken at recommended doses, researchers stress that people undergoing cancer treatment should consult their doctor before adding the supplement to their daily routine.
The next step is a prospective clinical trial to determine whether creatine supplementation can improve outcomes for patients receiving cancer immunotherapy.
The experimental approach described in this study has not been tested in humans or approved by the Food and Drug Administration as safe and effective for human use.
Research funding was provided by the UCLA Broad Stem Cell Research Center Rose Hills Foundation Innovator Grant. UCLA Health Johnson Comprehensive Cancer Center and UCLA Broad Stem Cell Research Center Abron Scholars Program. received a Magnolia Council Senior Investigator Grant Award and a fellowship from the Tower Cancer Research Foundation.
Potential therapeutic strategies identified in this study are also the subject of a patent application filed by the UCLA Technology Development Group on behalf of the University of California Board of Regents.
