(the standard of care). We found that it not only enhanced the activity of temozolomide, it greatly enhanced the activity of radiation therapy. In fact, when maintained on a KD and given radiation therapy, the tumors disappeared in nine of eleven mice, but radiation alone did not have this effect (1). This was very exciting and spurred our interest to continue these studies and try to dissect how the KD may be working.
Other effects of the ketogenic diet We and others have found that the KD is amazingly pluripotent (see illustration at right). That is, it has many effects on the tumor that far exceed the original idea that it restricts energy in the cancer cell. We found that the KD reduces the formation of new blood vessels (angiogenesis) and causes a reduction in swelling around the tumor (edema). This is what bevacizumab was designed to do. It reduces hypoxia and the expression of a gene called hypoxia-inducible factor 1a (HIF1a). Hypoxia is “reduced oxygen”, and tumor regions that are hypoxic are typically resistant to therapy. In addition, HIF-1a turns on a number of genes involved in tumor growth. It also reduces the expression of genes that may promote the cells’ ability to invade normal tissue (2). Most recently, we have found that the KD has effects on the immune system and it is likely to enhance the anti-tumor immune response in a manner similar to the goal of some newer immunotherapies. In addition to studies using animal brain tumor models, we and others have shown that the addition of ketones to mouse or human glioma cells grown in the laboratory causes the same effects, even in the presence of high levels of glucose. Cell growth is inhibited, the cells are more sensitive to radiation and chemotherapy and they migrate (move) less than cells grown without ketones.
In summary As more studies demonstrate the multitude of effects that altering metabolism can have on tumor growth, particularly in brain tumors, it becomes more apparent that if done correctly, decreasing blood glucose and increasing blood ketones through a properly managed ketogenic diet should inhibit the growth of the tumor while enhancing the efficacy of other therapies and preserving quality of life.
Above: The ketogenic diet reduces many of the pro-tumor characteristics that have been called "Hallmarks of Cancer" by Hanahan and Weinberg (Cell. 2011 Mar 4;144(5):646-74).
To this end we, and others, have opened clinical trials in humans to fully test the efficacy of the KD as an additional therapy for the treatment of brain tumors. These studies are continuing, as we try to understand the many effects this has and how to best use this information to enhance brain tumor patient survival. n
Ed Evans Foundation 'Walk the Vale' Walk
Reference List (1) Abdelwahab MG, Fenton KE, Preul MC, Rho JM, Lynch A, Stafford P, et al. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS ONE 2012;7:e36197. (2) Woolf EC, Curley KL, Liu Q, Turner GH, Charlton JA, Preul MC, et al. The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model. PLoS ONE 2015;10:e0130357.
ON Easter Monday, 6th April, 2015, 278 walkers took part in this annual Ed Evans Foundation event in the United Kingdom. With the sun shining, walkers chose either a short six-mile walk or a long eleven-mile walk, both of which took in the stunning scenery of the Welsh Vale of Glamorgan. 1,983 miles were walked and over £2,000 raised for the charity. The Ed Evans Foundation website is here: www.edevansfoundation.co.uk n
Brain Tumour
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