Journal
EPILEPSIA
Volume 58, Issue 5, Pages 893-900Publisher
WILEY
DOI: 10.1111/epi.13729
Keywords
Low-carbohydrate; High-fat; Biochemistry; Epilepsy; Predictor
Categories
Funding
- Department of Health's National Institute for Health Research (NIHR) Biomedical Research Centres' funding scheme
- University College London (UCL) Impact Studentship
- Epilepsy Society
- Wellcome Trust [084730]
- MRC [MC_PC_14140] Funding Source: UKRI
- Medical Research Council [MC_PC_14140] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0515-10073] Funding Source: researchfish
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Objective: In the absence of specific metabolic disorders, accurate predictors of response to ketogenic dietary therapies (KDTs) for treating epilepsy are largely unknown. We hypothesized that specific biochemical parameters would be associated with the effectiveness of KDT in humans with epilepsy. The parameters tested were -hydroxybutyrate, acetoacetate, nonesterified fatty acids, free and acylcarnitine profile, glucose, and glucose-ketone index (GKI). Methods: Biochemical results from routine blood tests conducted at baseline prior to initiation of KDT and at 3-month follow-up were obtained from 13 adults and 215 children with KDT response data from participating centers. One hundred thirty-two (57%) of 228 participants had some data at both baseline and 3 months; 52 (23%) of 228 had data only at baseline; 22 (10%) of 228 had data only at 3 months; and 22 (10%) of 228 had no data. KDT response was defined as 50% seizure reduction at 3-month follow-up. Results: Acetyl carnitine at baseline was significantly higher in responders (p < 0.007). It was not associated with response at 3-month follow-up. There was a trend for higher levels of free carnitine and other acylcarnitine esters at baseline and at 3-month follow-up in KDT responders. There was also a trend for greater differences in levels of propionyl carnitine and in -hydroxybutyrate measured at baseline and 3-month follow-up in KDT responders. No other biochemical parameters were associated with response at any time point. Significance: Our finding that certain carnitine fractions, in particular baseline acetyl carnitine, are positively associated with greater efficacy of KDT is consistent with the theory that alterations in energy metabolism may play a role in the mechanisms of action of KDT.
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