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 commonFat soluble compounds with alpha-tocopherol being the most common Natural sources include vegetables, nuts and nut oilsNatural sources include vegetables, nuts and nut oils Deficiency is rare and associated with posterior column degeneration and loss of large caliber peripheral nervesDeficiency 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 infantsExcess is only an issue in people on coumadin or in premature infants

Vitamin E Proposed Mechanisms of Action Decreases oxidation of LDLDecreases oxidation of LDL Inhibits smooth muscle cell growthInhibits smooth muscle cell growth Inhibits platelet adhesionInhibits platelet adhesion Improves endothelial functionImproves endothelial function In fat fed rabbits reduces atherosclerosisIn fat fed rabbits reduces atherosclerosis Clinical Cardiology 1993: 16:

Vitamin E Human Studies Iowa Women’s HealthIowa Women’s Health Prospective study of 34,000 postmenopausal womenProspective study of 34,000 postmenopausal women High dietary Vitamin E intake was associated with lower CAD riskHigh dietary Vitamin E intake was associated with lower CAD risk NEJM 1996: 334 (18):

Vitamin E Human Observational Studies Health Professionals follow up to the Physicians Health StudyHealth Professionals follow up to the Physicians Health Study 39,910 men ages ,910 men ages Subjects with the highest Vitamin E intake had a 36% lower risk of CAD events after 4 yearsSubjects with the highest Vitamin E intake had a 36% lower risk of CAD events after 4 years NEJM 1993: 328 (20):

Vitamin E Human Studies Nurse’s Health StudyNurse’s Health Study 87,245 women ages with no prior CAD87,245 women ages with no prior CAD Those taking > 100 iu of Vitamin E for > 2 years Had 40% lower risk of developing CAD after 8 years.Those taking > 100 iu of Vitamin E for > 2 years Had 40% lower risk of developing CAD after 8 years. NEJM 1993; 328 (20):

Vitamin E Randomized Trials Cambridge Heart Antioxidant Study (CHAOS)Cambridge Heart Antioxidant Study (CHAOS) 2002 patients with prior CAD prospectively randomized to Vitamin E ( iu/day)2002 patients with prior CAD prospectively randomized to Vitamin E ( iu/day) 77% reduction in nonfatal MI77% reduction in nonfatal MI No change in overall mortalityNo change in overall mortality Lancet 1996; 347 (9004):

Vitamin E Randomized Trials Alpha-tocopheral Beta Carotene Prevention Trial (ABC)Alpha-tocopheral Beta Carotene Prevention Trial (ABC) 50mg/day of Vitamin E had no effect on the risk of MI or death50mg/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 death50mg/day of Vitamin E plus 20mg/day of beta-carotene resulted in greater rate of coronary death Trial was mainly for lung cancer preventionTrial was mainly for lung cancer prevention NEJM 1994; 330 (15):

Vitamin C Less potent antioxidant than ELess potent antioxidant than E Inhibits platelet aggregationInhibits platelet aggregation Deficiency = ScurvyDeficiency = Scurvy Excess may lead to B12 deficiency or oxalate stonesExcess may lead to B12 deficiency or oxalate stones Less evidence than exists for Vitamin ELess evidence than exists for Vitamin E

Vitamin C Human Studies NHANES INHANES I 11,349 subjects taking Vitamin C supplements11,349 subjects taking Vitamin C supplements Subjects taking Vitamin C had a lower relative risk of CV death (.58)Subjects taking Vitamin C had a lower relative risk of CV death (.58) Epidemiology 1992; 3(3):

Vitamin C Human Studies The Nurse’s Health and the Health Professionals Follow up StudyThe Nurse’s Health and the Health Professionals Follow up Study Slightly lower relative risk (.8) in subjects in highest quintile of Vitamin C consumptionSlightly lower relative risk (.8) in subjects in highest quintile of Vitamin C consumption

Vitamin C and E Heart Protection Study 2x2 Trial2x2 Trial simvistatin 40 mg vs. placebosimvistatin 40 mg vs. placebo vitamin E 600 mg, vitamin C 250 mg, beta carotene 20 mg vs. placebovitamin E 600 mg, vitamin C 250 mg, beta carotene 20 mg vs. placebo Over 10,000 patients randomized to vitamin armOver 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 mortalityNo difference in vascular and nonvascular mortality No difference in cancer rateNo difference in cancer rate No difference in major vascular eventsNo difference in major vascular events Lancet 2002; 360: 23-33

