Nicotinamide riboside
(NR) is a pyridine-nucleoside form of vitamin B3 that functions as a
precursor to nicotinamide adenine dinucleotide or NAD+. NR has ...
Nicotinamide riboside
From Wikipedia, the free encyclopedia
Nicotinamide riboside (
NR) is a
pyridine-
nucleoside form of
vitamin B3 that functions as a precursor to
nicotinamide adenine dinucleotide or
NAD+.
[1][2] NR has been a recent focus of
life extension research after
David Sinclair published a study in 2013 showing NAD+ levels decrease with age in mice.
[3][4][5]
Discovery
Bacterial NAD precursor
NR was first described in 1944 as a growth factor, termed Factor V, for
Haemophilus influenza,
a bacterium that lives in and depends on blood. Factor V, purified from
blood was shown to exist in three forms: NAD+, NMN and NR. NR was the
compound that led to the most rapid growth of this bacterium.
[6] Notably,
H. influenza cannot grow on
nicotinic acid,
nicotinamide,
tryptophan or
aspartic acid, which were the previously known precursors of NAD+.
[7]
Eukaryotic NAD precursor vitamin
In 2000, yeast
Sir2 was shown to be an NAD+-dependent protein lysine deacetylase,
[8]
which led several groups to probe yeast NAD+ metabolism for genes and
enzymes that might regulate lifespan. Biosynthesis of NAD+ in yeast was
thought to flow exclusively through NAMN.
[9][10][11][12][13]
Surprisingly, when
NAD+ synthase (glutamine-hydrolysing)
was deleted from yeast cells, NR permitted yeast cells to grow. Thus,
these investigators proceeded to clone yeast and human nicotinamide
riboside kinases and demonstrate the conversion of NR to NMN by these
enzymes in vitro and in vivo. They also demonstrated that NR is a
natural product, the so-called hidden vitamin found in cow's milk.
[14][15]
Potential applications in human health
High dose nicotinic acid is used as an agent that elevates
high-density lipoprotein cholesterol, lowers low-density lipoprotein
cholesterol and lower free fatty acids through a mechanism that is not
completely understood. It was suggested that nicotinamide riboside might
possess such an activity by elevating NAD in the cells responsible for
reverse cholesterol transport.
[7]
An experiment with mice on high fat diet appears to support the
potential of treatment or prevention of dyslipidemia with nicotinamide
riboside.
[16]
The discovery that the
Wallerian degeneration
slow gene encodes a protein fusion with NMN adenylyltransferase 1
indicated that increased NAD+ precursor supplementation might oppose
neurodegenerative processes.
[7] NR blocks degeneration of surgically severed dorsal root ganglion neurons
ex vivo[17] and protects against noise-induced hearing loss in living mice.
[18][19]
Nicotinamide riboside prevents muscle, neural and menalocyte stem cell senescence
[20].
Increased muscular regeneration in mice has been observed after
treatment with nicotinamide riboside, leading to speculation that it
might improve regeneration of organs such as the liver, kidney, and
heart.
[21]
Commercialization
ChromaDex acquired intellectual property on uses and synthesis of NR from
Dartmouth College,
Cornell University, and
Washington University and began distributing NR as Niagen in 2013.
[22] ChromaDex completed a clinical study on nicotinamide riboside in 2015, demonstrating that it can increase the co-enzyme NAD+,
[23] and began a clinical trial in March 2016 to examine the benefits if taken daily for eight consecutive weeks.
[24]
See also
References
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