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Recent Studies Examine Cardiovascular Effects of Chocolate

Recent Studies Examine Cardiovascular Effects of Chocolate

Reviewed: Ding E, Hutfless S, Ding X, Girotra S. Chocolate and prevention of cardiovascular disease: a systematic review. Nutr & Metabol. 2006;3(2):1-12.

Reviewed: Faroque HMO, Leung M, Hope S, et al. Acute and chronic effects of flavonol-rich cocoa on vascular function in subjects with coronary artery disease: a randomized double-blind placebo-controlled study. Clin Sci. 2006;111:71-80.

Reviewed: Hermann F, Spieker IE, Ruschitzka F, et al. Dark chocolate improves endothelials and platelet function. Heart. 2006;92:119-120.

Several research articles have been published recently in scientific and medical journals concerning the benefits of products based on cocoa (Theobroma cacao, Sterculiaceae), including chocolate, for cardiovascular health. Chocolate, especially preparations made from the darker variety (i.e., chocolate without milk and a relatively high level of cocoa “liquor”), contains high levels of flavonoids, which have antioxidant and immunoregulatory properties. Dietary sources of flavonoids have attracted much medical interest in recent years due to flavonoids’ potential in protecting against cardiovascular disease (CVD). For instance, a 2007 meta-analysis recently assessed the effects of cocoa and tea intake on blood pressure, due to the high flavonoid contents of both dietary products. This analysis, which included 5 randomized, controlled trials concerning cocoa intake, found that diets rich in cocoa were associated with statistically significant reductions in systolic and diastolic blood pressure.1 Another 2007 study, in which 25 Japanese male participants consumed a daily placebo or cocoa-based drink for 12 weeks, found that daily intake of cocoa powder decreased the participants’ susceptibility of LDL (“bad” cholesterol) oxidation and increased HDL (“good”) cholesterol concentrations, which could lead to decreased incidences of arteriosclerotic disease.2

This present summary analyzes a systematic review and 2 clinical trials published in 2006, which address the effects of cocoa consumption directly in relation to CVD or assess particular potential cardiovascular benefits of chocolate.

Systematic Review by Ding et al

The authors of a recent article in Nutrition & Metabolism conducted a literature search of the MEDLINE database (National Library of Medicine, Bethesda, MD) for clinical, observational, and experimental studies regarding the relation between consumption of cocoa-based products (including chocolate) and CVD, published from January 1965 to June 2005. Approximately 400 articles were found, and 136 were selected for review. Randomized trials, with either a cross-sectional or parallel design, and prospective observational studies were the focus. The strength of the evidence of cocoa and chocolate beneficial effects was based on the study design and quality of individual studies, the consistency of findings across studies, and the biologic plausibility of the mechanisms involved. Relative risks were estimated and pooled according to a random-effects model.

Overall, evidence from the short-term randomized trials and from the epidemiologic studies of chocolate consumption suggested that “flavonoid intake from chocolate is likely protective against CVD, particularly CHD [coronary heart disease] mortality.” Evidence from laboratory experiments and randomized human clinical trials suggested that stearic acid (a saturated fat found in chocolate and other foods) has beneficial or neutral effects on clotting factors and blood pressure; thus, it is unlikely that stearic acid would adversely affect CVD risk. However, evidence from observational studies of the relation between stearic acid and CVD risk is inconclusive. A meta-analysis of 7 prospective clinical studies found that intake of chocolate flavonoids may lower the risk of mortality from CHD. Eight cohort studies consistently found that the risk of CHD mortality was lower with total or specific flavonoid intake. However, a large cohort study (n = 38,455 women) found a nonsignificant association between CHD mortality and flavonoid intake.

On the basis of this systematic review, the authors suggested that “stearic acid may be neutral, while flavonoids are likely protective against CVD.” Because dark chocolate contains substantially higher amounts of flavonoids than does milk chocolate, the authors recommend consumption of high flavonoid dark chocolate over other varieties and suggest that long-term randomized feeding trials be conducted to definitively determine the effect of chocolate consumption on cardiovascular disease risk. Additional research analyzing total antioxidant content of cocoa-based products indicates that cocoa powders are also excellent flavonoid sources.3

Clinical Trial by Faroque et al

A randomized, double-blind, placebo-controlled study of 40 patients with coronary artery disease was recently published in Clinical Science, which directly tested the cardiovascular benefits of chocolate. In this trial, subjects were randomly assigned to receive either a flavanol-rich chocolate bar and cocoa beverage (Mars, Inc. Hackettstown, NJ) daily (444 mg of flavanols and about 107 mg of epicatechin monomer daily) or a matching placebo (19.6 mg of flavanols and about 4.7 mg of epicatechin monomer daily) for 6 weeks. Flow-mediated dilation (FMD, a measurement used to determine heart disease risk) of the brachial artery and systemic arterial compliance (SAC) were measured at baseline, 90 minutes after consumption of the first beverage, and at weeks 3 and 6. The responses of soluble cellular adhesion molecules and of forearm blood flow (FBF) to infusions of 3–30 mcg of acetylcholine chloride (ACh) per minute and of 0.3–3 mcg of sodium nitroprusside (SNP) per minute, forearm ischemia, and isotonic forearm exercise were evaluated at baseline and at 6 weeks. Biomarkers of endothelial function [soluble intercellular cell adhesion molecule1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin] were also evaluated at baseline and at 6 weeks. Statistical differences with a P value greater than 0.05 were considered significant.