Fish Oil Omega -3 Fatty Acids Epidemiologic data suggests improved outcomes in patients eating fishEpidemiologic 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 intakeDART ( 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 supplementationGISSI 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) : Lancet 1999; 354 (9177) :

Olive Oil Oleic acid ( monounsaturated )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.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):

Nuts 80% of calories from fat: Monounsaturates and alpha-linolenic acid ( an omega -3)80% of calories from fat: Monounsaturates and alpha-linolenic acid ( an omega -3) Also rich in Vitamin E, folic acid, K+, Mg, flavanoidsAlso rich in Vitamin E, folic acid, K+, Mg, flavanoids 1/4 to 1/3 cup daily can reduce LDL levels by up to 10 %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%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 intakeNurse’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 intakePhysicians Health Study showed reduction in sudden and total CAD death, but not in nonfatal MI associated with nut intake BMJ 1996; 313 (7049): BMJ 1998; 317 (7169): Archives Internal Medicine 2002; 162:

Fats Good- monounsaturated-- olive oil, canola oil, nuts omega-3 -- fish, nutsGood- monounsaturated-- olive oil, canola oil, nuts omega-3 -- fish, nuts Bad- saturated-- red meat, cheese, butter trans- fatty acids-- processed foodsBad- saturated-- red meat, cheese, butter trans- fatty acids-- processed foods Omega-6 oils- (corn, soybean, sunflower) are probably neutral in effectOmega-6 oils- (corn, soybean, sunflower) are probably neutral in effect

Diets Postgraduate Medicine 2002; 112 (2) : 34-44

AHA Diet Step I-Step I- Total Fat < 30%, saturated fat <10%, cholesterol < 300mgTotal Fat < 30%, saturated fat <10%, cholesterol < 300mg Step II-Step II- Total Fat < 25%, saturated fat < 7%, cholesterol < 200mgTotal Fat < 25%, saturated fat < 7%, cholesterol < 200mg A paucity of evidence for improved outcomes exists for the AHA diets; and some evidence exists for continued disease progression and some evidence exists for continued disease progression BMJ 2001: 322(7289):

Mediterranean Diet Greece, Crete, parts of France and Italy display low rates of CADGreece, Crete, parts of France and Italy display low rates of CAD Monounsaturates and Omega-3 fatty acids are not limitedMonounsaturates and Omega-3 fatty acids are not limited Fresh fruits and vegetables, fish, nuts, moderate alcoholFresh fruits and vegetables, fish, nuts, moderate alcohol Low in trans fatty acidsLow in trans fatty acids

Mediterranean Diet DATA Lyon Diet Heart Study of 605 MI survivorsLyon Diet Heart Study of 605 MI survivors 55% reduction in risk of death and 50 % reduction in recurrent cardiac events over a 4 year period55% reduction in risk of death and 50 % reduction in recurrent cardiac events over a 4 year period Reduction not explained by changes in lipid factorsReduction not explained by changes in lipid factors Circulation 1999; 99 (6):

Mediterranean Diet DATA GISSI - PrevenzioneGISSI - Prevenzione Multivariate analysis showed fish, fruit, vegetables and olive oil all conferred benefit over a 4 year periodMultivariate analysis showed fish, fruit, vegetables and olive oil all conferred benefit over a 4 year period Circulation 2002; 105:

Mediterranean Diet Suggestions- Carbs and Proteins EATEAT Whole fruits and vegetablesWhole fruits and vegetables Whole grain cerealWhole grain cereal Bran, brown riceBran, brown rice Peas, beansPeas, beans Lean meat, fish, poultry, vegetable proteinLean meat, fish, poultry, vegetable protein DON’T EATDON’T EAT Refined carbohydratesRefined carbohydrates White bread, biscuitsWhite bread, biscuits Bacon, sausageBacon, sausage Processed fatty meatProcessed fatty meat High fat dairyHigh fat dairy

Mediterranean Diet Suggestions- Fats EATEAT Olive oilOlive oil FishFish Flaxseed, spinach, tree nutsFlaxseed, spinach, tree nuts DON’T EATDON’T EAT Trans-fatty acidsTrans-fatty acids Fast foodFast food DoughnutsDoughnuts Chips, crackersChips, crackers Margarine made with partially hydrogenated oilMargarine made with partially hydrogenated oil

Alcohol Evidence of cardioprotective effect of alcohol first appeared in Framingham dataEvidence 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 effectAt 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.Mechanisms include HDL raising, changes in inflammatory markers and improvement in insulin resistances. Lancet 2001; 357 (9258): 763-7