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 iScience, found that creatine boosts the activity of dendritic cells, specialized immune cells that detect tumors and activate the killer T cells responsible for destroying cancer. The findings, based on experiments in mice and human cells, build on previous research from the same laboratory showing that creatine also enhances the function of cancer-fighting T cells.
Creatine May Strengthen 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 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 remarkable promise, but it only works for a subset of patients,” said Lili Yang, the study’s senior author, a professor of microbiology, immunology and molecular genetics and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “What this study shows is that creatine doesn’t just help the T cells fighting cancer — it also energizes the entire infrastructure supports and guides them. That makes creatine a promising supplement to holistically support the immune response that modern immunotherapies depend on.”
Scientists Uncover Creatine’s Role in Dendritic Cells
To understand how creatine influences the immune system, researchers first examined the activity of metabolic genes in dendritic cells that had entered tumors in mice. They discovered that the gene responsible for producing the 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 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 far less capable of preparing T cells to recognize and attack tumors. When these creatine-deficient dendritic cells were grown 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
Researchers also tested whether increasing creatine levels could produce the opposite effect.
Daily creatine injections in mouse models of melanoma significantly slowed tumor growth while increasing both the number and activity of dendritic cells that had entered tumors. The treated dendritic cells also released higher levels of chemical signals that attracted additional immune cells into the tumor environment.
Using metabolomics analyses, the scientists found that creatine supplementation increased intracellular ATP levels in dendritic cells. ATP serves as the primary energy source that powers nearly every cellular process. By boosting these energy reserves, creatine helped maintain the inflammatory signaling pathways required 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 while competing with rapidly growing tumor cells for limited nutrients.
Potential Benefits for Cancer Vaccines
The team also explored creatine’s effects on human immune cells.
In laboratory experiments, creatine enhanced the activation of human monocyte-derived dendritic cells, which are commonly used to develop dendritic cell cancer vaccines. It also improved those cells’ ability to stimulate human T cells against a cancer-associated target.
The findings suggest that adding creatine during the production of dendritic cell vaccines could potentially 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’re administered,” said James Elsten-Brown, a co-first author and graduate student in Yang’s lab.
Overall, the results suggest creatine could strengthen the immune system’s anti-cancer defenses at multiple stages, beginning with the cells that detect cancer and initiate the body’s response.
“Understanding how to metabolically support dendritic cells is about supporting the entire anti-tumor response, not just the killer T cells at the end of it,” said Elliot Kang, a co-first author of the study and former undergraduate student researcher in Yang’s lab.
Human Trials Are Still Needed
Despite the encouraging findings, the researchers caution that the work remains at an early stage. The experiments were conducted in mice and human cells grown in the laboratory, not in 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, the researchers stress that anyone receiving cancer treatment should consult their physician before adding any supplement 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 UCLA Broad Stem Cell Research Center Rose Hills Foundation Innovator Grant; the UCLA Health Jonsson Comprehensive Cancer Center and UCLA Broad Stem Cell Research Center Ablon Scholars Program; and a Magnolia Council Senior Investigator Grant Award and a fellowship 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.
