Journal of proteome research | 2019
Metabolic framework for the improvement of autism spectrum disorders by a modified ketogenic diet: a pilot study.
Abstract
The ketogenic diet (KD) can improve the core features of autism spectrum disorders (ASD) in some children, but the effects on overall metabolism remain unclear. This pilot study investigated behavioural parameters in relation to blood metabolites and trace elements in a cohort of 10 typically developed controls (TC) and 17 children with ASD at baseline and following a 3-month treatment with a modified KD regimen. A non-targeted, multiplatform metabolomics approach was employed, including Gas Chromatography-Mass Spectrometry, 1H Nuclear Magnetic Resonance Spectroscopy, and Inductively Coupled Plasma-Mass Spectrometry. Associations between plasma metabolites, trace elements, and behavior scores were investigated. Employing a combination of metabolomics platforms, 118 named metabolites and 73 trace elements were assessed. Relative to TC, a combination of glutamate, galactonate, and glycerol discriminated ASD with 88% accuracy. ASD had higher concentrations of galactose intermediates, gut microbe-derived trimethylamine N-oxide and N-acetylserotonin, and lower concentrations of 3-hydroxybutyrate and selenium at baseline. Following 3mo KD intervention, levels of circulating ketones and acetylcarnitine were increased. KD restored lower selenium levels in ASD to that of controls and correlation analysis identified a novel negative correlation between changes in selenium and behaviour scores. Based on the different behavior responses to the KD, we found that high responders had greater concentrations of 3-hydroxybutyrate and ornithine, with lower galactose. These findings enhance our current understanding of metabolic derangements present in ASD and may be of utility in predicting favorable responses to KD intervention.