Lipids in Heart Disease Cancer By Jennifer Turley

Presentation Overview Lipids in Heart Disease • Incidence • Contributing factors • Prevention • Blood lipids • Dietary fat • Oxidation & antioxidants • Trans & omega 3 fatty acids • Other factors Lipids in Cancer • The cancer process • Diet & lifestyle & disease risk • P: S ratio • Dietary lipids & disease risk

Heart Disease Deaths per 100, 000 • #1 cause of death in America. • 1/3 die of atherosclerosis. • Myocardial infarction and stroke risk increase with atherosclerosis. Diet Related Alcohol Related Non-Diet Related

Atherosclerosis • Plaques: • Occlude arterial vessels. • Form from arterial wall injury. • Contain cholesterol (oxidized LDL), platelets, etc.

Hypertension • Is high blood pressure. • Is a leading cause of arterial wall injury. • Synergizes with atherosclerosis to cause heart disease and stroke.

Blood Pressure Classification of Measurements Category Systolic 1 Optimal <120 Pre-hypertension 120 -139 or 80 -89 Stage 1 hypertension 140 -159 or 90 -99 Stage 2 hypertension ≥ 160 or ≥ 100 1 Systolic Conjunction Blood Pressure in mm of mercury (Hg) 2 Diastolic and Diastolic 2 <80

Reducing Blood Pressure • DASH Diet (The Dietary Approach to Stop Hypertension) • Increase calcium, potassium and magnesium • Low-fat, fiber-rich, moderate protein & carbohydrate • Aerobic exercise • Healthy Body Weight

Who is Dying of Heart Disease? • • • 25 -34 years: Men at 3 X rate as Women 35 -44 years: Men at 2 X rate as Women 45 -64 years: Women catching up to men 65 -75 years: Women catching up to men 75 -80 years: Women = Men

What are the Risk Factors? • • • Elevated serum cholesterol Genetics Smoking tobacco & drinking alcohol Hypertension Diabetes Obesity Sedentary lifestyle Stress Male gender Consuming a low fiber & high fat diet

How can it be prevented? • Lifestyle changes • Less stress, no smoking • Healthy diet • Healthy fats, nutritionally adequate • Regular aerobic exercise • An hour a day • All positively affect blood lipid values and blood pressure

Elevated Serum Cholesterol & Increased Deaths from Heart Disease mg/dl total cholesterol

Blood Lipids Serum Triglycerides • VLDL • CHYLOMICRONS Serum Cholesterol • LDL (Bad, 77. 5%) • HDL (Good, 17. 5%) IDL (Neutral, 5%)

Lipid Carrier Molecules

Serum Triglycerides • Elevated levels are associated with heart disease. • High triglyceride levels thicken the blood causing hypertriglyceridemia. • Triglycerides are packaged primarily in Chylomicrons and Very Low Density Lipoproteins (VLDL). • A fasting 12 hour blood test is needed to determine an accurate triglyceride level. • <150 mg/dl is normal. • 450 mg/dl is like pumping ketchup, causes arterial damage contributing to heart disease and stroke.

Serum Cholesterol • Elevated levels are associated with atherosclerosis if 2 other risk factors exist. • Cholesterol is packaged as Low Density Lipoproteins (LDL) and High Density Lipoprotein (HDL). Intermediate Density Lipoprotein (IDL) is present to a minor extent. • HDL’s return cholesterol to the liver for synthesis of bile, hormones, and vitamins. • LDL’s delivers cholesterol to tissue and therefore have a higher plaque effect.

Blood Cholesterol Levels & Disease Risk Total Cholesterol LDL Cholesterol < 200 mg/dl Desirable/Low Risk 200 -239 mg/dl Borderline High Risk ≥ 240 mg/dl High Risk < 100 mg/dl Optimal 100 -129 mg/dl Near optimal 130 -159 mg/dl Borderline high 160 -189 mg/dl High ≥ 190 mg/dl Very high HDL Cholesterol < 40 Low (indicates risk) > 60 High

Blood Cholesterol Levels & Disease Risk Metabolic Syndrome: If Three or More of These Factors 1. 2. 3. 4. 5. Fasting Blood Triglycerides: ≥ 150 mg/dl HDL: <50 mg/dl ♀ <40 mg/dl ♂ Blood Pressure: ≥ 130/85 mm Hg Fasting Blood Glucose: ≥ 110 mg/dl Waist Circumference: >35” ♀ >40” ♂

