Diet Induced Ketosis for Brain Injury - A Feasibility Study: A Ketogenic Diet With MCT Supplementation as a Potential Treatment for Brain Injury in Adults

Abstract

At the Department of Highly Specialized Neurorehabilitation/Traumatic Brain Injury, Rigshospitalet (satellite department at Hvidovre Hospital), approximately 100 patients (pt.) are admitted with severe brain damage every year. From 2015 to 2017, 305 pt. were admitted. Out of the 305 pt., 162pt. (53%) had traumatic brain injury (TBI), 48pt. (16%) had apoplexy, 35pt. (12%) had other diagnoses (infections, tumors and almost drowning, etc.), 20pt. (7%) had spontaneous subarachnoid hemorrhage (SAH) and 24pt. (8%) had brain damage as a result of cardiac arrest.

TBI is a leading cause of injury-related morbidity and mortality worldwide. According to the Global Burden of Disease Study (2016), there were 27,08 million new cases of TBI globally in 2016. In Denmark, there were 17.302 new cases of TBI in 2016. Clinical studies have repeatedly shown major changes in cerebral energy metabolism after TBI. The secondary brain injury leads to metabolic cellular dysfunction, cerebral edema, and a complex injury cascade. The injury spread includes processes such as inflammation, edema, free radical damage, oxidative damage, ischemic injury, cerebral glucose metabolism disorder, and ion-mediated cell damage. Much of the neurological dysfunction that occurs in acute TBI also occurs in apoplexy, SAH and cerebral ischemia.

A very important adaptive metabolic response after brain injury is the utilization of alternative cerebral energy substrates, including lactate, but also ketone bodies (KB) such as β-hydroxybutyrate (BHB) and acetoacetate (AcAc). In addition to having a central role in the regulation of cerebral energy metabolism after brain injury, KB has other important neuroprotective properties, including attenuation of oxidative stress, apoptotic cell death, and microglial activation. Increasing KB metabolism through fasting or diet-induced ketosis promotes brain resistance to stress and injury, and attenuates acute cerebral injury. Therefore, supplementing with KB, e.g. through the use of a ketogenic diet (KD) with added medium chain fatty acids (MCT), has emerged as a potential non-pharmacological neuroprotective therapy.

KD has been used for many years for the treatment of refractory epilepsy in children and studies done on adults show promising results, but experience from several studies shows major compliance issues. KD has been shown to reduce cerebral edema and apoptosis, as well as improve cerebral metabolism and behavioral outcomes in TBI rodent models, but clinical human trials on adults with TBI are lacking. Apoplexy animal models show positive effects on pathological and functional outcomes of KD intervention or exogenous ketone administration. The only human trial of KD and apoplexy shows that KD is safe and tolerated by patients with acute apoplexy. Our hypothesis is that diet-induced ketosis will reduce the extent of secondary brain damage. The purpose of the trial is to investigate whether an intervention with a ketogenic diet supplemented with MCT is feasible for 6 weeks on hospitalized pt. with severe brain damage. This is the pre-study for a controlled study.