Understanding Cellular Oxidative Stress & Chronic Inflammation

1. Cellular Oxidative Stress &Chronic Inflammation, Part 1 W. Jean Dodds, DVM AHVMA 2016 Columbus, OH

2. Let’s Start at the Beginning •••

3. From Genetics – Epigenetics – Omics - Individualized Nutrition • Genetics = to understand predisposition to disease • Epigenetics = to understand programming • -Omics= to show efficacy • Individualized Nutrition = nutritional intervention & healing • Focus = improvement of health through diet • Question: How does nutrition modulate gene expression? • Answer: Through the genome & metabolism + epigenetic factors

4. Epigenetics Programming for Health and Longevity • Studies how the genome is programmed for health & longevity • Provides insights into metabolic regulation • Involves mechanisms of development, parental gene imprinting, and metabolic programming beyond genetic control • Modulates gene expression throughout life

5. How does Gene Expression and Epigenetics Relate to Cellular Oxidative Stress ?

6. Cellular Oxidative Stress • Involves genetic regulation & gene transcription in health & disease • Reflects elevation of intracellular free radicals • Free radicals are derivatives of reactive oxygen species (ROS) • Free radicals also include reactive nitrogen species (RNS) • Elevated levels damage cells and tissues; cause disease • Produced in large amounts during infection and disease • ROS and RNS exist even in normal health • Free radicals produced by mitochondria during energy production • Excess oxidative stress causes mitochondrial dysfunction (Mandelker, JAHVMA, 41:22-24, Winter , 2016)

9. Cellular Oxidative Stress & Chronic Disease • Oxygen-derived free radicals (ROS) always accompany mitochondrial energy production • Creating free radicals causes cell toxicity • Even in healthy state, ~ 25% of oxygen intake forms free radicals • In unhealthy states, up to75% of oxygen becomes free radicals • Common causes of oxidative stress: toxemia, infections, hypoxia-ischemia, hyperglycemia, xenobiotics (drug metabolism), hyperlipidemias, hyperproteinemias, cancers, phagocytic and immune reactions, and high metabolic rates • Aging tissues under oxidative stress (Mandelker, JAHVMA, 41:22-24, Winter , 2016)

10. Creating Diets Based on Epigenetic Factors • Diets for individual animals should be designed and tailored to their genome or genomic profile (i.e. Nutrigenomics) • To optimize physiological homeostasis, disease prevention and treatment, & productive, athletic, obedience or reproductive performances • This approach individualizes dietary intervention to prevent, mitigate or cure chronic diseases

11. Impact of Diet on Genome & Metabolism • GOAL – holistically understand how dietary components interact with/within cells & organisms to develop new strategies/products that are nutritious & safe • Promote and maintain health & prevent disease • Nutrition is the most important factor for human and animal health • Health is achieved by understanding molecular individualized, functional nutrition

12. Ideal diets include “Superfoods” What are they and how do they function ?

13. Functional Superfoods • Functional superfoodsare whole foods with a nutrient-rich composition that provide optimal well-being • Theyinclude certain botanicals, amino acids, vitamins and plant phytochemicals that activate disease-fighting genes and suppress genes that promote disease • Since each individual has a unique genome, a food benefitting one might not create the same effect for another -- could even prove harmful • Commercial prescription diets might work for certain subsets of animals, but are not individualized

14. Functional Superfoods Prebiotics • Oligosaccharides (FOS, MOS) • Lactulose • Spirulina Probiotics Omega-3 Fatty Acids

15. Functional Superfoods Bee Products • Raw Manuka Honey (not for the very young) • Bee Pollen • Royal Jelly • Propolis

16. Functional Superfoods Medicinal Mushrooms Anti-Cancer • Turkey Tail • Reishi, Cordyceps, Shitake • Maitake Other properties • anti-microbial • anti-diabetic

17. Functional Superfoods • Fatty Acids (ALA, EPA, DHA) • Avocado/Soybean Unsaponifiables • Nettle Leaf • Sprouted Seeds • Licorice

18. Functional Superfoods • Glucosamine/chondroitin • Ginger • MSM • Green Lipped Mussel • Raw Apple Cider Vinegar • Deer/ Elk Velvet

19. Functional Superfoods • Green (or Black) Tea Leaf Extract • DLPA (D,L phenylalanine) • Milk Thistle/ SAMe • Dietary Vegetables • Transfer Factor (Colostrum; Egg) • Yucca root

20. Functional Superfoods • Turmeric (curcumin) • Traumeel & Zeel (T-Relief) • White Kidney Bean Extract(starch blocker) • Boswellia • Hawthorn • King of Bitters (Andrographis paniculata)

21. Brain Health, Memory & Cognition

22. BRAIN HEALTH & MEMORY 10 foods for Brain Health and Memory • Leafy greens (folate, vit B 9) - kale, spinach, collard and mustard greens • Cruciferous vegetables (folate, carotenoids) - broccoli, cauliflower, bok choy, brussel sprouts • Beans/ legumes(choline) • Whole grains (gluten-free = quinoa, millet, rice, soy, corn, flax, tapioca) • Berries/cherries(anthocyanins, antioxidants, vits C & E)

