Creatine May Help the Immune System Attack Cancer

Creatine is most familiar as a staple of the fitness world. Athletes and weightlifters use it to gain muscle and train more intensely, and for most people, that is the full extent of its reputation.

However, fresh research from UCLA indicates that the molecule could serve a second, markedly different purpose connected with the immune system’s battle against cancer.

Published in iScience, the study reported that creatine helps switch on a group of immune cells responsible for determining whether the body launches an attack on a tumour in the first place.

The same lab had previously demonstrated that creatine powers cancer-destroying T cells. In this research, the scientists investigated an earlier stage: the cells that guide 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 them to T cells and indicate which danger should be targeted.

They also produce chemical signals that call in further immune cells. Patients generally have better outcomes when a tumour contains high numbers of active dendritic cells.

If these cells are weak or missing, tumours can frequently avoid being recognised. This broader perspective lies 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 available resources. By consuming nutrients and altering their local environment, they deprive nearby immune cells of fuel.

A dendritic cell in this environment progressively loses its capacity to work properly.

The team started by studying the genes that were most active in dendritic cells collected from mouse tumours. One gene was notably different from the others.

The gene encoding the creatine transporter - the protein that brings creatine into a cell - was far more elevated than in cells from healthy tissue. These cells evidently required additional creatine.

Removing creatine weakens cells

To find out why, the researchers worked with mice genetically engineered to lack this transporter. Their dendritic cells were severely impaired.

They died more quickly, showed very little activation and produced fewer signals that mobilise the immune system.

When placed with T cells in a dish, they caused those T cells to divide less and make fewer cancer-fighting molecules. Deprived of creatine, the cells appeared to lose their drive.

Immune cells become more active

The researchers then reversed the approach. They supplied healthy dendritic cells with additional creatine and observed them becoming more active.

A greater number of cells remained alive. They displayed more powerful activation markers. The cells also released larger amounts of the inflammatory messengers that initiate an immune response.

In mice with melanoma, daily creatine injections slowed tumour growth and filled tumours with more active dendritic cells.

These cells also produced more of the signals that attract additional immune reinforcements.

It comes down to energy

Why, then, can a muscle supplement have these effects? It is fundamentally a question of energy.

Creatine acts rather like a miniature rechargeable battery, holding and releasing the phosphate groups cells need to replenish ATP, their primary fuel source.

Dendritic cells treated with creatine contained more ATP and maintained stable reserves, even as tumour cells competed with them for limited resources.

When their energy stores were replenished, the system that activates these cells continued operating. Remove creatine, and that system began to fail.

Exploring the potential of creatine

Results in mice have limited reach, so the team also produced dendritic cells from human blood donors and treated them in the same manner.

Human cells reacted in the same way as mouse cells. They became more strongly activated and primed human T cells against a recognised cancer target.

This is significant because dendritic cells grown from blood are already used in 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 researched supplements available, has been safely used for decades and is very inexpensive.

Existing immunotherapies benefit only a proportion of patients, so any option that could expand that group 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

Conclusions should be approached cautiously. The work involved cells and mice rather than patients, while the principal tumour experiments relied on one melanoma model.

Creatine is also a complicated molecule because certain tumour cells may exploit it to support their own growth. Anyone receiving cancer treatment should consult their doctor before taking any supplement.

Nevertheless, the study highlights that well-known compounds may offer unanticipated benefits.

A supplement traditionally linked with muscle building could also assist the immune system in identifying and attacking cancer.