Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer’s disease: a pilot study

Neth, Bryan J.; Mintz, Akiva; Whitlow, Christopher T.; Jung, Youngkyoo; Sai, Kiran Solingapuram; Register, Thomas C.; Kellar, Derek; Lockhart, Samuel N.; Hoscheidt, Siobhan M.; Maldjian, Joseph A.; Heslegrave, Amanda; Blennow, Kaj; Cunnane, Stephen C.; Castellano, Christian‐Alexandre; Zetterberg, Henrik; Craft, Suzanne

doi:10.1016/j.neurobiolaging.2019.09.015

Cited by 160 publications

(229 citation statements)

References 69 publications

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“…Decreased butyrate in MCI inversely correlates with cerebrospinal fluid levels of Aβ42, with the ketogenic diet having utility in reversing this [17]. This is supported by other work showing the ketogenic diet to decrease cerebrospinal fluid levels of tau [155] and to improve cognition in a mild AD and metabolic syndrome patient [156]. Although larger controlled studies are clearly needed, it seems likely that the ketogenic diet will have some utility in MCI and AD, with effects that include an increase in gut microbiome-derived butyrate.…”

Section: Ketone Dietsupporting

confidence: 54%

Sirtuins, Mitochondria and the Melatonergic Pathway in Alzheimer’s Disease<strong> </strong>

Anderson¹,

Maes²

2020

Preprint

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Alzheimer's disease (AD) has been the subject of extensive investigation as to its biological underpinnings. However, this has produced little of therapeutic benefit or indeed provided any accepted biomarkers that could tailor treatment. This chapter reviews data on the main pathophysiologic processes that have been widely shown to be altered in AD, including circadian dysregulation, mitochondrial dysfunction, gut dysbiosis, and immune-glia-platelet activation. It is proposed that alterations in the gut microbiome, including gut dysbiosis and increased gut permeability drive changes in mitochondrial function that are intimately associated with significant variations in sirtuin expression. Both mitochondria-located and nucleus/cytoplasm located sirtuins can act on mitochondrial function in different cells and body systems to co-ordinate the ageing-associated changes that underpin AD. The sirtuins are therefore key aspect to a developmental model of AD that is more 'holistic' in perspective, thereby providing a framework for the detection of earlier biomarkers and more successful treatment for the heterogenous nature of AD pathoetiology.

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Section: Ketone Dietsupporting

confidence: 54%

Sirtuins, Mitochondria and the Melatonergic Pathway in Alzheimer’s Disease<strong> </strong>

Anderson¹,

Maes²

2020

Preprint

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“…MMKD differed from KD because it provided slightly higher consumption of carbohydrate such as vegetables and fruits, proteins derived from fish, and fats derived from olive oil. In this trial, an increased cerebral perfusion and cerebral ketone body uptake following MMKD has been reported [116].…”

Section: Ketogenic Dietmentioning

confidence: 63%

“…A recent pilot study evaluated neurological effects of a modified Mediterranean-ketogenic diet (MMKD) in older adults at risk for AD [116]. MMKD differed from KD because it provided slightly higher consumption of carbohydrate such as vegetables and fruits, proteins derived from fish, and fats derived from olive oil.…”

Section: Ketogenic Dietmentioning

confidence: 99%

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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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“…Clearly many systemic changes occur with dietary therapy, making it difficult to sort out key mechanisms of efficacy. To date a number of studies have examined changes in blood metabolites aside from ketone bodies and glucose, typically examining a limited number of predetermined compounds to address specific hypotheses [15][16][17][18][19][20][21]. While cerebrospinal fluid (CSF) is significantly more difficult to collect than blood, analysis of CSF metabolites may be more relevant to KD mechanisms in epilepsy [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Differential Ketogenic Diet-Induced Shift in CSF Lipid/Carbohydrate Metabolome of Pediatric Epilepsy Patients With Optimal Vs. No Anticonvulsant Response

Masino¹,

Ruskin²,

Freedgood³

et al. 2020

Preprint

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Background: The low carbohydrate, high fat ketogenic diet can be an effective anticonvulsant treatment in some pediatric patients with pharmacoresistant epilepsy. Its mechanism(s) of action, however, remain uncertain. Direct sampling of cerebrospinal fluid before and after metabolic therapy may reveal key changes associated with differential clinical outcomes. Methods: We performed metabolomic analysis of cerebrospinal fluid samples taken before and during ketogenic diet treatment in patients with optimal response (100% seizure remission) and patients with no response (no seizure improvement) to search for differential diet effects in hallmark metabolic compounds in these two groups. Optimal responders and non-responders were similar in age range and included males and females. Seizure types and the etiologies or syndromes of epilepsy varied but did not appear to differ systematically between responders and non-responders. Results: Principal component analysis showed a strong effect of ketogenic diet treatment on the cerebrospinal fluid metabolome. Longitudinal and between-subjects analyses revealed that many lipids and carbohydrates were changed significantly by ketogenic diet, with changes typically being of larger magnitude in responders. Notably, responders had more robust changes in glucose and the ketone bodies b-hydroxybutyrate and acetoacetate than non-responders; conversely, non-responders had significant increases in fructose and sorbose, which did not occur in responders. Conclusions: The data suggest that a differential and stronger metabolic response to the ketogenic diet may predict a better anticonvulsant response, and such variability is likely due to inherent biological factors of individual patients. Strategies to boost the metabolic response may be beneficial.

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Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer’s disease: a pilot study

Cited by 160 publications

References 69 publications

Sirtuins, Mitochondria and the Melatonergic Pathway in Alzheimer’s Disease<strong> </strong>

Sirtuins, Mitochondria and the Melatonergic Pathway in Alzheimer’s Disease<strong> </strong>

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

Differential Ketogenic Diet-Induced Shift in CSF Lipid/Carbohydrate Metabolome of Pediatric Epilepsy Patients With Optimal Vs. No Anticonvulsant Response

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Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer’s disease: a pilot study

Cited by 160 publications

References 69 publications

Sirtuins, Mitochondria and the Melatonergic Pathway in Alzheimer&rsquo;s Disease<strong> </strong>

Sirtuins, Mitochondria and the Melatonergic Pathway in Alzheimer&rsquo;s Disease<strong> </strong>

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

Differential Ketogenic Diet-Induced Shift in CSF Lipid/Carbohydrate Metabolome of Pediatric Epilepsy Patients With Optimal Vs. No Anticonvulsant Response

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Product

Resources

About

Sirtuins, Mitochondria and the Melatonergic Pathway in Alzheimer’s Disease<strong> </strong>

Sirtuins, Mitochondria and the Melatonergic Pathway in Alzheimer’s Disease<strong> </strong>