Nicotinamide riboside is uniquely and orally bioavailable in mice and humans

被引：506

作者：

Trammell, Samuel A. J. ^{[1
]}

Schmidt, Mark S. ^{[1
]}

Weidemann, Benjamin J. ^{[1
]}

Redpath, Philip ^{[2
]}

Jaksch, Frank ^{[3
]}

Dellinger, Ryan W. ^{[3
]}

Li, Zhonggang ^{[4
]}

Abel, E. Dale ^{[1
,4
]}

Migaud, Marie E. ^{[1
,2
]}

Brenner, Charles ^{[1
,4
]}

机构：

[1] Univ Iowa, Dept Biochem, Carver Coll Med, Iowa City, IA 52242 USA

[2] Queens Univ Belfast, Sch Pharm, John King Lab, Belfast BT7 1NN, Antrim, North Ireland

[3] ChromaDex Inc, 10005 Muirlands Blvd,Suite G, Irvine, CA 92618 USA

[4] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

美国国家卫生研究院; 英国生物技术与生命科学研究理事会;

关键词：

DIPHOSPHOPYRIDINE NUCLEOTIDE; NAD(+) SYNTHETASE; LIFE-SPAN; METABOLISM; ACID; MITOCHONDRIAL; BIOSYNTHESIS; NIACIN; FAT; MONONUCLEOTIDE;

D O I：

10.1038/ncomms12948

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

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