A regular drink of cocoa may help to improve walking performance and muscle health in people with peripheral artery disease (PAD), according to the results of a small, randomized Phase II clinical trial carried out by scientists at Feinberg School of Medicine at Northwestern University, Chicago. The study, involving 44 PAD patients aged 60 years and over, found that those who drank a beverage containing flavanol-rich cocoa three times a day for six months were able to walk up to 42.6 meters further in a 6-minute walking test. In contrast, walking performance declined in participants who drank a beverage that contained no flavanols. Participants who drank the flavanol-rich cocoa also had improved blood flow to their calves and some improved muscle function, compared with the placebo group.

“If our results are confirmed in a larger trial, these findings suggest that cocoa, a relatively inexpensive, safe and accessible product, could potentially produce significant improvements in calf muscle health, blood flow, and walking performance for PAD patients,” commented Mary McDermott, MD, the Jeremiah Stamler professor of medicine and preventive medicine at the Feinberg School of Medicine. “While we expected the improvements in walking, we were particularly pleased to see that cocoa treatment was also associated with increased capillary density, limb perfusion, mitochondrial activity, and an additional measure of overall skeletal muscle health.”

Lead study author McDermott and colleagues report the trial results in Circulation: Journal of the American Heart Association. Their paper is titled, “Cocoa to Improve Walking Performance in Older People With Peripheral Artery Disease: The Cocoa-Pad Pilot Randomized Clinical Trial.”

Peripheral artery disease is caused by narrowing of the arteries, which reduces blood flow from the heart to the legs. The condition affects more than 8.5 million people aged 40 years and older in the U.S. The most common symptoms of PAD are pain, tightness, cramping, weakness or other discomfort in leg muscles, especially while walking. People with lower extremity PAD typically can’t walk as far in as those without PAD in a six-minute walking distance test. “Without an effective therapeutic intervention, people with PAD typically decline in walking performance over time,” the authors wrote. “Few therapies are available for improving walking performance in people with PAD,” noted McDermott.

Preclinical evidence and preliminary findings in people without PAD have indicated that the cocoa flavanol compounds, including epicatechin, which are present in dark chocolate, can increase limb perfusion, improve skeletal muscle, mitochondrial activity, and boost muscle generation, the investigators commented. Given that epicatechins and flavanols have the potential to improve blood flow, the team hypothesized that these compounds in cocoa might increase mitochondrial activity and muscle health in the calves of patients with lower extremity PAD, potentially improving their walking ability.

To investigate this further, the researchers carried out a double-blind, randomized clinical trial in which 23 PAD patients aged 60 years or more were randomized to drink a flavanol-rich cocoa drink three times a day for six months, and another 21 PAD patients were given a matching, similarly tasting placebo beverage that contained no cocoa or flavanol.

The cocoa used in the study is a commonly available, natural unsweetened cocoa powder that is rich in the flavanol epicatechin, which is found in larger quantities in dark chocolate (>85% cacao) than in milk chocolate. Regular chocolate would not be expected to have the same effect. For each drink the participants mixed into milk or water the contents of a powder packet containing either their flavanol-rich cocoa (15 grams of cocoa and 75 mgs of epicatechin daily) or their placebo powder packet without cocoa or epicatechin.

Walking performance was measured at the beginning of the study and at six months, using a six-minute walking test that was carried out twice, 2.5 hours after drinking the beverage, and again at 24 hours after drinking the beverage. Participants were also given a treadmill-walking test, and blood flow to their legs was measured using magnetic resonance imaging (MRI).

Study individuals who consented also had a calf muscle biopsy taken to evaluate muscle health. McDermott noted, “in addition to reduced blood flow to the legs, people with peripheral artery disease have been shown to have damaged mitochondria in their calf muscles, perhaps caused by the reduced blood flow. Mitochondria are known as the powerhouse of the cell, converting food to energy. Previous research has shown that better mitochondrial health and activity are associated with better walking performance and improving the health of damaged mitochondria could lead to walking improvements.” The authors further commented, “To our knowledge, no prior randomized trials have tested the effects of chronically administered cocoa on change in walking performance, calf muscle biopsy characteristics, or calf muscle perfusion in people with PAD.”

The study results confirmed that walking improved significantly in people who consumed cocoa. The cocoa drink group were able to walk an average of almost 43 meters further in the six-minute walking test compared with their baseline results during the test performed at 2.5 hours after the final study beverage.

There was also increased mitochondrial activity, increased capillary density, and other improvements to muscle health in participants who consumed the cocoa. “Cocoa significantly improved calf muscle perfusion and calf muscle COX enzyme activity, capillary density, and abundance of central nuclei, compared to placebo,” the investigators wrote. “The effects on calf muscle suggest a durable benefit from the cocoa beverage.” In contrast, patients who drank the placebo beverage had a decline of 24.2 meters in their walking distance at 2.5 hours after the final study beverage compared to their baseline

Close up of cocoa powder [Copyright American Heart Association]
results. This is consistent with other studies, in which six-minute walk distance declined in people with PAD who received no treatment.

Cocoa appeared to have no effect on treadmill walking performance, but McDermott pointed out that treadmill walking and the six-minute walking test are distinct measures of walking endurance and do not respond identically to the same therapy. The improvement in 6-minute distance walking better reflects the type of walking required in daily life, and therefore, these results are a more relevant outcome for patients with PAD.

The authors acknowledged that there were limitations to the study. These included the small sample size; an imbalance between the two study groups in the number of participants of each sex, race and in body mass index, and a lack of data for overall dietary consumption. Nevertheless, the investigators concluded, “Results reported here showing significant benefits of cocoa on calf muscle COX enzyme activity (an indicator of mitochondrial activity), capillary density, and central myofiber nuclei compared to placebo, suggest that cocoa may have a durable beneficial effect on calf muscle in people with PAD, in addition to an acute effect previously reported … Further study is needed to definitively determine whether cocoa significantly improves walking performance in people with PAD.”

“Patients with PAD have difficulty walking that is as bad as people with advanced heart failure. Leg muscles don’t get enough blood supply in PAD leading to injury and in this study, cocoa appeared to be protecting the muscle and improving metabolism,” said Naomi Hamburg, MD, FAHA, Chair of the American Heart Association’s Peripheral Vascular Disease Council, who is the author of an editorial on the study in the same issue of the journal. Hamburg writes that the reported pilot study 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.” She added, “We know that exercise therapy helps people with PAD walk farther, and this early study suggests that cocoa may turn out to be a new way to treat people with PAD. We will need larger studies to confirm whether cocoa is an effective treatment for PAD, but maybe, someday, if the research supports it, we may be able to write a prescription for chocolate for our patients with PAD.”

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