Alternative Therapies in Alternative Therapies in Coronary Artery Disease:Coronary Artery Disease:

Vitamins, Supplements, Diets Vitamins, Supplements, Diets and Associated Topicsand Associated Topics

Carl R. Szot, MDCarl R. Szot, MD

December 2, 2002December 2, 2002

Vitamin EVitamin E

• Fat soluble compounds with alpha-tocopherol being the Fat soluble compounds with alpha-tocopherol being the most commonmost common

• Natural sources include vegetables, nuts and nut oilsNatural sources include vegetables, nuts and nut oils

• Deficiency is rare and associated with posterior column Deficiency is rare and associated with posterior column degeneration and loss of large caliber peripheral nervesdegeneration and loss of large caliber peripheral nerves

• Excess is only an issue in people on coumadin or in Excess is only an issue in people on coumadin or in premature infantspremature infants

Vitamin EVitamin EProposed Mechanisms of Proposed Mechanisms of

ActionAction

• Decreases oxidation Decreases oxidation of LDLof LDL

• Inhibits smooth Inhibits smooth muscle cell growthmuscle cell growth

• Inhibits platelet Inhibits platelet adhesionadhesion

• Improves Improves endothelial endothelial functionfunction

• In fat fed rabbits In fat fed rabbits reduces reduces atherosclerosisatherosclerosis

Clinical Cardiology 1993: 16: 116-118Clinical Cardiology 1993: 16: 116-118

Vitamin EVitamin EHuman StudiesHuman Studies

• Iowa Women’s HealthIowa Women’s Health

• Prospective study of 34,000 Prospective study of 34,000 postmenopausal womenpostmenopausal women

• High dietary Vitamin E intake was High dietary Vitamin E intake was associated with lower CAD riskassociated with lower CAD risk

NEJM 1996: 334 (18): 1156-62NEJM 1996: 334 (18): 1156-62

Vitamin EVitamin EHuman Observational Human Observational

StudiesStudies• Health Professionals follow up to the Health Professionals follow up to the

Physicians Health StudyPhysicians Health Study

• 39,910 men ages 40-7039,910 men ages 40-70

• Subjects with the highest Vitamin E Subjects with the highest Vitamin E intake had a 36% lower risk of CAD intake had a 36% lower risk of CAD events after 4 yearsevents after 4 years

NEJM 1993: 328 (20): 1450-1466NEJM 1993: 328 (20): 1450-1466

Vitamin E Vitamin E Human StudiesHuman Studies

• Nurse’s Health StudyNurse’s Health Study

• 87,245 women ages 34-59 with no prior 87,245 women ages 34-59 with no prior CADCAD

• Those taking > 100 iu of Vitamin E for > Those taking > 100 iu of Vitamin E for > 2 years Had 40% lower risk of developing 2 years Had 40% lower risk of developing CAD after 8 years.CAD after 8 years.

NEJM 1993; 328 (20): 1444-49NEJM 1993; 328 (20): 1444-49

Vitamin E Vitamin E Randomized TrialsRandomized Trials

• Cambridge Heart Antioxidant Study (CHAOS)Cambridge Heart Antioxidant Study (CHAOS)

• 2002 patients with prior CAD prospectively 2002 patients with prior CAD prospectively randomized to Vitamin E (400-800 iu/day)randomized to Vitamin E (400-800 iu/day)

• 77% reduction in nonfatal MI77% reduction in nonfatal MI

• No change in overall mortalityNo change in overall mortality

Lancet 1996; 347 (9004): 781-86Lancet 1996; 347 (9004): 781-86

Vitamin EVitamin ERandomized TrialsRandomized Trials

• Alpha-tocopheral Beta Carotene Prevention Alpha-tocopheral Beta Carotene Prevention Trial (ABC)Trial (ABC)

• 50mg/day of Vitamin E had no effect on the risk of 50mg/day of Vitamin E had no effect on the risk of MI or deathMI or death

• 50mg/day of Vitamin E plus 20mg/day of beta-50mg/day of Vitamin E plus 20mg/day of beta-carotene resulted in greater rate of coronary carotene resulted in greater rate of coronary deathdeath

• Trial was mainly for lung cancer preventionTrial was mainly for lung cancer preventionNEJM 1994; 330 (15): 1029-35NEJM 1994; 330 (15): 1029-35

Vitamin CVitamin 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 Excess may lead to B12 deficiency or

oxalate stonesoxalate stones• Less evidence than exists for Vitamin Less evidence than exists for Vitamin

