Role of ketones, ketogenic diets and intermittent fasting in ICU

To summarize the clinical evidence for beneficial effects of ketones, ketogenic diets and intermittent fasting in critical illness, and to review potential mechanisms behind such effects.

Recent evidence demonstrates that activation of a metabolic fasting response may be beneficial to recover from critical insults. Potential protective mechanisms are, among others, activation of ketogenesis and of damage removal by autophagy. Novel feeding strategies, including ketone supplements, ketogenic diets and intermittent fasting regimens, can activate these pathways - at least partially - in critically ill patients. Randomized controlled trials (RCTs) studying these novel feeding strategies as compared with standard care, are scarce and have not shown consistent benefit. Yet, all RCTs were small and underpowered for clinical endpoints. Moreover, in intermittent fasting studies, the duration of the fasting interval may have been too short to develop a sustained metabolic fasting response.

These findings open perspectives for the further development of fasting-mimicking diets. Ultimately, clinical benefit should be confirmed by RCTs that are adequately powered for clinically relevant, patient-centered endpoints.