title: An examination of biochemical parameters and their association with response to ketogenic dietary therapies.
abstract: 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 β-hydroxybutyrate, acetoacetate, nonesterified fatty acids, free and acylcarnitine profile, glucose, and glucose-ketone index (GKI).
  
  
  
  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.
  
  
  
  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 β-hydroxybutyrate measured at baseline and 3-month follow-up in KDT responders. No other biochemical parameters were associated with response at any time point.
  
  
  
  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.
authors.affiliation: UCL Great Ormond Street Institute of Child Health, London, United Kingdom.|Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Natasha E
authors.initials: NE
authors.lastname: Schoeler
authors.affiliation: Epilepsy Society, Chalfont St Peter, United Kingdom.
authors.forename: Gail
authors.initials: G
authors.lastname: Bell
authors.affiliation: Epilepsy Society, Chalfont St Peter, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Yuen
authors.affiliation: Department of Mathematics, Queens College, The City University of New York (CUNY), New York, New York, U.S.A.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Kapelner
authors.affiliation: Genetics and Genomic Medicine, UCL Institute of Child Health, London, United Kingdom.|Chemical Pathology, Great Ormond Street Hospital for Children, London, United Kingdom.|Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
authors.forename: Simon J R
authors.initials: SJR
authors.lastname: Heales
authors.affiliation: UCL Great Ormond Street Institute of Child Health, London, United Kingdom.|Great Ormond Street Hospital for Children, London, United Kingdom.|Young Epilepsy, Lingfield, United Kingdom.
authors.forename: J Helen
authors.initials: JH
authors.lastname: Cross
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, United Kingdom.|Epilepsy Society, Chalfont St Peter, United Kingdom.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sisodiya
mesh_terms: D000108:Acetylcarnitine / Q000097:blood; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D055423:Diet, Ketogenic; D004827:Epilepsy / Q000097:blood* / Q000178:diet therapy* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000108:Acetylcarnitine
keywords: Biochemistry; Epilepsy; High-fat; Low-carbohydrate; Predictor