Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study
Abstract 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 during metabolic therapy...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | Nutrition & Metabolism |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12986-020-00524-1 |
| _version_ | 1819163738763165696 |
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| author | Susan A. Masino David N. Ruskin Natalie R. Freedgood Marie Lindefeldt Maria Dahlin |
| author_facet | Susan A. Masino David N. Ruskin Natalie R. Freedgood Marie Lindefeldt Maria Dahlin |
| author_sort | Susan A. Masino |
| collection | DOAJ |
| description | Abstract 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 during metabolic therapy may reveal key changes associated with differential clinical outcomes. We characterized the relationship between seizure responsiveness and changes in lipid and carbohydrate metabolites. 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 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 β-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. |
| first_indexed | 2024-12-22T17:48:54Z |
| format | Article |
| id | doaj.art-21c582add8b24baa87904cbf6439a28a |
| institution | Directory Open Access Journal |
| issn | 1743-7075 |
| language | English |
| last_indexed | 2024-12-22T17:48:54Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Nutrition & Metabolism |
| spelling | doaj.art-21c582add8b24baa87904cbf6439a28a2022-12-21T18:18:12ZengBMCNutrition & Metabolism1743-70752021-03-0118111110.1186/s12986-020-00524-1Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot studySusan A. Masino0David N. Ruskin1Natalie R. Freedgood2Marie Lindefeldt3Maria Dahlin4Department of Psychology and Neuroscience Program, Trinity CollegeDepartment of Psychology and Neuroscience Program, Trinity CollegeDepartment of Psychology and Neuroscience Program, Trinity CollegeNeuropediatric Department, Astrid Lindgren Children’s Hospital, Karolinska HospitalNeuropediatric Department, Astrid Lindgren Children’s Hospital, Karolinska HospitalAbstract 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 during metabolic therapy may reveal key changes associated with differential clinical outcomes. We characterized the relationship between seizure responsiveness and changes in lipid and carbohydrate metabolites. 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 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 β-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.https://doi.org/10.1186/s12986-020-00524-1AcetoacetateAnticonvulsantβ-hydroxybutyrateCerebrospinal fluidGlucoseKetogenic diet |
| spellingShingle | Susan A. Masino David N. Ruskin Natalie R. Freedgood Marie Lindefeldt Maria Dahlin Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study Nutrition & Metabolism Acetoacetate Anticonvulsant β-hydroxybutyrate Cerebrospinal fluid Glucose Ketogenic diet |
| title | Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study |
| title_full | Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study |
| title_fullStr | Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study |
| title_full_unstemmed | Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study |
| title_short | Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study |
| title_sort | differential ketogenic diet induced shift in csf lipid carbohydrate metabolome of pediatric epilepsy patients with optimal vs no anticonvulsant response a pilot study |
| topic | Acetoacetate Anticonvulsant β-hydroxybutyrate Cerebrospinal fluid Glucose Ketogenic diet |
| url | https://doi.org/10.1186/s12986-020-00524-1 |
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