Metabolic perturbations associated with the consumption of a ketogenic medium-chain TAG diet in dogs with idiopathic epilepsy

Abstract

Consumption of diets containing medium-chain TAG (MCT) has been shown to confer neuroprotective effects. We aim to identify the global metabolic perturbations associated with consumption of a ketogenic diet (medium-chain TAG diet (MCTD)) in dogs with idiopathic epilepsy. We used ultra-performance liquid chromatography-MS (UPLC-MS) to generate metabolic and lipidomic profiles of fasted canine serum and made comparisons between the MCTD and standardised placebo diet phases. We identified metabolites that differed significantly between diet phases using metabolite fragmentation profiles generated by tandem MS (UPLC–MS/MS). Consumption of the MCTD resulted in significant differences in serum metabolic profiles when compared with the placebo diet, where sixteen altered lipid metabolites were identified. Consumption of the MCTD resulted in reduced abundances of palmitoylcarnitine, octadecenoylcarnitine, stearoylcarnitine and significant changes, both reduced and increased abundances, of phosphatidylcholine (PC) metabolites. There was a significant increase in abundance of the saturated C17 : 0 fatty acyl moieties during the MCTD phase. Lysophosphatidylcholine (17 : 0) (P=0·01) and PC (17:0/20:4) (P=0·03) were both significantly higher in abundance during the MCTD. The data presented in this study highlight global changes in lipid metabolism, and, of particular interest, in the C17 : 0 moieties, as a result of MCT consumption. Elucidating the global metabolic response of MCT consumption will not only improve the administration of current ketogenic diets for neurological disease models but also provides new avenues for research to develop better diet therapies with improved neuroprotective efficacies. Future studies should clarify the involvement and importance of C17 : 0 moieties in endogenous MCT metabolic pathways.

A multicenter randomized controlled trial of medium‐chain triglyceride dietary supplementation on epilepsy in dogs

“…The influence of dietary modification on seizure control has been extensively studied in human medicine 26‐29 and rodent epilepsy models, 30‐33 showing antiseizure effects to varying degrees. Similarly, there are effects of nutritional management and diets in dogs with epilepsy 23,24,34‐39 and paroxysmal dyskinesia 40‐43 …”

Dietary intervention for canine epilepsy: Two case reports

“…It was not a "ketogenic" diet, and thus may be less effective for some dogs than it was for Case 2. [13][14][15] The need for alternatives to current AEDs in dogs is underscored by their lack of efficacy in some cases and harmful side effects in others, 4 including-as detailed in Case 1's report-liver damage from prolonged use of phenobarbital. Anecdotally, Case 1's owners also reported that while in the process of researching his condition and customizing his diet, ingestion of a nonketogenic treat seemed to trigger a seizure event.…”

“…The diet-related improvements noted here are consistent with previous reports-including a randomized studyshowing that changes in diet can reduce seizures and improve behavior. [13][14][15] The need for alternatives to current AEDs in dogs is underscored by their lack of efficacy in some cases and harmful side effects in others, 4 including-as detailed in Case 1's report-liver damage from prolonged use of phenobarbital. In addition, AEDs can have adverse behavioral effects, as observed prominently in Case 2.…”

“…10 Therefore, a diet consisting mainly of raw meats has had anecdotal success based on the theory that dietary deficiencies and grains in commercial product can cause or trigger epileptic seizures. One study of 21 dogs found that seizures were reduced significantly in dogs fed a proprietary ketogenic MCT (KMCT) diet for 3 months 13,14 whereas no improvement was seen in dogs fed a standard diet for the same duration. Furthermore, although most neuroscience research in mammals is conducted in rodents, canines provide different opportunities due to the natural occurrence of epilepsy.…”

“…1,12 To date, a compelling body of controlled studies regarding diet-based therapies for dogs with seizures remains limited. One study of 21 dogs found that seizures were reduced significantly in dogs fed a proprietary ketogenic MCT (KMCT) diet for 3 months 13,14 whereas no improvement was seen in dogs fed a standard diet for the same duration. For 3 subjects, seizures appeared to stop entirely, demonstrating a 100% reduction in seizure frequency.…”