Brain Cancer

Ketogenic therapy and brain tumours

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A seizure may be the first indication of a brain tumour with the location, cell type and grade determining the most appropriate medical intervention advised.

NOTE: World Health Organisation grade 1 and 2 tumours are described as ‘low grade’ or benign, while grades 3 and 4 are described as ‘high grade’, malignant or cancerous (1)

Ketogenic therapy in the management of seizures associated with low grade brain tumours

In cases of relatively slow growing ‘low grade’ tumours, the time taken for the tumour to progress, if at all, is unknown and intervention may be minimal with a ‘watch and wait’ approach advised.

Those living with drug resistant epilepsy as a result of these tumours cope with the combined psychological and quality of life impacts of two unpredictable and potentially life limiting medical conditions and the side effects associated with the treatments for these conditions; with no active part that they can play in their symptom management.

Ketogenic therapy has significant potential as a treatment option to manage the drug resistant epilepsy in such cases; reducing seizure frequency, intensity and recovery time.  Adults also readily report an increase in alertness and energy as positive ‘side effects’ of the therapy, leading to an enhanced sense of wellbeing and control over day to day life.  Clinical experience relates to five UK cases and as yet unpublished. Please refer to the article; Ketogenic diet therapy: Epilepsy and brain tumours (2) for further information.

Ketogenic therapy in the management of brain cancer (malignant brain tumours)

Cancer metabolism: the focus on glucose

In 1924, Otto Warburg first proposed that cancer cells were different from normal healthy cells in the way that they obtained their energy for survival and growth.  He recognised their abnormal focus on deriving energy from the fermentation of glucose in the presence of oxygen (aerobic glycolysis) rather than using the more efficient and fuel flexible mitochondrial based system (oxidative phosphorylation) favoured by healthy cells (3).

Why the focus on brain cancer?

Contrary to improvements in the quality of life and survival for many cancers, the outcome for those with brain cancer has not improved in decades.  These aggressive cancers are known to be made up of a variety of cell types and this makes them less susceptible to targeted therapies. However, it is generally agreed that most brain cancer cells have dysfunctional energy metabolism and a high dependency on glucose, therefore research teams are now looking at ways to exploit this and turn it into an active and effective component of brain cancer management.

The ketogenic diet and glucose control

A ketogenic diet is low in carbohydrate, provides adequate amounts of protein, generous amounts of fats and readily controls calorie intake.  As carbohydrate intake is reduced, the body seeks to burn fats in preference to carbohydrates (no longer available in abundance) and this  triggers a cascade of biochemical changes in the body ; producing a sustained level of ketones in the blood and  flattening post-meal glucose peaks and maintaining the blood glucose levels at the lower end of the normal range.

It is known from studies of the ketogenic diet in epilepsy that healthy brain cells adapt with ease to this shift in the availability of fuel and readily use ketones as their primary energy source. However it is suggested that brain cancer cells may not adapt so readily and could be impaired by this shift.

The published evidence:

Human case reports

The use of a MCT (medium chain triglyceride)  ketogenic diet as an additional component in the management of two paediatric cases of brain cancer was first reported in 1995 (4). They found a 21.8% average decrease in glucose uptake at the tumour sites (using PET – FDG scans), with one patient exhibiting significant clinical improvements in mood and skill development during the 8 week study and continuing on the regime for 12 months. Both patients were reported to be enjoying a good quality of life four and five years after diagnosis.

In 2007, the use of a restricted ketogenic diet (around 600kcals /day, leading to a 20% loss in body weight) was reported in a 65 year old woman (5). Standard therapy was maintained and progression was tracked using PET – FDG scans.    After two months treatment, no discernible brain cancer tissue was detected. However, 10 weeks after suspension of the strict dietary therapy, MRI evidence of recurrence was found.

A small retrospective study of 53 patients with glioblastoma multiforme, of which 6 were on a ketogenic diet alongside standard therapy was published in 2014 (6). The authors reported that the ketogenic diet was safe and well tolerated and appeared to significantly reduce circulating blood glucose levels even when high dose steroids were used alongside. They concluded that this MAY improve the response to standard treatment and prognosis and recommended that further research be carried out to confirm this.

