The Anti-Inflammatory Diet and Disease

1. The Anti-Inflammatory Diet and Disease

2. Evolution in the United States

4. Alternative Food Pyramid

5. New US Food Advice

6. Food Business • Intensive chicken and cow farming • antibiotics • fertilizers • GMOs • Pesticides • Preservatives • Relies on cheap raw materials such as corn, soy, wheat, sugar, palm oil

9. Inflammation:A common final pathway • Cardiovascular disease • Cancer • Neurodegenerative disease • Autoimmune disease • DM • Obesity

10. What is Inflammation? • Complex orchestration of pro-inflammatory and anti-inflammatory events • Mediated by eicosanoids • Prostaglandins, thromboxanes, leukotrienes, • Hydroxylated fatty acids, lipoxins, prostamides, isoprostanoids • Silent inflammation vs. painful inflammation

11. Phases of inflammation • Initiating event- • Pro-inflammatory attack response/cellular destruction • Anti-inflammatory healing response/Cellular rejuvenation

15. Figure 1. The complex crosslink between comorbidities, lifestyle factors and proinflammatory changes, subsequently leading to atherothrombosis.PAI: Plasminogen activator inhibitor; TIMP: Tissue inhibitor of metalloproteinase.

17. Mechanisms of Obesity-Induced Hypertension Mechanisms involved in the pathogenesis of obesity-induced hypertension. PAI-1, plasminogen activator inhibitor-1; Tx-A2, thromboxane A2; IL-6, interleukin-6; IL-1β, interleukin-1β; TNFα, tumor necrosis factor-α; CRP, C-reactive protein; ROS, reactive oxygen species; FFAs, free-fatty acids; VCAM-1, vascular cell adhesion molecule-1; ICAM-1, inter-cellular adhesion molecule-1; NO, nitric oxide; ET-1, endothelin-1; RAS, rennin–angiotensin system; SNS, sympathetic nervous system; AgRP, agouti-related peptide; NPY, neuropeptide Y; POMC, proopiomelanocortin; ARC, arcuate nucleus; α-MSH, α-melanocyte-stimulating hormone; MC3R, melanocortin 3 receptor; MC4R, melanocortin 4 receptor.

18. Smoking Promotes Vascular Damage via Inflammation

21. Omega 6 Fatty Acid (Linoleic Acid) Omega 3 Fatty Acids (alpha-linolenic acid) Δ6-Desaturase Gamma-linolenic acid (GLA) Evening Primrose Oil Borage Oil Black Current Oil Eicosapentaenoic Acid (EPA) COX Lipoxygenase Δ5-Desaturase Arachidonic Acid Prostaglandins PGE1, PGE3 (Favorable) Less Inflammatory Leukotrienes Cyclo-oxygenase (COX) Lipoxygenase Docosahexaenoic acid (DHA) Prostaglandins (PGE2) (Inflammatory) Leukotrienes

22. Arachidonic Acid (in cell membrane) Phospholipase A-2 Steroids Free AA Colchicine Aspirin Cyclo-oxygenase Pathway Lipoxygenase Pathway Sulfasalazine NSAIDs Leukotriene Inhibitors: Accolate, Singulair, Zyflo COX II Inhibitors: Celebrex, Vioxx, Mobic Prostaglandins & Thromboxanes Leukotrienes

23. FAT IS GOOD!! • Depending on what kind…. • Omega 3 fatty acids (fish oils-EPA, DHA; plant sources -ALA) • Mono-unsaturated fats (canola and olive oils) • Decreased fat consumption since the 1960’s associated with obesity epidemic—CHO intake has increased dramatically • Glycemic index/glycemic load

24. Types of fats • Saturated: beef and other animal fats, dairy • Monounsaturated (omega-9): olive and canola oils

25. Polyunsaturated fats (essential FA’s): • Omega-6: Linoleic acid (LA)--vegetable oils, seeds, nuts Gamma Linolenic Acid (GLA)--borage and primrose oil Arachidonic Acid(AA)--meat products — Omega-3: Alpha Linolenic Acid (ALA)--legumes, leafy vegetables, flax, flaxseed and canola oils) Eicosopentanoic acid (EPA)-fish oil Docosahexanoic acid (DHA)--fish oil, breast milk

26. Avoid or Reduce • Trans-fatty acids BAD! • Omega-6 fatty acids • Margarine • Corn oil, cottonseed oil, grapeseed oil, peanut oil, safflower oil, sesame oil, soybean oil, sunflower oil, partially hydrogenated oils • Any product with long shelf life (crackers, pastries, chips)

30. How much Omega-3 fats do you need? • Strive for Omega 6: Omega-3 ratio of 4:1 (usual SAD (Standard American Diet) 16:1 • Maintenance 2.5 g/d • Improve hear function 5 g/d • Treat chronic pain 7.5 g/d • Treat neurological disease >10g/d Sears, The Anti-Inflammation Zone, 2005

31. Types of Fish Oil • Fish • Contamination with PCB, dioxin, and Hg • Higher in AA than fish oil • Crude fish oil • High contamination • Health food grade • Still some contamination with PCB’s and dioxins • Ultra-Refined EPA/DHA Concentrates • Removal of PCB’s and other toxins • Can be used in high doses (“weapons grade”)

32. Requirements for an Ultra-refined EPA/DHA concentrate • Total long-Chain Omega-3 >60% • Dioxins< 1 ppt • Mercury <10 ppb • PCB’s<30 ppb

