July 2017 Issue

Antioxidants: Cocoa — Tasty Dessert and Good Medicine?
By Carrie Dennett, MPH, RDN, CD
Today's Dietitian
Vol. 19, No. 7, P. 12

Could cocoa be a delicious way to help lower the risk of cardiovascular disease (CVD) and age-related cognitive decline? Research to date suggests yes, but it's too early to definitively "prescribe" chocolate for anything other than pleasure.

Cocoa's connection with health began hundreds of years ago, when the Mayan and Aztec people of Mexico and Central America used cocoa powder to treat a variety of diseases.1 More recently, interest in the health benefits of cocoa was piqued with the discovery that the Kuna Indians, an indigenous people living in Panama and Colombia, who consume large amounts of cocoa daily, don't experience an age-related increase in blood pressure and have lower rates of deaths from CVD compared with nonindigenous people of that region. It's thought that the protection is due to cocoa flavanols.2

What Is a Flavanol?
Flavanols (also known as flavan-3-ols) are a subfamily of the flavonoid family of polyphenols, one group of what we commonly call phytochemicals or phytonutrients. Flavanols are found in many fruits and vegetables but are especially rich in tea, wine, and cocoa.3 Cocoa contains high amounts of the flavanols epicatechin and catechin, as well as various procyanidins. It also contains small amounts of other polyphenols, such as quercetin.3

Because chronic inflammation has been implicated as a root cause of many chronic diseases, there's a research focus on the identification of bioactive compounds—such as cocoa flavanols—that may have anti-inflammatory benefits. As with other flavonoids, flavanols have antioxidant properties, and out of the 50 foods with the highest antioxidant capacity, five are cocoa based.3 Cocoa's biological properties likely go beyond its antioxidant capacity.4 In particular, the molecular structure of the type of flavanols in cocoa appears to protect against several biomarkers of CVD.5

Potential Health Benefits
Chronic inflammation is a necessary step in the development of atherosclerosis and CVD. It's also a factor in the development and progression of several types of cancer.3 Many risk factors for CVD have an inflammatory component, including elevated LDL cholesterol, smoking, elevated blood sugar, type 2 diabetes, hypertension, infections, and elevated C-reactive protein.3

Evidence that flavanols have anti-inflammatory effects exists, but it's sparse. Many, but not all, cell culture studies have demonstrated that cocoa compounds have a variety of anti-inflammatory effects in intestinal cells. Similarly, many animal studies have found that a high-cocoa diet reduces inflammation, but some haven't.3 Some of the best evidence to date supports a role for cocoa consumption in reducing or preventing inflammation of the blood vessels.4 In animal studies, cocoa products have been shown to improve cholesterol levels and inhibit atherosclerosis of the aorta.1 Dietary intervention studies using flavanols also suggest a potentially beneficial effect on blood vessel function—including blood pressure—but data from observational studies are inconclusive.6

A 2015 study found that daily intake of up to 2,000 mg of cocoa flavanols for six weeks in healthy adults, while safe, wasn't associated with significant changes in blood pressure compared with a control group that didn't receive the flavanols.7 Results of a 2010 meta-analysis were more promising, suggesting that intake of dark chocolate or other flavanol-rich cocoa products for two weeks or longer is better than placebo for lowering blood pressure in hypertensive subjects. However, chocolate or cocoa intake didn't lower average blood pressure below 140/80 mm Hg, nor did it reduce blood pressure significantly in normotensive subjects. The different effects seen between subjects with normal or high blood pressure are consistent with findings from other meta-analyses.8

There are also mixed results on overall cardiovascular health benefits. A 2014 systematic review and meta-analysis found that dietary intakes of the six classes of flavonoids, including flavanols, significantly decreased CVD risk.5 A 2012 review found that both acute and chronic chocolate or cocoa intake improved endothelial function and had promising effects on insulin levels and insulin resistance, but no effect on other CVD risk biomarkers.9

Regarding diabetes risk, the research generally suggests that polyphenol-rich cocoa products have healthful effects on fasting and postprandial blood sugar, and cocoa products that also contain cocoa fiber may be even more beneficial.3 Data from the Physician's Health Study suggest that self-reported chocolate intake is significantly associated with a reduced risk of developing type 2 diabetes in younger and normal-weight men, but this was based on a single question on a baseline food frequency questionnaire about average yearly intake of chocolate.10

While observational studies, such as the Physicians Health Study, have limitations when it comes to linking a specific food—or component of a food—to a specific health outcome, the randomized trials to date have been small and short. To clarify the potential health benefits of cocoa, the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) will investigate whether taking daily supplements of cocoa flavanols or a common multivitamin decreases the risk of developing heart disease, stroke, and cancer. This randomized, placebo-controlled, double-blinded trial currently is enrolling 18,000 women aged 65 or older and men aged 60 or older for four years of treatment and follow-up.11

"In the last decade, smaller, short-term randomized trials suggest that cocoa flavanols may be linked with improvements in blood pressure, lipids, and insulin sensitivity, among other mechanisms," says Howard Sesso, ScD, MPH, COSMOS study colead and an associate professor of medicine at Harvard Medical School and director of nutrition research in the division of preventive medicine at Brigham and Women's Hospital in Boston. "However, it remains unclear whether any short-term vascular improvements translate to long-term prevention of cardiovascular disease."