EE

Vitamin C Vitamin C Human StudiesHuman Studies

• NHANES INHANES I

• 11,349 subjects taking Vitamin C 11,349 subjects taking Vitamin C supplementssupplements

• Subjects taking Vitamin C had a Subjects taking Vitamin C had a lower relative risk of CV death (.58)lower relative risk of CV death (.58)

Epidemiology 1992; 3(3): 194-202Epidemiology 1992; 3(3): 194-202

Vitamin CVitamin CHuman StudiesHuman Studies

• The Nurse’s Health and the Health The Nurse’s Health and the Health Professionals Follow up StudyProfessionals Follow up Study

• Slightly lower relative risk (.8) in Slightly lower relative risk (.8) in subjects in highest quintile of subjects in highest quintile of Vitamin C consumptionVitamin C consumption

Vitamin C and EVitamin C and EHeart Protection StudyHeart Protection Study

• 2x2 Trial2x2 Trial• simvistatin 40 mg vs. placebosimvistatin 40 mg vs. placebo• vitamin E 600 mg, vitamin C 250 mg, beta vitamin E 600 mg, vitamin C 250 mg, beta

carotene 20 mg vs. placebocarotene 20 mg vs. placebo

• Over 10,000 patients randomized to Over 10,000 patients randomized to vitamin armvitamin arm

Lancet 2002; 360: 23-33Lancet 2002; 360: 23-33

Vitamin C and EVitamin C and EHeart Protection StudyHeart Protection Study

• No difference in vascular and No difference in vascular and nonvascular mortalitynonvascular mortality

• No difference in cancer rateNo difference in cancer rate

• No difference in major vascular No difference in major vascular eventsevents

Lancet 2002; 360: 23-33Lancet 2002; 360: 23-33

Fish OilFish OilOmega -3 Fatty AcidsOmega -3 Fatty Acids

• Epidemiologic data suggests improved outcomes Epidemiologic data suggests improved outcomes in patients eating fishin patients eating fish

• DART ( Diet and Reinfarction Trial) showed 29% DART ( Diet and Reinfarction Trial) showed 29% reduction in all cause mortality after 2 years of reduction in all cause mortality after 2 years of increased fish/fish oil intakeincreased fish/fish oil intake

• GISSI Prevenzione showed a 45% decrease in SCD GISSI Prevenzione showed a 45% decrease in SCD and 20% decrease in all cause mortality after 3 1/2 and 20% decrease in all cause mortality after 3 1/2 years of supplementationyears of supplementation

Lancet 1989; 2 (8666) : 757-61Lancet 1989; 2 (8666) : 757-61Lancet 1999; 354 (9177) : 447-55Lancet 1999; 354 (9177) : 447-55

Olive OilOlive Oil

• Oleic acid ( monounsaturated )Oleic acid ( monounsaturated )

• In a trial comparing an AHA Step I diet, an In a trial comparing an AHA Step I diet, an average American control diet and an olive oil average American control diet and an olive oil enriched diet showed similar reductions of LDL enriched diet showed similar reductions of LDL compared to control, but unchanged HDL with compared to control, but unchanged HDL with olive oil ( decreased 4 % with Step II.) olive oil ( decreased 4 % with Step II.) Triglycerides fell 13% with olive oil but increased Triglycerides fell 13% with olive oil but increased 11% with the Step II diet.11% with the Step II diet.

AMJ Clinical Nutrition 1999; 70(6): 1009-15AMJ Clinical Nutrition 1999; 70(6): 1009-15

NutsNuts

• 80% of calories from fat: Monounsaturates 80% of calories from fat: Monounsaturates and alpha-linolenic acid ( an omega -3)and alpha-linolenic acid ( an omega -3)

• Also rich in Vitamin E, folic acid, K+, Mg, Also rich in Vitamin E, folic acid, K+, Mg, flavanoidsflavanoids

• 1/4 to 1/3 cup daily can reduce LDL levels 1/4 to 1/3 cup daily can reduce LDL levels by up to 10 % by up to 10 %

Nuts- DataNuts- Data

• Health Professionals Follow Up Study showedHealth Professionals Follow Up Study showed increased intake of alpha-linolenic acid lowered MI increased intake of alpha-linolenic acid lowered MI risk by 60%risk by 60%

• Nurse’s Health Study showed 35% CAD reduction Nurse’s Health Study showed 35% CAD reduction associated with nut intakeassociated with nut intake

• Physicians Health Study showed reduction in Physicians Health Study showed reduction in sudden and total CAD death, but not in nonfatal MI sudden and total CAD death, but not in nonfatal MI associated with nut intakeassociated with nut intake