23. Brain Health And Memory 10 foods for brain health and memory (cont’d) • Omega 3 fatty acids(antioxidant, anti-inflammatory) • Yellow Squash, asparagus, tomatoes, carrots, beets (folate, vit A, iron) • Nuts (omega fatty acids, vit E & B6, folate, magnesium) CAUTION macademia, walnuts are unsafe for pets • Seeds (zinc, choline, vit E) • Spices (antioxidant, anti-inflammatory)

24. Brain Health And Memory Other Superfoods • Eggs - high in quality protein and choline for brain and memory • Kiwis - antioxidant-rich, vits A, C & E, potassium, high in fiber • Quinoa - high in protein and fiber, iron, zinc, vit E, selenium • Salmon - high omega-3 and iron, low calorie and low saturated fat • Sweet Potatoes - high in vits A & C, calcium, potassium

25. Brain Health And Memory • Mediterranean type diet- fish, nuts (for dogs: not macadamia, walnut or hickory nuts; brazil nuts and cashews are high in fat, pistachios, pecans , almonds can be moldy (aflatoxins); some dogs = peanut reactive); whole gluten-free grains; olive oil, fresh produce • Avoid Trans Fats & Saturated Fats - less dairy, red meat, fried foods • Heart-Healthy diet - also good for the brain • Plenty of Omega-3 Fatty Acids - 26% less brain lesions • Smaller meals throughout the day • Eat Fruits, Vegetables, and Berries - of various colors • Green and Black Tea - enhances memory and alertness; put on body and sores, in foods

26. Canine Cognitive Dysfunction

27. Improving Cognitive Function Nutrients of benefit include: • Milk thistle and SAMe (S-adenosylmethionine) • Phosphatidylserine & Phosphatidylcholine • Medium-chain triglycerides (MCTs) • DHA and EPA omega-3 fatty acids • Anthocyanins • Avoiding Glutens • Avoiding carbs with high Glycemic Index

28. Milk Thistle and SAMe Silibinin (milk thistle extract) preventsimpairment of both short-term memory and recognition memory • chemoprevention for cancer as well • works as antioxidant, protecting hippocampus against oxidative damage SAMe (S-adenosyl methionine) improves neuron membrane fluidity • increases levels of serotonin and dopamine metabolites • reduces symptoms of depression in people • may help Alzheimer’s patients

29. Phosphatidylserine • Phospholipid manufactured primarily from soy lecithin • Beneficial effects for those at risk of dementia and cognitive dysfunction • Commercial animal products combine phosphatidylserine with gingko biloba, vitamin E, pyridoxine (vitamin B6) and grape-skin extract • Improves canine cognitive function, decreases sleeping problems, apathy and disorientation • Increases playful behavior and response to commands

30. Phosphatidylcholine • Phospholipid choline, critical for cell membrane structure and function • Increases production of acetylcholine • Helps reverse signs of cognitive and other neurological disorders of aging pets

31. Medium-Chain Triglycerides (MCTs) • MCTs, like coconut oil, break down and absorb rapidly into bloodstream, unlike fats, providing a quick source of non-carbohydrate energy • Readily cross blood-brain barrier, supplying up to 20% of brain energy requirement • Important for ketone production • Help body use omega-3 fatty acids more efficiently • Improve age-related cognitive decline by providing alternative source of brain energy

32. DHA & EPA Omega-3 Fatty Acids • Fight obesity, decrease inflammation, combat arthritis and cancer, and promote overall health • Benefit neurotransmission and cognition, plus brain health and structure, since the brain contains up to 60% fat • Used together to benefit mood • EPA from marine sources such as fish oil can decrease the cytokines associated with depression • Individuals reactive to white fish (including sardines and herring) or salmon oils can use krill oil, anchovy oil, and plant oils (olive, borage, moringa, coconut, sunflower)

33. Anthocyanins • Give berries their rich pigment; antioxidants; also benefit cognitive health of senior dogs • Most potent is aronia, the chokeberry. Greater antioxidant than all other berries; anti-cancer; anti-bacterial, anti-viral and even anti-diabetic; and anti-inflammatory

34. Avoiding Glutens • Protect brain function in elderly people and pets plus those with gluten intolerance by avoiding wheat, barley, rye, oats unless labeled gluten-free, kamut, spelt, and coucous • Linked with impairment of brain function, including learning disabilities, attention-deficit-hyperactivity disorder, and memory problems • Gluten sensitivity may manifest exclusively as a neurological disease

35. Gluten-Thyroid Connection

36. Gluten-Thyroid Connection Autoimmune thyroid disease (Hashimoto & Graves) = gluten intolerance Gliadin from gluten (wheat, barley, rye, oats, kamut, spelt, coucous) resembles thyroid gland protein Eliminate gluten totally from diet

37. With High Glycemic Index (GI) Avoiding Carbs • Impaired glucose metabolism caused by sugary foods can promote brain starvation, leading to memory problems, like canine cognitive dysfunction • Foods with high GI can also lead to hunger-related behavioral problems • Simple carbohydrates digest and absorb quickly (hence rapid rise and fall in blood sugar concentrations), so pets feel hungry again quickly