Bioavailability, Dosage, and Health Claims
Of course, any potential health benefits from cocoa flavanols are dependent on their bioavailability, or how well our bodies absorb, distribute, metabolize, and eliminate them. Some are absorbed in the small intestine and can later be detected in the blood, while others are less well absorbed and may have localized effects in the gastrointestinal tract. Still others are metabolized by the intestinal microbiota, producing metabolites that may be more bioavailable and easily absorbed in the colon. These metabolites may have biological properties of their own.3

Results from the European Prospective Investigation into Cancer, Norfolk study suggest that the level of habitual flavanol intake from all sources in Europe and the United States is unlikely to have a significant effect on CVD risk.6 The authors also mentioned that it's unclear what an adequate intake is to glean health benefits, and that it's also unclear whether it should be based on individual flavanols, such as epicatechin, or on a collective group of compounds like cocoa flavanols.6

The European Food Safety Authority approved two claims in 2013: that cocoa flavanols help maintain normal blood pressure and endothelium-dependent vasodilation, which contributes to normal blood flow.3 The amount needed to achieve this effect is 200 mg of cocoa flavanols daily, about the amount in 2.5 g of high-flavanol cocoa powder or 10 g of high-flavanol dark chocolate.3 However, the authors of a 2016 study said that 100 mg of the flavanol epicatechin is needed to achieve these benefits, and that 200 mg of cocoa flavanols includes only 46 mg of epicatechin. They added that 900 mg of flavanols, containing about 256 mg of epicatechin, may be needed to decrease blood pressure in certain individuals.12

Unfortunately for consumers, packaging on commercially sold chocolate doesn't provide a reliable estimate of flavanol content. Researchers who analyzed the flavanol content of 41 commercial chocolate brands found that the samples highest in cocoa content weren't highest in flavanols.13 For that reason, Sesso says the COSMOS trial will be testing a specific quantity of cocoa flavanols (600 mg) in a cocoa extract supplement, a quantity based upon the results of previous clinical trials.

"While cocoa is a key ingredient in milk or dark chocolate, product labels do not provide information on its cocoa flavanol content—and it is not necessarily related to the 'percent cacao' on the packaging," Sesso says. "Processing the cocoa bean affects its flavanol content, and with chocolate comes fat and calories. For COSMOS, we chose to focus our investigation on the bioactive components of the cocoa bean as the mechanism through which there may be reductions in cardiovascular events."

Pending more definitive research findings on the health effects of cocoa flavanols, dietitians can best counsel clients and patients to enjoy chocolate in moderation as part of a balanced diet containing a variety of plant foods that are rich in flavanols or other phytonutrients. It also may be helpful to gently caution patients about the "health halo" effect that may lead them to consume amounts larger than they would normally.

— Carrie Dennett, MPH, RDN, CD, is the nutrition columnist for The Seattle Times and speaks frequently on nutrition-related topics. She also provides nutrition counseling via the Menu for Change program in Seattle.


References

1. Guan H, Lin Y, Bai L, et al. Dietary cocoa powder improves hyperlipidemia and reduces atherosclerosis in apoE deficient mice through the inhibition of hepatic endoplasmic reticulum stress. Mediators Inflamm. 2016;2016:1937572.

2. Jumar A, Schmieder RE. Cocoa flavanol cardiovascular effects beyond blood pressure reduction. J Clin Hypertens (Greenwich). 2016;18(4):352-358.

3. Goya L, Martín MÁ, Sarriá B, Ramos S, Mateos R, Bravo L. Effect of cocoa and its flavonoids on biomarkers of inflammation: studies of cell culture, animals and humans. Nutrients. 2016;8(4):212.

4. Pérez-Cano FJ, Castell M. Flavonoids, inflammation and immune system. Nutrients. 2016;8(10):659.

5. Wang X, Ouyang YY, Liu J, Zhao G. Flavonoid intake and risk of CVD: a systematic review and meta-analysis of prospective cohort studies. Br J Nutr. 2014;111(1):1-11.

6. Vogiatzoglou A, Mulligan AA, Bhaniani A, et al. Associations between flavan-3-ol intake and CVD risk in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk). Free Radic Biol Med. 2015;84:1-10.

7. Ottaviani JI, Balz M, Kimball J, et al. Safety and efficacy of cocoa flavanol intake in healthy adults: a randomized, controlled, double-masked trial. Am J Clin Nutr. 2015;102(6):1425-1435.

8. Ried K, Sullivan T, Fakler P, Frank OR, Stocks NP. Does chocolate reduce blood pressure? A meta-analysis. BMC Med. 2010;8:39.

9. Hooper L, Kay C, Abdelhamid A, et al. Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr. 2012;95(3):740-751.

10. Matsumoto C, Petrone AB, Sesso HD, Gaziano JM, Djoussé L. Chocolate consumption and risk of diabetes mellitus in the Physicians' Health Study. Am J Clin Nutr. 2015;101(2):362-367.

11. COcoa Supplement and Multivitamin Outcomes Study. COSMOS Trial website. http://www.cosmostrial.org/

12. Vlachojannis J, Erne P, Zimmermann B, Chrubasik-Hausmann S. The impact of cocoa flavanols on cardiovascular health. Phytother Res. 2016;30(10):1641-1657.

13. Alañón ME, Castle SM, Siswanto PJ, Cifuentes-Gómez T, Spencer JP. Assessment of flavanol stereoisomers and caffeine and theobromine content in commercial chocolates. Food Chem. 2016;208:177-184.