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The Case for Going Coo-coo for Cacao -data, from the dark side- David L. Katz, MD, MPH, FACPM, FACP Director, Prevention Research Center Yale University.

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Presentation on theme: "The Case for Going Coo-coo for Cacao -data, from the dark side- David L. Katz, MD, MPH, FACPM, FACP Director, Prevention Research Center Yale University."— Presentation transcript:

1 The Case for Going Coo-coo for Cacao -data, from the dark side- David L. Katz, MD, MPH, FACPM, FACP Director, Prevention Research Center Yale University School of Medicine Medical Contributor, ABC News All Candy Expo June 6, 2006

2 Heart Disease: same as it ever was, and maybe even worse…

3 What it is… Adult Population 100% Time Time Overweight / Obesity Insulin Resistance Diabetes Mellitus Cardiovascular Disease

4 And What it SHALL be… Children !! 100% Time Time Overweight / Obesity Insulin Resistance Diabetes Mellitus Cardiovascular Disease

5 Obesity, BMI, CVD and Phenols CVD leading cause of death in the U.S. for both men and women and in all racial and ethnic groups Not just a disease of the elderly Heart disease accounts for 1 million deaths each year of these 160,000 were 35-65 years old

6 Obesity and CVD Elevated BMI and obesity have been recognized as major risk factors for CVD Results from NHANES 2003-2004 show that an estimated 66% of U.S. adults are either overweight or obese A retrospective study of individuals who died of CVD showed that the deceased population had a higher BMI than the general population (Kern 2004) Obesity increases risk of hypertension, diabetes, coronary heart disease and congestive cardiac failure

7 Cardiovascular Risk Factors, Old… Hyperlipidemia Hypertension Diabetes Obesity Etc.

8 …And New IRS concomitants CRP/inflammatory markers Small dense LDL Lp(a) Coronary Calcification Fibrinogen Hyperhomocysteinemia Oxidative stress Vascular Dysfunction Wood D. Established and emerging cardiovascular risk factors. Am Heart J. 2001;141(2suppl):S49-S57 Howard BV et al. Curr Atheroscler Rep. 2000;2:476-81

9 Incriminating Evidence, Beyond the Usual Suspects… Calcification Hecht HS et al. Am J Cardiol. 2001;87:406-412 CRP/Inflammation Bell DS. Endocrin Pract. 2000;6:272-6 Frohlich M et al. Diabetes Care. 2000;23:1835-9 Pradhan AD et al. JAMA. 2001;286:327-34 Koenig W. Cardiol Rev. 2001;9:31-5 Small, dense LDL Lamarche B et al. Diabetes Metab. 1999;25:199-211 Fibrinogen/Hypercoagulability Bruno G et al. Diabetes Metab Res Rev. 2001;17:124-30 Endothelial Dysfunction Tooke J. Diabetes Obes Metab. 1999;1s1:s17-22 Tooke JE et al. Diabet Med. 1999;16:710-5 Shechter M et al. Am J Cardiol. 2000;86:1256-59

10 Cocoa… To the rescue?

11 Chocolate: bittersweet history chocolate, per se, is a product of the seeds of the cacao tree, indigenous to Central and South America. Initially used by meso-American peoples to brew a bitter drink, chocolate has been in the human diet for over 2000 years. The origins of chocolate as a sweet delicacy can be traced to the 16th century, and conquest of Central America and Mexico by the Spanish. Cacao was among the spoils of war, and thus introduced to European epicures. The addition of sugar to cacao likely first occurred in Spain.

12 Not all chocolate is created equal- And neither is all saturated fat: In solid dark chocolate, nearly 80% of the fat is saturated. The predominant fatty acid in cocoa butter is stearic acid, an 18- carbon molecule. Whereas shorter-chain saturated fatty acids such as myristic acid (14 carbons), and palmitic acid (16 carbons) are associated with increases in LDL cholesterol and atherogenesis, stearic acid is not (Sanders TA, Berry SE. Influence of stearic acid on postprandial lipemia and hemostatic function. Lipids. 2005;40:1221-7). Thus, the fat in dark chocolate is at worst neutral with regard to health effects, if not actually salubrious.

