Cocoa to Improve Walking Performance in Older People With Peripheral Artery Disease: The Cocoa-Pad Pilot Randomized Clinical Trial

Rationale: Cocoa and its major flavanol component, epicatechin, have therapeutic properties that may improve limb perfusion and increase calf muscle mitochondrial activity in people with lower extremity peripheral artery disease (PAD).

Objective: In a phase II randomized clinical trial, to assess whether six months of cocoa improved walking performance in people with PAD, compared to placebo.

Methods and Results: Six-month double blind randomized clinical trial in which participants with PAD were randomized to either cocoa beverage vs. placebo beverage. The cocoa beverage contained 15 grams of cocoa and 75 mgs of epicatechin daily. The identical appearing placebo contained neither cocoa nor epicatechin. The two primary outcomes were six-month change in six-minute walk distance measured 2.5 hours after a study beverage at 6-month follow-up and 24 hours after a study beverage at 6-month follow-up, respectively. A one-sided P value <0.10 was considered statistically significant. Of 44 PAD participants randomized (mean age: 72.3 years (+7.1), mean ankle brachial index 0.66 (+0.15)), 40 (91%) completed follow-up. Adjusting for smoking, race, and body mass index, cocoa improved six-minute walk distance at 6-month follow-up by 42.6 meters (90% Confidence Interval (CI): +22.2,+∞, P=0.005) at 2.5 hours after a final study beverage and by 18.0 meters (90% CI:-1.7, +∞, P=0.12) at 24 hours after a study beverage, compared to placebo. In calf muscle biopsies, cocoa improved mitochondrial cytochrome c oxidase activity (P=0.013), increased capillary density (P=0.014), improved calf muscle perfusion (P=0.098), and reduced central nuclei (P=0.024), compared to placebo.

Conclusions: These preliminary results suggest a therapeutic effect of cocoa on walking performance in people with PAD. Further study is needed to definitively determine whether cocoa significantly improves walking performance in people with PAD. Clinical Trial Registration: NCT02876887.

Article published in https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.119.315600