Nicotinamide riboside is uniquely and orally bioavailable in mice and humans

被引：481

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

共 57 条

[1] Altman LawrenceK., 1987, WHO GOES 1 STORY SEL
[2] INFLUENCE OF NICOTINIC ACID ON SERUM CHOLESTEROL IN MAN
ALTSCHUL, R
HOFFER, A
STEPHEN, JD
[J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1955, 54 (02) : 558 - 559
[3] NAD+ metabolism in health and disease
Belenky, Peter
Bogan, Katrina L.
Brenner, Charles
[J]. TRENDS IN BIOCHEMICAL SCIENCES, 2007, 32 (01) : 12 - 19
[4] Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+
Belenky, Peter
Racette, Frances G.
Bogan, Katrina L.
McClure, Julie M.
Smith, Jeffrey S.
Brenner, Charles
[J]. CELL, 2007, 129 (03) : 473 - 484
[5] Nicotinamide Riboside and Nicotinic Acid Riboside Salvage in Fungi and Mammals QUANTITATIVE BASIS FOR Urh1 AND PURINE NUCLEOSIDE PHOSPHORYLASE FUNCTION IN NAD+ METABOLISM
Belenky, Peter
Christensen, Kathryn C.
Gazzaniga, Francesca
Pletnev, Alexandre A.
Brenner, Charles
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (01) : 158 - 164
[6] Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans
Bieganowski, P
Brenner, C
[J]. CELL, 2004, 117 (04) : 495 - 502
[7] Eukaryotic NAD+ synthetase Qns1 contains an essential, obligate intramolecular thiol glutamine amidotransferase domain related to nitrilase
Bieganowski, P
Pace, HC
Brenner, C
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (35) : 33049 - 33055
[8] Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast Sir2 and human SIRT1
Bitterman, KJ
Anderson, RM
Cohen, HY
Latorre-Esteves, M
Sinclair, DA
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (47) : 45099 - 45107
[9] Nicotinic acid nicotinamide and nicotinamide riboside:: A molecular evaluation of NAD+ precursor vitamins in human nutrition
Bogan, Katrina L.
Brenner, Charles
[J]. ANNUAL REVIEW OF NUTRITION, 2008, 28 : 115 - 130
[10] PARP-1, a determinant of cell survival in response to DNA damage
Bouchard, WJ
Rouleau, M
Poirier, GG
[J]. EXPERIMENTAL HEMATOLOGY, 2003, 31 (06) : 446 - 454

← 1 2 3 4 5 6 →