KetoNiFast: Cyclic Enteral Daytime Feeding With Ketogenic Nighttime Fasting

There is increasing evidence that a circadian rhythm of feeding (cyclic feeding) could be beneficial for critical ill patients. Cyclic feeding and fasting are assumed to have positive effects on the gut microbiome resulting in optimization of host responses to gastrointestinal pathogens. Another positive effect of cyclic feeding potentially results from activation of a "fasting response", inducing repair pathways such as ketogenesis, mitochondrial biogenesis, anti-inflammatory pathways, antioxidant defenses and autophagy processes. The activation of these repair pathways could diminish cellular stress and promote cellular recovery in critical ill patients. A randomized controlled trial by van Dyck et al. could show that fasting-mimicking intervals of 12 hours are sufficient to generate a metabolic fasting response without risking a caloric deficit. This fasting response can be enhanced by additional supplementation of exogenous ketones. A cyclic enteral nutrition with 12 hours of daytime feeding and 12 hours of ketogenic nighttime fasting compared to a continuous enteral feeding for 24 hours can potentially improve the reconstitution of critically ill Intensive Care patients. This improved reconstitution can be measured by maintenance of muscle mass (measured by ultrasound of the musculus rectus femoris), urea/creatinine ration, length of ventilation, length of ICU and hospital stay, 30-day mortality, ICU mobility scale.

Inclusion criteria

• written informed consent to participate in this study
• admission to ICU
• enteral nutrition

Exclusion criteria

• Severe liver dysfunction / liver failure (Child Pugh >7 points / category B)
• Severe kidney dysfunction (KDIGO stage 3)
• Total pancreatectomy / insulin dependent diabetes mellitus (IDDM)
• Pregnancy / lactation
• Hemoglobin concentration < 80g/l
• Severe metabolic disorders / severe autoimmune diseases
• Refractory metabolic or respiratory acidosis
• Dysfunction of mitochondrial transport of fatty acids
• Dysfunction of oxidation of fatty acids
• Dysfunction of gluconeogenesis, production and reduction of ketones
• Intermittent Porphyria
• Severe cardiac arrhythmias / cardiomyopathy
• Contraindication against enteral nutrition
• Lack of informed consent