Nicotinamide riboside is uniquely and orally bioavailable in mice and humans

By Samuel A. J. Trammell, Mark S. Schmidt, Benjamin J Weidemann, P. Redpath, F. Jaksch, R. Dellinger, Zhonggang Li, E. Abel, Marie E. Migaud, Charles Brenner. Nature Communications, 2016

665 citations recorded by the source corpus.

Nicotinamide riboside (NR) is in wide use as an NAD+ precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD+ metabolism in humans. We report that human blood NAD+ can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD+ with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD+ metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD+, is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD+ repletion. NAD+ is an important coenzyme that mediates cellular metabolism and defends against stresses due to age and overnutrition. Here the authors demonstrate unique bioavailability of the NAD+ precursor vitamin nicotinamide riboside (NR) in mice and humans, and show that NR safely elevates human NAD+.

Subfields: Geriatrics and Gerontology, Oncology, Physiology

View Paper: https://www.semanticscholar.org/paper/cebe2f21a142cf0e45122a452e27e2bafc9080cf

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Citations in the corpus

Mitochondrial dysfunction in pathophysiology of heart failure (2018, background): “Prior studies also showed that NR was safe and well tolerated in normal individuals (159, 160).”
Therapeutic potential of NAD-boosting molecules: the in vivo evidence (2018, positive): “In rodents, NR is more efficient in boosting NAD+ than NA and NAM (Trammell et al., 2016a), possibly due to increased uptake (Imai, 2009; Imai and Guarente, 2014; Ratajczak et al., 2016; Revollo et al., 2007a).”
NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism (2018, background): “A recent study reported that oral NR supplementation is bioavailable for NAD biosynthesis in healthy volunteers and that NR exhibits unique and superior pharmacokinetics compared to NA and NAM in mice (128).”
NAD+ intermediates: The biology and therapeutic potential of NMN and NR (2017, positive): “NR also protects against diabetic and chemotherapy-induced neuropathy in mice (Hamity et al., 2017; Trammell et al., 2016b), raising hopes that it could have a role in the management of chronic pain.”