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Anti-aging Research > Nicotinamide riboside
Nicotinamide riboside
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News & Research:
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Study: Popular dietary supplement increases breast cancer risk, brain metastasis
- U. of Missouri, 11/14/22 - "While previous studies
have linked commercial dietary supplements like nicotinamide riboside (NR), a
form of vitamin B3, to benefits related to cardiovascular, metabolic and
neurological health, new research from the University of Missouri has found NR
could actually increase the risk of serious disease, such as development of
breast cancer and brain metastasis ... The international team of researchers led
by Elena Goun, an associate professor of chemistry at MU, discovered high levels
of NR could not only increase someone’s risk of developing triple-negative
breast cancer, but also could cause the cancer to metastasize or spread to the
brain. Once the cancer reaches the brain, the results are deadly because no
viable treatment options exist at this time, said Goun, who is the corresponding
author on the study." - Note: It seems like a long stretch that because
it shows up under a special light that it causes triple-negative breast cancer
that metastasizes to the brain.
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NMN and NR: How These NAD+ Precursors Measure Up - elysiumhealth.com -
"NMN is a precursor to NAD+, or nicotinamide adenine
dinucleotide, meaning it becomes NAD+ through a series of chemical
transformations ... However, NMN is like a large bed that movers are trying to
get through a door: It doesn’t enter the cell easily. One way for NMN to enter
the cell is for it to chemically transform into another molecule (called
nicotinamide riboside, or NR) before it can enter the cell. NR has earned a name
for itself as a highly efficient precursor to NAD+ and can enter the cell as is.
NMN, meanwhile, sometimes becomes NR before entering the cell, where it
chemically transforms back to NMN and then ultimately becomes NAD+"
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What’s the Difference Between NAD+ and NADH? - Elysiumhealth.com -
"When NAD+ is converted to NADH, it gains two things:
First, a charged hydrogen molecule (H+) and next, two electrons. As electrons
are negatively charged, the combination of the positively charged NAD+ and H+,
coupled with two electrons, effectively cancel each other out and neutralize the
resulting NADH molecule. This is why NADH does not have a "+" sign next to it.
The charge of a molecule informs how it interacts with other molecules. For
example, NADH can’t do what NAD+ does, and vice versa."
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Mohs Surgeons Favor
Nicotinamide for Chemoprevention in Survey - Medscape, 4/20/21 -
"Approximately three-quarters of Mohs surgeons recommended nicotinamide for
prevention of keratinocyte carcinoma" - See
nicotinamide at Amazon.com.
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NAD+ can restore age-related muscle deterioration, research finds -
Science Daily, 1/20/21 - "Although aggregated
proteins have been suggested to contribute to brain aging, this is the first
time that they have been shown to contribute to muscle aging and to directly
damage mitochondria. "These abnormal proteotoxic aggregates could serve as
novel biomarkers for the aging process, beyond the brain and muscle," says
Auwerx ... the researchers fed worms the vitamin nicotinamide riboside and
the antitumor agent Olaparib, both of which boost the levels of nicotinamide
adenine dinucleotide (NAD+), a biomolecule that is essential for maintaining
mitochondrial function, and whose levels decline during aging ... The
encouraging results led the researchers to test nicotinamide riboside in
aged mice. The treatment also activated the mitochondrial defense systems
and reduced the number and size of amyloid aggregates in different skeletal
muscle tissues ... Drugs that boost mitochondrial quality control could
therefore be tested in the clinic to reverse these age-related proteotoxic
aggregates and rejuvenate tissues" - See
nicotinamide riboside at Amazon.com.
