Ketogenic diet, seizure control, and cardiometabolic risk in adult patients with pharmacoresistant epilepsy: a review

Abstract Pharmacoresistant epilepsy causes serious deleterious effects on the patient’s health and quality of life. For this condition, a ketogenic diet (KD) is a treatment option. The KD is a general term for a set of diets that contain high amounts of fat and low content of carbohydrates. The most prominent KD treatments are classical KD (4:1 ratio of fat to carbohydrate), modified Atkins diet (2:1 to 1:1 ratio), medium-chain triglycerides KD (with medium-chain triglyceride as a part of the fat content), and low glycemic index KD (using low glycemic carbohydrates). KD has been widely prescribed for children with epilepsy but not for adult patients. One of the main concerns about adult use of KD is its cardiovascular risk associated with high-fat and cholesterol intake. Therefore, this narrative review provides comprehensive information of the current literature on the effects of KD on lipid profile, glycemic-control biomarkers, and other cardiometabolic risk factors in adult patients with pharmacoresistant epilepsy.

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A 48‐year‐old female, with a family history of AD PSEN1 mutation, who developed mild cognitive impairment and tried ketogenic diet‐associated medium‐chain triglyceride as treatment

Alzheimer s & Dementia ◽

10.1002/alz.039482 ◽

2020 ◽

Vol 16 (S6) ◽

Author(s):

Gustavo Melo de Andrade Lima ◽

Marta Corrado ◽

Marcela Marques de Oliveira Gregório ◽

Paulo Henrique Ferreira Bertolucci

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Family History ◽

Ketogenic Diet ◽

Medium Chain Triglyceride ◽

Medium Chain ◽

Psen1 Mutation ◽

History Of

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Clinical effects of one year of chemotherapy with a modified medium-chain triglyceride ketogenic diet on the recurrence of stage IV colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e15709 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e15709-e15709 ◽

Cited By ~ 4

Author(s):

Kenji Furukawa ◽

Kyosuke Shigematus ◽

Yoshie Iwase ◽

Wakako Mikami ◽

Hiroko Hoshi ◽

...

Keyword(s):

Colon Cancer ◽

Ketogenic Diet ◽

Medium Chain Triglyceride ◽

Stage Iv ◽

Clinical Effects ◽

Medium Chain ◽

One Year

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Alternative Therapies for Epilepsy

10.1093/med/9780199937837.003.0046 ◽

2017 ◽

Author(s):

Carl E. Stafstrom

Keyword(s):

Ketogenic Diet ◽

Medium Chain Triglyceride ◽

Dietary Therapy ◽

Promising Alternative ◽

Seizure Reduction ◽

Modified Atkins Diet ◽

Dietary Restrictions ◽

Patients With Epilepsy ◽

Low Glycemic Index

Up to one third of patients with epilepsy suffer from seizures that are refractory to medications. For these patients, many of whom are not surgical candidates, dietary therapies provide a promising alternative. The best known dietary therapy is the ketogenic diet, which was developed in the 1920s; newer variants of the ketogenic diet, such as the medium-chain triglyceride diet, modified Atkins diet, and low glycemic index treatment, afford excellent seizure control with fewer dietary restrictions. Together, dietary approaches offer drug-resistant patients hope for seizure reduction and an improved quality of life.

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Efficacy and Safety of a Ketogenic Diet in Children and Adolescents with Refractory Epilepsy—A Review

Nutrients ◽

10.3390/nu12061809 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1809 ◽

Cited By ~ 4

Author(s):

Jana Wells ◽

Arun Swaminathan ◽

Jenna Paseka ◽

Corrine Hanson

Keyword(s):

Ketogenic Diet ◽

Medium Chain Triglyceride ◽

Epileptic Seizures ◽

Diet Therapy ◽

Direct Result ◽

Individual Response ◽

Modified Atkins Diet ◽

Patients With Epilepsy ◽

The Brain

Epilepsy in the pediatric and adolescent populations is a devastating condition where individuals are prone to recurrent epileptic seizures or changes in behavior or movement that is the direct result of a primary change in the electrical activity in the brain. Although many children with epilepsy will have seizures controlled with antiseizure medications (ASMs), a large percentage of patients are refractory to drug therapy and may consider initiating a ketogenic diet. The term Ketogenic Diet or Ketogenic Diet Therapy (KDT) refers to any diet therapy in which dietary composition results in a ketogenic state of human metabolism. Currently, there are 4 major Ketogenic diet therapies—the classic ketogenic diet (cKD), the modified Atkins diet (MAD), the medium chain triglyceride ketogenic diet (MCTKD) and the low glycemic index treatment (LGIT). The compositions of the 4 main KDTs differ and limited evidence to distinguish the efficacy among different diets currently exists. Although it is apparent that more randomized controlled trials (RCTs) and long-term studies are needed to evaluate efficacy, side effects and individual response to the diet, it is imperative to study and understand the metabolic profiles of patients with epilepsy in order to isolate which dietary restrictions are necessary to maximize clinical benefit.

