Chocolate Cocoa Guilty Healthy

ChocolateGuilty Pleasure or Healthy Supplement?Laura S. Latham, PharmD;1 Zeb K. Hensen, MD;2 Deborah S. Minor, PharmD2

From the Department of Pharmacy, University of Mississippi Medical Center, Jackson, MS;1 and Department of Medicine, University of Mississippi

Medical Center, Jackson, MS2

Dark chocolate and other cocoa products are popular in thepopulation as a whole, but their overall health benefitremains controversial. Observations from the Kuna Indianpopulation have shown an impressive cardiovascular healthbenefit from cocoa. For various reasons, this benefit has notbeen as robust as in other populations. Additionally, severalmechanisms have been proposed that might confer cocoaspossible health benefit, but no consensus has been reachedon cocoas physiologic role in promoting cardiovascularhealth. Flavanols, as well as theobromine, may contribute toenhancements in endothelial function and subsequentimprovements in various contributors to cardiovascular

disease (CVD) including hypertension, platelet aggregationand adhesion, insulin resistance, and hypercholesterolemia.While the benefits of cocoa may be altered at the variousstages of growth, development, and production, it appearsthat for many people healthy dark chocolate may, indeed,provide a pleasurable role in CVD risk reduction. Theobjectives of this review are to discuss the associations ofcocoa with decreased blood pressure and improved CVDrisk, to describe the possible mechanisms for these potentialbenefits, and to highlight considerations for the use of cocoaas a dietary supplement. J Clin Hypertens (Greenwich).2014;16:101106. 2013 Wiley Periodicals, Inc.

Patients are frequently on the lookout for a pleasurableway to approach their health. With this in mind, darkchocolate and cocoa products have garnered attention asa dietary supplement and approach to decrease bloodpressure (BP) and modify other cardiovascular disease(CVD) risk factors.1 An extract from the Theobromacacao tree, cocoa is a rich source of plant polyphenols, aheterogeneous group of molecules found primarily infruits and vegetables. Cocoa is especially rich in flavanols,a polyphenol subtype proposed as the mediator forcardiovascular benefits.2 Flavanols are also found inother plant-based foods (Table I).1,3 While the contribu-tions of the various components of these foods continueto evolve, the flavanol content appears to augment thecardiovascular benefits. Regular dietary intake of plant-derived foods and beverages is inversely associated withthe risk of CVD among the general population.4

Interest in the effect of cocoa on CVD began withobservations among the Kuna Indian population in theSan Blas Islands of Panama. This group had distinctivelylow rates of hypertension and CVD, coupled with anabsence of the age-related increases in BP observed inother populations.1,5 Environmental, rather thangenetic, factors appeared to confer this protectiverole.1,5 Unique to this population was their cocoaintake. On average, traditional island-dwelling KunaIndians consume approximately four 8-ounce cups ofunprocessed cocoa beverages per day.5,6 Even inpatients older than 65 years, the mean BP was 110/

70 mm Hg.5,6 Conversely, migrant Kuna Indians con-sume up to 10 times less cocoa and experience a BPincrease with age and hypertension prevalence compa-rable to Western populations.1,5,6 Salt consumptionamong the island-dwelling population was equivalent orgreater compared with migrant Indians and there wereno significant differences in body mass index (BMI).1,5

Independent of cocoa, sodium, and weight, other factorsmay influence the observed changes in BP. Physicalactivity, smoking status, stress level, and diet may alsobe related to the CVD risk increase experienced with themigrant Kuna population.5

For many, dietary changes and other lifestyle modi-fications are effective for the prevention and treatmentof hypertension and are critical for reduction of CVD.4

In this review, we discuss the clinically relevant effectsof cocoa, focusing on possible mechanisms involved inthe cardiovascular response to cocoa and the potentialimplications associated with consumption.

