Cocoa to Improve Walking Performance in Older People with Peripheral Artery Disease: The COCOA-PAD Pilot Randomized Clinical Trial

Mary M. McDermott, Michael H. Criqui, Kathryn Domanchuk, Luigi Ferrucci, Jack M. Guralnik, Melina R. Kibbe, Kate Kosmac, Christopher M. Kramer, Christiaan Leeuwenburgh, Lingyu Li, Donald Lloyd-Jones, Charlotte A. Peterson, Tamar S. Polonsky, James H. Stein, Robert Sufit, Linda Van Horn, Francisco Villarreal, Dongxue Zhang, Lihui Zhao, Lu Tian

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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 6 months of cocoa improved walking performance in people with PAD, compared with placebo. Methods and Results: Six-month double-blind, randomized clinical trial in which participants with PAD were randomized to either cocoa beverage versus placebo beverage. The cocoa beverage contained 15 g of cocoa and 75 mg of epicatechin daily. The identical appearing placebo contained neither cocoa nor epicatechin. The 2 primary outcomes were 6-month change in 6-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 1-sided P<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 6-minute walk distance at 6-month follow-up by 42.6 m ([90% CI, +22.2 to +∞] P=0.005) at 2.5 hours after a final study beverage and by 18.0 m ([90% CI,-1.7 to +∞] P=0.12) at 24 hours after a study beverage, compared with placebo. In calf muscle biopsies, cocoa improved mitochondrial COX (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=0.033), compared with 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: URL: Http:// Unique identifier: NCT02876887.

Original languageEnglish
Pages (from-to)589-599
Number of pages11
JournalCirculation Research
StateAccepted/In press - 2020

Bibliographical note

Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.


  • clinical trial
  • intermittent claudication
  • mitochondria
  • muscles
  • peripheral artery disease

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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