Idiopathic Epilepsy when fed as an adjunct to veterinary therapy. Cognitive Dysfunction Syndrome MEDICAL INDICATIONS

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1 * MEDICAL INDICATIONS Idiopathic Epilepsy when fed as an adjunct to veterinary therapy *as an adjunct to veterinary therapy

2 CANINE COGNITIVE DYSFUNCTION SYNDROME CDS DEFINITION Age-related neurodegenerative disorder characterized by gradual and progressive cognitive decline 14% of dogs 8 11 but only 1.9% are diagnosed INCIDENCE Most commonly affects older dogs years: 3.4% years: 5% years: 23.3% >14 years: 41% Randomized, double-blinded STUDY DESIGN 3-month study of dogs fed a diet containing MCT oil and a unique blend of Dogs diagnosed by veterinarian with CDS using DISHAA (DISHA Anxiety) RESULTS In 90 days, dogs significantly improved across all DISHAA categories D I S H A A Disorientation Interaction with people and/or pets altered Sleep/wake cycles altered House soiling Activity altered (decline in activity, restlessness, repetitive movements) Anxiety MECHANISM OF ACTION HOW MCT OIL NOURISHES THE BRAIN OF SENIOR DOGS UNIQUE BLEND OF NUTRIENTS A concentrated source of MCT oil Supports healthy circulation, blood pressure and brain function When added to a dog s daily diet, MCTs are easy to digest and are converted by the liver into an additional brain energy source, ketones, including βhb. EPA DHA Supports brain structure and function. EPA helps reduce inflammation. Help reduce oxidative stress Ketones are used very efficiently by the brain of senior dogs, helping address the change in glucose metabolism Used in energy metabolism and DNA maintenance B

PATENT PENDING triglyceride manage dogs with with mediumwith chain medium triglyceride oil to chain triglyceride oil to help nutritionally manage dogs with epilepsy Epilepsy is the #1

Syndrome diagnosed with neurological conditions1 EPADHA HEALTH BENEFITS EPADHA B BENEFIT NEUROLOGIC HEALTH Helps nutritionally manage dogs with idiopathic epilepsy (as an adjunct to veterinary

adult dogs as established by AAFCO INGREDIENTS oil (MCT oil) oil and a unique blend of Antioxidant vitamins C&E P rotein Omega-3 fatty acids BREEDS WITH GENETIC PREDISPOSITION BTO EPILEPSY 3

by epilepsy MECHANISM MCTs may have direct anti-seizure effects by being a noncompetitive AMPA receptor antagonist MCTs are converted to β-hydroxybutyrate which can act as an alternative

antioxidant vitamins C and E to support a healthy immune system, including a high level of vitamin E to help reduce oxidative stress High in protein to help maintain lean muscle mass Omega-3

and control diet for 3 months Dogs on medication but still having seizures ( 3 seizures in last 3 months) 1 2 Labrador Retriever, Belgian Shepherd, Petit Basset Griffon Vendeen, Boxer, Irish

could be affected PU RI N A PRO P L A N V E TE R I NA RY D I E TS NC NE URO CA R E CANINE EPILEPSY OVERVIEW Goal of Epilepsy Management REDUCE OR ELIMINATE SEIZURE ACTIVITY Reduction in

OVER THE COURSE OF 90 DAYS: RESULTS Most dogs with idiopathic epilepsy showed a reduction in seizure frequency in 90 days when fed a test diet with MCT oil, as an adjunct to veterinary therapy.

Typical antiepileptic drugs (phenobarbital and potassium bromide) are GABAergic enhancing inhibitory neurotransmission Experts believe MCTs (c-10 decanoic acid) may have direct anti-seizure

