Can a carbohydrate restricted diet help treat childhood brain tumours?

Brain tumours are the leading cause of cancer related death in children and are one of the most challenging childhood cancers to diagnose and to treat. Only 50-60-% of children diagnosed with a brain tumour are cured and 60% of those cured are left with a disability affecting quality of survival.

Ependymoma and high grade glioma account for up to a quarter of all children diagnosed with a brain tumour. Compared to other childhood brain tumours 5-year survival rates are relatively poor. It has been reported that 39-64% of those diagnosed with an ependymoma will still be alive 5 years after diagnosis and that 15-35% of those diagnosed with a high grade glioma will survive this length of time. In addition, tumour recurrences are common with treatment options becoming more limited and many children dying from the disease. We therefore would like to investigate other treatment options which could be used in conjunction with standard therapies.

Normal cells in the body get the energy they require to grow and divide from glucose, a sugar derived from carbohydrates in our diet. If the body doesn’t have enough glucose, normal cells can instead use ‘ketone bodies’ which are produced from fatty acids by the liver. Cancer cells have defects which mean that they are dependent on glucose as an energy source and cannot use ketone bodies. We are therefore interested in investigating whether a carbohydrate restricted diet (e.g. the ketogenic diet) would starve the brain tumour cells whilst still providing ketone bodies for normal brain cells to survive. If this is the case then a ketogenic diet would provide a useful way of attacking cancer cells. We have already shown that approximately 85% of ependymoma and 75% of paediatric high grade gliomas have an amenable enzyme profile and therefore may benefit from the diet.

In order to do this we would like to grow brain tumour cells and normal brain cells as 3-dimensional balls of cells (spheroids) in different amounts of glucose. We intend to grow the cells in a glucose range that includes the amount known to be in the body when a person is following the ketogenic diet, and glucose amounts above and below this. Two different ketone body drugs will be added to see if these help the cells to survive the low glucose conditions. We will then measure the size of the spheroids after seven days, and see whether the cells are still alive and whether the enzymes needed to survive the ketogenic diet are present.

The James Lind Alliance priority setting partnerships were created to identify clinical research questions of greatest importance to the patients and families actually affected by brain tumours. One of the top 10 questions raised was the effect of lifestyle factors including diet and sleep on tumour growth, therefore indicating a need for diet therapy options and possible interest from families to the ketogenic diet. We therefore feel that it is timely to perform this research which will give us vital information to support a clinical trial into the ketogenic diet in paediatric brain tumours.