Dataset Information

Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease.

ABSTRACT:

Introduction

We assessed the feasibility and cognitive effects of a ketogenic diet (KD) in participants with Alzheimer's disease.

Methods

The Ketogenic Diet Retention and Feasibility Trial featured a 3-month, medium-chain triglyceride-supplemented KD followed by a 1-month washout in clinical dementia rating (CDR) 0.5, 1, and 2 participants. We obtained urine acetoacetate, serum ?-hydroxybutyrate, food record, and safety data. We administered the Alzheimer's Disease Assessment Scale-cognitive subscale and Mini-Mental State Examination before the KD, and following the intervention and washout.

Results

We enrolled seven CDR 0.5, four CDR 1, and four CDR 2 participants. One CDR 0.5 and all CDR 2 participants withdrew citing caregiver burden. The 10 completers achieved ketosis. Most adverse events were medium-chain triglyceride-related. Among the completers, the mean of the Alzheimer's Disease Assessment Scale-cognitive subscale score improved by 4.1 points during the diet (P = .02) and reverted to baseline after the washout.

Discussion

This pilot trial justifies KD studies in mild Alzheimer's disease.

SUBMITTER: Taylor MK

PROVIDER: S-EPMC6021549 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease.

Taylor Matthew K MK Sullivan Debra K DK Mahnken Jonathan D JD Burns Jeffrey M JM Swerdlow Russell H RH

Alzheimer's & dementia (New York, N. Y.) 20171206

<h4>Introduction</h4>We assessed the feasibility and cognitive effects of a ketogenic diet (KD) in participants with Alzheimer's disease.<h4>Methods</h4>The Ketogenic Diet Retention and Feasibility Trial featured a 3-month, medium-chain triglyceride-supplemented KD followed by a 1-month washout in clinical dementia rating (CDR) 0.5, 1, and 2 participants. We obtained urine acetoacetate, serum β-hydroxybutyrate, food record, and safety data. We administered the Alzheimer's Disease Assessment Scal ...[more]

PMID: 29955649

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Project description:BackgroundBrain 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.MethodsWe 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.ResultsWe 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.ConclusionsThis 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 registrationThis trial is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12618001450202 . The trial was registered on August 28, 2018.

Project description:BackgroundNo curative therapy for mitochondrial disease (MD) exists, prioritizing supportive treatment for symptom relief. In animal and cell models ketones decrease oxidative stress, increase antioxidants and scavenge free radicals, putting ketogenic diets (KDs) on the list of management options for MD. Furthermore, KDs are well-known, safe and effective treatments for epilepsy, a frequent symptom of MD. This systematic review evaluates efficacy and safety of KD for MD.MethodsWe searched Pubmed, Cochrane, Embase and Cinahl (November 2020) with search terms linked to MD and KD. From the identified records, we excluded studies on Pyruvate Dehydrogenase Complex deficiency. From these eligible reports, cases without a genetically confirmed diagnosis and cases without sufficient data on KD and clinical course were excluded. The remaining studies were included in the qualitative analysis.ResultsOnly 20 cases (14 pediatric) from the 694 papers identified met the inclusion criteria (one controlled trial (n = 5), 15 case reports). KD led to seizure control in 7 out of 8 cases and improved muscular symptoms in 3 of 10 individuals. In 4 of 20 cases KD reversed the clinical phenotype (e.g. cardiomyopathy, movement disorder). In 5 adults with mitochondrial DNA deletion(s) related myopathy rhabdomyolysis led to cessation of KD. Three individuals with POLG mutations died while being on KD, however, their survival was not different compared to individuals with POLG mutations without KD.ConclusionData on efficacy and safety of KD for MD is too scarce for general recommendations. KD should be considered in individuals with MD and therapy refractory epilepsy, while KD is contraindicated in mitochondrial DNA deletion(s) related myopathy. When considering KD for MD the high rate of adverse effects should be taken into account, but also spectacular improvements in individual cases. KD is a highly individual management option in this fragile patient group and requires an experienced team. To increase knowledge on this-individually-promising management option more (prospective) studies using adequate outcome measures are crucial.

Dataset Information

Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease.

Introduction

Methods

Results

Discussion

Publications

Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease.

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