Journal Article

The ketogenic diet as a potential treatment and prevention strategy for Alzheimer's disease

Rucklidge, Julia J., Broom, Gina M., Shaw, Ian C.

2019

Overview

•Impaired brain glucose metabolism and amyloid β plaques are associated with Alzheimer's disease pathology.•Ketones provide an alternative metabolic precursor to glucose in the brain.•Ketogenic diets likely reduce amyloid plaques and may reverse their neurotoxicity.•Modern diets high in carbohydrates may contribute to increasing Alzheimer's incidence.•The ketogenic diet (including carbohydrate restriction) might be useful in the management of Alzheimer's disease. The prevalence of Alzheimer's disease, a chronic neurodegenerative condition, is increasing as is the need for effective treatments and preventions. The underlying pathology of Alzheimer's is not yet fully understood, so existing research has focused on understanding the prominent features of the disease. These include amyloid plaques, which accumulate in the brains of those with Alzheimer's disease; impaired glucose metabolism; and neuronal cell death. Emerging evidence suggests that a low-carbohydrate, high-fat ketogenic diet may help to mitigate the damage associated with these pathologies. The ketogenic diet could alleviate the effects of impaired glucose metabolism by providing ketones as a supplementary energy source. In addition, this diet may help to reduce the accumulation of amyloid plaques while reversing amyloid β toxicity. Research has begun to identify early underlying mechanisms in Alzheimer's disease that could be targeted by new prevention strategies. Glycation of the ApoE protein leads to impaired transportation of important lipids, including cholesterol, to the brain, resulting in lipid deficiencies that could explain progression to the later pathologies of the disease. In this review, we hypothesize that the ketogenic diet could be an effective treatment and prevention for Alzheimer's disease, but both ketone production and carbohydrate restriction may be needed to achieve this.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Alzheimer disease / Alzheimer Disease - diet therapy / Alzheimer Disease - metabolism / Alzheimer Disease - prevention & control / Alzheimer's disease / Amyloid / Amyloid beta-Peptides - metabolism / Amyloid β / Apolipoprotein E / Apoptosis / Brain / Brain - metabolism / Brain research / Carbohydrates / Cell death / Cholesterol / Cognitive ability / Dementia / Diet / Diet, Ketogenic / Dietary intervention / Disease prevention / energy / Energy Metabolism - drug effects / Energy sources / Glucose / Glucose metabolism / glycation / Glycosylation / High carbohydrate diet / High fat diet / Humans / Ketogenesis / Ketogenic diet / Ketones / Ketones - metabolism / Lipids / Low carbohydrate diet / Low fat diet / Metabolism / Neurodegenerative diseases / neurons / Neurons - metabolism / Nutrient deficiency / Pathology / Protein transport / Proteins / Senile plaques / Therapeutic applications / Toxicity