Preclinical studies (animals)

In 2010, studies on a mouse model of glioblastoma multiforme reported that an unrestricted ketogenic diet  (a) specifically retarded tumour growth; (b) prevented increases in reactive oxygen species associated with tumour growth and (c) shifted overall gene expression in cancer tissue to that seen in the normal brain ( 7). In 2012 the same research group reported that a KD significantly enhanced the effect of radiation in the same model (8). This team are currently undertaking a human trial (Clinicaltrials.com NCT02046187) to see if ketogenic therapy can increase survival and enhance the effects of standard radiation and chemotherapy treatments used to treat glioblastoma multiforme.

For over a decade Professor Tom Seyfried and associated researchers have been studying the concept of cancer as a metabolic disease (9). In 2012 they proposed that a restricted ketogenic diet (combined with drugs to control glucose and glutamine availability), could be a viable alternative to the standard of care for managing glioblastoma multiforme(10). In 2013, studies on a mouse model of metastatic cancer reported that a positive impact of ketogenic diet on survival time could be further enhanced when combined with hyperbaric oxygen therapy (11).

For a recent, more detailed discussion of the research evidence and hypotheses relating to brain cancer and ketogenic diet, please refer to; The ketogenic diet for the treatment of malignant glioma (12)

Further information

Ketogenic therapy is not a panacea and certainly not suitable for all.  It involves a significant change in food choice and requires preparation, training, guidance and monitoring from an experienced ketogenic support team to ensure that it is timely, safe and tailored to the needs of the individual alongside their standard therapy.

If you have a brain tumour and would like to consider ketogenic therapy, please do read the section on ‘ketogenic therapy for adults’, discuss this with your clinical neuro-oncology team and ask them to contact Matthews Friends for further support.

In the meantime, please refer to the “Eating for Health & Wellbeing” section of this website for guidance on simple mainstream dietary shifts that may enhance your overall nutrient intake and help to improve the balance of your blood glucose levels.

1. http://www.braintumourresearch.org/types-of-brain-tumour. Accessed June 2014
2. Wood S. Ketogenic Diet Therapy – Epilepsy & brain tumours. CN 2013  Vol 13, N0.5
   Access via http://www.nutrition2me.com/resource-centre/free-to-view-articles

3. Warburg O. The origin of cancer cells. Science 1956 123: 309-314
4. Nebeling L, Miraldi F, Shurin SB, Lerner E. Effects of a Ketogenic Diet on tumour metabolism and nutritional status in pediatric oncology patients: two case reports. Journal of American College of Nutrition 1995 Vol 14, No2: 202-208
5. Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P, Seyfried TN. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted diet: Case report. Nutrition & Metabolism 2010 7:33 http://www.nutritionandmetabolism.com/content/7/1/33
6. Champ CE, Palmer JD, Volek JS, Werner-Wasik M, Andrews DW, Evans JJ, Glass J, Kim l, Shi W. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. Journal of Neurooncology 2014 117:125-131
7. Stafford P, Adelwahab MG, Kim DY, Preul MC, Rho JM, Scheck AC. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutrition & Metabolism 2010  7:74 http://www.nutritionandmetabolism.com/content/7/1/74
8. Abdelwahab MG, Fenton KE, Preul MC, Rho JM, Lynch A, Stafford P, Scheck AC. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS One 2012 7(5): e36197 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0036197
9. Seyfried TH, Shelton LM. Cancer as a metabolic disease. Nutrition & Metabolism 2010 7:7 http://www.nutritionandmetabolism.com/content/7/1/7
10. Seyfried TH, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Is the restricted Ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer. Epilepsy Research 2012 100: 310-326 (Special issue on Dietary treatments for epilepsy & other neurological disorders)
11. Poff A, Ari C, Seyfried TN, D’Agostino DP. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer. PLoS One 2013 8(6): e65522 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0065522
12. Woolf EC, Scheck AC. The ketogenic diet for the treatment of malignant glioma. Journal of Lipid Research Feb 2014 e.pub ahead of print http://www.jlr.org/content/early/2014/02/06/jlr.R046797.full.pdf

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