Creatine is widely recognised as a staple supplement in fitness. Many athletes and weightlifters use it to increase muscle mass and push harder in training, and for most people the story ends there.
However, fresh research from UCLA indicates the same molecule may also play a very different part - one connected to the immune system and its ability to combat cancer.
In a study published in iScience, researchers reported that creatine helps switch on a set of immune cells that influence whether the body mounts an attack on a tumour in the first place.
The same laboratory had previously shown that creatine can fuel cancer-destroying T cells. In this work, the team moved a step earlier in the chain, focusing on the cells that guide those T cells towards their targets.
Dendritic cells trigger attacks
Dendritic cells function as the immune system’s scouts. They pick up pieces of a tumour, transport those fragments to T cells, and indicate which danger should be pursued.
They also send out chemical signals that call other immune cells into action. When tumours contain large numbers of active dendritic cells, patient outcomes are typically better.
When dendritic cells are scarce or ineffective, tumours are more likely to go unnoticed. That broader perspective underpins the study.
“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.
A clue inside tumors
Tumours are fierce competitors for limited resources. They consume nutrients and alter the local environment, leaving nearby immune cells short of usable fuel.
In those conditions, a dendritic cell gradually loses the capacity to do its job properly.
To begin, the researchers analysed which genes were most active in dendritic cells taken from mouse tumours. One gene stood out clearly from the rest.
The gene encoding the creatine transporter - the protein responsible for bringing creatine into cells - was far more active than in dendritic cells from healthy tissue. The pattern suggested these cells were demanding additional creatine.
Removing creatine weakens cells
To understand the reason, the team studied mice engineered to lack this transporter. Their dendritic cells were severely compromised.
They died more quickly, showed minimal activation, and produced fewer of the signals that normally mobilise the immune response.
When placed with T cells in a dish, those T cells multiplied less and made fewer molecules involved in killing cancer. Without creatine, the dendritic cells appeared to lose their drive.
Immune cells become more active
Next, the researchers tested the opposite approach. They provided normal dendritic cells with extra creatine and observed a marked shift.
A greater number of cells stayed alive. Indicators of activation were stronger. The cells released higher levels of inflammatory messengers that help launch an immune response.
In mice with melanoma, daily injections of creatine slowed tumour growth and increased the number of active dendritic cells within the tumours.
Those dendritic cells also produced more of the signals that attract additional immune cells.
It comes down to energy
Why would a supplement associated with muscle have these effects? The explanation centres on cellular energy.
Creatine acts like a small rechargeable battery, storing and donating phosphate groups that help regenerate ATP, the cell’s primary energy source.
Dendritic cells given creatine maintained higher ATP levels and kept those reserves steadier even while tumour cells competed for scarce resources.
With energy stores maintained, the internal machinery responsible for switching these cells on kept functioning. When creatine was depleted, that machinery faltered.
Exploring the potential of creatine
Findings in mice have limits, so the researchers also generated dendritic cells from human blood donors and ran similar tests.
The human cells reacted in the same way as the mouse cells: they activated more strongly and trained human T cells to recognise a known cancer target.
This point matters because dendritic cells derived from blood already underpin certain cancer vaccines.
“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.
A safe, promising supplement
Creatine is among the most thoroughly studied supplements, has a long history of safe use over decades, and is inexpensive.
Since many existing immunotherapies benefit only a portion of patients, anything that could expand that benefit is worth investigating.
“Immunotherapy has shown remarkable promise, but it only works for a subset of patients,” said Lili Yang, the study’s senior author and a professor of microbiology, immunology and molecular genetics 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.”
Further testing is needed
It is important not to overinterpret the results. The experiments were conducted in cells and in mice rather than in patients, and the main tumour tests relied heavily on a single melanoma model.
Creatine is also not straightforward, because certain tumour cells may be able to exploit it to support their own growth. Anyone undergoing cancer treatment should speak with their doctor before adding any supplement.
Even so, the findings highlight how familiar compounds can have unexpected relevance.
A supplement long linked to building muscle may also help the immune system detect and attack cancer.
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