FLAVANOL CONTENTStructurally, flavanols exist as low-molecular-weightmonomeric compounds, such as epicatechin, which have

Address for correspondence: Deborah S. Minor, PharmD, Division ofGeneral Medicine/Hypertension, Department of Medicine, University ofMississippi Medical Center, 2500 North State Street, Jackson, MS 39216E-mail: [email protected]

Manuscript received: August 12, 2013; revised: September 18, 2013;accepted: September 27, 2013DOI: 10.1111/jch.12223

TABLE I. Flavanol Concentrations Found in Food3

Source Flavanol Content, mg/kg or mg/L

Chocolate 460610

Legume-type beans 350550

Apricots 100250

Grapes 30175

Blackberries 130

Apples 20120

Green tea 100800

Black tea 60500

Red wine 80300

The Journal of Clinical Hypertension Vol 16 | No 2 | February 2014 101

REVIEW PAPER

effects on the vascular endothelium,7 or as complexhigher-molecular-weight oligomeric and polymeric com-pounds (eg, procyanidins), which are less vasoactive.2,8

The profile and ratio of the various flavanols in cocoaproducts vary considerably and can be altered at manystages of growth, development, and production.1,7,8

Flavanol content in cocoa products is dependent on thecrop cultivar type, post-harvest handling practices, andmanufacturer processing techniques.2 Fresh and fer-mented cocoa beans contain approximately 10% flava-nols (100 mg/g) prior to processing, while the cocoapowder consumed by the Kuna Indians contains about3.6% flavanols. In contrast, cocoa-rich dark chocolatecontains approximately 0.5% flavanols. Milk and whitechocolate have lower flavanol content or even flavanol-free composition, respectively.1 Because flavanols arebitter and often considered unpalatable, processes areused for flavor enrichment. The cocoa powder consumedby the Kuna Indians would be unpleasurable to mostindividuals in the Western population. Fermentation,roasting up to 120C, and dutching (ie, alkalizing), aswell as the addition of sugar, milk, vanilla, and emulsi-fiers, are techniques used to improve cocoas palatabil-ity.7,9 These modifications, however, can practicallyeliminate the presence of flavanols in finished products,and thus may abrogate the potential CVD benefits ofcocoa.9 The percentage of cocoa is not a reliableindicator of the flavanol content present in a givenproduct. As a result, a 70% cocoa bar from one companymay contain an entirely different flavanol compositionthan a 70% cocoa product from another supplier.1

MECHANISMS AND EFFECTS ON CVD RISKFACTORSObservational studies support the association betweenhigh cocoa intake and reduced CVD.10,11 Based on theKuna Indian observations, investigational trials weredesigned to further define the cardiovascular and anti-hypertensive effects of cocoa consumption. Although avariety of mechanisms have been proposed, many of thefindings involve improvements in endothelial function.Prospective studies have demonstrated an associationbetween endothelial dysfunction and increased risk ofCVD. Endothelial function may improve following theconsumption of flavanol-rich cocoa, with subsequentimprovement of various contributors to CVD includinghypertension, platelet aggregation and adhesion, insulinresistance, and hypercholesterolemia.12

For the purpose of this review, we searched forpublished studies from 2003 to 2013 addressing the useof cocoa in the management of CVD risk factors. UsingPubMed, we searched by the following MeSH termsindividually and in combination: cocoa, dark choc-olate, flavanols, hypertension, human, plate-lets, lipids, cardiovascular disease, and insulin.We also reviewed the Natural Medicine ComprehensiveDatabase. Table II highlights examples of studiesdesigned to assess the effects of cocoa on cardiovascularrisk factors.

While intriguing, significant limitations apply to all ofthe cocoa studies reviewed. The paucity of availabledata may also indicate a publication bias in favor ofpositive findings. White chocolate was often used as acontrol, thus preventing participant blinding. Flavanolcontent of test foods, when reported, varies consider-ably among studies, complicating interpretations andcomparisons. Additionally, most studies had a relativelysmall sample size, were of short duration, and measuredonly surrogate markers of CVD risk. This limits thegeneralizability of the results as well as translation toany long-term clinical implications or benefits. Whilethe following observations are provoking, confirmationis needed in well-controlled, well-designed studies.

Blood PressureThe relationship between BP and CVD risk is contin-uous and independent of other risk factors, and smallreductions in BP can lead to substantial decreases inCVD.4 One suggested pathway for the benefits of cocoaon BP and CVD involves endothelial nitric oxide (NO).Cocoa intake increases NO generation. This processmay be triggered by upregulation of endothelial NOsynthase (eNOS), which synthesizes NO from L-argi-nine. Enhancement of NO by cocoa leads to vasodila-tion and BP reduction, as well as prevention ofleukocyte adhesion and migration, smooth muscle cellproliferation, and platelet adhesion and aggregation.3,13