3 PATENT PENDING triglyceride manage dogs with with mediumwith chain medium triglyceride oil to chain triglyceride oil to help nutritionally manage dogs with epilepsy Epilepsy is the #1 condition in dogs with a unique triglycerideenhanced manage dogs with blend of and with medium chain triglyceride oil to medium chain triglyceride manage dogs with Cognitive Dysfunction Syndrome diagnosed with neurological conditions1 EPADHA HEALTH BENEFITS EPADHA B BENEFIT NEUROLOGIC HEALTH Helps nutritionally manage dogs with idiopathic epilepsy (as an adjunct to veterinary therapy) COGNITIVE HEALTH Helps nutritionally manage dogs with GENERAL HEALTH Complete and balanced nutrition formulated to meet the nutritional needs for growth of puppies and maintenance of adult dogs as established by AAFCO INGREDIENTS oil (MCT oil) oil and a unique blend of Antioxidant vitamins C&E P rotein Omega-3 fatty acids BREEDS WITH GENETIC PREDISPOSITION BTO EPILEPSY 3 Most idiopathic seizures commence between 1 and 3 years of age RESEARCH AND RESULTS STUDY DESIGN 9 Randomized, placebo-controlled, double-blinded, crossover design 1 in 111 dogs are affected by epilepsy MECHANISM MCTs may have direct anti-seizure effects by being a noncompetitive AMPA receptor antagonist MCTs are converted to β-hydroxybutyrate which can act as an alternative energy source to compensate for decreased glucose metabolism by the brain A unique blend of arginine, EPA DHA, antioxidants, and B-vitamins to help support cognitive health Contains antioxidant vitamins C and E to support a healthy immune system, including a high level of vitamin E to help reduce oxidative stress High in protein to help maintain lean muscle mass Omega-3 fatty acids to help support brain health and EPA to help reduce inflammation 21 dogs completed 6-month study of dogs with idiopathic epilepsy; dogs fed a test diet with MCT oil for 3 months and control diet for 3 months Dogs on medication but still having seizures ( 3 seizures in last 3 months) 1 2 Labrador Retriever, Belgian Shepherd, Petit Basset Griffon Vendeen, Boxer, Irish Wolfhound, English Springer Spaniel, Vizsla, Bernese Mountain Dog, Standard Poodle, Belgian Shepherd, Border Collie, Australian Shepherd, Border Terrier While most prevalent, any breed/dog could be affected PU RI N A PRO P L A N V E TE R I NA RY D I E TS NC NE URO CA R E CANINE EPILEPSY OVERVIEW Goal of Epilepsy Management REDUCE OR ELIMINATE SEIZURE ACTIVITY Reduction in seizure frequency of at least 50% is considered successful. 4 Over two-thirds of dogs continue to have seizures long-term. OVER THE COURSE OF 90 DAYS: RESULTS Most dogs with idiopathic epilepsy showed a reduction in seizure frequency in 90 days when fed a test diet with MCT oil, as an adjunct to veterinary therapy. 6,7,8 of dogs showed a reduction in seizure frequency of dogs showed a 50% or greater reduction in seizure frequency of dogs achieved complete seizure freedom A NOVEL MECHANISM OF ACTION Typical antiepileptic drugs (phenobarbital and potassium bromide) are GABAergic enhancing inhibitory neurotransmission Experts believe MCTs (c-10 decanoic acid) may have direct anti-seizure effects via blockage of AMPA receptors inhibiting excitatory neurotransmission; enhancing typical antiepileptic therapy10 MCT Oil Synapse GluA1 AMPA receptor % of dogs remain poorly controlled despite appropriate medication % 14% % MCTs block AMPA receptor Presynaptic Postsynaptic X Cell Membrane

CANINE EPILEPSY OVERVIEW Epilepsy is the #1 condition in dogs diagnosed with neurological conditions

epilepsy 1 BREEDS WITH GENETIC PREDISPOSITION TO EPILEPSY 3 Labrador Retriever, Belgian Shepherd,

Mountain Dog, Standard Poodle, Border Collie, Australian Shepherd, Border Terrier While most

ACTIVITY Reduction in seizure frequency of at least 50% is considered successful.

4 CANINE EPILEPSY OVERVIEW Epilepsy is the #1 condition in dogs diagnosed with neurological conditions 1 Most idiopathic seizures commence between 1 and 3 years of age 2 1 in 111 dogs are affected by epilepsy 1 BREEDS WITH GENETIC PREDISPOSITION TO EPILEPSY 3 Labrador Retriever, Belgian Shepherd, Petit Basset Griffon Vendeen, Boxer, Irish Wolfhound, English Springer Spaniel, Vizsla, Bernese Mountain Dog, Standard Poodle, Border Collie, Australian Shepherd, Border Terrier While most prevalent, any breed/dog could be affected Goal of Epilepsy Management REDUCE OR ELIMINATE SEIZURE ACTIVITY Reduction in seizure frequency of at least 50% is considered successful. 4 Over two-thirds of dogs continue to have seizures long-term % of dogs remain poorly controlled despite appropriate medication. 6,7,8

