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

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

Total Water Intake and Urine Measures of Hydration in Adult Dogs Drinking Tap Water or a Nutrient-Enriched Water

Water intake and urine measures were evaluated in dogs offered tap water (TW) or a nutrient-enriched water (NW) supplement while fed dry food with ad libitum TW in a bucket. Baseline (day-7) urine specific gravity (USG) was analyzed from healthy, adult small breed dogs (n = 21; 2–11 years). Dogs (N = 16) were selected with ≥1.015 USG, then equally divided into 2 groups balanced for USG. Groups received either TW or NW in a bowl for 56 days. Dose for each dog was 0.5:1 water-to-calorie ratio (mL:kcal ME/d) from days 1–49 to evaluate sustained intake of a moderate volume, or 2:1 water-to-calorie ratio from days 50–56 to evaluate short-term intake of a large volume, based on baseline food calorie intake. Daily food calorie and total liquid intake (TLI; g/d; sum of NW or TW in a bowl and bucket water) was used to calculate weekly intake. USG was measured on days −7, 14, 42, 56. Calorie intake was not different (P > 0.49). A significant (P < 0.001) time-by-treatment interaction resulted for TLI with baseline similar between groups and no difference between weeks for the TW group. Following baseline, NW group had increased (P < 0.05) TLI every week, except for week 2 (P = 0.07). A significant (P < 0.002) time-by-treatment interaction resulted for USG, with baseline similar between groups and no difference between sampling days for the TW group (varied by ≤ 0.006 g/mL), whereas NW group was lower (P < 0.01) on days 42 (1.018 g/mL) and 56 (1.014 g/mL) vs. baseline (1.026 g/mL). This study indicates that all dogs offered the NW supplement increased their TLI and produced a more dilute urine, which suggests an improvement in indices associated with chronic hydration

A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy

Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. Dogs were fed either MCTD or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. Seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. Seizure frequency was significantly lower when dogs were fed the MCTD (2·31/month, 0–9·89/month) in comparison with the placebo diet (2·67/month, 0·33–22·92/month, P=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall <50 % reduction in seizures (38·87 %, 35·68–43·27 %) and six showed no response. Seizure day frequency were also significantly lower when dogs were fed the MCTD (1·63/month, 0–7·58/month) in comparison with the placebo diet (1·69/month, 0·33–13·82/month, P=0·022). Consumption of the MCTD also resulted in significant elevation of blood β-hydroxybutyrate concentrations in comparison with placebo diet (0·041 (sd 0·004) v. 0·031 (sd 0·016) mmol/l, P=0·028). There were no significant changes in serum concentrations of glucose (P=0·903), phenobarbital (P=0·422), potassium bromide (P=0·404) and weight (P=0·300) between diet groups. In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment

Efficacy of medium chain triglyceride oil dietary supplementation in reducing seizure frequency in dogs with idiopathic epilepsy without cluster seizures : a non-blinded, prospective clinical trial

This study was fully funded by Nestlé Purina ResearchDespite appropriate antiseizure drug (ASD) treatment, around two-thirds of dogs with idiopathic epilepsy (IE) have seizures long-term and 20-30per cent of affected dogs remain poorly controlled. The current study aim is to test in a field trial the efficacy and tolerability of a commercially available diet enriched with 6.5per cent medium chain triglyceride (MCT) oil in dogs (n=21) with at least a tier 1 idiopathic epilepsy diagnosis, without cluster seizures, in 10 veterinary practices across Europe. Each dog's quality of life (QoL), ataxia, sedation and frequency and severity of seizures were recorded by owners throughout the study. The mean seizure frequency per month, averaged over the entire 84-day study, significantly (P=0.04) decreased 32per cent compared with the baseline monthly seizure frequency recorded during the month immediately before feeding the diet. Similarly, the seizure days rate (days/month) also declined (P8.5/10) in 20 of the 21 dogs before starting the diet and this remained unchanged during the trial. This study demonstrates the use of a diet enriched with MCTs as an adjunct to ASD treatment may have some antiseizure properties for dogs diagnosed with IE, as demonstrated in previous studies

Efficacy evaluation of a commercially available MCT enriched therapeutic diet on dogs with idiopathic epilepsy treated with zonisamide: a prospective, randomized, double-blinded, placebo-controlled, crossover dietary preliminary study

