title: Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.
abstract: 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.
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Samuel A J
authors.initials: SA
authors.lastname: Trammell
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Schmidt
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Weidemann
authors.affiliation: John King Laboratory, School of Pharmacy, Queens University Belfast, Belfast BT7 1NN, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Redpath
authors.affiliation: ChromaDex, Inc., 10005 Muirlands Blvd, Suite G, Irvine, California 92618, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Jaksch
authors.affiliation: ChromaDex, Inc., 10005 Muirlands Blvd, Suite G, Irvine, California 92618, USA.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Dellinger
authors.affiliation: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Zhonggang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.|Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: E Dale
authors.initials: ED
authors.lastname: Abel
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.|John King Laboratory, School of Pharmacy, Queens University Belfast, Belfast BT7 1NN, UK.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Migaud
authors.affiliation: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.|Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Charles
authors.identifier: 0000-0002-4955-3226
authors.initials: C
authors.lastname: Brenner
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D055442:Metabolome; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009243:NAD / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D011726:Pyridinium Compounds; D014815:Vitamins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011726:Pyridinium Compounds; D014815:Vitamins; C018613:nicotinamide-beta-riboside; D009243:NAD; D009536:Niacinamide; C018348:nicotinic acid adenine dinucleotide