Therapeutic Lifestyle Changes (TLC) Diet Summary of the TLC Diet Total Fat SFA PUFA MUFA Trans Fatty Acids Carbohydrates Proteins Cholesterol Plant stanols/sterols Soluble Fiber Total Calories 25%-35% of Calories <7% of Calories ≤ 10% of Calories ≤ 20% of Calories As low as possible 50%-60% of Calories ~15% of Calories <200 mg/day 2 g/day 10 g-25 g/day Balance energy intake and expenditure to maintain desirable body weight and prevent weight gain. Expend 200 Calories/day in moderate physical activity. Examples of Food in a 2200 Calorie One Day TLC Diet Grains Vegetables Fruits Low Fat Dairy Lean Meat/Fish/Alternatives Eggs Oils 7 ounce equivalents with ½ whole grains 3 cup equivalents 2 cup equivalents 3 cup equivalents 6 ounce equivalents, soy protein may replace some animal product <2 yolks/week 6 teaspoon equivalents

Dietary Fat & Lipoproteins • SFA: Increase LDL • PUFA : Decrease LDL & HDL • MUFA: Decrease LDL • Cholesterol: Can Increase LDL • Phospholipids: Not indicated in heart disease

Fatty Acid Composition of Common Fats

Oxidation of Fat • The double bonds of polyunsaturated fatty acids are targets for oxidation (damage by oxygen species). • The double bond breaks with oxidation generating lipid fragments that are very sticky. (-CH 2 CH=CHCH 2 - to CH 2 CHO + CH 2 CHO). • The sticky fragments contribute to atherosclerotic plaque formation.

Antioxidants • Antioxidants: Prevent oxidation reactions, react with oxygen radical species directly, & prevent heart disease • Antioxidants vitamins include: vitamin E (alpha-tocopherol), vitamin C (L-ascorbic acid), beta-carotene (provitamin A) • Minerals with antioxidant cofactor functions include: Zinc, Copper, & Iron

Hydrogenation of Fat • Trans fatty acids levels are high in processed foods containing partially hydrogenated oils. • The double bonds from PUFA & MUFA are removed by hydrogenation (adding hydrogen). • The fatty acid becomes more saturated. • Is used in the process of making margarine. • The softer the margarine the less trans fat. • Stick margarine & shortening are highly hydrogenated and partially hydrogenated.

Hydrogenation of Fat H+ H+ spotlight Unsaturation Saturation +H 2

Partial Hydrogenation of Fat • Is done in the food industry. • Many of the double bonds from PUFA & MUFA are removed and many can be chemically modified to a trans fatty acid (TFA) configuration. • TFAs contribute to heart disease.

Cis vs. Trans Fatty Acids • Cis: • The naturally occurring configuration in PUFA & MUFA. • Hydrogen atoms are on the same side of the double bond in the fatty acid Carbon chain. • Trans: • Form during the partial hydrogenation process. • A chemical “Fluke” • Hydrogen atoms are on the opposite side of the double bond in the fatty acid Carbon chain.

The Chemical Structure of Cis & Trans Fatty Acids spotlight

Trans Fatty Acids are Detrimental to Health • TFAs contribute to heart disease by increasing LDL & decreasing HDL cholesterol & increasing triglycerides. • An intake of 2 -3% of energy from TFAs has greater than predicted negative effects from the marked adverse blood lipid changes. TFAs may also contribute to inflammation, endothelial cell dysfunction, and diabetes (insulin resistance). • Intake should be < 1% of energy to as low as possible.

Consumer Keys for Avoiding Trans Fatty Acids • Read the nutrition facts panel. TFA free is defined as ≤ 0. 5 gm/serving. • Avoid foods with partially hydrogenated oils in the ingredient list (such as cookies, chips, doughnuts) on the food label. • Bake with vegetable oils. • Use margarines that are soft. Choose margarines that are trans fatty acid free. • Avoid deep-fat fried foods like french fries, corn chips, doughnuts, & chicken nuggets. • Avoid high meat and dairy product intake as a natural TFA source from bacterial action on unsaturated fatty acids in the ruminants stomach.

Omega-3 Fatty Acids Heart Healthy Omega carbon Linoleic Acid An Omega-6 fatty acid Omega carbon Alpha-Linolenic Acid An Omega-3 fatty acid

How Do Omega-3 Fatty Acids Work? • They affect the synthesis of eicosanoid hormone like compounds such as prostaglandins & leukotrienes. • The compounds produced from omega 3 fatty acids: • Decrease blood clotting (prevent plaque build-up) • Decrease blood pressure (prevent atherosclerosis) • Decrease blood total cholesterol, LDL cholesterol, & triglycerides & increase HDL cholesterol) • Decrease inflammation (prevent arthritis, asthma) • Increase immunity (prevent cancer)

American Heart Association omega 3 fatty acid recommend • Consume 0. 5 -1. 8 grams of omega-3 fatty acids per day as fatty fish or supplements. • The omega-3 fatty acids in fish are called EPA & DHA. • Consume 1. 5 -3. 0 grams alpha-linolenic acid (an omega-3 fatty acid) per day. • Plant sources of omega-three fatty acids flax seed, walnuts, & canola oil.

