Ketogenic diet and its effects on tumour growth and ‘wasting syndrome’

Professor Ashok Venkitaraman, Director of the Cancer Science Institute of Singapore at the National University of Singapore, together with Assistant Professor Tobias Janowitz, Principal Investigator at the Cold Spring Harbor Laboratory in New York, and an international group of researchers from the USA and UK, have discovered that ketogenic diets delay tumour growth but accelerate cachexia, a wasting syndrome, an unintended side effect that could cause death.

The researchers also found that dexamethasone might help to optimise the benefits of ketogenic diets by delaying cachexia.

Ketogenic diets, a double-edged sword in fighting cancer

Ketogenic diets, characterised by their high-fat and low-carbohydrate composition, have recently attracted attention as potential adjuvants that increase the efficacy of cancer therapy. This stems from speculation that cancers feed on sugar, and hence adopting a ketogenic high-fat diet may enhance anti-cancer therapies and improve clinical outcomes by ‘starving’ the tumour of its energy source.

In their recent study, the research team showed, using two different experimental models, that such diets can indeed slow cancer growth – but unexpectedly, they cause a ‘wasting syndrome’ (cachexia) which worsens the disease prognosis. Prof Venkitaraman explained, “Special diets may help to make cancer therapy more effective. However, our research highlights that dietary interventions affect many organ systems beyond just cancer cells, leading to both deleterious and positive consequences. The mechanism we have identified raises critical questions regarding the use of high-fat or starvation diets in the treatment of cancer. Further investigation is needed to fully understand the balance of benefits and risks associated with these dietary approaches.”

Means to address cachexia

The study also found that dexamethasone, a potent glucocorticoid, which improves appetite and increases endogenous glucose production, can delay cachexia. When taken together with a ketogenic diet, such drugs may allow suppression of tumour growth, without the undesirable effects of cachexia. New combinations of this kind may be necessary to optimise dietary intervention as a part of cancer therapy. Ultimately, more work is needed to translate this preclinical research for the benefit of patients suffering from cancer.

The team reported their ground-breaking findings in the prestigious scientific journal Cell Metabolism on 12 June 2023.