Objectives 4/4/2013. Healing with Fats and Fatty Acids-- an Integrative approach. Inflammation Nation. A silent attack on the modern human race

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relationship between inflammation, obesity and chronic diseases.

1 Healing with Fats and Fatty Acids-- an Integrative approach Tracy S. Hunter, RPh, MS, PhD Professor Wingate University School of Pharmacy Charlotte Metro-area, NC 1 Objectives Explain the relationship between inflammation, obesity and chronic diseases. Advise patients on combating inflammation by selecting appropriate oils Explain the significance of fish oils in combating inflammation Describe the fatty acid pathway Inflammation Nation A silent attack on the modern human race 3 1

2 What is Chronic Low Grade Inflammation? Two types of Inflammation Acute, Painful Insidious, Painless Silent Chronic Inflammation attacks tissues on a cellular level 4 What does CLG Inflammation look like? Heart Disease, High CHO, BP, Strokes Mood Disorders, Depression, Anxiety Brain Degeneration, Alzheimer s, Senility Obesity, Diabetes, Cancer Joint Pain, Swelling, Arthritis Atopic Disorders, Allergies, Asthma, Eczema and Acne Poor Recovery, Healing, and Immune Response 5 What causes Silent Inflammation? Fatty Acid IMBALANCE Omega-6 : Omega-3 6 2

Major increase in Omega-6 intake Major decrease in Omega-3 intake 7 To

3 What causes Silent Inflammation? Ideal Balance Omega-6:Omega-3 = 1:1 Modern Diet style is 10:1 to 20 : 1 Major increase in Omega-6 intake Major decrease in Omega-3 intake 7 To advise your patients to do Building on a healthy diet Add SUPPLEMENTATION Reduce Omega-6 Vegetable Oil intake Diet style Changes 3

4 Reduce Omega-6 Vegetable Oil intake Increase Omega-3s: Switch to Grass-fed Meats and Wild Fish / Game & Range-fed Eggs Increase Colorful Fruits and Vegetables(Polyphenols = antioxidants / anti-inflammatory Reduce Fast, White Carbs (breads, grains, cereals & sugar 10 Fighting Reactionary Fat Phobia AIDS IN ABSORPTION OF FAT-SOLUBLE VITAMINS PROMOTES BRAIN FUNCTIONING SUPPORTS GOOD HEALTH PROTECTS YOUR BODY 11 Omega-6 FA : Omega-3 FA Omega-6 Fatty Acids Grains (Corn) Grain-fed Animal Protein Vegetable Oils Corn oil Canola Cottonseed Peanut Sunflower Safflower Soy Omega-3 Fatty Acids Cold water fatty fish (Wild) Grass fed meats, game & range fed eggs Flax, hemp & walnuts Fish Oil Supplements 12 4

Omega-3 Index A measure of the amount of EPA+DHA in red blood cell membranes expressed as the percent

4.6% Omega-3 Index = 4.6% Harris WS et al. Prev Med 2004;39:212-220.

Docosahexaenoic acid (DHA) Polyunsaturated Short chain Polyunsaturated Long-chain Polyunsaturated

5 Omega-3 Index A measure of the amount of EPA+DHA in red blood cell membranes expressed as the percent of total fatty acids There are 64 fatty acids in this model membrane, 3 of which are EPA or DHA 3/64 = 4.6% Omega-3 Index = 4.6% Harris WS et al. Prev Med 2004;39: Primary Omega-3 fats Fatty Acid Category Source Alpha-linolenic (ALA) Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA) Polyunsaturated Short chain Polyunsaturated Long-chain Polyunsaturated Long-chain Plants Fish Fish 14 Heart Health Blood Vessels Cardio Vascular Health High Blood Pressure Plaques, Clots, Strokes High Cholesterol 15 5