Omega-3 Fatty Acids in Fish • Best Sources: • • • Good Sources: Salmon Herring Mackerel Tuna Whitefish To avoid mercury contamination, eat fish that live closer to the surface and have a shorter lifespan. • • Cod Flounder Halibut Mahi Orange Roughy Sea Bass Clams Scallops

Homocysteine in Heart Disease • Homocysteine is an amino acid intermediate of cysteine & methionine metabolism. • Elevated levels of homocysteine cause arterial wall damage & contribute to heart disease. • Folic acid (folate), B 6 & B 12 function as cofactors for the enzymes driving the inter conversion of cysteine & methionine, thus adequate intakes prevent hyperhomocystemia. methionine homocysteine

Other Factors in Heart Disease • High doses of Niacin: Increases HDL, decreases LDL. • Statin type cholesterol lowering drugs: Reduce the synthesis of cholesterol in the liver. • Cholesterol absorption inhibitor drugs. • Benecol spreads: Contain plant stanol esters that reduce the absorption of cholesterol in the digestive tract. • Wine: Reduces blood viscosity. Red wine and/or grape juice increases HDL. • Alcohol: 1 serving per day decreases risk of a cardiovascular accident. It is an anticoagulant. • Aerobic Activity: Increases HDL, decreases LDL. • Soluble Fiber: Decreases LDL. • Soy Protein: Increases HDL, decreases LDL.

Lipids in Cancer • Cancer is the 2 nd leading cause of death in Americans. • It is characterized by uncontrolled cell growth. • It occurs through a process of initiation, promotion, and progression.

Carcinogenesis

Cancer Risk • Increased Cancer Risk by Lifestyle Practices – Smoking tobacco, UV light, Obesity, Sedentary Lifestyle • Increased Cancer Risk by Dietary Practices – – – ~ 45% of all cancer deaths are diet-related Low F&V, antioxidant nutrient, & fiber intake High total fat and PUFA, sodium intake P: S ≥ 3: 1 + high fat diet = cancer risk P: S ≤ 0. 33: 1 (or ≤ 1: 3) + high fat diet = heart disease risk

Sample P: S Ratio Calculation • Kathy ate a high fat diet. – 104 gm PUFA & 30 gm SFA • What is her P: S ratio? Ø 104 ÷ 30 = 3. 47. This # is placed in the P position of the ratio – The S position is always assigned the # 1 • The P: S is 3. 47: 1 • Is the ratio increasing disease risk? – This P: S ratio is increasing risk for cancer – Remember that you do want enough PUFA to get your essential (linoleic and alpha-linolenic) fatty acid needs met.

Dietary Lipids & Disease Risk Dietary Factor Heart Disease Cancer Low fat intake Prevents disease Does not contribute to disease Contributes to disease (20 -25% of total Calories) Moderate fat intake (25 -35% of total Calories) High fat intake (>35% of total Calories)

Fatty Acids & Disease Risk High SFA Low MUFA Low PUFA Increases total blood cholesterol, LDL (is not ideal) Low SFA Low MUFA High PUFA Decreases total blood Increases cancer risk cholesterol, HDL & LDL (is tumorgenic) (is not ideal) Low SFA Decreases total blood High MUFA cholesterol, LDL Adequate PUFA (is ideal) Is associated with heart disease (is atherogenic) Is not associated with cancer or heart disease risk (is not tumorgenic or atherogenic)

Summary How to prevent heart disease • Avoid dietary cholesterol & saturated fat. • Avoid hydrogenated or partially hydrogenated fat (trans-fatty acids). • Consume MUFA and omega 3 fatty acids. • Protect PUFA, MUFA, & LDL with antioxidants. • Consume adequate folate to prevent hyperhomocystemia. • Consume soluble fiber, soy, and plant stanols/sterols. • Avoid cigarette smoking. • Exercise (especially aerobic).

Summary How to prevent cancer • Choose to eat mostly plant foods. – Eat plenty & a variety of whole grains, fruits, & vegetables! • Avoid high fat diets especially saturated fat & omega-6 fatty acids. • Consume an antioxidant-rich diet. • Practice all aspects of a sound diet: Calorie control, adequacy, balance, moderation, and variety. References for this presentation are the same as those for this topic found in module 3 of the textbook