Abstract Background Idiopathic epilepsy (IE) is a common, chronic brain dysfunction in dogs. Recently, the effect of feeding a diet enriched with medium-chain triglycerides (MCTs) on seizure frequency has been evaluated in several studies in dogs with IE. However, most dogs with IE in previous studies were treated with phenobarbital as the main antiseizure medication (ASM). In Japan, zonisamide (ZNS) is the most prescribed ASM for dogs with IE. The interaction between ZNS and various nutrients including MCTs and the potential effects on treatment efficacy resulting from combining these therapies have not been previously studied. A prospective, randomized, double-blinded, placebo-controlled, crossover dietary study was conducted. Dogs (n = 7) treated with ZNS were fed either a placebo diet (PL) or Purina ProPlan Veterinary Diet NeuroCare (NC) for 3 months, after which treatments were crossed over and continued for another 3 months. Seizure frequency (seizures/month; sz/m), blood tests including concentrations of ZNS and β-hydroxybutyric acid, and owner’s visual analogue scale score were collected from all dogs for both treatment periods. Results There was no significant difference in the seizure frequency between PL (2.95 ± 0.80 sz/m) and NC (1.90 ± 0.57 sz/m) during the 6 months of trial. Three of 7 dogs showed ≥ 50% seizure reduction, and 1 of those 3 dogs achieved seizure freedom in NC period. However, 2 of 7 dogs had no changes in epileptic seizure frequency, 2 of 7 dogs had a deterioration in seizure frequency in the NC period. Feeding the MCT diet concurrent with ZNS showed no apparent adverse effects and did not affect ZNS concentration. Conclusions This study indicated that the commercially available MCT-enriched diet (NC) can be safely used concurrently with ZNS for dogs with IE

Diurnal changes in core body temperature, day/night locomotor activity patterns, and actigraphy-generated behavioral sleep in aged canines with varying levels of cognitive dysfunction

Core body temperature (CBT) rhythm, locomotor activity, and actigraphy-sleep were evaluated in geriatric dogs with cognitive dysfunction. Dogs (n=33; 9–16 yrs) performed a spatial working memory task and divided into three memory groups: Low, Moderate, and High, with subsequent evaluation of learning and attention. Rectal CBT was recorded 6 times over a 17.5 h period and Actiwatch® activity monitoring system for 5 days while housed indoors with 12 h light/dark schedule. Rhythm of daily activity data was evaluated using the traditional cosinor analysis and generation of non-parametric measures of interdaily stability, intradaily variability, and relative amplitude. CBT differed with time (F (5, 130)=11.36, p<0.001), and was the highest at 19:00C. CBT at 19:00 was positively related (p<0.01) to memory (r(31)=0.50) and 3-domain cognitive performance index (memory, learning, attention; r(31)=0.39). Total daytime or night-time activity did not differ between memory groups, but hourly counts at 8:00 were positively related (p<0.05) to memory (r(31)=0.52), learning (r(31)=0.36), and 3-domain cognitive performance index (r(31)=0.53). There were no significant differences between age or memory groups for any circadian rhythm measures. Daytime naps were inversely related to memory accuracy (r(31)=−0.39; p<0.05) and BT at 15:00 (r(30)=−0.51; p<0.01). Lower peak BT and increased napping may predict some aspects of cognitive performance of working memory, learning, and/or attention processes in these geriatric dogs, but minimal diurnal rhythm disruption of locomotor activity is observed when these cognitive processes decline

Environmental and Physiological Factors Associated With Stamina in Dogs Exercising in High Ambient Temperatures

This IACUC approved study was performed to evaluate the environmental, physiological, and hematological components that contribute to stamina following successive bouts of exercise that included searching (5-min), agility (5-min), and ball retrieve (&lt;10-min). Regularly exercised dogs (N = 12) were evaluated on five separate occasions. The population consisted of eight males and four females ranging in age from 8 to 23 months, which included six Labrador retrievers, three German shepherds, and one each English springer spaniel, German wirehaired pointer, and Dutch shepherd. The exercise period was up to 30 min with 5 min of intermittent rest between the exercise bouts or until a designated trainer determined that the dog appeared fatigued (e.g., curled tongue while panting, seeking shade, or voluntary reluctance to retrieve). At the end of the exercise period, pulse rate (PR), core temperature, blood lactate, and venous blood gas were collected. The median outdoor temperature was 28.9°C (84°F) (IQR; 27.2–30°C/81–86°F) and median humidity was 47% (IQR; 40–57%). Median duration of exercise was 27 min (IQR; 25–29). No dog showed signs of heat stress that required medical intervention. The components used to measure stamina in this study were total activity, post-exercise core body temperature (CBT), and increase in CBT. When controlling for breed, total activity, as measured by omnidirectional accelerometer device, could be predicted from a linear combination of the independent variables: pre-exercise activity (p = 0.008), post-exercise activity (p &lt; 0.001), outdoor temperature (p = 0.005), reduction in base excess in extracellular fluid compartment (BEecf) (p = 0.044), and decrease in TCO2 (p = 0.005). When controlling for breed and sex, increase in CBT could be predicted from a linear combination of the independent variables: study day (p = 0.005), increase in PR (p &lt; 0.001), increase in lactate (p = 0.001), reduction in BEecf (p = 0.031), increase in glucose (p = 0.044), increase in hematocrit (p = 0.032), and increase in hemoglobin (p = 0.038). This study suggests that the influence of outdoor temperature, pre- and post-exercise activity, and the metabolic parameters are important components of stamina associated with exertion