6 Physiological Effects of Omega-3s Omega-3s increase HDL-cholesterol levels Arrhythmia threshold Endothelium dependent vasodilation Atherosclerotic plaque stability Omega-3s decrease Triglyceride levels Platelet aggregation & adhesion Inflammation (IL-6, TNF alpha) Blood pressure & heart rate Sympathetic nervous system activity Vrablík et al Effect of Lipid-Lowering Therapies on Triglyceride Reduction Omega Fibrates Immediate-release niacin Extended-release niacin Statins Ezetimibe AHA Recommendations for Omega-3 FA Intake Population Patients without documented CHD Patients with documented CHD Patients needing triglyceride lowering Recommendation Eat a variety of (preferably oily) fish at least twice a week. Include oils and foods rich in α-linolenic acid (flaxseed, canola, and soybean oils; flaxseeds; and walnuts) Consume ~1 g of EPA+DHA per day, preferably from oily fish. EPA+DHA supplements could be considered in consultation with the physician 2 4 g of EPA+DHA per day provided as capsules under a physician s care Kris-Etherton PM et al. Circulation 2002;106:

7 19 Brain Health Brain Synapses Pediatric Development Breast Feeding Mood State Depression, Anxiety Senility Alzheimer s 20 Joint Health Joint Pain and Swelling Arthritis Performance Recovery 21 7

Cod Liver Oil High Potency: 850 mg EPA+DHA/g (Omega-3 acid ethyl esters) 1 tsp (RDA for vitamin D; 2 RDA for vitamin

8 Fish Ways to Get 1 g/d EPA+DHA 2 3 oz salmon, sardines, mackerel per day Dietary Supplements Low Potency: 300 mg EPA+DHA/g (Typical drug store capsules; 8 or 3 daily) Mid Potency: mg EPA+DHA Drugs & Dietary Supplements Cod Liver Oil High Potency: 850 mg EPA+DHA/g (Omega-3 acid ethyl esters) 1 tsp (RDA for vitamin D; 2 RDA for vitamin A) 22 Supplement 23 Processing of Fish oil supplements Cold press Distilled Micro-distilled Ethyl Esters Triglycerides 24 8

EPA to DHA and DHA to EPA 3 ALA LLA A-AA EPA DHA 1 2 3 THE 3 FAT FAMILIES

9 Omega-3 Acid Ethyl Esters 90% Omega-3 EPA 465 mg DHA 375 mg Other Omega-3 60 mg Other FA 10 mg Omega-6 80 mg Omega-7 and mg 25 Conversion of EPA to DHA and DHA to EPA 3 ALA LLA A-AA EPA DHA THE 3 FAT FAMILIES AND THEIR ASSOCIATED PG FAMILIES FATS 1 FATS 2 FATS 3 PG 1 PG 2 PG

10 1 2 3 Most food oils: Safflower, Corn, Sunflower, Peanut, Evening Primrose, Black Currant Seed THE 3 FAT FAMILIES AND THEIR DIETARY SOURCES Red Meats, Dairy, Mollusks, Shellfish Cold Weather Oils: Linseed, Walnut, Cold Water Fish FATS 1 FATS 2 FATS 3 PG 1 PG 2 PG 3 28 PG 2 Family causes: Inflammation Blood Pressure Cholesterol Blood Clotting Natural Killer Cell Activity PG 1 and PG 2 Do the Opposite of PG 2 29 SIMPLIFIED ESSENTIAL FATTY ACID FLOWCHART 1 STEPS IN PG PRODUCTION FROM FATS IN DIET 3 LA Delta-6-Desaturase ALA GLA ELONGASE 2 ELONGASE LLA A-AA DGLA AA EPA PG 1 PG 2 LT TX PG 3 10

