Ketogenic diet exhibits anti‐inflammatory properties

Dupuis, Nina; Curatolo, Niccolò; Benoist, Jean‐François; Auvin, Stéphane

doi:10.1111/epi.13038

Cited by 154 publications

(108 citation statements)

References 13 publications

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“…After 1 month, the ketogenic diet-fed mice demonstrated increased plasma β-hydroxybutyrate, weighed less than standard chow-fed mice, and according to the homeostatic assessment of insulin resistance (HOMA-IR) calculation (Matthews et al 1985) showed evidence of enhanced peripheral insulin sensitivity. Brains from the ketogenic diet-fed mice contained less tumor necrosis factor α (TNFα) mRNA, a finding consistent with other data that indicate ketogenic diets reduce inflammation (Dupuis et al 2015; Ruskin et al 2009). We did not observe reduced brain levels of COX subunit proteins, as we found in our liver study.…”

Section: Discussionsupporting

confidence: 88%

A bioenergetics systems evaluation of ketogenic diet liver effects

Hutfles

Wilkins

Koppel

et al. 2017

Appl. Physiol. Nutr. Metab.

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Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for one month on a ketogenic or standard chow diet. Compared to the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered. The pattern of changes observed can be used to inform a broader systems overview of how ketogenic diets affect liver bioenergetics.

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Section: Discussionsupporting

confidence: 88%

A bioenergetics systems evaluation of ketogenic diet liver effects

Hutfles

Wilkins

Koppel

et al. 2017

Appl. Physiol. Nutr. Metab.

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“…Animal studies of the KD report direct anti-inflammatory effects of the KD [43,44]. Considering the metabolic changes that govern seizure reduction, it is plausible to hypothesize that behavioral changes in children with ASD are explained by similar mechanisms.…”

Section: Discussionmentioning

confidence: 99%

A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder

Lee

Corley

Pang

et al. 2018

Physiology & Behavior

100

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Purpose The ketogenic diet is a low-carbohydrate, moderate protein, high-fat diet that has emerged as a potential treatment for autism spectrum disorder. Autism spectrum disorder is a neurodevelopmental disorder of social communication, and restricted, repetitive behaviors and interests in need of novel therapies. An open-label clinical trial was done in Honolulu, Hawaii to test a modified ketogenic diet for improvement of core clinical impairments in children with ASD. Intervention A modified ketogenic gluten-free diet regimen with supplemental MCT was completed in 15 children ages 2 to 17 years for 3 months. Clinical (ADOS-2, CARS-2) and biochemical measures were performed at baseline and 3-months on the ketogenic diet. Main outcome Children administered a modified ketogenic gluten-free diet with supplemental MCT significantly improved core autism features assessed from the ADOS-2 after 3 months on diet (P = 0.006). No significant difference was observed in restricted and repetitive behavior score (P = 0.125) after 3 months on the diet protocol. Substantial improvement (> 30% decrease ADOS-2 total score) was observed in six participants, moderate improvement (> 3 units) in two participants, and minor/no improvement in seven participants. Ten participants assessed at a six-month time point sustained improvement in total ADOS-2 and social affect subdomain scores comparing baseline and 6 months (P = 0.019; P = 0.023), but no significant improvement in restricted and repetitive behavior scores were noted (P = 0.197). Significant improvements in CARS-2 items after 3 months of the modified ketogenic protocol were observed in imitation, body use, and fear or nervousness (P = 0.031, P = 0.008, P = 0.039). The percent change on ADOS-2 score from baseline to 3 months was associated with baseline high-density lipoprotein levels (ρ = −0.67, P = 0.007) and albumin levels (ρ = −0.60, P = 0.019). Moreover, the percent change from baseline to 3 months in ADOS-2 scores was significantly associated with percent change in high-density lipoprotein levels (ρ = 0.54, P = 0.049) and albumin levels (ρ = 0.67, P = 0.010). Conclusions A modified gluten-free ketogenic diet with supplemental MCT is a potentially beneficial treatment option to improve the core features of autism spectrum disorder and warrants further investigation. Trial registration Trial Registry: Clinicaltrials.gov Registration Number: NCT02477904URL: https://www.clinicaltrials.gov/ct2/show/NCT02477904?term=ketogenic+diet&cond=Autism&rank=1

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“…Of interest, KD therapy exerts a major inherent anti-inflammatory activity, which appears to be independent of PUFA’s [30 • ]. The metabolically regulated transcription factors of the family of peroxisome proliferator activated receptors (PPAR) are involved in mitochondrial biogenesis and the control of genes involved in anti-inflammatory and anti-oxidant pathways.…”

Section: Ppars and Inflammatory Pathwaysmentioning

confidence: 99%

New insights into the mechanisms of the ketogenic diet

Boison

2017

Current Opinion in Neurology

196

139

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Purpose of review High-fat, low-carbohydrate ketogenic diets (KDs) have been used for almost a century for the treatment of epilepsy. Used traditionally for the treatment of refractory pediatric epilepsies, in recent years the use of KDs has experienced a revival to include the treatment of adulthood epilepsies as well as conditions ranging from autism to chronic pain and cancer. Despite the ability of KD therapy to suppress seizures refractory to antiepileptic drugs and reports of lasting seizure freedom, the underlying mechanisms are poorly understood. This review explores new insights into mechanisms mobilized by KD therapies. Recent findings KDs act through a combination of mechanisms, which are linked to the effects of ketones and glucose restriction, and to interactions with receptors, channels, and metabolic enzymes. Decanoic acid, a component of medium chain triclycerides, contributes to seizure control through direct AMPA receptor inhibition, whereas drugs targeting lactate dehydrogenase reduce seizures through inhibition of a metabolic pathway. KD therapy also affects DNA methylation, a novel epigenetic mechanism of the diet. Summary KD therapy combines several beneficial mechanisms that provide broad benefits for the treatment of epilepsy with the potential to not only suppress seizures but also to modify the course of the epilepsy.

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Ketogenic diet exhibits anti‐inflammatory properties

Cited by 154 publications

References 13 publications

A bioenergetics systems evaluation of ketogenic diet liver effects

A bioenergetics systems evaluation of ketogenic diet liver effects

A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder

New insights into the mechanisms of the ketogenic diet

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