Ketogenic diets and Ketone suplementation: A strategy for therapeutic intervention

Abstract

Ketogenic diets and orally administered exogenous ketone supplements are strategies to increase serum ketone bodies serving as an alternative energy fuel for high energy demanding tissues, such as the brain, muscles, and the heart. The ketogenic diet is a low-carbohydrate and fat-rich diet, whereas ketone supplements are usually supplied as esters or salts. Nutritional ketosis, defined as serum ketone concentrations of ≥ 0.5 mmol/L, has a fasting-like effect and results in all sorts of metabolic shifts and thereby enhancing the health status. In this review, we thus discuss the different interventions to reach nutritional ketosis, and summarize the effects on heart diseases, epilepsy, mitochondrial diseases, and neurodegenerative disorders. Interest in the proposed therapeutic benefits of nutritional ketosis has been growing the past recent years. The implication of this nutritional intervention is becoming more evident and has shown interesting potential. Mechanistic insights explaining the overall health effects of the ketogenic state, will lead to precision nutrition for the latter diseases.

Keywords: ketogenic diet; ketone bodies; ketone supplementation; nutritional ketosis; precision nutrition.

FIGURE 1

Effects of ketogenic diet and ketone body supplementation and downstream metabolism, exemplified for skeletal muscle. The liver produces ketone bodies during fasting, starvation, in carbohydrate restriction, or prolonged intense exercise. These ketone bodies can be used for input in the TCA cycle in various tissues, including the muscle to generate ATP. The Cori cycle, also known as lactic acid cycle, is the pathway in which lactate is transported to the liver and converted into glucose. Glucose-alanine cycle is the pathway in which alanine is transported to the liver and converted into glucose. KB, ketone bodies (acetoacetic acid/acetoacetate, acetone and beta-hydroxybutyric acid); TG, triglycerides; FFA, free fatty acids; Acetyl CoA, Acetyl coenzyme A; TCA, tricarboxylic acid; ATP, Adenosine triphosphate.