RESUMO
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.
RESUMO
BACKGROUND: Brain energy metabolism is impaired in Alzheimer's disease (AD), which may be mitigated by a ketogenic diet. We conducted a randomized crossover trial to determine whether a 12-week modified ketogenic diet improved cognition, daily function, or quality of life in a hospital clinic of AD patients. METHODS: We randomly assigned patients with clinically confirmed diagnoses of AD to a modified ketogenic diet or usual diet supplemented with low-fat healthy-eating guidelines and enrolled them in a single-phase, assessor-blinded, two-period crossover trial (two 12-week treatment periods, separated by a 10-week washout period). Primary outcomes were mean within-individual changes in the Addenbrookes Cognitive Examination - III (ACE-III) scale, AD Cooperative Study - Activities of Daily Living (ADCS-ADL) inventory, and Quality of Life in AD (QOL-AD) questionnaire over 12 weeks. Secondary outcomes considered changes in cardiovascular risk factors and adverse effects. RESULTS: We randomized 26 patients, of whom 21 (81%) completed the ketogenic diet; only one withdrawal was attributed to the ketogenic diet. While on the ketogenic diet, patients achieved sustained physiological ketosis (12-week mean beta-hydroxybutyrate level: 0.95 ± 0.34 mmol/L). Compared with usual diet, patients on the ketogenic diet increased their mean within-individual ADCS-ADL (+ 3.13 ± 5.01 points, P = 0.0067) and QOL-AD (+ 3.37 ± 6.86 points, P = 0.023) scores; the ACE-III also increased, but not significantly (+ 2.12 ± 8.70 points, P = 0.24). Changes in cardiovascular risk factors were mostly favourable, and adverse effects were mild. CONCLUSIONS: This is the first randomized trial to investigate the impact of a ketogenic diet in patients with uniform diagnoses of AD. High rates of retention, adherence, and safety appear to be achievable in applying a 12-week modified ketogenic diet to AD patients. Compared with a usual diet supplemented with low-fat healthy-eating guidelines, patients on the ketogenic diet improved in daily function and quality of life, two factors of great importance to people living with dementia. TRIAL REGISTRATION: This trial is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12618001450202 . The trial was registered on August 28, 2018.
