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An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers.

Abstract

OBJECTIVES

The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels.

BACKGROUND

Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR), improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials.

METHODS

In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed.

RESULTS

Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss) were observed for both NR (p = 0.03) and NAD+ (p = 0.001); the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008).

CONCLUSIONS

Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.

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  • Authors+Show Affiliations

    ,

    Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.

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    Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle, Washington, United States of America.

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    Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle, Washington, United States of America.

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    Department of Pharmacy, University of Washington School of Pharmacy, Seattle, Washington, United States of America.

    ,

    Northwest Metabolomics Research Center, Department of Anesthesiology & Pain Medicine; University of Washington, Seattle, Washington, United States of America. Mitochondria and Metabolism Center, Department of Anesthesiology & Pain Medicine; University of Washington, Seattle, Washington, United States of America.

    ,

    Northwest Metabolomics Research Center, Department of Anesthesiology & Pain Medicine; University of Washington, Seattle, Washington, United States of America. Mitochondria and Metabolism Center, Department of Anesthesiology & Pain Medicine; University of Washington, Seattle, Washington, United States of America.

    ,

    Mitochondria and Metabolism Center, Department of Anesthesiology & Pain Medicine; University of Washington, Seattle, Washington, United States of America.

    ,

    Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle, Washington, United States of America. Department of Pharmacy, University of Washington School of Pharmacy, Seattle, Washington, United States of America.

    Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.

    Source

    PloS one 12:12 2017 pg e0186459

    MeSH

    Administration, Oral
    Adult
    Dietary Supplements
    Female
    Healthy Volunteers
    Humans
    Infant, Newborn
    Male
    Middle Aged
    NAD
    Niacinamide
    Young Adult

    Pub Type(s)

    Clinical Trial
    Journal Article

    Language

    eng

    PubMed ID

    29211728