Starvation of Cancer via Induced Ketogenesis and Severe Hypoglycemia

TL;DR

This paper proposes a novel cancer treatment strategy that involves inducing severe hypoglycemia after keto-adaptation to selectively starve tumor cells while sparing most normal tissues.

Contribution

It introduces a new approach combining keto-adaptation with controlled hypoglycemia to target cancer cells, which is a novel therapeutic concept.

Findings

Keto-adaptation reduces glucose dependence of normal tissues.

Severe hypoglycemia can be safely induced post keto-adaptation.

Potential for rapid tumor cell necrosis through glucose deprivation.

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 ketoadaptation. We hypothesize that our therapeutic hypoglycemia treatment has potential to rapidly induce tumor cell necrosis.