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Supplement makes (mouse) moms' milk better; pups benefit for life - Science
Daily, 1/22/19 - "Mother mice given the NR supplement lost weight faster and
produced more milk than mothers not fed NR. In addition to increasing the
quantity of milk the moms produced, NR supplementation also increased the
quality of the milk, which contained higher levels of a protein factor that
promotes brain development ... The advantages to the pups being nursed by
NR-supplemented moms were striking and long-lasting. The pups were bigger and
had better metabolic health than pups nursed by non-supplemented moms. As
adults, they also had better motor coordination, better learning and memory, and
were less anxious and more resilient to stress ... NR-supplementation in mice
returned liver levels of NAD back to or above normal, and supercharged
lactation, so that NR-fed moms produced more milk and the milk contained higher
levels of a growth factor called brain-derived neurotrophic factor (BDNF) that
enhances brain development"
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Dietary
supplement shows promise for reversing cardiovascular aging - Science Daily,
3/29/18 - "a new University of Colorado Boulder
study published today indicates that when people consume a natural dietary
supplement called nicotinomide riboside (NR) daily, it mimics caloric
restriction, aka "CR," kick-starting the same key chemical pathways
responsible for its health benefit ... Supplementation also tends to improve
blood pressure and arterial health ... it is well tolerated and appears to
activate some of the same key biological pathways that calorie restriction
does ... Half were given a placebo for six weeks, then took a 500 mg
twice-daily dose of nicotinamide riboside (NR) chloride (NIAGEN). The other
half took NR for the first six weeks, followed by placebo ... The
researchers found that 1,000 mg daily of NR boosted levels of another
compound called nicotinamide adenine dinucleotide (NAD+) by 60 percent. NAD+
is required for activation of enzymes called sirtuins, which are largely
credited with the beneficial effects of calorie restriction ... in 13
participants with elevated blood pressure or stage 1 hypertension
(120-139/80-89 mmHg), systolic blood pressure was about 10 points lower
after supplementation. A drop of that magnitude could translate to a 25
percent reduction in heart attack risk"
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Vitamin nicotinamide riboside protects mice from diabetes complications
- Science Daily, 5/27/16 - "As had been shown in
previous studies, NR greatly protected the prediabetic and T2D mice from
weight gain due to the high-fat diet. But the new study also showed that NR
had other beneficial effects on whole body metabolism in the prediabetic and
T2D mice. It protected high-fat fed mice from hepatic steatosis -- the
build-up of fat globules in the liver -- which was severe in the prediabetic
and T2D mice that did not receive NR. NR also reduced liver damage in the
mice on high-fat diets, and greatly improved blood sugar levels in the
prediabetic and T2D mice ... NR also protected against peripheral nerve
damage, or neuropathy, a common, serious complication of prediabetes and T2D
... about 60 to 70 percent of people with diabetes have some form of
neuropathy. Peripheral neuropathy is a leading cause of diabetic foot ulcers
and limb amputation in people with T2D" - See See
nicotinamide riboside at Amazon.com.
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Vitamin stops the aging process of organs - Science Daily, 4/28/16 -
"As mice, like all mammals, age, the regenerative
capacity of certain organs (such as the liver and kidneys) and muscles
(including the heart) diminishes. Their ability to repair them following an
injury is also affected. This leads to many of the disorders typical of
aging ... We gave nicotinamide riboside to 2-year-old mice, which is an
advanced age for them ... This substance, which is close to vitamin B3, is a
precursor of NAD+, a molecule that plays a key role in mitochondrial
activity. And our results are extremely promising: muscular regeneration is
much better in mice that received NR, and they lived longer than the mice
that didn't get it ... Parallel studies have revealed a comparable effect on
stem cells of the brain and skin ... So far, no negative side effects have
been observed following the use of NR, even at high doses" - See
nicotinamide riboside at Amazon.com.
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Beyond Resveratrol: The Anti-Aging NAD Fad - Scientific American,
3/11/15 - "A prominent theory of aging holds that
decaying of mitochondria is a key driver of aging. While it's not clear why
our mitochondria fade as we age, evidence suggests that it leads to
everything from heart failure to neurodegeneration, as well as the complete
absence of zipping around the supper table ... NAD boosters might work
synergistically with supplements like resveratrol to help reinvigorate
mitochondria and ward off diseases of aging. Elysium is banking on this
potential synergy—its NR-containing supplement includes a resveratrol-like
substance called pterostilbene (pronounced tero-STILL-bean), which is found
in blueberries and grapes ... Why pterostilbene instead of resveratrol? ...