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Ketogenic diet for epilepsy treatment

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20160116 ◽

2016 ◽

Vol 74 (10) ◽

pp. 842-848 ◽

Cited By ~ 18

Author(s):

Letícia Pereira de Brito Sampaio

Keyword(s):

Ketogenic Diet ◽

Refractory Epilepsy ◽

Medium Chain Triglyceride ◽

Modified Atkins Diet ◽

The Past ◽

Atkins Diet ◽

Low Carbohydrate ◽

History Of ◽

Index Treatment ◽

Low Glycemic Index

ABSTRACT The ketogenic diet (KD), a high-fat, low-carbohydrate, and adequate-protein diet is an established, effective nonpharmacologic treatment option for intractable childhood epilepsy. The KD was developed in 1921 and even though it has been increasingly used worldwide in the past decade, many neurologists are not familiar with this therapeutic approach. In the past few years, alternative and more flexible KD variants have been developed to make the treatment easier and more palatable while reducing side effects and making it available to larger group of refractory epilepsy patients. This review summarizes the history of the KD and the principles and efficacy of the classic ketogenic diet, medium-chain triglyceride(s) (MCT) ketogenic diet, modified Atkins diet, and low glycemic index treatment.

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The effect of the classical and medium chain triglyceride ketogenic diet on vitamin and mineral levels

Journal of Human Nutrition and Dietetics ◽

10.1111/j.1365-277x.2011.01172.x ◽

2011 ◽

Vol 25 (1) ◽

pp. 16-26 ◽

Cited By ~ 19

Author(s):

S. S. Christodoulides ◽

E. G. Neal ◽

G. Fitzsimmons ◽

H. M. Chaffe ◽

Y. M. Jeanes ◽

...

Keyword(s):

Ketogenic Diet ◽

Medium Chain Triglyceride ◽

Medium Chain ◽

Mineral Levels

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The Medium-Chain Triglyceride Ketogenic Diet

Dietary Treatment of Epilepsy: Practical Implementation of Ketogenic Therapy ◽

10.1002/9781118702772.ch9 ◽

2013 ◽

pp. 78-88

Author(s):

Elizabeth Neal

Keyword(s):

Ketogenic Diet ◽

Medium Chain Triglyceride ◽

Medium Chain

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Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium-chain triglyceride ketogenic diet

Epilepsia ◽

10.1111/epi.13833 ◽

2017 ◽

Vol 58 (8) ◽

pp. 1423-1429 ◽

Cited By ~ 12

Author(s):

Aziza Khabbush ◽

Michael Orford ◽

Yi-Chen Tsai ◽

Tricia Rutherford ◽

Maura O'Donnell ◽

...

Keyword(s):

Ketogenic Diet ◽

Octanoic Acid ◽

Medium Chain Triglyceride ◽

Decanoic Acid ◽

Acid Oxidation ◽

Medium Chain ◽

Mechanistic Insight ◽

Insight Into

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Identifying the Molecular Mechanism of the Medium Chain Triglyceride (Ketogenic) Diet

10.1093/med/9780190497996.003.0033 ◽

2016 ◽

Author(s):

Matthew C. Walker ◽

Robin S.B. Williams

Keyword(s):

Ketogenic Diet ◽

Seizure Control ◽

Medium Chain Triglyceride ◽

Decanoic Acid ◽

In Vivo Models ◽

Principal Mechanism ◽

Excitatory Neurotransmitter ◽

Medium Chain

The medium chain triglyceride (MCT) ketogenic diet provides a highly effective and commonly used approach for treating drug-resistant epilepsy. It is associated with elevated levels of two MCT-derived fatty acids, decanoioc and octanoic acids. Researchers have identified a role for decanoic acid and a range of novel related chemicals in seizure control in multiple acute in vitro and in vivo models. A principal mechanism of decanoic acid is direct inhibition of AMPA receptors, key excitatory neurotransmitter receptors widely recognized as a target for seizure control. These data suggest a therapeutic mechanism of the MCT ketogenic diet through a direct fatty acid–dependent mechanism, independent of ketosis. This discovery will enable the development of an improved and, potentially, better-tolerated diet and the generation of a corresponding pharmaceutical approach. The diet should be termed the MCT diet, as the consequent ketosis may not be necessary for seizure control.

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