3% 2% 3% 2%2% 1% 4% 5% 6% 22%

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1 Fariborz Farsad Pharm D/BCPS 3% 2% 3% 2%2% % Malignant neoplasms Diseases of heart 4% 5% 6% 2% 22% 29% Other causes of death Cerebrovascular diseases Chronic lower respiratory diseases Accidents (unintentional injuries) Diabetes mellitus Alzheimer's disease Influenza pneumonia Nephritis, nephrotic syndrome nephrosis Intentional self- harm (suicide) Chronic liver disease cirrhosis Source: Statistics Canada Online Statistics are for all ages, both sexes in all of Canada A DISEASE OF INFLAMMATION Damage to heart blood vessels Fatty plaque Reduces blood flow Heart attack High blood pressure Plaque rupture Thrombosis Stroke endothelial synthesis of PGI2 prostacylcin), & NO (nitric oxide) ( PGI 2 = vasodilator, platelet adhesion/aggregation NO = vasodilator, platelet & WBC (monocyte) adhesion Adhesion of monocytes onto endothelium --> transmigration into subendothelial space (artery wall) -- > change to macrophages Endothelial dysfunction --> increased flux of LDL into artery wall ١

2 Oxidation = process by which free radicals (oxidants) attack damage target molecules / tissues Targets of free radical attack: DNA - carbohydrates Proteins - PUFA s>>> MUFA s>>>>> SFA s LDL can be oxidatively damaged: PUFA s are oxidized trigger oxidation of apob00 protein --> oxldl OxLDL is engulfed by macrophages in subendothelial space High Load Medium Load Low Load Food Glycemic Index Glycemic Corn flakes White bread Sweetened cereals Potato chips Chocolate cy Whole wheat bread G reen vegetables, mushrooms, tomatoes Banana 65 3 Basmati rice 50 2 Apple 38 6 Boiled potato 65 9 Lentils 22 4 Carrots 85 5 Nuts 5 Green Beans 30 0 load Source: Foster- Powell, K., e t al International table of glycemic index glycemic load values: A merican Journal of Clinical Nutrition, 76: 5-56 Many metabolic processes involve oxidation reactions can produce free radicals Free radicals are also produced by: Pollution Ultraviolet light Toxic substances Radiation Tobacco smoke Asbestos ٢

3 Steal electron Free radicals are destabilizing from stable compounds, generate more unstable free radicals Cause damage to: Cell membranes Low- density lipoproteins (bad cholesterol) Proteins in the cell Genetic material (DNA) Major factors in development of chronic diseases Antioxidants herbs vitamins flavonoids estrogens beta-carotene amino acids lipid-lowering agents monounsaturated fats Slow or prevent damage to body cell s May improve immune function lower risk for infection cancer C arotenoids beta carotene (familiar ) Vitamin C Vitamin E Found in colorful fruits/veggies grains 3/ 98 5 Nutrient itamin E Antioxidants at a glance RDI 3 U Dietary Sources I Vegetable oils (soy, corn, olive, 00 cotton- seed, safflower, sunflower), Evidence V IU may lower heart disease risk by nuts, sunflower seed, wheat germ 30%-40% Vitamin C 60 m g Citrus fruits, strawberries, tomatoes, no evidence that RDI in cantaloupe, broccoli, asparagus, supplement form can peppers, spinach, potatoes prevent CHD or cancer ß-carotene NA Dark green, yellow, orange may protect against vegetables: spinach, collard green CHD macular broccoli, carrots, peppers, sweet degeneration potatoes; yellow fruits: peaches Selenium 70 u g Egg yolks, tuna, seafood, chicken, ug may lower 55 ug liver, whole grains, plant grown in prostate cancer risk selenium- rich soil ( west of Mississippi) 2/ Cengage Wadswort - h ٣