5 PATENT PENDING triglyceride manage dogs with with mediumwith chain medium triglyceride oil to chain triglyceride oil to help nutritionally manage dogs with epilepsy Epilepsy is the #1 condition in dogs with a unique triglycerideenhanced manage dogs with blend of and with medium chain triglyceride oil to medium chain triglyceride manage dogs with Cognitive Dysfunction Syndrome diagnosed with neurological conditions1 EPADHA HEALTH BENEFITS EPADHA B BENEFIT NEUROLOGIC HEALTH Helps nutritionally manage dogs with idiopathic epilepsy (as an adjunct to veterinary therapy) COGNITIVE HEALTH Helps nutritionally manage dogs with GENERAL HEALTH Complete and balanced nutrition formulated to meet the nutritional needs for growth of puppies and maintenance of adult dogs as established by AAFCO INGREDIENTS oil (MCT oil) oil and a unique blend of Antioxidant vitamins C&E Protein Omega-3 fatty acids BREEDS WITH GENETIC PREDISPOSITION BTO EPILEPSY 3 Most idiopathic seizures commence between 1 and 3 years of age RESEARCH AND RESULTS STUDY DESIGN 9 Randomized, placebo-controlled, double-blinded, crossover design 1 in 111 dogs are affected by epilepsy MECHANISM MCTs may have direct anti-seizure effects by being a noncompetitive AMPA receptor antagonist MCTs are converted to β-hydroxybutyrate which can act as an alternative energy source to compensate for decreased glucose metabolism by the brain A unique blend of arginine, EPA DHA, antioxidants, and B-vitamins to help support cognitive health Contains antioxidant vitamins C and E to support a healthy immune system, including a high level of vitamin E to help reduce oxidative stress High in protein to help maintain lean muscle mass Omega-3 fatty acids to help support brain health and EPA to help reduce inflammation 21 dogs completed 6-month study of dogs with idiopathic epilepsy; dogs fed a test diet with MCT oil for 3 months and control diet for 3 months Dogs on medication but still having seizures ( 3 seizures in last 3 months) 1 2 Labrador Retriever, Belgian Shepherd, Petit Basset Griffon Vendeen, Boxer, Irish Wolfhound, English Springer Spaniel, Vizsla, Bernese Mountain Dog, Standard Poodle, Belgian Shepherd, Border Collie, Australian Shepherd, Border Terrier While most prevalent, any breed/dog could be affected PU RI N A PRO P L A N V E TE R I NA RY D I E TS NC NE URO CA R E CANINE EPILEPSY OVERVIEW Goal of Epilepsy Management REDUCE OR ELIMINATE SEIZURE ACTIVITY Reduction in seizure frequency of at least 50% is considered successful. 4 Over two-thirds of dogs continue to have seizures long-term. OVER THE COURSE OF 90 DAYS: RESULTS Most dogs with idiopathic epilepsy showed a reduction in seizure frequency in 90 days when fed a test diet with MCT oil, as an adjunct to veterinary therapy. 6,7,8 of dogs showed a reduction in seizure frequency of dogs showed a 50% or greater reduction in seizure frequency of dogs achieved complete seizure freedom A NOVEL MECHANISM OF ACTION Typical antiepileptic drugs (phenobarbital and potassium bromide) are GABAergic enhancing inhibitory neurotransmission Experts believe MCTs (C10:0 decanoic acid) may have direct anti-seizure effects via blockage of AMPA receptors inhibiting excitatory neurotransmission; enhancing typical antiepileptic therapy10 MCT Oil Synapse GluA1 AMPA receptor % of dogs remain poorly controlled despite appropriate medication % 14% % MCTs block AMPA receptor Presynaptic Postsynaptic X Cell Membrane

Learn more at www.purinaproplanvets.com For more information, visit www.purinaproplanvets.com or call us at 1-800-222-VETS (8387), 8:00 am to 4:30 pm CST, Monday-Friday PURINA TRADEMARKS ARE OWNED BY SOCIÉTÉ DES PRODUITS NESTLÉ S.

1988;10:27-30. 3 Berendt M, Farquhar RG, Mandigers PJJ, et al.

6 Learn more at For more information, visit or call us at VETS (8387), 8:00 am to 4:30 pm CST, Monday-Friday PURINA TRADEMARKS ARE OWNED BY SOCIÉTÉ DES PRODUITS NESTLÉ S.A. ANY OTHER MARKS ARE PROPERTY OF THEIR RESPECTIVE OWNERS. PRINTED IN USA. VET 0303A Veterinary Medicine Landscape Dashboard 2 Skerritt G. Canine Epilepsy. In Practice. 1988;10: Berendt M, Farquhar RG, Mandigers PJJ, et al. International veterinary epilepsy task force consensus report of epilepsy definition, classification and terminology in companion animals. BMC Vet Res 2015;11: Packer RMA, Shihab NK, Torres BBJ, et al. Responses to Successive Anti-Epileptic Drugs in Canine Idiopathic Epilepsy. Vet Rec Arrol L, Penderis J, Garosi L, et al. Aetiology and Long-Term Outcome of Juvenile Epilepsy in 136 Dogs. Vet Rec.2012;170: Podell M, Fenner W. Bromide Therapy in Refractory Canine Idiopathic Epilepsy. J Vet Intern Med. 1993;7: Trepanier L, Schwark W, Van Schoick A, et al. Therapeutic Serum Drug Concentrations in Epileptic Dogs Treated with Potassium Bromide Alone or in Combination with Other Anticonvulsants: 122 cases ( ). J Am Vet Med Assoc.1998;213: Schwartz-Porsche D, Loscher W, Frey H. Therapeutic Efficacy of Phenobarbital and Primidone in Canine Epilepsy: A Comparison. J Vet Pharmacol Ther. 1985;8: 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 Nov 14;114(9): Chang P-S, Augustin K, Boddum K, et al. Seizure Control by Decanoic Acid through Direct AMPA Receptor Inhibition. Brain. 2015;25: 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:

Canine Epilepsy: Current Management and Nutritional Advances

Canine Epilepsy: Current Management and Nutritional Advances Contents Canine epilepsy is frequently encountered in general practice, with refractory patients being referred to specialists. Most veterinary