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

Neves, Gabriela Silveira; Lunardi, Mariana dos Santos; Lin, Kátia; Rieger, Débora Kurrle; Ribeiro, Leila; Moreira, Júlia Dubois

doi:10.1093/nutrit/nuaa112

Cited by 14 publications

(12 citation statements)

References 95 publications

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“… 9 , 11 This is important as dyslipidemia may have lasting consequences in young children affecting metabolism, growth and development, as well as future metabolic disease risk. 32 Herein we provide evidence that (i) probiotic administration can counteract some of the dyslipidemia caused by the KD in an IS model; (ii) a probiotic blend does not impact KD induced seizure mitigation and (iii) the mechanism by which probiotics are protective likely involves the upregulation of lipid oxidation involving the energy sensor AMPK.…”

Section: Discussionmentioning

confidence: 82%

Probiotics counteract hepatic steatosis caused by ketogenic diet and upregulate AMPK signaling in a model of infantile epilepsy

Nikpoor

Tompkins

et al. 2022

eBioMedicine

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Background Infantile spasms syndrome (IS) is a type of epilepsy affecting 1.6 to 4.5 per 10,000 children in the first year of life, often with severe lifelong neurodevelopmental consequences. Only two first-line pharmacological treatments currently exist for IS and many children are refractory to these therapies. In such cases, children are treated with the ketogenic diet (KD). While effective in reducing seizures, the diet can result in dyslipidemia over time.Methods Employing a neonatal Sprague-Dawley rat model of IS, we investigated how the KD affects hepatic steatosis and its modulation by a defined probiotic blend. A combination of multiple readouts, including malondialdehyde, fatty acid profiles, lipid metabolism-related enzyme mRNA expression, mitochondrial function, histone deacetylase activity, cytokines and chemokines were evaluated using liver homogenates.Findings The KD reduced seizures, but resulted in severe hepatic steatosis, characterized by a white liver, triglyceride accumulation, elevated malondialdehyde, polyunsaturated fatty acids and lower acyl-carnitines compared to animals fed a control diet. The KD-induced metabolic phenotype was prevented by the co-administration of a blend of Streptococcus thermophilus HA-110 and Lactococcus lactis subsp. lactis HA-136. This probiotic blend protected the liver by elevating pAMPK-mediated signaling and promoting lipid oxidation. The strains further upregulated the expression of caspase 1 and interleukin 18, which may contribute to their hepatoprotective effect in this model.Interpretation Our results suggest that early intervention with probiotics could be considered as an approach to reduce the risk of hepatic side effects of the KD in children who are on the diet for medically indicated reasons.

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Section: Discussionmentioning

confidence: 82%

Probiotics counteract hepatic steatosis caused by ketogenic diet and upregulate AMPK signaling in a model of infantile epilepsy

Nikpoor

Tompkins

et al. 2022

eBioMedicine

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“…Chronic elevations in blood LDL-C and TC concentrations may raise the risk of cardiovascular disease, particularly in adult patients on long-term KD treatment. 32 Before the diagnosis of KD, persons with a higher cardiovascular risk should be screened to ensure that the patient understands the risks and advantages of dietary therapy.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of ketogenic diet therapy in children diagnosed with drug-resistant epilepsy: a single-center experience

Yıldırım¹,

Yağcı²,

Uygur³

et al. 2022

Turk J Pediatr

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Background. We evaluate here the effect of the ketogenic diet (KD) on children with drug-resistant epilepsy (DRE) in terms of clinical effectiveness, anthropometric measurements, and some electroencephalogram (EEG) and biochemical findings. Methods. Included in the study were 18 children (median age 70 months, 61.1% female) who received the classical KD and modified Atkins diet (MAD) for at least one year due to DRE. The patients` demographic and laboratory data; weight, height and body mass index values; EEG and electrocardiographic findings; abdominal ultrasonography findings; and biochemical parameters were recorded at baseline and at 12 months after the initiation of the diet. A reduction of ≥50% in the number of seizures was accepted as a response to KD. Results. Classic KD was chosen for 14 patients (77.8%), and MAD for four patients (22.2%). The response to KD therapy (≥50% reduction) was 55.5% (n = 10) (p = 0.008), and one patient even became seizure-free. By the 12th month of treatment, 10 patients had experienced a reduction of more than 50% in epileptiform discharges, as indicated by EEG findings. There was no difference in seizure reduction between the patients who received classical KD and MAD. A total of 11.1% of the children lost weight during KD treatment. The most common side effect was constipation (n = 10, 55.6%). At the end of one year of treatment, total cholesterol and low density lipoprotein cholesterol (LDL-C) LDL-C levels had increased dramatically, while fasting blood glucose levels had decreased significantly. Conclusions. Our study suggests that KD treatment provides good clinical efficacy in the treatment of pediatric DRE, and can significantly reduce the frequency of epileptic discharges. Also, total cholesterol and LDL-C levels increased significantly, and fasting blood glucose levels decreased significantly compared to the baseline levels.

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“…The ketogenic diet is characterized by reduced carbohydrate content and high-fat consumption and subsequent use of ketone bodies as the primary energy source, reducing glucose use by the brain. This diet may have mood-stabilizing properties through altered excitatory/inhibitory status affecting the signaling of the neurotransmitters dopamine, GABA, and glutamate, as well as more effective ATP production with a reduction of reactive oxygen species production [ 66 , 67 ]. Another study currently undergoing recruitment is a pilot RCT with 8 weeks of a healthy Nordic diet versus a control diet for individuals with MDD [ 68 ].…”

Section: Dietary Interventions As An Emergent Strategy In the Treatme...mentioning

confidence: 99%

A Possible Antidepressive Effect of Dietary Interventions: Emergent Findings and Research Challenges

Ceolin

Breda

Koning

et al. 2022

Curr Treat Options Psych

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

Cited by 14 publications

References 95 publications

Probiotics counteract hepatic steatosis caused by ketogenic diet and upregulate AMPK signaling in a model of infantile epilepsy

Probiotics counteract hepatic steatosis caused by ketogenic diet and upregulate AMPK signaling in a model of infantile epilepsy

Evaluation of ketogenic diet therapy in children diagnosed with drug-resistant epilepsy: a single-center experience

A Possible Antidepressive Effect of Dietary Interventions: Emergent Findings and Research Challenges

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