In patients with cardiovascular risk factors, a cocoadrink high in flavanol content (176185 mg) rapidlyincreased circulating levels of bioactive NO by morethan a third. In turn, flow-mediated vasodilation, acommonly used marker to quantify endothelial func-tion, was increased.14 Furthermore, this flavanol-relatedincrease in vasodilation and improvement in endothelialfunction can be reversed by L-NG-monomethyl arginine,a competitive eNOS inhibitor, resulting in a significantreduction in blood flow.3,14 It can be argued, therefore,that the reduced BP and cardiovascular risk in individ-uals who consume flavanol-rich foods is the result of thefavorable effect on eNOS activity.15

Cocoa flavanols also exert antioxidant effects.Consumption of 40 g of commercially available darkchocolate (74% cocoa) significantly improves plasmaantioxidant status 2 hours after ingestion.16 It is likelythat, in addition to eNOS induction and NO concen-tration elevation, a reduction in oxidative stress occursfrom cocoa ingestion. NO breakdown by reactiveoxidant species is reduced, which contributes toenhanced endothelial function, especially under condi-tions with a high oxidative stress burden, such assmoking.16 In addition, antioxidants may prevent NOtransformation into peroxynitrite, a powerful oxidant,and thus protect against vascular damage.3

Another mechanism by which flavanols may lower BPis by inhibition of angiotensin-converting enzyme(ACE).2 ACE inhibition is a highly utilized andevidence-based therapeutic approach to the treatmentof hypertension. In vitro and, more recently, in vivo

102 The Journal of Clinical Hypertension Vol 16 | No 2 | February 2014

Guilty Pleasure or Healthy Supplement? | Latham et al.

studies support the occurrence of ACE inhibition byflavanols.17,18 In healthy volunteers, the average inhibi-tion of ACE activity was 18% 3 hours after intake of75 g of dark chocolate, a level consistent with themagnitude achieved with the ACE inhibitor class ofmedications.18

Several randomized controlled trials have investigatedthe effects of dark chocolate on BP in patients withhypertension. Trials published in 2003 and 2005 usedsimilar designs with patients randomized to receiveeither 100 g of dark chocolate or 90 g of flavanol-free

white chocolate daily for 2 weeks. After a 7-daywashout period, patients were crossed over to thealternative treatment. Dark chocolate consumptiondecreased systolic BP (SBP) and diastolic BP (DBP;meanstandard deviation) by 5.12.4 mm Hg and1.82.0 mm Hg, respectively, in the 2003 trial and11.97.7 mm Hg and 8.55.0 mm Hg in the 2005trial.19,20 In both studies, the reduction in BP followingdark chocolate consumption reached statistical signifi-cance. White chocolate consumption did not reduceBP.19,20 In 2007, the effects of lower doses of dark

TABLE II. Study Examples: Cocoa and Cardiovascular Risk Factors

References Design/Duration No. Intervention Observed Intervention Effect

Taubert13 Randomized, single-blind,

parallel groupa/18 wk

44 DC (6.3 g, 30 mg flavanol) vs

WC (5.6 g, flavanol-free)

NO poolband in SBPb and DBPb

Heiss14 Randomized, double-blind,

crossover/ 2 h, 2 d total

11 Cocoa drink 100 mL with

high (176185 mg) vs

low (

chocolate (6.3 g of chocolate containing 30 mg offlavanols) and white chocolate (5.6 g of flavanol-freechocolate) were assessed over 18 weeks.13 Comparedwith baseline, SBP was significantly reduced by2.91.6 mm Hg and DBP by 1.91.0 mm Hg in thedark chocolate group. Again, white chocolate had nosignificant effect. These findings suggest that habitualintake of low doses of dark chocolate may havesustained antihypertensive effects.13 Other studies,however, have shown no effect of dark chocolate onBP. One study found that consumption of a flavanol-rich cocoa drink for 2 weeks did not significantly reduceBP in patients with primary hypertension.21 Anotherrandomized controlled trial found no significantchanges in BP following flavanol-rich cocoa intake inhealthy adults.22

A 2012 meta-analysis of 20 studies revealed astatistically significant BP-reducing effect of flavanol-rich cocoa products compared with controls, with meanreductions of 2.77 mm Hg and 2.20 mm Hg in SBP andDBP, respectively.1 This meta-analysis provides addi-tional support that dark chocolate may have a small butclinically significant BP-lowering effect. Generally, a3 mm Hg reduction in SBP is estimated to reduce therelative risk of stroke mortality by 8%, coronary arterydisease mortality by 5%, and all-cause mortality by4%.2

