Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial

Mary M. McDermott (), Christopher R. Martens, Kathryn J. Domanchuk, Dongxue Zhang, Clara B. Peek, Michael H. Criqui, Luigi Ferrucci, Philip Greenland, Jack M. Guralnik, Karen J. Ho, Melina R. Kibbe, Kate Kosmac, Donald Lloyd-Jones, Charlotte A. Peterson, Robert Sufit, Lu Tian, Stephanie Wohlgemuth, Lihui Zhao, Pei Zhu and Christiaan Leeuwenburgh
Additional contact information
Mary M. McDermott: Department of Medicine
Christopher R. Martens: Department of Kinesiology & Applied Physiology
Kathryn J. Domanchuk: Department of Medicine
Dongxue Zhang: Department of Medicine
Clara B. Peek: Department of Medicine
Michael H. Criqui: Division of Preventive Medicine
Luigi Ferrucci: Division of Intramural Research
Philip Greenland: Department of Medicine
Jack M. Guralnik: Department of Epidemiology and Public Health
Karen J. Ho: Department of Surgery
Melina R. Kibbe: Department of Surgery
Kate Kosmac: Department of Physical Therapy
Donald Lloyd-Jones: Department of Medicine
Charlotte A. Peterson: Center for Muscle Biology
Robert Sufit: Department of Neurology
Lu Tian: Department of Health Research and Policy
Stephanie Wohlgemuth: Department of Physiology and Aging
Lihui Zhao: Department of Preventive Medicine
Pei Zhu: Department of Medicine
Christiaan Leeuwenburgh: Department of Physiology and Aging

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. −10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed. Clinical Trials.gov registration: NCT03743636.

Date: 2024
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DOI: 10.1038/s41467-024-49092-5

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