33. What is an anti-inflammatory diet? • Lose fat • Eat small meals • Have some protein at every meal but reduce red meat and dairy (Avoid charred, overcooked foods) • Cold water fish (salmon, mackerel, sardines, herring) • Eat primarily fruits and vegetables • Leafy green vegetables, nuts, flaxseeds or oil • Take your fish oil

34. Anti-inflammatory Lifestyle • Exercise • Quit smoking • Weight loss • Stress management • Vagal nerve stimulation via abdominal breath work • Treatment of depression • Social support

35. Arachidonic Acid (in cell membrane) Phospholipase A-2 Onions/ Apples Quercetin Turmeric Curcumin Rosemary Ursolic acid Red Pepper Capsaicin Ginger Onions/Apples Quercetin Turmeric Curcumin, Feverfew Perthenolides Free AA Onions/Apples Quercitin Cyclo-oxygenase Pathway Lipoxygenase Pathway Boswellia Bosellic Acid Rosemary Carnosol Prostaglandins & Thromboxanes Leukotrienes

36. Mediterranean Diet • More tolerable than low fat diets and associated with improved long term weight loss (McManus 2001) • Risk reduction of death from CAD = 0.67 compared to usual AHA diet (Trichopoulou et al, 2003)

38. Something fishy?

39. American Heart Association Recommendations ·Healthy individuals should take two servings of fish(salmon, sardines, tuna, mackerel, trout) weekly along with flaxseed, canola, and soybean oil ·  Patients with CHD should consume higher doses, 1 g/d of EPA + DHA, which may require fish oil supplementation • Utilize complex carbohydrates, higher in fiber and lower in glycemic load to reduce risk of CHD AHA Recommendations: Intake of omega-3 fatty acids. Women’s Health in Primary Care. 2003.6(1): 25-26 (Consensus opinion) Hu F, Willett W.Optimal diets for prevention of coronary heart disease. JAMA. 2002;288:2569-2578 {Systematic review}

40. Indications from other studies • Eating fish as little as once a week reduces the risk of sudden death in men • Eating fish twice a week reduces CHD risk in women • Fish intake reduces Alzheimer’s risk Harper, Beyond the Mediterranean Diet: the Role of Omega-3 Fatty Acids in the Prevention of CAD, Prev Cardiol, 2003 Morris, Consumption of fish and n-3 fatty acids and risk of Alzheimer dz,. Arch Neurol, 2003

41. How intake of Omega-3 Fatty Acids is helpful • Stabilization of atherosclerotic plaques • Reduction of inflammation by mediation prostaglandin synthesis pathway • Improved ratio of omega-3 to omega 6 FA reduces arachidonic acid and pro-inflammatory, pro-platelet aggregatory cytokines • Enhances PGE1 and PGE 3 and less inflammatory leukotrienes(see diagram) Thies F, et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaque: RCT, Lancet, 2003;361:477-85 Harper, Beyond the Mediterranean Diet: the Role of Omega-3 Fatty Acids in the Prevention of CAD, Prev Cardiol, 2003;6(3):134-46

42. AHRQ study • Most studies show very low cardiovascular mortality in populations with high fish consumption • Strongest, most consistent effect of omega-3 fatty acids was reduction in triglycerides from 10-33%

43. A word about… • Glycemic Index (rate of absorption of glucose) • Glycemic Load (ratio between GI and CHO content) • www.glycemicindex.com

44. High Glycemic/Load Foods Increase: • Inflammation • Risks of heart disease, diabetes • Examples include: • White bread, glucose (GI= 100) • Potatoes, white rice • Pastries, white flour • Sweets, carbonated soft drinks

46. Lower GI/GL reduces risk • Whole grains • Fruits • Vegetables • Legumes • Or…mixing high GI/GL foods with those with lower GI/GL

49. Superfoods to decrease inflammation • BEANS • Pinto, navy, Great Northern, lima, garbanzo(chickpeas), black beans, lentils, green beans, sugar snap peas, and green peas • BLUEBERRIES • Purple grapes, cranberries, boysenberries, raspberries, strawberries, currants, blackberries, cherries, and all other varieties of fresh, frozen, or dried berries • BROCCOLI • Brussel sprouts, cabbage, kale, turnips, cauliflower, collards, bok choy, mustard green, Swiss chard • OATS • Wheat germ, ground flaxseed, brown rice, barley, wheat, buckwheat, rye, millet, bulgur, wheat, amaranth, quinoa, triticale, kamut, yellow corn, wild rice, spelt, couscous • ORANGES • Lemons, white, and pink grapefruit, kumquats, tangerines, limes • PUMPKIN • Carrots, butternut squash, sweet potatoes, orange bell peppers

50. Superfoods to decrease inflammation SALMON • Alaskan halibut, canned albacore tuna, sardines, herring, trout, sea bass, oysters, and clams SOY • Tofu, soymilk, soy nuts, edamame, tempeh, miso SPINACH • Kale, collard, Swiss chard, mustard greens, turnip greens, bok choy, romaine lettuce, orange bell peppers TEA – GREEN OR BLACK TOMATOES • Red watermelon, pink grapefruit, Japanese persimmons, red-fleshed papaya, strawberry, guava TURKEY • Skinless chicken breast WALNUTS • Almonds, pistachios, sesame seeds, peanuts, pumpkin, and sunflower seeds, macadamia nuts, pecans, hazelnuts cashews YOGURT • Kefir