High fat and low carbohydrate supplies are linked to decreased epilepsy disease burden globally

Objectives Epilepsy is one of the major neural disorders globally. Ketogenic diets with high fat, low carbohydrate and moderate to low protein contents are well-established as interventions for epilepsy, particularly the intricate ones, exemplifying that modifying dietary compositions might have profound effects on established epilepsy. However, most of the diet-related epilepsy interventions have focused on dividual nutrients or specific diets with set nutrient compositions. An important unanswered question is whether specific macronutrient exposure through diets and food environments are linked to epilepsy and could potentially extend to primary preventive qualities. Methods Macronutrient supply, gross domestic product (GDP), and epilepsy disease burden data were collated from more than 150 countries spanning from 1990 to 2018. Nutritional geometry generalized additive mixed models (GAMMs) were carried out for analysis. Results GAMM modelling unravelled the interactive effects of nutrient supplies and socioeconomic status on epilepsy disease burden. Carbohydrate supply was associated with increased epilepsy while fat supply had the opposite effect. A high fat low carbohydrate supplies dietary environment, similar to ketogenic diets, was linked to the lowest epilepsy disease burden. These associations were conserved across sexes and were not confounded by the total energy supply. Conclusions A high fat low carbohydrate supplies dietary environment is associated with decreased epilepsy disease burden, hinting a plausible primary preventive role. This might expand the clinical application of ketogenic diets and inform future nutrient-based epilepsy treatment and/or prevention. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This project is supported by the Norman Ernest Bequest Fund. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors