Purina Pro Plan NeuroCare NC PDF

Medium Chain Triglycerides: Canine NC Impact NeuroCare in dog cerebral function Ana Carolina Bartolomeu, DVM Nestlé Purina PetCare Portugal 1 Hi! I’m Carolina, Vet Advocacy Manager at Nestlé Purina @ Would you like...

Medium Chain Triglycerides: Canine NC Impact NeuroCare in dog cerebral function Ana Carolina Bartolomeu, DVM Nestlé Purina PetCare Portugal 1 Hi! I’m Carolina, Vet Advocacy Manager at Nestlé Purina @ Would you like to learn more about small animal nutrition? Toolkits that will help you explain basic nutrition to pet owners PurinaInstitute.com/CentreSquare 4  FREE ACCESS! www.purinainstitute.com/sign-up REGISTER! REGISTER! www.purinainstitute.com/sign-up ➔ Get a free nutrition e-book Access here: 5 Neurocare: Scientific support Epilepsy: Definition “Epilepsy is a complex neurologic problem, where abnormal electric activity between brain neurons results in recurrent episodes of sensorial changes, loss off conscience or seizures. Seizures can take to abnormal motor activity, behaviour changes or autonomic nervous system alterations. Platt., 2014 7 Epilepsy: Prevalence Exact prevalence unknown but the estimation is that 1 in each 111 dogs suffers from epilepsy a 5. 2016 Veterinary Landscape Dashboard. 8 IDIOPATHIC EPILEPSY: CURRENT SITUATION Even when medicated, 2/3 of epileptic dogs continue to suffer seizures and in 1/3 of the cases, these seizures are difficult to control yy Persistent Seizures Difficult to control Seizures 9  IDIOPATHIC EPILEPSY: Antiepileptic drugs (AED) Secondary effects AED The secondary effects of AED are a major concern to pet owners2 Ansiety Weigh gain anxiety Polydipsia excess thrist (soif) Ataxia Polyphagia lack of muscle coordination grosse faim Lethargy Polyuria lack of energy excess production of urine Quality of life loss Some pacients don’t respond to a Resistance to AED combination of 3 different drugs 2 Chang Y, Mellor DJ, Anderson TJ. Idiopathic epilepsy in dogs: owners’ perspectives on management with phenobarbitone and/or potassium bromide. J Small Anim Pract 2006;47:574-581. 10 IDIOPATHIC EPILEPSY: NEW TREATMENTS Even when medicated, 2/3 of epileptic dogs continue to suffer seizures and in 1/3 of the cases, these seizures are difficult to control In a Purina study, only 4% of vets mentioned that they were completely Persistent seizures or very satisfied with current epilepsy treatment options Urgent need to find new treatments yy that can help to treat difficult clinical cases and improve patients quality of life Difficult to control seizures 11 IDIOPATHIC EPILEPSY: Complementary treatments? Neuro stimulation − Vagus nerve stimulation − Trancranial magnetic stimulation − Thalamic stimulation Surgery Nutrition support Acupuncture Chinese traditional Medicine 12 here no identifiable structural or metabolic cause can be found. It is presumed to have a genetic origin. IDIOPATHIC EPILEPSY New nutritional approaches 4 8 IE: New management approaches - nutritional support Nutritional support 1 2 Hypoallergenic diets Omega 3 3 4 Ketogenic diets Medium Chain Triglycerides Diet 14 IE: New management approaches - nutritional support Omega 3 supplementation Nutritional 1 support Anti-inflammatory effects (Taha et al., 2010) Do seizures cause inflammation? Studies in rats: short or prolonged seizures lead to an induction of inflammatory mediators in brain regions of seizure activity onset and propagation Seizure → activation of perivascular glia → release cytokines and prostaglandins Inflammatory brain processes could constitute a common and crucial mechanism in the pathophysiology of seizures and epilepsy (Vezzani et al., 2011) Other studies didn’t see the same effects (Matthew et al., 2012) 15 IE: New management approaches - nutritional support Omega 3 supplementation 1 Increased omega-3 fatty acids to help reduce inflammation E.g. PURINA® PRO PLAN® JM Joint Mobility provides Fish oils enhanced levels of omega-3 fatty acids such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) Linseed which improve biomarkers of canine osteoarthritis 1 DECREASED inflammation Dietary omega-3 fatty acids help increase the production of anti-inflammatory mediators INCREASED inflammation Dietary omega-6 fatty acids help increase the production of pro- inflammatory mediators Chicken fat Vegetable fat IE: New management approaches - nutritional support Dietary therapy 2 Hypoallergenic diets Possibility that certain foods or allergens may induce convulsions – reported in children (Frediani et al., 2004) No published peer-reviewed reports in dogs Lujan et al., 2004 → Pilot study → 7 out of 8 AED resistant dogs had skin or gastrointestinal allergies. − Treatment with an exclusion diet → 7 dogs showed reduction in seizure frequency Controlled prospective studies are necessary before advising use of hypoallergenic diet for epilepsy in dogs Frediani T, Pelliccia A, Aprile A, Ferri E, Lucarelli S. Partial idiopathic epilepsy: recovery after allergen-free diet.2004.Pediatr Med Chir. May-Jun;26(3):196-7. 17 IE: New management approaches - nutritional support 2 Hypoallergenic diets Hydrolysis of proteins to smaller, low molecular weight fractions is a Average molecular potent means of reducing the weight of protein in Canine HA: 14,600 D antigenicity of a diet Average molecular weight of Average molecular Hydrolysis also reduces the hydrolysed soy weight of protein in Average molecular weight antigenicity through altering protein: 11,500 D Feline HA St/Ox: 15,600 of non-hydrolysed soy D protein: 29,000 D protein structures1 Protein size likely to cause an allergic reaction = 18-36 kDa 18,000-36,000 Daltons Range of common food allergens The average molecular weight of soy hydrolysate in Feline HA St/Ox is 15.6 kDa 0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 1. Carlotti D. Food Allergy in Dogs and Cats: Current Dermatological Perspectives. 2017. http://www.ddlzagreb.hr/wp-content/uploads/2015/06/food- allergy-in-dogs-and-cats.pdf IE: New management approaches - nutritional support Nutritional support 3 Tradicional Ketogenic diets Traditional ketogenic diets in humans Appeared in 1920, tested in children suffering from IE Offer high level of fat, low level of protein and carbohydrates 11,12,13 Use of “normal” fat as energy source 11. Law TH, Davies ES, Pan Y, et al. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy. Br J Nutr 2015:1-10. 12. Neal EG, Chaffe H, Schwartz RH, et al. A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia 2009;50:1109-1117 13. Kossoff EH, Wang HS. Dietary therapies for epilepsy. Biomed J. 2013;36(1):2-8 19  IE: New management approaches - nutritional support Nutritional support 3 Tradicional Ketogenic Diets Traditional ketogenic diets in dogs Although successful in humans, they even seem to may increase seizures frequency in dogs suffering from epilepsy. This poor outcome may be related to: − Nutritional deficiencies A study14 showed no significant − Lack of palatability donc pas envie de manger car la food leur donne pa enviedifferences in the frequency of seizures in dogs medicated and eating a normal diet ou eating a ketogenic diet 14. Patterson E. Results of a Ketogenic Food Trial for Dogs with Idiopathic Epilepsy. American College of Veterinary Internal Medicine. 2005. 20  IE: New management approaches - nutritional support Nutritional support 4 MCT – Medium Chain Triglycerides Diet Glucose metabolism in the brain is changed in epileptic patients Epilepsy → glucose hypometabolism – Energetic needs are increased during epileptic seizures – Less use of glucose in several brain areas between epileptic seizures MCT-liver-ketone bodies-neuron-oxidate-energy NEED OF AN ALTERNATIVE ENERGY SOURCE IN THE BRAIN ✓ BRAIN – limited capacity to use Long Chain Fatty Acids as energy source Medium Chain Fatty Acids coming from MCT can be easily oxidated and used by the bran as energy source ✓ Neurons can oxidate ketone bodies 21 IE: New management approaches - nutritional support Nutritional support 4 MCT – Medium Chain Triglycerides Diet Medium Chain Triglycerides can offer an alternative energy source to the brain MCTs (C8–C10) are metabolised in the liver into ketone bodies 22 IE: New management approaches - nutritional support Nutritional support 4 MCT – Medium Chain Triglycerides Diet Specialist believe that MCFA (c-10 decanoic acid) can have an inhibiting effect of epileptic brain storm propagation, blocking (neurotransmission excitatory inhibition) 23 Neurocare: Scientific support  Neurocare: Scientific support I Dr. Artur Varejão 5 Clinical cases – not responding to medication Dr. António Ferreira Results: Improvement in all cases & 1 Seizure fee (FMV Lisboa) Neurocare: Scientific support Science behind MCTs «A randomised trial of medium chain TAG diet as treatment for dogs with idiopathic epilepsy», by Tsz Hong Law et al., 2015. British Journal of Nutrition. Study summary: Comparison between the consumption of a ketogenic diet containing MCTs 6,5% and a standard (placebo) diet in dogs suffering from non-totally controlled idiopathic epilepsy, although treated with anti-epileptic drugs The dogs were fed with a diet containing TCMs* or a placebo diet during 3 months; after this period the diets were changed between the 2 groups Inclusion requests: 3 epileptic seizures in the last 3 months, although treated with anti-epileptic drugs 17 breeds Grup 1 MCT Diet LCT Diet Grup 2 LCT Diet MCT Diet Phase 1 (3 months) Phase 2 (3 months) 27 15. Law TH, Davies ES, Pan Y, et al. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy. Br J Nutr. 2015 Nov 14;114(9):1438-47. Science behing RESULTS 1 Epileptic seizures frequency was significantly lower in the group of dogs that were being fed with MCT diet The frequency of days with epileptic seizures was also significantly lower when the dogs were being fed with MCT diet. From: Law TH, Davies ES, Pan Y, et al. A randomised trial of a medium-chain TAG diet as treatment for dogs with Seizures ≥50% epileptic idiopathic epilepsy. Br J Nutr. 2015 Nov 14;114(9):1438-47. absence seizure reduction Epileptic seizure reduction 28  Science behind MCTs RESULTS 2 MCTs diet resulted in a significant rise of β- hydroxybutyrate in blood truc transformer en ketone bodie There was no changes in phenobarbital, potassium bromide or glucose levels in blood as well as body condition scores. CONCLUSIONSS Seizures ≥50% epileptic These results showed anti absence seizure reduction epileptic properties associated with ketogenic diets and MCTs evidence as a complementary clinical therapeutic option in Epileptic seizure idiopathic epilepsy reduction 29 3 Cognitive Dysfunction Syndrome 8  Before Now N Life expectancy  Before Now N Life expectancy is increasing in dogs 45 M dogs with +7 years in USA and Europe Estimation that 25 to 50% of European dogs are +7 Life expectancy Definition Canine Cognitive Dysfunction Syndrome (CCDS) is a neurodegenerative condition that develops in senior dogs. Signs: Progressive cognitive impairment o Disorientation o Interaction changes (people and animals) o Sleep pattern modifications o Urine/ feces elimination places o Activity changes o Higien o Learning and memory imparment o Stimulus response decrease 33  CCDS: Diagnosis Eliminate other causes Observe signs Diagnosis CCDS is diagnosed after other possible causes are eliminated ❑ Sensory organs problems ❑ Physical conditions ❑ Pain ❑ Renal/ hepatic ❑ Incontinence ❑ Cardiac/ respiratory diseases ❑ Metabolic (diabetes, Cushing), etc  CCDS Prevelance Estimation: – 22% of dogs with 8 or plus years are affected by CCDS, but only 1,9% are diagnosed * Underdiagnosed in potentially >85% of affected animals** 1.9% of diagnosed dogs CCDS >8 years * Salvin HE, McGreevy PD, Sachdev PS, & Valenzuela MJ. Under diagnosis of canine cognitive dysfunction: a cross-sectional survey of older companion dogs. Vet J. 2010; 184: 277–81. ** Chang P., et al., 2015. Seizure control by decanoic acid through direct AMPA receptor inhibition. Brain pages: 1-13.  CCDS Risk Factors Olders dogs are more often affected, and the risk increases with age* No apparent breed or sex predisposition 68% 28% 22% 15-16 years 10-12 years +7 years * Salvin HE, McGreevy PD, Sachdev PS, & Valenzuela MJ. Under diagnosis of canine cognitive dysfunction: a cross-sectional survey of older companion dogs. Vet J. 2010; 184: 277–81. CCSD Signs Clinical signs (Landsberg et al., 2011) Pathogenesis Many structural and metabolic changes in the aging brain. These changes may contribute to CCDS signs development Like in the human brain, the dog brain uses glucose as the primary energy source and requires a constant energy supply. Aging reduces the brain capacity to use glucose as energy source, which may affect memory, learning capabilities, attention and decision making  Cerebral atrophy Increased ventricles  CCDS Treatment Early diagnose and treatment intervention may help improve the dog quality of life* Drugs – Selegiline Environment modifications/ training - eg. Less modifications in the house and propor stimulation ( new toys, training and stimulation) Diet change * Landsberg GM, Nichol J, Araujo JA. Cognitive dysfunction syndrome, a disease of canine and feline brain aging. Vet Clin Small Animal. 2012; 42: 749-768..  