Starvation of cancer via induced ketogenesis and severe hypoglycemia

Abstract

Neoplasms are highly dependent on glucose as their substrate for energy production and are generally not able to catabolize other fuel sources such as ketones and fatty acids. Thus, removing access to glucose has the potential to starve cancer cells and induce apoptosis. Unfortunately, other body tissues are also dependent on glucose for energy under normal conditions. However, in human starvation (or in the setting of diet-induced ketogenesis), the body "keto-adapts" and glucose requirements of most tissues drop to almost nil. Exceptions include the central nervous system (CNS) and various other tissues which have a small but obligatory requirement of glucose. Our hypothesized treatment takes keto-adaptation as a prerequisite. We then propose the induction of severe hypoglycemia by depressing gluconeogenesis while administering glucose to the brain. Although severe hypoglycemia normally produces adverse effects such as seizure and coma, it is relatively safe following keto-adaptation. We hypothesize that our therapeutic hypoglycemia treatment has potential to rapidly induce tumor cell necrosis.

A systematic review of the use of ketogenic diets in adult patients with cancer

“…From hypothetical conjecture based on academic modelling supported by animal and cellular studies, there are sound theoretical bases for KDs suppressing tumour growth . However, strong conclusive evidence in clinical practice is still lacking.…”

“…Studies followed a variable F : CHO + P ratio and thus the ketosis may have been affected by levels of carbohydrate and protein. It was originally proposed that carbohydrate should be maintained below 20 g day –1 , although no data exist to define what level of carbohydrate represents a threshold for maintenance of ketosis . Studies in this review used a great variation of carbohydrate, reaching 70 g day –1 .…”

“…Data from cellular and animal studies support and extend Warburg's conclusions (13)(14)(15)(16) . Reviews concentrating on tumour-suppressive mechanisms behind the diet combine the available data from cellular, animal and clinical studies (14,(17)(18)(19) . Clinical evidence alone was reviewed in four articles.…”

Spontaneous Regression of Clear Cell Carcinoma of the Endometrium

“…There is convincing evidence of glucose metabolism and factors affecting it being important for tumour cell survival, progression and regression of tumours [16]- [18].…”

Is It Possible To Induce The "Spontaneous Regression" Of Cancer? A Mechanism of Activation for the Innate Immune Response

“…However there is doubtful that hypoglycemia itself will induce spontaneous regression of cancer [11]. Starvation, ketogenic diet, calorically restricted ketogenic diet all of these slow down the tumor growth [12] and are intensively investigated as the alternative approach for the cancer treatment, that is able to induce tumor cell necrosis (see the recent progress in the review [13]). What is intriguing, repeated application of the Coley's vaccine, should induce the deep hypoglycemia also, because the bacterial infection commonly induce hypoglycemia [11,14].…”