While resveratrol has hogged the anti-aging spotlight over the past decade,
unsung researchers in places like Oxford, Miss., have quietly shown that
pterostilbene is a kind of extra-potent version of resveratrol. The
pterostilbene molecule is nearly identical to resveratrol's except for a
couple of differences that make it more "bioavailable" (animal studies
indicate that about four times as much ingested pterostilbene gets into the
bloodstream as resveratrol). Test-tube and rodent studies also suggest that
pterostilbene is more potent than resveratrol when it comes to improving
brain function, warding off various kinds of cancer and preventing heart
disease." - Note: This was a year old article that showed up on my
Facebook. I read some of the reviews on Amazon. Nothing gets my goat more
that people who think something that delays aging has to give you a buzz
such as caffeine. That said, some of the reviews for nicotinamide riboside
said it negatively affected their sleep and made them for fatigued and
depressed. The negative reviews for Niagen seems to be from those that think
it has to give you a buzz (err!!). I'm sticking with this for now: Reserveage Nutrition - Resveratrol with Pterostilbene 500mg, Cellular Age-Defying Formula, 60 veg capsules
at Amazon.com.
Also see Niagen at Amazon.com.
Abstracts:
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Nicotinamide riboside
ameliorates high-fructose-induced lipid metabolism disorder in mice via
improving FGF21 resistance in the liver and white adipose tissue - Food
Funct 2022 Nov 14 - "Fructose has been reported to
acutely elevate the circulating fibroblast growth factor 21 (FGF21) levels,
which ultimately causes FGF21 resistance. FGF21 resistance is suggested to
result in lipid metabolism disorder. Nicotinamide riboside (NR) can alleviate
lipid metabolism disorder in mice. It is unknown whether NR supplementation
would alleviate lipid metabolism disorder in high-fructose exposed mice via
improving FGF21 resistance ... In conclusion, we found that NR supplementation
could ameliorate high-fructose-induced lipid metabolism disorder by improving
FGF21 resistance in the liver and WAT, which may be related to the regulation of
inflammation mediated by the SIRT1/NF-κB signaling pathway" - See
nicotinamide riboside at Amazon.com.
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Nicotinamide riboside and
caffeine partially restore diminished NAD availability but not altered energy
metabolism in Alzheimer's disease - Aging Cell 2022 Jun 21 -
"The redox co-factor nicotinamide adenine dinucleotide
(NAD) declines with age, and NAD deficits are specifically associated with
dysfunctional energy metabolism in late-onset Alzheimer's disease (LOAD).
Nicotinamide riboside (NR), a dietary NAD precursor, has been suggested to
ameliorate the aging process or neurodegeneration. We assessed whether NR with
or without caffeine, which increases nicotinamide mononucleotide transferase
subtype 2 (NMNAT2), an essential enzyme in NAD production, modulates
bioenergetic functions in LOAD ... although NR and caffeine can partially
restore diminished NAD availability, increasing NAD alone may not be sufficient
to boost or restore energy metabolism in brain aging or alter aberrant energy
management in LOAD. Nicotinamide riboside might still be of value in combination
with other agents in preventive or therapeutic intervention strategies to
address the aging process or age-associated dementia" - See
nicotinamide riboside at Amazon.com.
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Preclinical and clinical
evidence of NAD + precursors in health, disease, and ageing - Mech Ageing
Dev 2021 Sep 10 - "NAD+ is a fundamental molecule in
human life and health as it participates in energy metabolism, cell signalling,
mitochondrial homeostasis, and in dictating cell survival or death. Emerging
evidence from preclinical and human studies indicates an age-dependent reduction
of cellular NAD+, possibly due to reduced synthesis and increased consumption.