11 SIMPLIFIED ESSENTIAL FATTY ACID FLOWCHART 1 STEPS IN PG PRODUCTION FROM FATS IN DIET 3 LA Delta-6-Desaturase ALA GLA 2 LLA A-AA DGLA AA EPA PG 1 PG 2 LT TX PG 3 31 Delta-6-Desaturase Activators B-6 Magnesium Zinc High Protein Diet Decreased Temperature ATP Inhibitors Dietary Sources Trans Fats Saturated Fats Arachidonic Acid High Blood Glucose Alcohol Lifestyle/Environmental Stress Starvation/Fasting Smoking Heavy Medal Toxicity Aging 32 DELTA-5-DESATURASE 1 STEPS IN PG PRODUCTION FROM FATS IN DIET 3 LA Delta-6-Desaturase ALA GLA 2 LLA A-AA DGLA Delta-5-Desaturase AA EPA PG 1 PG 2 LT TX PG 3 11

12 The Balance The relationship 0f D-6-D with D-5-D governs conversion of Omega-6 fatty acids to Healthy PG1 Bottom Line: D-6-D activity increases PG1 and PG3 Strengthens Immunity Fights Inflammations 34 Delta-5-Desaturase Inhibitors EPA Activators Uncontrolled BG Elevated Insulin levels Result: Facilitates conversion of GLA to AA 35 INSULIN S EFFECT ON EFA = INCREASES PG2 STEPS IN PG PRODUCTION FROM FATS IN DIET LA ALA Delta-6-Desaturase GLA DGLA BLOCKED BY SESAMIN X AA LLA A-AA EPA PG 1 PG 2 LT TX PG 3 PG:prostaglandins LT:leukotrienes TX:thromboxanes 12

TRANS FATS BLOCKS D6D / PG1 & PG3 FAMILIES AND

PRODUCTION FROM FATS IN DIET 1 3 LA X GLA DGLA

CYCLOOXYGENASE ALA X LLA A-AA EPA PG 1 PG 2 LT

blood cholesterol like saturated fat & should be

Trans fatty acids 38 Trans fat Health Risks

13 TRANS FATS BLOCKS D6D / PG1 & PG3 FAMILIES AND INCREASE INFLAMMATION & PAIN STEPS IN PG PRODUCTION FROM FATS IN DIET 1 3 LA X GLA DGLA TRANS FATS Delta-6-Desaturase X 2 AA CYCLOOXYGENASE ALA X LLA A-AA EPA PG 1 PG 2 LT TX PG 3 37 Formed during hydrogenation, the process that solidifies liquid fats. Research suggests that trans fatty acids effect blood cholesterol like saturated fat & should be avoided in the diet. WHY are they SO BAD? Trans fatty acids 38 Trans fat Health Risks Alzheimer s Cancer Obesity Liver dysfunction Infertility in women Major depressive disorder 39 13

14 Trans fat Health Risks Cholesterol ratio Lower HDL C-reactive Protein (CRP) Coronary heart disease 40 Trans Fats

43 Mechanism Behind Fish Oil's Health Benefits

15 43 Mechanism Behind Fish Oil's Health Benefits Lipoxins Resolvins Protectins 44 Novel antiinflammatory and proresolving actions of lipoxins, resolvins, and protectins in the vasculature. Spite M, and Serhan C N Circulation Research 2010;107: Copyright American Heart Association 15

16 Key cellular actions of lipoxins and resolvins. Spite M, and Serhan C N Circulation Research 2010;107: Copyright American Heart Association SOURCES AND EFFECTS Family Derived From Main Effects Lipoxins Arachidonic Acid (AA), esp. in presence of omega-3 EPA & DHA from fish oil Potent triggers that end acute inflammation 47 SOURCES AND EFFECTS Family Derived From Main Effects Resolvins Omega-3 EPA & DHA from fish oil Trigger the resolution phase of acute inflammation 48 16

17 SOURCES AND EFFECTS Family Derived From Main Effects Protectins Omega-3 DHA from fish oil Especially active in protecting brain tissue by promptly ending acute inflammation 49 Summary & Questions 50 17

Essential Fatty Acids Essential for Good Health SIE

Page 1 of 6 Essential Fatty Acids Essential for Good Health SIE By Yousry Naguib, PhD Essential fatty acids (EFAs) must be obtained through the diet and cannot be synthesized by the human body. EFAs are