BP is clearly influenced by diet as documented by theDietary Approaches to Stop Hypertension (DASH)eating plan. Adoption of this type of diet rich in fruits,vegetables, and low-fat dairy products is associated withan 8 mm Hg to 14 mm Hg reduction in SBP and 5 mmHg decrease in DBP.23 Additionally, certain dietarysupplements (coenzyme Q10, fish oil, garlic, and vita-min C) have evidence of antihypertensive effects. The BPreduction following cocoa intake is not as robust as thatexhibited by the DASH diet or these dietary supple-ments.24 Although cocoa may be consumed as a part ofa healthy DASH diettype approach to BP management,insufficient evidence exists to recommend it as asupplement for additional antihypertensive effects.

Platelet FunctionPlatelet dysfunction is another hallmark of CVD, andthe ability of flavanols to reduce platelet activity mightpartly explain the beneficial effects of these com-pounds.25 Cocoa reduces adenosine diphosphate/colla-gen-activated, platelet-related primary hemostasiswithin hours of ingestion. As a result, platelet aggrega-tion and adhesion are diminished. Flavanols exertadditional antiplatelet effects by reducing glycoproteinIIb/IIIa expression.3,26 A significant reduction in plateletadhesion was observed in young smokers shortly afterconsuming flavanol-rich dark chocolate; however, thiseffect was not sustained after 4 weeks of daily con-sumption.26 Platelet aggregation was also reduced inparticipants who consumed 100 g of dark chocolate,with no effect after ingestion of white or milk choco-late.27 Sex-specific differences in platelet response have

been reported. Men experienced a significant reductionin both platelet activity and aggregation while womenhad only a reduction in platelet aggregation.28 Thisstudy concluded that high-flavanol dark chocolate has apositive effect on platelet function in both sexes, but thebenefits may be greater in men.28

Insulin ResistanceImpairment of insulin-stimulated production of NOfrom the vascular endothelium contributes to metabolicinsulin resistance.21 The resulting decreases in insulin-stimulated blood flow reduces the delivery of insulinand metabolic substrates to skeletal muscle. Thus, byameliorating NO bioavailability, flavanols maydecrease insulin resistance. Insulin resistance has beenreported to be reduced in patients with hypertensionafter a 15-day diet that included 100 g of flavanol-richcocoa daily.29

Alteration in the insulin-signaling pathway has beensuggested as a contributor to cognitive dysfunctionbecause of insulins pivotal role in modulating brainfunction. Chronic dysglycemia is thought to furthercontribute to cognitive dysfunction by promoting thedevelopment of cerebral microvascular disease andinflammation.30 Elderly individuals who consumed atleast 520 mg of flavanols daily demonstrated significantimprovement in cognitive performance that was associ-ated with a reduction in insulin resistance.30 Com-pounds such as flavanol-rich cocoa that improveendothelial function concurrently decrease insulin resis-tance, enhance insulin sensitivity, and increase b-cellfunction.3,20,21 Dietary inclusion of flavanols could beone approach to maintain and improve cardiovascularhealth and cognitive function.

LipidsIncreased concentrations of low-density lipoproteincholesterol (LDL-C) are associated with the develop-ment of atherosclerosis, while a negative correlationexists between increased high-density lipoprotein cho-lesterol (HDL-C) and CVD. Evidence also indicates thatoxidized LDL-C progresses to fatty streak formationand has a pathogenic role in atherosclerosis.31 ImprovedLDL-C and HDL-C concentrations and LDL-C resis-tance to oxidation may contribute to a reduction ofatherosclerosis. Flavanol substances lower LDL-C byinhibiting cholesterol absorption in the digestive tract,inhibiting LDL-C biosynthesis, suppressing hepaticsecretion of apolipoprotein B, and increasing hepaticexpression of LDL-C receptors.31 The pathwaysthrough which flavanols elevate plasma HDL-C con-centrations remain unclear, but a potential mechanisminvolves inhibition of vascular endothelial activation viaapolipoprotein A1.31 Lastly, flavanols increase theresistance of LDL-C to oxidation by either scavengingchain-initiating oxygen radicals or chelating transitionalmetal ions.31

