Time-Restricted Ketogenic Diet in Huntington's Disease: A Case Study

Abstract

Huntington's disease (HD) is a progressive, fatal neurodegenerative disorder with limited treatment options. Substantial evidence implicates mitochondria dysfunction in brain and skeletal muscle in the pathogenesis of HD. Metabolic strategies, such as fasting and ketogenic diets, theoretically enhance brain and muscle metabolism and mitochondria function, which may improve the clinical symptoms of HD. We report the case of a 41-year-old man with progressive, deteriorating HD who pursued a time-restricted ketogenic diet (TRKD) for 48 weeks. Improvements were measured in his motor symptoms (52% improvement from baseline), activities of daily living (28% improvement), composite Unified HD Rating Scale (cUHDRS) score (20% improvement), HD-related behavior problems (apathy, disorientation, anger, and irritability improved by 50–100%), and mood-related quality of life (25% improvement). Cognition did not improve. Weight remained stable and there were no significant adverse effects. This case study is unique in that a patient with progressive, deteriorating HD was managed with a TRKD, with subsequent improvements in his motor symptoms, activities of daily living, cUHDRS score, most major HD-related behavior problems, and quality of life. Our patient remains dedicated to his TRKD, which continues to provide benefit for him and his family.

The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice

“…Several studies support the idea that mitochondrial disfunction in the nervous system and skeletal muscle is implicated in HD pathological processes. In this aspect, a case report study was performed on a 41 year old man with developing and worsening HD who followed a period-limited KD for 48 weeks [ 84 ]. He exhibited a 52% improvement in his motor symptoms, a 28% improvement with respect to his daily living activities, and a 20% improvement in his combined Unified HD Rating Scale (cUHDRS).…”

“…He exhibited a 52% improvement in his motor symptoms, a 28% improvement with respect to his daily living activities, and a 20% improvement in his combined Unified HD Rating Scale (cUHDRS). Moreover, his HD-associated behavioral difficulties such as apathy, disorientation, anger, and irritability were improved by 50–100%, and his mood-associated quality of life by 25% [ 84 ].…”

Dietary fasting and time-restricted eating in Huntington’s disease: therapeutic potential and underlying mechanisms

“…Another study found that 5 weeks of TRE (18-h fast/6-h feed) improved insulin sensitivity, blood pressure, and oxidative stress in men with prediabetes [ 112 ]. Recently, and intriguingly, a case study in a 41-year-old male HD patient with progressively deteriorating symptoms, reported that a 48-week combined metabolic strategy of TRE paired with a ketogenic diet resulted in improvements of motor symptoms, activities of daily living, composite Unified HD Rating Scale (UHDRS) score, and psychiatric symptoms [ 113 ]. Since this is a case study, it is not possible to precisely determine the mechanism of the improvements.…”

Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases

“…Signs of intestinal dysbiosis were observed in a group of AD rats and patients with MCI after KD consumption [37]. Intermittent fasting reduced hippocampal Aβ deposition, whereas KD worsened gut dysbiosis by increasing Proteobacteria and failed to improve memory function in an AD model of rats receiving Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) infusion [229]. A KD also resulted in a further increase in Enterobacteriaceae among patients with MCI [205].…”

“…As the beneficial effects of dietary intervention with KD are mediated through KB production, interest in KBs and KD has been increasing. KBs and KD have been used in the treatment of various neurological diseases, including epilepsy, cerebral ischemia, Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), Huntington’s disease (HD), depression, mood and anxiety disorders, and autism spectrum disorder (ASD) [ 11 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. Section 3 describes the latest findings from recent preclinical and clinical studies on the therapeutic potential of KBs and KD in cerebral ischemia and the two most common neurodegenerative diseases, AD and PD.…”