13 The power of the dark side- Dark chocolate & cocoa are (potentially) concentrated sources of: Flavonoids Fiber Magnesium Arginine Caffeine Theobromine

14 Summary of Chocolate And Cocoa Feeding Trials AuthorYearSubjectsTrial DesignDurationInterventionOutcome Kondo199612Cross over1 meal per and post Cocoa 35 g vs. none Dec LDL oxidation Rein200030Parallel1 meal 2 & 6 hrs Cocoa 300 mlDecreased platelet activation Decreased platelet function Wang200020CrossoverI meal 1 week phase Procyanidin – 27,35,80 g vs none Increased anti oxidant capacity Okasabe200120ParallelDaily 2 weeks Cocoa powder 36g/day vs sugar Decreased LDL oxidation Schram2001 1 meal 1 week35 g chocolate vs.09 g procyanidin Decreased platelet activation Holt200218Crossover1 meal 2 hrs 25 g semi sweetDecreased platelet function Heiss2003 20Crossover1 meal, 1 day/phase Cocoa beverage 100 ml Improved endothelial function Taubert2003 13Cross overDaily 14 daysDark chcolate 100 g vs white chocolate 90 gms Lower systolic BP Engler200421ParallelDaily 2 weeksHigh vs low flavonoid Improved endothelial function Grassi2004 15CrossoverDaily 14 daysDark vs white choclate Lower BP, lower LDL

15 Summary of Chocolate And Cocoa Feeding Trials, cont. AuthorYearSubjectsTrial DesignDurationInterventionOutcome Wiswedel200420Crossover1 meal 1 week washout High flavanol vs low flavanol Lower lipid peroxidation Mursu200445ParallelDaily 3 weeksDark chocolate vs white chocolate Increased HDL concentration Zhu20058Parallel1 mealCocoa beverage high flavanoid Reduced susceptibility to free radical hemolysis Vlachopolus200517Crossover1 meal, 1 day/phase Dark chocolate vs. none Improved endothelial function Fraga200528ParallelDail, 14 daysHigh flavanol milk chocoalte vs low flavanol Lower BP, lower LDL

16 Iron fist, velvet glove: Dark chocolate ameliorates most cardiac risk factors.

17 Blood Pressure Grassi D, Lippi C, Necozione S, Desideri G, Ferri C. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr. 2005;81:611-4 Grassi D, Necozione S, Lippi C, Croce G, Valeri L, Pasqualetti P, Desideri G, Blumberg JB, Ferri C. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension. 2005;46:398-405

18 Platelet Aggregation Innes AJ, Kennedy G, McLaren M, Bancroft AJ, Belch JJ. Dark chocolate inhibits platelet aggregation in healthy volunteers. Platelets. 2003;14:325-7 Pearson DA, Holt RR, Rein D, Paglieroni T, Schmitz HH, Keen CL. Flavanols and platelet reactivity. Clin Dev Immunol. 2005;12:1-9

19 Oxidation / Inflammation Mao TK, Powell J, Van de Water J, Keen CL, Schmitz HH, Hammerstone JF, Gershwin ME. The effect of cocoa procyanidins on the transcription and secretion of interleukin 1 beta in peripheral blood mononuclear cells. Life Sci. 2000;66:1377-86 Mursu J, Voutilainen S, Nurmi T, Rissanen TH, Virtanen JK, Kaikkonen J, Nyyssonen K, Salonen JT. Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans. Free Radic Biol Med. 2004;37:1351-9 Wan Y, Vinson JA, Etherton TD, Proch J, Lazarus SA, Kris-Etherton PM.Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans. Am J Clin Nutr. 2001;74:596-602

20 Insulin Resistance Grassi D, Lippi C, Necozione S, Desideri G, Ferri C. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr. 2005;81:611-4

