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Alternative Therapies in Coronary Artery Disease: Vitamins, Supplements, Diets and Associated Topics Carl R. Szot, MD December 2, 2002 Vitamin E • Fat soluble compounds with alpha-tocopherol being the most common • Natural sources include vegetables, nuts and nut oils • Deficiency is rare and associated with posterior column degeneration and loss of large caliber peripheral nerves • Excess is only an issue in people on coumadin or in premature infants Vitamin E Proposed Mechanisms of Action • Decreases oxidation of LDL • Improves endothelial function • Inhibits smooth muscle cell growth • In fat fed rabbits reduces atherosclerosis • Inhibits platelet adhesion Clinical Cardiology 1993: 16: 116-118 Vitamin E Human Studies • Iowa Women’s Health • Prospective study of 34,000 postmenopausal women • High dietary Vitamin E intake was associated with lower CAD risk NEJM 1996: 334 (18): 1156-62 Vitamin E Human Observational Studies • Health Professionals follow up to the Physicians Health Study • 39,910 men ages 40-70 • Subjects with the highest Vitamin E intake had a 36% lower risk of CAD events after 4 years NEJM 1993: 328 (20): 1450-1466 Vitamin E Human Studies • Nurse’s Health Study • 87,245 women ages 34-59 with no prior CAD • Those taking > 100 iu of Vitamin E for > 2 years Had 40% lower risk of developing CAD after 8 years. NEJM 1993; 328 (20): 1444-49 Vitamin E Randomized Trials • Cambridge Heart Antioxidant Study (CHAOS) • 2002 patients with prior CAD prospectively randomized to Vitamin E (400-800 iu/day) • 77% reduction in nonfatal MI • No change in overall mortality Lancet 1996; 347 (9004): 781-86 Vitamin E Randomized Trials • Alpha-tocopheral Beta Carotene Prevention Trial (ABC) • 50mg/day of Vitamin E had no effect on the risk of MI or death • 50mg/day of Vitamin E plus 20mg/day of beta-carotene resulted in greater rate of coronary death • Trial was mainly for lung cancer prevention NEJM 1994; 330 (15): 1029-35 Vitamin C • • • • Less potent antioxidant than E Inhibits platelet aggregation Deficiency = Scurvy Excess may lead to B12 deficiency or oxalate stones • Less evidence than exists for Vitamin E Vitamin C Human Studies • NHANES I • 11,349 subjects taking Vitamin C supplements • Subjects taking Vitamin C had a lower relative risk of CV death (.58) Epidemiology 1992; 3(3): 194-202 Vitamin C Human Studies • The Nurse’s Health and the Health Professionals Follow up Study • Slightly lower relative risk (.8) in subjects in highest quintile of Vitamin C consumption Vitamin C and E Heart Protection Study • 2x2 Trial • simvistatin 40 mg vs. placebo • vitamin E 600 mg, vitamin C 250 mg, beta carotene 20 mg vs. placebo • Over 10,000 patients randomized to vitamin arm Lancet 2002; 360: 23-33 Vitamin C and E Heart Protection Study • No difference in vascular and nonvascular mortality • No difference in cancer rate • No difference in major vascular events Lancet 2002; 360: 23-33 Fish Oil Omega -3 Fatty Acids • Epidemiologic data suggests improved outcomes in patients eating fish • DART ( Diet and Reinfarction Trial) showed 29% reduction in all cause mortality after 2 years of increased fish/fish oil intake • GISSI Prevenzione showed a 45% decrease in SCD and 20% decrease in all cause mortality after 3 1/2 years of supplementation Lancet 1989; 2 (8666) : 757-61 Lancet 1999; 354 (9177) : 447-55 Olive Oil • Oleic acid ( monounsaturated ) • In a trial comparing an AHA Step I diet, an average American control diet and an olive oil enriched diet showed similar reductions of LDL compared to control, but unchanged HDL with olive oil ( decreased 4 % with Step II.) Triglycerides fell 13% with olive oil but increased 11% with the Step II diet. AMJ Clinical Nutrition 1999; 70(6): 1009-15 Nuts • 80% of calories from fat: Monounsaturates and alpha-linolenic acid ( an omega -3) • Also rich in Vitamin E, folic acid, K+, Mg, flavanoids • 1/4 to 1/3 cup daily can reduce LDL levels by up to 10 % Nuts- Data • Health Professionals Follow Up Study showed increased intake of alpha-linolenic acid lowered MI risk by 60% • Nurse’s Health Study showed 35% CAD reduction associated with nut intake • Physicians Health Study showed reduction in sudden and total CAD death, but not in nonfatal MI associated with nut intake BMJ 1996; 313 (7049): 84-90. BMJ 1998; 317 (7169): 1341-5 Archives Internal Medicine 2002; 162: 1382-87 Fats • Good• Bad- monounsaturated-- olive oil, canola oil, nuts omega-3 -- fish, nuts saturated-- red meat, cheese, butter trans- fatty acids-- processed foods • Omega-6 oils- (corn, soybean, sunflower) are probably neutral in effect Diets Plan Fat Carbohydrate Ornish Pritikin Very Low (10%) Very High Low (20-30%) High Mediterranean Zone Moderate ( 30-35%) Moderate Sugar Busters Protein Power Atkins High ( > 45%) Low AHA Step I & Step II Weight Watchers DASH Postgraduate Medicine 2002; 112 (2) : 34-44 AHA Diet • Step I• Total Fat < 30%, saturated fat <10%, cholesterol < 300mg • Step II• Total Fat < 25%, saturated fat < 7%, cholesterol < 200mg A paucity of evidence for improved outcomes exists for the AHA die and some evidence exists for continued disease progression BMJ 2001: 322(7289): 757-63 Mediterranean Diet • Greece, Crete, parts of France and Italy display low rates of CAD • Monounsaturates and Omega-3 fatty acids are not limited • Fresh fruits and vegetables, fish, nuts, moderate alcohol • Low in trans fatty acids Mediterranean Diet DATA • Lyon Diet Heart Study of 605 MI survivors • 55% reduction in risk of death and 50 % reduction in recurrent cardiac events over a 4 year period • Reduction not explained by changes in lipid factors Circulation 1999; 99 (6): 779-85 Mediterranean Diet DATA • GISSI - Prevenzione • Multivariate analysis showed fish, fruit, vegetables and olive oil all conferred benefit over a 4 year period Circulation 2002; 105: 1887-903 Mediterranean Diet Suggestions- Carbs and Proteins • EAT • DON’T EAT • • • • • • • • • • Whole fruits and vegetables Whole grain cereal Bran, brown rice Peas, beans Lean meat, fish, poultry, vegetable protein Refined carbohydrates White bread, biscuits Bacon, sausage Processed fatty meat High fat dairy Mediterranean Diet Suggestions- Fats • EAT • Olive oil • Fish • Flaxseed, spinach, tree nuts • DON’T EAT • • • • • Trans-fatty acids Fast food Doughnuts Chips, crackers Margarine made with partially hydrogenated oil Alcohol • Evidence of cardioprotective effect of alcohol first appeared in Framingham data • At levels of consumption of greater than two drinks/day for men and one drink /day for women all cause mortality overwhelms cardioprotective effect • Mechanisms include HDL raising, changes in inflammatory markers and improvement in insulin resistances. Lancet 2001; 357 (9258): 763-7