Ketogenic Diets for Cancer. I. “What makes you think that ketone bodies will help?”

Dr. Eugene Fine and I will described the problem as laid out in our campaign at Experiment.com. The campaign intends to follow Dr. Fine’s pilot study of ten advanced cancer patients on ketogenic diets and the in vitro jobs that we are carrying out in parallel.We got good feedback and some good questions and we want to continue the scientific interaction and keep the community intact that has been started on the”lab notes” at Experiment.  We’ll recapitulate some of the points made during the  campaign and you can”ask the investigators” in remarks.

“What makes you think ketone bodies can help?”

Most direct experimental studies, however, must be considered preliminary and it’s reasonable to ask why we believed ketone bodies may help.

The evidence supporting carbohydrate restriction, or particularly ketogenic diets in cancer remains largely indirect and speculative. Our recent perspective  summarized a number of the relevant evolutionary and mechanistic variables: the fundamental theme rests with the role of this glucose-insulin axis in boosting growth and proliferation, the overriding characteristic of cancer sells. So it has been observed for some time that individuals with diabetes have greater risk of cancer. Epidemiological and other kinds of studies are generally consistent with the idea although distinct cancers are more or less closely connected with diabetes. Drugs employed as diabetes treatment, especially metformin, have been found to have beneficial effects in cancer as well. Metformin lowers the chance of developing cancer although the effects on mortality aren’t clear cut. We made the situation, in our critical review that dietary carbohydrate restriction is the first line of treatment for type 2 diabetes and the ideal adjunct for pharmacology in type 1 diabetes.

cancer-diabetes

The association between cancer and diabetes in conjunction with the advantages of carbohydrate restriction in diabetes comprise one big connection. In dietary strategies, however, it’s total caloric reduction that has received the most attention and, in fact, experiments show that if implemented as stated, calorie restriction represents a reliable approach to prevention and treatment of cancer, particularly in animal models. It is unknown how much of the effect is because of de facto reduction in particular macronutrients but when tested, carbohydrate reduction as the way of reducing calories prove best. We cited a significant study by Tannenbaum. He discovered, in 1945 (!) That a carcinogen-induced sarcoma in mice was repressed by reduction in total calories but if  decreased by especially lowering the carbohydrate intake, there was an improved response.

tannenbaum_low-carb_cr

Odd in that this appears in complex scientific papers where the downstream effects of the stimulation may pinpoint twenty molecular elements and where the molecular targets of the”nutrients” are characterized and may specifically be the insulin receptor and the related IGF-1 (insulin-like growth factor -1) receptor. (Insulin is most likely important in that it stimulates IGF-1 activity by lowering the degree of the associated binding proteins). In such studies, where total caloric reduction is the independent variable, the participation of insulin and the insulin-dependent downstream pathways are shown to be involved.

It is now appreciated that the Warburg effect, the apparent reliance of tumors on glucose for fuel, is a key observation that has been insufficiently explored. The effect offers motivation and clues for investigating the metabolic approach to cancer. Warburg believed that all cancers showed this phenotype which is not true but a large number do; of significance is that one that doesn’t, prostate cancer, is the outlier in the figure above on relation to diabetes. 

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