21 And Endothelial Function Improvement in endothelial function has been seen in healthy adults –Vlachopoulos C, Aznaouridis K, Alexopoulos N, Economou E, Andreadou I, Stefanadis C. Effect of dark chocolate on arterial function in healthy individuals. Am J Hypertens. 2005;18:785- 91; Fisher ND, Hughes M, Gerhard-Herman M, Hollenberg NK. Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans. J Hypertens. 2003;21:2281-6 and in adults with cardiac risk factors –Sies H, Schewe T, Heiss C, Kelm M. Cocoa polyphenols and inflammatory mediators. Am J Clin Nutr. 2005;81(1 Suppl):304S-312S

22 One risk factor- to rule them all?

23 Endothelial Dysfunction ED precedes clinical atherosclerosis, 1 is prominent in the presence of coronary risk factors, and improves with risk modification 2,3 1. Glasser SP, et al. Am Heart J, 1996 2. Anderson TJ, et al. N Engl N Med, 1995 3. Stroes ES, et al. Lancet, 1995

24 Role of Nitric Oxide

25 Endothelial function testing Brachial artery compression Cuff release: shear stress NO release Vasodilatation (Vasoconstriction) BP cuff Inflation




29 EF Studies at Yale PRC: Katz DL, Evans MA, Nawaz H, Njike VY, Chan W, Comerford BP, Hoxley ML. Egg consumption and endothelial function: a randomized controlled crossover trial. Int J Cardiol. 2005;99:65-70 Katz DL, Evans MA, Chan W, Nawaz H, Comerford BP, Hoxley ML, Njike VY, Sarrel PM. Oats, antioxidants and endothelial function in overweight, dyslipidemic adults. J Am Coll Nutr. 2004;23:397-403 Sarrel PM, Nawaz H, Chan W, Fuchs M, Katz DL. Raloxifene and endothelial function in healthy postmenopausal women. Am J Obstet Gynecol. 2003;188:304-9 Katz DL, Nawaz H, Boukhalil J, Chan W, Ahmadi R, Giannamore V, Sarrel PM. Effects of oat and wheat cereals on endothelial responses. Prev Med. 2001;33:476-84 And others in press.

30 Current Trial- Effects of Acute Ingestion of Dark Chocolate on Endothelial Function in Adults with BMI between 25-35 kg/m 2 : A Randomized, Single Blind, Placebo Controlled Trial

31 With thanks to- Dr. Zubaida Faridi Dr. Valentine Njike

32 Specific Aims To assess the acute effects of solid, dark chocolate on endothelial function measured as flow mediated dilation (FMD) of the brachial artery in overweight adults To determine the acute effects of solid, dark chocolate on blood pressure in overweight individuals

33 Study Design Randomized, single-blind, placebo controlled crossover trial

34 Subjects Inclusion Criteria Ages between 30 -75 BMI between 25-35 kg/m 2 Waist circumference above 88 cm in women and 102 cm in men Non-smoker No strenuous exercise at least 8 hours prior to scanning

35 Methods The study consisted of the following phases: Phase 1: Dose response test Phase 2: Acute effects of ingestion of solid dark chocolate vs. placebo on endothelial function [75g (6 blocks of 100g bar provided] Phase 3: Acute effects of ingestion of sugar free cocoa vs. cocoa with sugar vs. placebo [22g (2 cups (8 oz ) of ~10g cocoa beverage] Phase 4: Sustained effects of 6 weeks consumption of sugar free cocoa vs. cocoa with sugar vs. placebo -(on-going)

36 Subjects, Cont Exclusion Criteria Failure to meet inclusion criteria Anticipated inability to complete study protocol for any reason Current eating disorder Diagnosed coronary artery disease Diabetes Sleep apnea Current or impending pregnancy Vasoactive medication use

37 Methods 45 subjects were randomly assigned to one of the treatment sequences: dark chocolate then placebo or placebo then dark chocolate Participants underwent endothelial function testing using high frequency ultrasound and blood pressure measurement pre and post ingestion of 75 gms of solid, dark chocolate or low flavonoid placebo Participants fast overnight for 12 hrs before each test dose

