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; Christiaan Leeuwenburgh

doi:10.1038/s41467-024-49092-5

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, Christiaan Leeuwenburgh

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Article number	5046
Journal	Nature communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-49092-5
State	Published - Dec 2024

Funding

Dr. McDermott reports research funding from Helixmith and other research support from ArtAssist, and Mars. The remaining authors report no competing interests. Funded by the American Heart Association, Grant Numbers 18SFRN33900097, 18SFRN33900136, and 18SFRN33970010. Nicotinamide riboside was provided by ChromaDex. Resveratrol was provided by ReserveAge

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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McDermott, M. M., Martens, C. R., Domanchuk, K. J., Zhang, D., Peek, C. B., Criqui, M. H., Ferrucci, L., Greenland, P., Guralnik, J. M., Ho, K. J., Kibbe, M. R., Kosmac, K., Lloyd-Jones, D., Peterson, C. A., Sufit, R., Tian, L., Wohlgemuth, S., Zhao, L., Zhu, P., & Leeuwenburgh, C. (2024). Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial. Nature communications, 15(1), Article 5046. https://doi.org/10.1038/s41467-024-49092-5

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title = "Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial",

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.",

author = "McDermott, {Mary M.} and Martens, {Christopher R.} and Domanchuk, {Kathryn J.} and Dongxue Zhang and Peek, {Clara B.} and Criqui, {Michael H.} and Luigi Ferrucci and Philip Greenland and Guralnik, {Jack M.} and Ho, {Karen J.} and Kibbe, {Melina R.} and Kate Kosmac and Donald Lloyd-Jones and Peterson, {Charlotte A.} and Robert Sufit and Lu Tian and Stephanie Wohlgemuth and Lihui Zhao and Pei Zhu and Christiaan Leeuwenburgh",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41467-024-49092-5",

language = "English (US)",

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McDermott, MM, Martens, CR, Domanchuk, KJ, Zhang, D, Peek, CB, Criqui, MH, Ferrucci, L, Greenland, P, Guralnik, JM, Ho, KJ, Kibbe, MR, Kosmac, K, Lloyd-Jones, D, Peterson, CA, Sufit, R, Tian, L, Wohlgemuth, S, Zhao, L , Zhu, P & Leeuwenburgh, C 2024, 'Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial', Nature communications, vol. 15, no. 1, 5046. https://doi.org/10.1038/s41467-024-49092-5

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T1 - Nicotinamide riboside for peripheral artery disease

T2 - the NICE randomized clinical trial

AU - McDermott, Mary M.

AU - Martens, Christopher R.

AU - Domanchuk, Kathryn J.

AU - Zhang, Dongxue

AU - Peek, Clara B.

AU - Criqui, Michael H.

AU - Ferrucci, Luigi

AU - Greenland, Philip

AU - Guralnik, Jack M.

AU - Ho, Karen J.

AU - Kibbe, Melina R.

AU - Kosmac, Kate

AU - Lloyd-Jones, Donald

AU - Peterson, Charlotte A.

AU - Sufit, Robert

AU - Tian, Lu

AU - Wohlgemuth, Stephanie

AU - Zhao, Lihui

AU - Zhu, Pei

AU - Leeuwenburgh, Christiaan

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

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

Abstract

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