Mary M McDermott1,2, Michael H Criqui3, Kathryn Domanchuk1, Luigi Ferrucci4, Jack M Guralnik5, Melina R Kibbe6, Kate Kosmac7, Christopher M Kramer8, Christiaan Leeuwenburgh9, Lingyu Li1, Donald Lloyd-Jones1,2, Charlotte A Peterson7, Tamar S Polonsky10, James H Stein11, Robert Sufit12, Linda Van Horn2, Francisco Villarreal13,14, Dongxue Zhang1, Lihui Zhao2, Lu Tian15. 1. From the Departments of Medicine (M.M.M., K.D., L.L., D.L.-J., D.Z.), Northwestern University Feinberg School of Medicine, Chicago, IL. 2. Preventive Medicine (M.M.M., D.L.-J., L.V.H., L.Z.), Northwestern University Feinberg School of Medicine, Chicago, IL. 3. Department of Family Medicine, University of California at San Diego (M.H.C.). 4. Division of Intramural Research, National Institute on Aging, Baltimore, MD (L.F.). 5. Department of Epidemiology, University of Maryland, Baltimore (J.M.G.). 6. Department of Surgery, University of North Carolina School of Medicine, Chapel Hill (M.R.K.). 7. Department of Rehabilitation Sciences, University of Kentucky College of Health Sciences, Lexington (K.K., C.A.P.). 8. Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville (C.M.K.). 9. Department of Aging and Geriatric Research, University of Florida, Gainesville (C.L.). 10. Department of Medicine, University of Chicago, IL (T.S.P.). 11. Department of Medicine, University of Wisconsin, Madison (J.H.S.). 12. Neurology (R.S.), Northwestern University Feinberg School of Medicine, Chicago, IL. 13. Divisions of Cardiology (F.V.), University of San Diego, CA. 14. Endocrinology (F.V.), University of San Diego, CA. 15. Department of Health Research and Policy, Stanford University, CA (L.T.).
Abstract
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://www.clinicaltrials.gov. Unique identifier: NCT02876887. Visual Overview: An online visual overview is available for this article.
RCT Entities:
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 PADparticipants 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://www.clinicaltrials.gov. Unique identifier: NCT02876887. Visual Overview: An online visual overview is available for this article.
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