Several prospective studies have demonstrated a ben-efit of flavanol-rich cocoa products on cholesterol. In



hypertensive patients, daily consumption of 100 g offlavanol-rich chocolate over 2 weeks led to a significant12% reduction of LDL-C and total cholesterol.20

Another study found that daily consumption of 75 g ofdark chocolate over 3 weeks increased HDL-C concen-tration up to 14% and inhibited lipid peroxidation inhealthy adults.32 A 2007 study of hypercholesterolemicpatients also demonstrated lipid improvements over12 weeks with consumption of 26 g of cocoa powderdaily. A 12.6% reduction in LDL-C, 23.4% elevation inHDL-C, and suppression of oxidized LDL-C (expressedas 9.4% prolongation in lag time) was observed with allendpoints except LDL-C reduction reaching signifi-cance.33

Conflicting results exist about the effect of cocoa onHDL-C concentrations. Studies that demonstrated anHDL-C increase with cocoa used theobromine-freeproducts as the comparator or control.34 In studieswhere the control contained theobromine, no HDL-Cbenefit was observed. A recent study showed that dailyconsumption of 850 mg of pure theobromine indepen-dently and significantly increased HDL-C concentra-tions by 6.12 mg/dL in healthy patients, an effect notseen with the cocoa treatment arm (150 mg theobro-mine).34 This finding suggests that theobromine incocoa, rather than flavanols, may contribute to or evenbe responsible for the HDL-C benefit.

OTHER CONSIDERATIONS FOR COCOAINTAKEAlthough the positive effects of chocolate and cocoaproducts seem apparent, precautions exist. An obviousconcern with the high intake of most commerciallyavailable products is the significant caloric (about500 kcal/100 g), saturated fat, and sugar content.Excess caloric intake can lead to adverse metaboliceffects, including weight gain and blood glucose eleva-tions, negating the positive effects of cocoa.35 This is aparticular concern with our current obesity epidemicand national recommendations for decreased fat andsugar intake among the general population. Althoughless palatable, cocoa-based products with little or nosugar or added fat are certainly preferred. In most trialspreviously cited, body weight and glucose concentra-tions over the study period were found to be unaffectedwith the doses provided. Again, studies were typicallyconducted over a short time, and long-term conse-quences are unknown.While chocolate has been reported to cause gastroin-

testinal complaints, migraine headaches, and jitteriness,these effects have not been demonstrated in clinicaltrials.1 Chocolate contains caffeine, possibly increasingthe risk of tachyarrhythmias and sleep disturbances.Caffeine intake may also lead to medication interac-tions. Increased central nervous system stimulanteffects, decreased sedative effects, decreased theophyl-line clearance, and increased risk of clozapine toxicityare among the potential interactions. Additionally,cocoa itself may potentiate the effects of anticoagu-

lants.36 Typical serving sizes of chocolate do not containenough caffeine to warrant concern; however, overallcaffeine intake from all sources must be considered.37

In clinical trials, the amount of dark chocolateingested ranged from 6.3 g to 105 g daily, containing30 mg to 1080 mg (mean 545.5 mg) of flavanols. Ingeneral, 6 g are equal to one small square of a 100 g (3.5ounce) dark chocolate bar, although exact concentra-tions are often difficult to identify.1 In addition to otherstudy limitations identified, cocoa preparations used asdietary supplements have the same concerns as otherproducts for which there is no quality oversight. Contentinconsistencies, lack of standardization, and variableformulations make product selection challenging andspecific dosing recommendations difficult to determine.From another perspective, dark chocolate may offer arelatively safe and inexpensive approach to supportCVD prevention in patients at risk. The estimatedincremental cost-effectiveness ratio was $50,000 peryears of life saved when only $42 per person per year wasspent on a prevention strategy utilizing dark chocolate.38

CONCLUSIONSFor centuries, cocoa has been recognized for its delec-table taste and proposed health benefits, perhaps as justwishful thinking for many. Research suggests that cocoadoes indeed exert beneficial cardiovascular effects,mediated largely through the flavanol components.3

