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

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

doi:10.1016/j.nut.2018.10.003

Cited by 124 publications

(93 citation statements)

References 32 publications

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“…These observations, as well as the current lack of success of anti-AD therapies or nutritional interventions to change the course of AD, suggest that KD or KS might be of therapeutic interest in these patients. A potential benefit of KDs in AD was already claimed in media and some scientific reports [14,15]. However, as few works have brought about a critical review of existing data, we hereby propose a comprehensive and translational review of KD efficiency in both preclinical and clinical AD or ageing studies.…”

Section: Introductionmentioning

confidence: 95%

Are ketogenic diets promising for Alzheimer’s disease? A translational review

et al. 2020

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Background: Brain amyloid deposition and neurofibrillary tangles in Alzheimer's disease (AD) are associated with complex neuroinflammatory reactions such as microglial activation and cytokine production. Glucose metabolism is closely related to neuroinflammation. Ketogenic diets (KDs) include a high amount of fat, low carbohydrate and medium-chain triglyceride (MCT) intake. KDs lead to the production of ketone bodies to fuel the brain, in the absence of glucose. These nutritional interventions are validated treatments of pharmacoresistant epilepsy, consequently leading to a better intellectual development in epileptic children. In neurodegenerative diseases and cognitive decline, potential benefits of KD were previously pointed out, but the published evidence remains scarce. The main objective of this review was to critically examine the evidence regarding KD or MCT intake effects both in AD and ageing animal models and in humans. Main body: We conducted a review based on a systematic search of interventional trials published from January 2000 to March 2019 found on MEDLINE and Cochrane databases. Overall, 11 animal and 11 human studies were included in the present review. In preclinical studies, this review revealed an improvement of cognition and motor function in AD mouse model and ageing animals. However, the KD and ketone supplementation were also associated with significant weight loss. In human studies, most of the published articles showed a significant improvement of cognitive outcomes (global cognition, memory and executive functions) with ketone supplementation or KD, regardless of the severity of cognitive impairments previously detected. Both interventions seemed acceptable and efficient to achieve ketosis. Conclusion: The KD or MCT intake might be promising ways to alter cognitive symptoms in AD, especially at the prodromal stage of the disease. The need for efficient disease-modifying strategies suggests to pursue further KD interventional studies to assess the efficacy, the adherence to this diet and the potential adverse effects of these nutritional approaches.

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Section: Introductionmentioning

confidence: 95%

Are ketogenic diets promising for Alzheimer’s disease? A translational review

et al. 2020

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“…The KD represents a particular dietary pattern capable of inducing and maintaining a chronic state of ketosis, that is, a metabolic condition where the body mainly uses ketone bodies (KBs) instead of glucose as the major fuel to produce energy [81]. The most powerful condition that can induce ketosis is fasting [82].…”

Section: Ketogenic Dietmentioning

confidence: 99%

Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review

et al. 2020

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Alzheimer’s disease (AD) is the most common form of senile dementia, accounting for up to 70% of dementia cases. AD is a slowly progressive disease, which causes global mental deterioration by affecting various cognitive areas. A growing body of evidence has demonstrated that lifestyle habits and nutritional patterns could delay the natural course of the neurodegeneration process. There is no single dietary pattern unequivocally proven to prevent AD. Nevertheless, epidemiological data suggest that by adopting several dietary habits, especially if accompanied with a healthy lifestyle, the negative consequences of AD could potentially be delayed. Alongside with others, two specific eating patterns have been well investigated concerning their potential beneficial effect on cognitive status: the Mediterranean diet (MedDi) and the Ketogenic Diet (KD). Despite the different underlying mechanisms, both of them have demonstrated a fairly profitable role in reducing or delaying cognitive impairment. The aim of the present narrative review is to overview the existing research on the efficacy of MedDi and KD against AD-related cognitive decline, focusing on the proposed protective mechanisms of action. Although the current knowledge on this complex topic does not allow us, at this point, to make exhaustive conclusions, this information could be of help in order to better characterize the possible role of MedDi and KD as nonpharmacological therapies in the treatment of AD and, more generically, of neurodegenerative disorders.

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“…It was later used for a variety of neurological diseases, such as Alzheimer's disease, Parkinson's disease, etc. [27][28]. Although it is known that a KD promotes high ketone body levels, high fat, low carbohydrates, low calories and other "immediacy" properties [29][30], this study suggests that the ketogenic diet may mediate steroid metabolism reprogramming to treat spinal cord injury rats This study is the rst to reach this conclusion.…”

Section: Discussionmentioning

confidence: 71%

Ketogenic diet-mediated steroid metabolism reprogramming improves the immune microenvironment and myelin growth of spinal cord injury rats through gene analysis and co-expression network analysis

Zeng

Huang

Yang

et al. 2020

Preprint

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Background The ketogenic diet has been widely used in the treatment of various nervous system and metabolic-related diseases. Our previous research found that a ketogenic diet exerts a protective effect and promotes functional recovery after spinal cord injury. However, the mechanism of treatment is still unclear. In this study, different dietary feeding methods were used to detect myelin expression and gene level changes between different groups.Result We established 15 RNA-Seq cDNA libraries and divided them into 4 groups (SCI_KD, SCI_SD, Sham_KD and Sham_SD), and a total of 32,883 genes were detected by RNA-seq. First, KEGG pathway enrichment of upregulated differentially expressed genes (DEGs) in the SCI_KD and SCI_SD groups and GSEA analysis of the two groups found that a ketogenic diet significantly improved the steroid anabolic pathway in rats with spinal cord injury. Through cluster analysis, PPI analysis and visualization of iPath metabolic pathways, Sqle, Sc5d, Cyp51, Dhcr24, Msmo1, Hsd17b7, and Fdft1 changed significantly in the pathway. Second, through WGCNA analysis, all samples are placed in a gene network to analyse the correlation between gene modules and phenotypes. After module analysis, GO function and KEGG analysis showed that rats fed a ketogenic diet showed significantly reduced immune-related pathways, including those associated with immune and infectious diseases.Conclusion A ketogenic diet may improve the immune microenvironment and myelin growth in rats with spinal cord injury through reprogramming of steroid metabolism.

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

Cited by 124 publications

References 32 publications

Are ketogenic diets promising for Alzheimer’s disease? A translational review

Are ketogenic diets promising for Alzheimer’s disease? A translational review

Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review

Ketogenic diet-mediated steroid metabolism reprogramming improves the immune microenvironment and myelin growth of spinal cord injury rats through gene analysis and co-expression network analysis

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