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

Abstract

Background: Medium-chain triglyceride (MCT) enriched diet has a positive effect on seizure control and behavior in some dogs with idiopathic epilepsy (IE).Objective: To evaluate the short-term efficacy of MCTs administered as an add-on dietary supplement (DS) to a variable base diet to assess seizure control and antiseizure drug's (ASD) adverse effect profiles.Animals: Twenty-eight dogs with International Veterinary Epilepsy Task Force Tier II (IVETF) level diagnosis of treated IE with 3 or more seizures in the last 3 months were used.Methods: A 6-month multicenter, prospective, randomized, double-blinded, placebocontrolled crossover trial was completed, comparing an MCT-DS with a control-DS.A 9% metabolic energy-based amount of MCT or control oil was supplemented to the dogs' diet for 3 months, followed by a control oil or MCT for another 3 months, respectively. Dogs enrolled in this study satisfied most requirements of IE diagnosis stated by the IVETF II level. If they received an oil DS or drugs that could influence the metabolism of the investigated DS or chronic ASD, the chronic ASD medication was adjusted, or other causes of epilepsy were found, the dogs were excluded from the study.Abbreviations: ASD, antiseizure drug; BHB, beta hydroxybutyric acid; C10, decanoic acid = capric acid; C8, octanoic acid = caprylic acid; DS, dietary supplement; IE, idiopathic epilepsy; ITTA, intention to treat analysis; IVETF II, International Veterinary Epilepsy Task Force Tier II; KBr, potassium bromide; LEV, levetiracetam; MBW, metabolic body weight; MCT, medium-chain triacylglyceride; ME, metabolic energy; PB, phenobarbital; QoL, quality of life; RER, resting energy requirement; RVC, Royal Veterinary College; VAS, visual analog score.

Research priorities for idiopathic epilepsy in dogs: Viewpoints of owners, general practice veterinarians, and neurology specialists

“…Evidence for the efficacy of MCT supplementation to the diets of dogs with IE is increasing, with reductions in epileptic seizures, behavioral and cognitive comorbidities both when combined within a kibble diet [56][57][58] and when added as a supplement to a dog's base diet. 59,60 Understanding the mechanisms behind these positive effects (eg, impacts on the dog microbiome and metabolome 61 ), and identifying profiles of dogs most likely to respond to this dietary intervention is a future priority for MCT research. Evidence for CBD oil supplementation in dogs with IE is in its relative infancy, with a preliminary randomized control study indicating that although the CBD-treated group had a 33% decrease in the group median for mean monthly seizure frequency compared with the placebo-treated group, the proportion of dogs considered treatment "responders" (ie, ≥50% decrease in seizure activity) was similar between the 2 groups.…”

Beneficial Effects of Exogenous Ketogenic Supplements on Aging Processes and Age-Related Neurodegenerative Diseases

“…It has also been demonstrated that administration of EKSs-generated therapeutic ketosis may evoke beneficial effects on CNS diseases [ 34 , 38 , 39 ]. For example, KEs, KSs and MCT oils can evoke anti-seizure and anti-epileptic effects [ 36 , 40 , 41 , 42 ], anxiolytic influence [ 26 , 43 , 44 ], regeneration of nervous system injuries [ 45 ] and alleviating effects on neurodegenerative diseases (such as Alzheimer’s disease) [ 41 , 46 , 47 , 48 ]. These beneficial effects were induced likely through ketosis-evoked neuroprotective effects, for example, by improved mitochondrial functions, enhanced ATP levels, decreased inflammatory processes and decreased oxidative stress [ 23 , 24 , 34 , 49 , 50 ].…”

Age- and Sex-Dependent Modulation of Exogenous Ketone Supplement-Evoked Effects on Blood Glucose and Ketone Body Levels in Wistar Albino Glaxo Rijswijk Rats

“…Moreover, EKSs are well-tolerated and can generate therapeutic ketosis (ketone levels = 1–7 mM) while maintaining a normal diet ( Clarke et al, 2012 ; Hashim and VanItallie, 2014 ; Ari et al, 2016 ; Stubbs et al, 2017 ). Consequently, EKS administration-generated therapeutic ketosis may be a safe alternative method ( D’Agostino et al, 2013 ; Ari et al, 2016 ; Stubbs et al, 2017 ) to circumvent dietary restrictions and adverse effects by KDs (e.g., nephrolithiasis, growth retardation, constipation, and hyperlipidemia) ( Branco et al, 2016 ) and to treat not only several CNS diseases, such as epilepsy, psychiatric diseases (e.g., anxiety), neurodegenerative disorders (e.g., Alzheimer’s disease), and cancer ( Newport et al, 2015 ; Kovács et al, 2017 , 2019a ; Berk et al, 2020 ), but also, among others, non-alcoholic fatty liver disease, obesity, cardiovascular disease, glucose intolerance, and type 2 diabetes ( Han et al, 2020 ).…”