The effects of cocoa are likely the result of modificationsof NO activity. Increased NO bioavailability mayexplain the improvement in endothelial function andthe potentially beneficial effects on BP, platelet function,insulin resistance, and lipids.3 Unfortunately, like otherdietary supplements, unresolved issues regarding dosingand the lack of clarity surrounding product componentsmake it difficult to recommend chocolate for healthbenefits. Further investigation is needed before cocoaproducts should be recommended as a treatment optionfor BP reduction or other CVD parameters.35 Insuffi-cient evidence exists to recommend cocoa as a supple-ment specifically for CVD risk reduction. A prudentapproach is consideration of the inclusion of healthydark chocolate in moderation as a part of overalllifestyle modifications for the prevention or treatment ofcardiovascular risk factors.35 While chocolate can be ahealthy supplement, potential benefits may be dimin-ished with the excess caloric intake caused by consum-ing most commercially available chocolates, making thisguilty pleasure a particular concern in our obesepopulation. However, addition of healthy darkchocolate to a well-balanced calorically appropriatediet offers a pleasurable and palatable option with littleburden for many people.

Disclosures: The authors have no conflicts of interest or financial disclosuresto declare.

References1. Ried K, Sullivan TR, Fakler P, et al. Effect of cocoa on blood pressure.

Cochrane Database Syst Rev. 2012;8:183.

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2. Grassi D, Desideri G, Ferri C. Blood pressure and cardiovascular risk:what about cocoa and chocolate? Arch Biochem Biophys.2010;501:112115.

3. Corti R, Flammer AJ, Hollenberg NK, Luscher TF. Cocoa andcardiovascular health. Circulation. 2009;119:14331441.

4. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of thejoint national committee on prevention, detection, evaluation, andtreatment of high blood pressure. Hypertension. 2003;42:12061252.

5. McCullough ML, Chevaux K, Jackson L, et al. Hypertension, theKuna, and the epidemiology of flavanols. J Cardiovasc Pharmacol.2006;47(Suppl 2):S103S109.

6. Hollenberg KN. Vascular action of cocoa flavanols in humans: theroots of the story. J Cardiovasc Pharmacol. 2006;47(Suppl 2):S99S102.

7. Egan BM, Laken MA, Donovan JL, Woolson RF. Does darkchocolate have a role in the prevention and management of hyper-tension?: commentary on the evidence. Hypertension. 2010;55:12891295.

8. Heiss C, Keen CL, Kelm M. Flavanols and cardiovascular diseaseprevention. Eur Heart J. 2010;31:25832592.

9. Beckett ST. The Science of Chocolate, 2nd ed. Cambridge, UK: TheRoyal Society of Chemistry; 2008: 240.

10. Buijsse B, Weikert C, Drogan D, et al. Chocolate consumption inrelation to blood pressure and risk of cardiovascular disease inGerman adults. Eur Heart J. 2010;31:16161623.

11. Mink PJ, Scrafford CG, Barraj LM, et al. Flavonoid intake andcardiovascular disease mortality: a prospective study in postmeno-pausal women. Am J Clin Nutr. 2007;85:895909.

12. Erdman JW Jr, Balentine D, Arab L, et al. Flavonoids and hearthealth: proceedings of the ILSI North America Flavonoids Workshop,May 31-June 1, 2005, Washington, DC. J Nutr. 2007;1:718S737S.

13. Taubert D, Roesen R, Lehmann C, et al. Effects of low habitual cocoaintake on blood pressure and bioactive nitric oxide: a randomizedcontrolled trial. JAMA. 2007;298:4960.

14. Heiss C, Kleinbongard P, Dejam A, et al. Acute consumption offlavanol-rich cocoa and the reversal of endothelial dysfunction insmokers. J Am Coll Cardiol. 2005;46:12761283.

15. Balzer J, Rassaf T, Heiss C, et al. Sustained benefits in vascularfunction through flavanol-containing cocoa in medicated diabeticpatients: a double-masked, randomized, controlled trial. J Am CollCardiol. 2008;51:21412149.

16. Hermann F, Spieker LE, Ruschitzka F, et al. Dark chocolate improvesendothelial and platelet function. Heart. 2006;92:119120.

17. Actis-Goretta L, Ottaviani JI, Fraga CG. Inhibition of angiotensinconverting enzyme activity by flavanol-rich foods. J Agric Food Chem.2006;54:229234.

18. Persson IA, Persson K, Hagg S, Andersson RG. Effects of cocoaextract and dark chocolate on angiotensin-converting enzyme andnitric oxide in human endothelial cells and healthy volunteers anutrigenomics perspective. J Cardiovasc Pharmacol. 2011;57:4450.

19. Taubert D, Berkels R, Roesen R, Klaus W. Chocolate and bloodpressure in elderly individuals with isolated systolic hypertension.JAMA. 2003;290:10291030.