No significant differences in FMD, SAC, or FBF were observed between groups at baseline. Neither FMD nor SAC changed significantly, acutely or chronically, in either group. No significant differences in the cell adhesion molecules or in FBF responses to ischemia, exercise, SNP, or ACh were observed in the flavanol group between baseline and 6 weeks. ICAM-1 and E-selectin did not differ significantly between the 2 treatment groups at baseline or at 6 weeks. VCAM-1 concentrations were significantly lower in the placebo group than in the flavanol group at baseline, but did not change significantly after treatment with flavanols for 6 weeks. Several well-established measures of vascular endothelial function were investigated in response to flavanol consumption for 6 weeks. The results indicated that the treatment was safe but that the consumption of flavanol-rich cocoa did not improve endothelial vascular function or SAC in patients with coronary artery disease. The authors noted that their results contrast with those of an earlier similar study, which tested younger study participants with fewer cardiovascular risk factors.4 They suggested the possibility that the number of cardiovascular disease risk factors and severity of disease were too great for flavanol to exert a positive effect over the time frame in their study. The authors recommended that “short- and long-term studies of younger subjects with single identifiable untreated cardiovascular [disease] risk factors should be the subject of future investigation.”

No significant effect was noted on either systolic or diastolic blood pressure, mean arterial pressure, or heart rate. It is possible that the use of concomitant vasoactive medication for treatment of hypertension and ischemic heart disease in the study population may have offset any potential antihypertensive effect of flavanol-rich cocoa. Finally, these researchers point out that “the lack of improvement on tests of vascular function with flavanol-rich cocoa does not signify a neutral impact on clinical vascular end points. Large and longer-term studies will be required to address such clinical questions.”

Clinical Trial by Hermann et al

A second clinical trial, published in Heart, examined the effects of dark chocolate on endothelial cell dysfunction and platelet activation in male smokers. The first part of the Swiss study (conducted at the Cardiovascular Center, University Hospital in Zurich) enrolled 25 male smokers who were not taking any medication or dietary supplements. All subjects refrained from eating polyphenol-rich foods for 24 hours before the study. Endothelial cell function was measured by ultrasound before and after the subjects ate 40 g of dark chocolate containing 70% cocoa (Nestle Noir Intense, Nestle SA, Vevey, Switzerland). The subjects’ endothelial cell function improved 2-8 hours after eating the dark chocolate.

The second part of the study enrolled 20 male smokers, divided into 2 parallel groups—the first group ate 40 g of dark chocolate and the second group ate 40 g of white chocolate (Nestle Galak, Nestle SA, Vevey, Switzerland), which contains only 4% cocoa and much lower levels of flavonoids and polyphenols. Dark chocolate significantly improved FMD (P=0.026 vs. baseline). The effect started 2 hours after ingestion and lasted about 8 hours. White chocolate did not have a significant effect on FMD. Shear stress dependent platelet function, a.k.a. blood platelet adhesion at the site of plaque, was significantly reduced by dark chocolate after 2 hours, compared to the baseline (P=0.03), but was not affected by white chocolate. Vascular flow response and glyceryl trinitrateinduced vasodilation were not affected by white or dark chocolate. Total antioxidant status significantly increased 2 hours after subjects ate dark chocolate compared to the baseline (P=0.03), but remained unchanged for the white chocolate group.

This study shows that eating commercially available dark chocolate significantly improves endothelial and platelet dysfunction in male smokers, possibly due to the presence of high levels of antioxidants. In addition, the results indicate that dark chocolate may have a direct effect on the vascular endothelium. The authors note that further study is needed to elucidate the mechanism of action and to confirm these initial results. Interestingly, a trial published in 2007 has already helped to corroborate these results. In that trial, 11 male subjects with smoking-related endothelial dysfunction consumed a high-flavanol cocoa beverage daily for one week, and the results showed that this treatment led to a sustained reversal of endothelial dysfunction.5 Future studies that include women and non-smokers are also needed. The authors of this trial conclude “…a small daily treat of dark chocolate may substantially increase the amount of antioxidant intake and beneficially affect vascular health.”

—Brenda Milot, ELS; Marissa Oppel, MS; and Courtney Cavaliere
  1. Taubert D, Roesen R, Schomig E. Effect of cocoa and tea intake on blood pressure. Arch Intern Med. 2007;167:626-634.

  2. Baba S, Osakabe N, Kato Y, et al. Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. Am J Clin Nutr. 2007;85:709-717.

  3. Gu L, House S, Wu X, Ou B, Prior R. Procyanidin and catechin content and antioxidant capacity of cocoa and chocolate products. JAFC 2006; 54:4057-4061. Abstract available at: cgi-bin/abstract.cgi/jafcau/2006/54/i11/abs/jf060360r.html.

  4. Heiss C, Dejam A, Kleinbongard P, Schewe T, Sies H, Kelm M. Vascular effects of cocoa rich in flavan-3-ols. JAMA. 2003;290:1030-1031.

  5. Heiss C, Finis D, Kleinbongard P, et al. Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week. J Cardiovasc Pharmacol. 2007;49:74-80.