Cocoa a Novel Rx for Peripheral Artery Disease?

Batya Swift Yasgur, MA, LSW

February 26, 2020

Cocoa, which is rich in flavanols, may improve walking performance in patients with peripheral artery disease (PAD), a pilot trial suggests.

Investigators randomly assigned 44 patients age 60 or above to receive a cocoa beverage or a placebo beverage. They found that, at the end of the study period, participants who drank the cocoa three times daily had significantly greater improvements in 6-minute walk distance compared with the group on placebo.

Moreover, those who drank the cocoa beverage showed improvement in perfusion to the legs and improvement in calf skeletal muscle characteristics, including improved function of the mitochondria, compared with their counterparts who drank the placebo beverage.

"Few therapies are available for improving walking performance in people with PAD," lead author Mary McGrae McDermott, MD, professor of medicine at Northwestern University Feinberg School of Medicine in Chicago, Illinois, said in a release.

"Our study showed both improved health in blood flow to the legs, improvements in 6-minute walk distance, and also improved calf skeletal muscle health in people who drank cocoa, compared to those who drank placebo," she told | Medscape Cardiology.

The study was published online February 14 in Circulation Research.

Therapeutic Properties

Cocoa flavanols, including epicatechin, that are present in dark chocolate "have therapeutic properties that may improve walking performance in people with PAD," the authors write. In particular, cocoa may increase limb perfusion and improve skeletal muscle mitochondrial activity and muscle regeneration.

In animal studies and some preliminary studies of human beings, cocoa flavanols were shown to improve blood flow and muscle health, McDermott said.

"Since people with PAD have difficulty walking due to blood flow problems, we thought this particular therapy may be particularly beneficial for people with PAD," she added.

To investigate the question, the researchers randomly assigned 44 patients with PAD (mean age: 72.3 years [± 7.1], mean ankle brachial index 0.66 [± 0.15]) to drink milk or water mixed with the contents of a powder packet containing either flavanol-rich cocoa (15 g of cocoa and 75 mg of epicatechin; n = 23) or placebo (n = 21) three times daily for a 6-month period.

The researchers measured walking performance using the 6-minute walking test at the beginning of the study and at 6 months, at which point the test was administered twice: 2.5 hours after drinking the beverage, and then 24 hours later, with improvement on the both tests considered to be the primary outcomes.

Additionally, patients underwent a treadmill walking test, MRI to measure blood flow to the legs, and a calf muscle biopsy to assess muscular health.

Calorie Concerns

At 6-month follow-up, after adjusting for confounding variables including smoking, race, and body mass index (BMI), the researchers found that, compared with placebo, the cocoa improved 6-minute walk distance by 42.6 meters (90% confidence interval [CI]: +22.2, +∞, P = .005) at 2.5 hours after the final study beverage and by 18 meters (90% CI: 1.7, +∞, P = .12) at 24 hours after the study beverage.

Drinking the cocoa beverage was associated with other improvements compared with the placebo.

  • Improved mitochondrial cytochrome c oxidase activity in calf muscles, as demonstrated by biopsy (P = .013)

  • Improved calf muscle perfusion, as demonstrated by cardiovascular MRI (P = .098)

  • Increased capillary density (P = .014)

  • Reduced central nuclei (P = .024)

There were no statistically significant differences in treadmill walking time or brachial artery flow-mediated dilation between consumers of cocoa vs those who drank placebo.

"Cocoa flavanols are readily available and accessible and safe, so it would be reasonable to recommend cocoa flavanols for people with PAD," McDermott commented.

However, she added several caveats.

The cocoa used in the study was dark cocoa powder, containing >85% cacao, rather than milk chocolate or chocolate with lower cacao content.

"A lot of chocolate that is available over the counter is alkalized, which improves taste and palatability but removes the beneficial cocoa flavanols that have therapeutic effects; moreover, lots of cocoa comes with calories, sugar, and fat, so weight gain is a potential concern from consuming chocolate," she said.

Prescribe More Chocolate?

Commenting on the study for | Medscape Cardiology, Eduardo Ramacciotti, MD, PhD, head of vascular surgery at Hospital e Maternidade Dr Christovao da Gama in São Paulo, Brazil, called it "an interesting paper."

Ramacciotti, who was not involved with the study, said that "despite the fact that it is a small phase 2 study, it shows improvements in walking distance for patients with PAD that took cocoa vs placebo."

He noted that only "a few medications" are available to treat PAD and that "we expect to have zero side effects with cocoa, which is good."

Most patients with this condition "usually are taking medications for different conditions and cocoa is unlikely to interact with them," he suggested.

"Larger trials are warranted to confirm the benefit of cocoa to improve walking distance in intermittent claudication patients with PAD," Ramacciotti said.

Also commenting on the study for | Medscape Cardiology, William R. Hiatt, MD, professor of medicine, division of cardiology, University of Colorado School of Medicine in Aurora, said that, "while potentially interesting, I think it is too early to determine if cocoa is clinically effective to treat claudication."

Hiatt, who was not involved with the study, agreed that "independent confirmation of the results from this trial" is necessary.

In an accompanying editorial, Reiko Matsui, MD, and Naomi Hamburg, MD, both of the Whitaker Cardiovascular Institute, Boston University School of Medicine, Massachusetts, write that "taken together, the pilot study by McDermott and colleagues provides compelling preliminary evidence to support a potential benefit of epicatechin-rich cocoa on walking ability along with protection from worsening of calf muscle perfusion, skeletal muscle injury, and mitochondrial dysfunction."

They add that, although more research is necessary to confirm the findings, "someday we may be able to prescribe eating more chocolate to our patients with PAD."

The study was funded by the National Institute on Aging and the intramural office of the National Institute on Aging. It was also funded in part by the NIH's Office of Dietary Supplements. The cocoa beverage and matching placebo were provided by the Hershey Company. McDermott has received other research support from Helixmith, Reserveage, Chromadex, and ArtAssist that are unrelated to the current study. The other authors' disclosures are listed on the original article.

Hamburg has consulting relations with Merck, Bayer, and Sanifit and has equity interest in Acceleron Pharma. Hamburg and Matsui are supported by the National Institutes of Health. Hiatt and Ramacciotti have disclosed no relevant financial relationships.

Circ Res. Published online February 14, 2020. Abstract, Editorial

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