Creatine is most familiar as a staple of the fitness scene. Sportspeople and weightlifters use it to increase muscle and push training intensity, and for many that is where the story stops.
However, new research from UCLA indicates the molecule may also play a very different part - one connected to the immune system and its battle with cancer.
In a study published in iScience, scientists 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 lab had previously shown that creatine powers cancer-killing T cells. In this work, the team moved a step upstream, focusing on the cells that steer those T cells towards their targets.
Dendritic cells trigger attacks
Dendritic cells function as the immune system’s scouts. They gather pieces of a tumour, transport those fragments to T cells, and indicate which danger should be pursued.
They also secrete chemical signals that bring in other immune cells. When tumours contain large numbers of active dendritic cells, patient outcomes tend to be better.
When dendritic cells are weak or missing, tumours can often avoid being noticed. That broader perspective sits at the heart of the research.
“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 tumours
Tumours compete aggressively for resources. They consume nutrients and remodel their environment, leaving nearby immune cells short on fuel.
A dendritic cell exposed to those conditions gradually loses the ability to do its job.
To begin, the researchers investigated which genes were most active in dendritic cells taken from mouse tumours. One gene stood out clearly.
The gene for the creatine transporter - the protein that brings creatine into cells - was far more active than in dendritic cells from healthy tissue. The cells appeared to be demanding more creatine.
Removing creatine weakens cells
To understand what that meant, the team used mice engineered to lack the transporter. Their dendritic cells were in poor condition.
They died sooner, struggled to switch on properly, and produced fewer of the signals that help mobilise the immune system.
When these dendritic cells were placed with T cells in a dish, the T cells multiplied less and made fewer cancer-fighting molecules. Without creatine, the cells seemed to lose the drive to function.
Immune cells become more active
Next, the researchers tested the opposite approach. They supplied normal dendritic cells with additional creatine and observed a marked change.
More cells stayed alive. Signs of activation were stronger. The dendritic cells released higher levels of inflammatory messengers that help kick-start an immune response.
In mice with melanoma, daily creatine injections reduced the pace of tumour growth and filled tumours with a greater number of active dendritic cells.
Those dendritic cells also produced more of the signals that call in additional immune support.
It comes down to energy
Why would a supplement associated with muscle have these effects? The explanation centres on energy.
Creatine acts like a small rechargeable battery, holding and releasing phosphate groups that cells use to replenish ATP, their primary energy source.
Dendritic cells given creatine contained more ATP and maintained those reserves even as tumour cells competed fiercely for limited resources.
With energy stores maintained, the cellular systems responsible for activation kept running. When creatine was depleted, those systems faltered.
Exploring the potential of creatine
Findings in mice have limits, so the team also grew dendritic cells from human blood donors and treated them in the same way.
The human dendritic cells reacted much like the mouse cells: they activated more strongly and trained human T cells to recognise a known cancer target.
This matters because dendritic cells produced 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 extensively studied supplements, has a long history of safe use, and is inexpensive.
Because today’s immunotherapies benefit only a proportion of patients, any strategy that could expand that benefit warrants investigation.
“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 mice rather than in patients, and the main tumour work relied heavily on a single melanoma model.
Creatine is also not straightforward, as some 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 research highlights that familiar compounds can have unexpected applications.
A supplement best known for helping build muscle may also assist the immune system in identifying and attacking cancer.
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