CCDS Treatment - Drugs Early diagnose and treatment intervention may help improve the dog quality of life* Selegiline 1st approved drug for CCDS Selective and irreversible Inhibition of monoamino oxidase B reduce breakdown of dopamine dopamine responsible for movement, mood, cognition Other drugs like nicergoline, propentofylline are also used In a study with 641 dogs suffering from CCDS treated with selegiline, 77.2% showed clinical signs general improvement 1 * Landsberg GM, Nichol J, Araujo JA. Cognitive dysfunction syndrome, a disease of canine and feline brain aging. Vet Clin Small Animal. 2012; 42: 749-768.. CCDS Treatment – Environment and behaviour intervention Environment modifications can help the dog movements inside the house, turn the space less confuse, more interesting and stimulating. 1 More accessible E.g. Ramp 2 Short but frequent walks Allow urination and defecating in the correct place Diapers? CCDS Treatment – Environment and behaviour intervention Environment modifications can help the dog movements inside the house, the space less confuse, more interesting and stimulating. 3 Less confuse home Limit modifications around the house Limit the access to just some house areas 4 Stimulation Frequent new toys, regular controlled exercise, help to maintain cognitive capabilities in senior dogs CCDS: Nutrional approach 1 Antioxidants and mitochondrial cofactors Antioxidants L-carnitine α-Lipoic acid 2 Medium Chain Triglyrecides and antioxidants Respond to glucose metabolism decline and reduce oxidative stress Approved therapy for Alzheimer’s disease in humans Studied in dogs Antioxidants MCTs 46 CCDS: Nutrional approach - MCTs Cognitive decline in dogs associated with glucose and energetic metabolism reduction Ketone bodies can be used as energetic substrate 47 CCDS: Nutrional approach - MCTs MCT supplementation is proven that has the following impact on the aging dog brain: accumulation de ça ds Improves mitochondrial function cerveau=disrupt cell function=inflammation=neuronal death=cognitive donc on stop ça pr plein de truc mais pr energy surtout car generate ATP Reduces beta Increase polyunsaturated amyloid protein fatty acids precursors (involved in neuronal structure maintenance that declines with age) 48  CCDS: Nutrional approach - MCTs What does scientific evidence shows? In a Purina study, with senior dogs, the ones that were feed with a diet containing 5.5% MCT showed a significant better performance in cognitive assessment tests (Pan et al., 2010): The authors concluded that MCT supplementation improves significantly cognitive capacities in senior dogs, including attention, memory, learning capacity, and training skills 49  CCDS: Nutrional approach - MCTs What does scientific evidence shows? In a Purina study, with senior dogs, the ones that were feed with a diet containing 5.5% MCT showed a significant better performance in cognitive assessment tests (Pan et al., 2010): For cognitive decline prevention and senior dogs specific needs support, we recomend a diet containing MCTs to dogs >7 years (medium & large breeds) or > 9 years (small breeds) 50  CCDS: Nutrional approach - MCTs When we have already several areas affected, and many cognitive dysfunction signs, a higher level od MCTs + brain proctective nutrients can improve the signs? 51 CCDS: 2 or + affected DISHAA categories CCDS: Nutrional approach - MCTs Pan et al. 2016, Dietary supplementation with medium chain TAG has long lasting cognition- enhancing effects in aged dogs Objetive: evaluate MCT supplementation at a higher level + a combination of brain protective nutrients blend containing DHA, EPA , B vitamins, antioxidants and arginine Senior dogs evaluation, using a list of questions covering all 6 DISHAA: disorientation, social interaction, sleep pattern, basic commands, anxiety and general activity 87 dogs. 3 groups: control (0% TCM), 6.5% TCM and 9% TCM Evaluation at days 30 and 90 Grup 1 Grup 2 Grup Grup33 Control diet 6.5% TCM + BPB 9% 9%TCM TCM++BPB BPB CCDS: Nutrional approach - MCTs Grup 2 Results: The dogs from the 6.5% TCMs + Brain Protective Blend group showed a statistically significant improvement in all 6 DISHAA categories 6.5% TCM + BPB The majority of the improvements were detected as early as 30 days after starting the new diet 53  CCDS: Nutrional approach - MCTs Group 1 Grup 3 Control Diet 9% TCMs + CPC (0% TCM) Control diet dogs didn’t show significant The diet with 9% TCM had positive improvement in disorientation