20. Grassi D, Necozione S, Lippi C, et al. Cocoa reduces blood pressureand insulin resistance and improves endothelium-dependent vasodila-tion in hypertensives. Hypertension. 2005;46:398405.

21. Muniyappa R, Hall G, Kolodziej TL, et al. Cocoa consumption for2 wk enhances insulin-mediated vasodilatation without improvingblood pressure or insulin resistance in essential hypertension. Am JClin Nutr. 2008;88:16851696.

22. Engler MB, Engler MM, Chen CY, et al. Flavonoid-rich darkchocolate improves endothelial function and increases plasma epi-catechin concentrations in healthy adults. J Am Coll Nutr.2004;23:197204.

23. Vollmer WM, Sacks FM, Ard J, et al. Effects of diet and sodiumintake on blood pressure: subgroup analysis of the DASH-sodiumtrial. Ann Intern Med. 2001;135:10191028.

24. Rasmussen CB, Glisson JK, Minor DS. Dietary supplements andhypertension: potential benefits and precautions. J Clin Hypertens(Greenwich). 2012;14:467471.

25. Vita JA. Polyphenols and cardiovascular disease: effects on endothelialand platelet function. Am J Clin Nutr. 2005;1(Suppl):292S297S.

26. Flammer AJ, Sudano I, Wolfrum M, et al. Cardiovascular effects offlavanol-rich chocolate in patients with heart failure. Eur Heart J.2012;33:21722180.

27. Innes AJ, Kennedy G, McLaren M, et al. Dark chocolate inhibitsplatelet aggregation in healthy volunteers. Platelets. 2003;14:325327.

28. Ostertag LM, Kroon PA, Wood S, et al. Flavan-3-ol-enriched darkchocolate and white chocolate improve acute measures of plateletfunction in a gender-specific waya randomized-controlled humanintervention trial. Mol Nutr Food Res. 2013;57:191202.

29. Grassi D, Desideri G, Necozione S, et al. Blood pressure is reducedand insulin sensitivity increased in glucose-intolerant, hypertensivesubjects after 15 days of consuming high-polyphenol dark chocolate. JNutr. 2008;138:16711676.

30. Desideri G, Kwik-Uribe C, Grassi D, et al. Benefits in cognitivefunction, blood pressure, and insulin resistance through cocoa flavanolconsumption in elderly subjects with mild cognitive impairment: theCocoa, Cognition, and Aging (CoCoA) study. Hypertension.2012;60:794801.

31. Baba S, Natsume M, Yasuda A, et al. Plasma LDL and HDLcholesterol and oxidized LDL concentrations are altered in normo-and hypercholesterolemic humans after intake of different levels ofcocoa powder. J Nutr. 2007;137:14361441.

32. Mursu J, Voutilainen S, Nurmi T, et al. Dark chocolate consumptionincreases HDL cholesterol concentration and chocolate fatty acidsmay inhibit lipid peroxidation in healthy humans. Free Radic BiolMed. 2004;37:13511359.

33. Baba S, Osakabe N, Kato Y, et al. Continuous intake of polyphenoliccompounds containing cocoa powder reduces LDL oxidative suscep-tibility and has beneficial effects on plasma HDL-cholesterol concen-trations in humans. Am J Clin Nutr. 2007;85:709717.

34. Neufingerl N, Zebregs YE, Schuring EA, Trautwein EA. Effect ofcocoa and theobromine consumption on serum HDL-cholesterolconcentrations: a randomized controlled trial. Am J Clin Nutr.2013;97:12011209.

35. Desch S, Schmidt J, Kobler D, et al. Effect of cocoa products on bloodpressure: systematic review and meta-analysis. Am J Hypertens.2010;23:97103.

36. Pearson DA, Holt RR, Rein D, et al. Flavanols and platelet reactivity.Clin Dev Immunol. 2005;12:19.

37. Caffeine. DRUGDEX [Intranet Database]. Version 5.1. GreenwoodVillage, CO: Thomas Reuters (Healthcare) Inc; 2013.

38. Zomer E, Owen A, Magliano DJ, et al. The effectiveness and costeffectiveness of dark chocolate consumption as prevention therapy inpeople at high risk of cardiovascular disease: best case scenarioanalysis using a Markov model. BMJ. 2012;344:e3657.



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