BMJ 1996; 313 (7049): 84-90. BMJ 1998; 317 (7169): 1341-5BMJ 1996; 313 (7049): 84-90. BMJ 1998; 317 (7169): 1341-5Archives Internal Medicine 2002; 162: 1382-87Archives Internal Medicine 2002; 162: 1382-87

FatsFats

• GoodGood- - monounsaturated-- olive oil, canola oil, monounsaturated-- olive oil, canola oil, nuts nuts omega-3 -- fish, nuts omega-3 -- fish, nuts

• BadBad- - saturated-- red meat, cheese, butter saturated-- red meat, cheese, butter trans- fatty trans- fatty acids-- processed foodsacids-- processed foods

• Omega-6 oilsOmega-6 oils- - (corn, soybean, sunflower) are (corn, soybean, sunflower) are probably neutral in effectprobably neutral in effect

DietsDiets

Plan Fat Carbohydrate

OrnishPritikin

Very Low (10%) Very High

AHA Step I & Step IIWeight Watchers

DASHLow (20-30%) High

MediterraneanZone

Moderate ( 30-35%) Moderate

Sugar BustersProtein Power

Atkins

High ( > 45%) Low

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

AHA DietAHA Diet

• Step I-Step I-• Total Fat < 30%, Total Fat < 30%,

saturated fat <10%, saturated fat <10%, cholesterol < cholesterol < 300mg300mg

• Step II-Step II-• Total Fat < 25%, Total Fat < 25%,

saturated fat < 7%, saturated fat < 7%, cholesterol < cholesterol < 200mg200mg

A paucity of evidence for improved outcomes exists for the AHA diets;A paucity of evidence for improved outcomes exists for the AHA diets; and some evidence exists for continued disease progressionand some evidence exists for continued disease progression

BMJ 2001: 322(7289): 757-63BMJ 2001: 322(7289): 757-63

Mediterranean DietMediterranean Diet

• Greece, Crete, parts of France and Italy display low Greece, Crete, parts of France and Italy display low rates of CADrates of CAD

• Monounsaturates and Omega-3 fatty acids are not Monounsaturates and Omega-3 fatty acids are not limitedlimited

• Fresh fruits and vegetables, fish, nuts, moderate Fresh fruits and vegetables, fish, nuts, moderate alcoholalcohol

• Low in trans fatty acidsLow in trans fatty acids

Mediterranean DietMediterranean DietDATADATA

• Lyon Diet Heart Study of 605 MI survivorsLyon Diet Heart Study of 605 MI survivors

• 55% reduction in risk of death and 50 % 55% reduction in risk of death and 50 % reduction in recurrent cardiac events over reduction in recurrent cardiac events over a 4 year perioda 4 year period

• Reduction not explained by changes in Reduction not explained by changes in lipid factorslipid factors

Circulation 1999; 99 (6): 779-85Circulation 1999; 99 (6): 779-85

Mediterranean DietMediterranean DietDATADATA

• GISSI - PrevenzioneGISSI - Prevenzione

• Multivariate analysis showed fish, Multivariate analysis showed fish, fruit, vegetables and olive oil all fruit, vegetables and olive oil all conferred benefit over a 4 year periodconferred benefit over a 4 year period

Circulation 2002; 105: 1887-903Circulation 2002; 105: 1887-903

Mediterranean DietMediterranean DietSuggestions- Carbs and ProteinsSuggestions- Carbs and Proteins

• EATEAT

• Whole fruits and Whole fruits and vegetablesvegetables

• Whole grain cerealWhole grain cereal• Bran, brown riceBran, brown rice• Peas, beansPeas, beans• Lean meat, fish, poultry, Lean meat, fish, poultry,

vegetable proteinvegetable 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 DietMediterranean DietSuggestions- FatsSuggestions- 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 Margarine made with

partially hydrogenated oilpartially hydrogenated oil

AlcoholAlcohol

• Evidence of cardioprotective effect of alcohol first Evidence of cardioprotective effect of alcohol first appeared in Framingham dataappeared in Framingham data

• At levels of consumption of greater than two At levels of consumption of greater than two drinks/day for men and one drink /day for women all drinks/day for men and one drink /day for women all cause mortality overwhelms cardioprotective effectcause mortality overwhelms cardioprotective effect

• Mechanisms include HDL raising, changes in Mechanisms include HDL raising, changes in inflammatory markers and improvement in insulin inflammatory markers and improvement in insulin resistances.resistances.

Lancet 2001; 357 (9258): 763-7Lancet 2001; 357 (9258): 763-7