38 Methods, Cont At each visit BARS scans were done at baseline (before intervention) and 2 hours following intervention

39 Variables Endothelial function was assessed as flow-mediated dilatation, or FMD; this was calculated as the percent change in diameter post- occlusion of brachial artery at 60 seconds relative to the measurement at baseline before cuff inflation To account for variability in the strength of the stimulus that triggered endothelial reactivity (i.e., hyperemic flow), FMD was divided by flow at 15 seconds post-cuff deflation to create a stimulus-adjusted response measure or SARM Blood Pressure: Diastolic and Systolic

40 Outcome Measures The difference in the change in FMD between dark chocolate and placebo (ΔI-ΔP) The difference in the change in SARM between dark chocolate and placebo (ΔI-ΔP) The difference in the change in blood pressure between dark chocolate and placebo (ΔI-ΔP)

41 Results Table 1. Baseline Values Variable Dark Chocolate (n=45)Placebo (n=45) p-value Mean ± SD Age (years)52.78 ± 11.03 1.0000 Weight (lbs)179.11 ± 22.23 178.84 ± 22.420.9549 Body Mass Index (kg/m²)30.14 ± 3.31 30.09 ± 3.260.9396 Room Temperature (ºF)72.00 ± 0.21 72.04 ± 0.670.6744 Diastolic Blood Pressure (mmHg)68.64 ± 11.77 69.87 ± 11.660.6218 Systolic Blood Pressure (mmHg)124.80 ± 16.95 122.82 ± 15.180.5613 Flow Mediated Dilation or FMD (%)*7.36 ± 3.55 9.10 ± 4.820.0553 Stimulus Adjusted Response Measure or SARM*0.08 ± 0.08 0.07 ± 0.170.6319 *Occasional missing; SD=Standard deviation; p-values obtained from student ttest

42 Results, Cont Table 2. Change in Outcome Measures from Baseline after Treatment Assignment Variable Dark Chocolate (n=45)Placebo (n=45)Between Group Mean ± SD p-value Systolic Blood Pressure (mmHg)-3.24 ± 5.822.68 ± 6.64<.0001 Within Group p-value0.00050.0104---- Diastolic Blood Pressure (mmHg)-1.40 ± 3.91 2.73 ± 6.36 0.0004 Within Group p-value0.02060.0067---- Flow Mediated Dilation or FMD (%)4.28 ± 3.432.73 ± 6.36<.0001 Within Group p-value<.00010.0007---- Stimulus Adjusted Response Measure0.04 ± 0.100.01 ± 0.180.3120 Within Group p-value0.01290.7902----

43 Results, Cont Error bars indicate 95% CI

44 Cocoa results- Hot off the presses-

45 In this sample of overweight adults, acute ingestion of both dark chocolate & cocoa significantly improved endothelial function and blood pressure Conclusion

46 In need of attention: The flavanols in chocolate contribute to its bitterness Lesschaeve I, Noble AC. Polyphenols: factors influencing their sensory properties and their effects on food and beverage preferences. Am J Clin Nutr. 2005;81:330S-335S Long-term health effects are not known with confidence Buijsse B, Feskens EJ, Kok FJ, Kromhout D. Cocoa intake, blood pressure, and cardiovascular mortality: the Zutphen Elderly Study. Arch Intern Med. 2006;166:411-7 Kris-Etherton PM, Keen CL. Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Curr Opin Lipidol. 2002;13:41-9 Scalbert A, Manach C, Morand C, Remesy C, Jimenez L. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr. 2005;45:287-306 Dose, diet, substitutions, and calories Salutary effects have been seen with between 150mg and 500mg of flavonoids. This translates into between 1 and 3.5 cups of tea, and from 40 g (1.4 oz) to 125 g (4.4 oz) of flavonoid-rich chocolate.

47 If it sounds too good to be true- its chicanery, or… CHOCOLATE! Ariefdjohan MW, Savaiano DA. Chocolate and cardiovascular health: is it too good to be true? Nutr Rev. 2005;63(12 Pt 1):427-30

48 Thank you. Yale Prevention Research Center 130 Division St. Derby, CT 06418

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