4 Continued endothelial dysfunction (inflammatory response) Accumulation of oxldl in macrophages (= foam cells) Migration accumulation of: smooth muscle cells, additional WBC s (macrophages, T- lymphocytes) Calcific deposits Change in extracellular proteins, fibrous tissue formation LDL HDL High risk = VLDL ( TG) Prevent oxidation from being initiated 2. Halt oxidation once it has begun Antioxidant vitamins (vitamins C, E, carotenoids) 3. Repair oxidative damage Flavanoids other phytochemicals Antioxidant enzyme systems Minerals required: Mn, Cu, Zn, Se EAT LESS A Dietary Approach Simple carbs Sugar associates White flour White rice S aturated & Trans fats EAT 70% dark chocolate Green tea Red Wine MORE Complex carbs Fruits Vegetables Legumes Whole grains P olyunsaturated & mono-unsaturated fats It s not all that bad! 70% dark chocolate cacao polyphenols have been proven to dilate arteries (by releasing NO) decrease platelet aggregation. Milk prevents the absorption of the polyphenols G reen tea studies have shown that green tea reduces mortality rates by 25% for coronary disease 60% with stroke R ed grape contains the powerful antioxidant resveratrol has been shown to restrict the formation of blood clots ۴

5 Flavonoids belong to a class of antioxidants called p olyphenols ( or p hytochemicals ) from p lants. In a diet, f ruits, vegetables, tea, wine c hocolate are major sources of a ntioxidants, which have been shown to h ave protective effects against c ardiovascular disease. Da rk chocolate contains higher amounts of f lavonoids than milk chocolate. Relation between cholesterol carbohydrate source (/dl) Cholesterol Source: W initz, M., et al Effect of dietary carbohydrate on serum cholesterol levels. A rchives of Biochemistry Biophysics, 08: Non-oxidized/non- fermented product of the l eaves polyphenols m g EGCG major polyphenol epigallocatechin 5 28 epicatechin gallate 7 7 epicatechin caffeine Tea components shown to inhibit carcinogenesis in animals. Protective effect against human cancers? Not conclusive yet. Possible mechanisms A ntioxidant activity protects DNA Inhibition of cell proliferation Inhibition of metastasis Induction of apoptosis growth arrest Modulation of carcinogen-metabolizing enzymes Modulation of cancer cell methylation Reversal of tumor cell multi-drug resistance Antioxidant Improved brachial artery dilation Lower serum cholesterol, LDL-C trigs Antifibrinolytic Reduced blood pressure Reduced inflammatory response Increased energy expenditure (wgt control) University of Geneva found the Catechin may trigger weight loss by stimulating the body to burn calories decreasing body fat. 20 Epidemiologically samples drank green tea for 3 months or more Resulted in 9.6 % reducing in BF % 2. % reducing in WHR Increases noradrenaline which activates of brown fat tissue to fighting white fat located around our waistline, hips thighs. - American Journal of Clinical Nutrition, Nov. 999 ۵

6 Coffee 80 Cola Black tea 30 Oolong tea Green tea 20 White tea 5 Decaf tea 5-0 Herbal tea 0 Although observational studies support a cardio- protective effects of antioxidants, clinical trials are disappointing In the mean time, Americans spend an estimate $ 700 million on vitamin supplements 3/ In Europe, those living in the south consume greater amounts of fruits vegetables containing the antioxidants beta- carotene, vitamin E vitamin C, have lower rates of CAD than those living in the north CoQ 0 = Ubiquinone CoQ0: Fat- soluble compound found in hydrophobic portion of mitochondrial membrane Approx. 0% rate of s tatin related myalgia Statins reduce Co- Q 0 levels 25-40% Depletion of skeletal muscle mitochondrial Co-Q 0 may lead to m yalgia myopathy NEJM 997; 337: / From Marcoff et al. JACC 2007 Co-Q 0 supplementation increases plasma level in patient taking statins Multiple observational anecdotal reports of improvement in myalgia with Co-Q 0 2 small romized trials in patients with history of myalgia did show benefit Overall, Co-Q 0 harmless, inexpensive, may reduce statin-related myalgia Drugs: Beta blockers, Clonidine, Hydralazine, Hydroclorthiazide Statins Glucophage, Glyburide, Phenothiazines, Desipramine, Haloperidol, Imipramine, Chlorpromazine, Trimipramine Doxepin Adriamycin ۶