and social results in some cases, but only in the interaction behavior. The improvements group of dogs that consumed it – verified in some categories may be related to, several dogs refused it - Partial benefits from the combination of brain protective nutrients also present in all diets in this study - Placebo effect (entering a study) * Pan Y (2017) Efficacy of a Therapeutic Diet on Dogs with Signs of Cognitive Dysfunction Syndrome. ACVIM Forum 2017 CCDS: Nutrional approach - MCTs Summary – MCTs helpd dogs with CDS because, Glucose is the primary substrate used by the brain as energy source, but it can also use ketone bodies as alternative energy source Cognitive decline in dogs is linked with the reduction of glucose metabolism in the brain and energy metabolism in general CCDS: Nutrional approach - MCTs Summary – MCTs helpd dogs with CDS because, Offering the brain ketone bodies produced by MCT metabolism turned available an alternative energy substrate and reduce the deficits linked to glucose hypometabolism MCTs are converted into ketone bodies in the liver Brain Liver Aging Brain GUT PORTAL VEIN Alternative energy MCFA can reach source mitochondrias without the help of arginine 56  CCDS: Nutrional approach - MCTs CONCLUSIONS The results from this scientific study support that the diet containing 6.5% MCTs + Combination of Nutrients: Brain Protective Blend - destinated to canine cognitive dysfunctio clinical signs treatment * Pan Y (2017) Efficacy of a Therapeutic Diet on Dogs with Signs of Cognitive Dysfunction Syndrome. ACVIM Forum 2017 CCDS: Nutrional approach - MCTs Summary – MCTs helpd dogs with CDS because, Adding this, MCTs showed that they may have other beneficial effects in the senior dog brain, – Improve mitochondrial function – Reduce beta amyloid protein precursors – Increase the level of polyunsaturated fatty acids (PUFA are involved in neuronal structure maintenance, reduce in senior dogs) 4 PRO PLAN NEUROCARE 1 Presentation 2 Indications 3 Benefits 8 Presentation Purina ProPlan Veterinary Diet Neurocare NC 60  a 4 PRO PLAN NEUROCARE 1 Presentation 2 Indications 3 Benefits 8 Indications Cerebral function– Idiopathic Epilepsy Cognitive function – CCDS 63 4 PRO PLAN NEUROCARE 1 Presentation 2 Indications 3 Benefits 8 Benefits Nutrients in PPVD Canine NeuroCare NC Canine NC Neurocare Nutrients Dry formula Moisture 7.5% Protein 30% Fat 15% Fiber 1.5% Carbohidrates 38.5% MCTs 6.5% EPA + DHA 0.4% Vitamin E 519 IU/ kg Vitamin C 82 mg/ kg Arginine 2.2% Selenium 0.5mg/ kg B Vitamins 210 mg/ kg ME 3.67 kcal/ g 65 Benefits Benefits Characteristics Supports blood flow, blood pressure ARGININE SUPPLEMENTATION and cerebral function Helps to reduce inflammation and OMEGA 3 FATTY ACIDS (EPA and DHA) supports brain function Added antioxidants Reduces oxidative stress in the brain (Vitamins C and E) Alternative energy soured to the MCTs supplementation (6.5%) brain, proved as supports cerebral and B vitamins function and cognition 66 Benefits PPVD Canine NeuroCare MCTs: Ketogenic diet that offer an alternative energy source to the brain 1st and only diet with 6,5% MCTs The brain usually uses glucose as primary energy source If glucose metabolism is compromised → neurons can benefit from an alternative energy source as, Ketone bodies MCFA 67 Benefits TCMs can have anti–seizure effect Specialist believe that MCFA (c-10 decanoic acid) can have an inhibiting effect of epileptic brain storm propagation, blocking (neurotransmission excitatory inhibition) 68  Benefits PPVD Canine NeuroCare NC CEREBRAL FUNCTION: Formulated with MCTs and neuroprotective nutrients, clinically proven as can improve cerebral function In a study with +9 years dogs diagnosed with CCDS, a diets containing 6,5% MCTs and a blend of neuroprotective nutrients showed a significant improvement in the 6 groups of DISHAA signs after 90 days (most of improvements were observed after 30 days) NeuroCare contains MCTs and a combination of neuroprotective nutrients in levels at least (or event more) as the ones used in the study 69 QUESTIONS  Thank you! [email protected] Benefícios e características Benefícios Chave de PPVD Canine NeuroCare NC Cães alimentados com óleo contendo TCM + combinação específica de nutrientes, melhoraram o desempenho em todas as 6 categorias do DISHAA, após 90 dias * *Pan et al. Internal report. Effect of MCT and BPB on symptoms of dogs with CDS- a clinical study (draft) 72