In preclinical models, NAD+ repletion extends healthspan and / or lifespan and
mitigates several conditions, such as premature ageing diseases and
neurodegenerative diseases. These findings suggest that NAD+ replenishment
through NAD+ precursors has great potential as a therapeutic target for ageing
and age-predisposed diseases, such as Alzheimer's disease. Here, we provide an
updated review on the biological activity, safety, and possible side effects of
NAD+ precursors in preclinical and clinical studies. Major NAD+ precursors
focused on by this review are nicotinamide riboside (NR), nicotinamide
mononucleotide (NMN), and the new discovered dihydronicotinamide riboside (NRH)"
- See nicotinamide riboside at Amazon.com
and nicotinamide mononucleotide at Amazon.com.
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Nicotinamide mononucleotide
supplementation enhances aerobic capacity in amateur runners: a randomized,
double-blind study - See nicotinamide
mononucleotide at Amazon.com - J Int Soc Sports Nutr 2021 Jul 8 -
"Recent studies in rodents indicate that a combination
of exercise training and supplementation with nicotinamide adenine dinucleotide
(NAD+) precursors has synergistic effects. However, there are currently no human
clinical trials analyzing this ... This study investigates the effects of a
combination of exercise training and supplementation with nicotinamide
mononucleotide (NMN), the immediate precursor of NAD+, on cardiovascular fitness
in healthy amateur runners ... The participants were randomized into four
groups: the low dosage group (300 mg/day NMN), the medium dosage group (600
mg/day NMN), the high dosage group (1200 mg/day NMN), and the control group
(placebo) ... NMN increases the aerobic capacity of humans during exercise
training, and the improvement is likely the result of enhanced O2 utilization of
the skeletal muscle" - See nicotinamide mononucleotide at Amazon.com.
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NAD + and NAFLD - Caution,
Causality, and Careful Optimism - J Physiol 2021 May 1 -
"The prevalence of non-alcoholic fatty liver disease
(NAFLD) is increasing worldwide, and new treatments are direly needed.
Nicotinamide adenine dinucleotide (NAD+ ) has been proposed as a potential
target to prevent and reverse NAFLD. NAD+ is an important redox factor for
energy metabolism and is used as a substrate by a range of enzymes, including
sirtuins (SIRT), which regulates histone acetylation, transcription factor
activity and mitochondrial function. NAD+ is also a precursor for reduced
nicotinamide adenine dinucleotide phosphate (NADPH), which is an important
component of the antioxidant defense system. NAD+ precursors such as
nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are available
as over-the-counter dietary supplements, and oral supplementation with these
precursors increases hepatic NAD+ levels and prevent hepatic lipid accumulation
in pre-clinical models of NAFLD. Moreover, NAD+ precursors were found to improve
hepatic mitochondrial function and decrease oxidative stress in pre-clinical
NAFLD models. NAD+ repletion also prevents NAFLD progression to non-alcoholic
steatohepatitis (NASH), as NAD+ precursor supplementation is associated with
decreased hepatic stellate cell activation, and decreased fibrosis. However,
initial clinical trials have only shown modest effects when NAD+ precursors were
administrated to people with obesity. We review the available pre-clinical
investigations of NAD+ supplementation for targeting NAFLD, and discuss how data
from the first clinical trials can be reconciled with observations from
preclinical research" - See nicotinamide adenine dinucleotide at Amazon.com.
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Nicotinamide riboside
supplementation alters body composition and skeletal muscle acetylcarnitine
concentrations in healthy obese humans - Am J Clin Nutr. 2020 Apr 22 -
"A randomized, double-blinded, placebo-controlled,
crossover intervention study was conducted in 13 healthy overweight or obese
men and women. Participants received 6 wk NR (1000 mg/d) and placebo
supplementation ... NR increased body fat-free mass (62.65% ± 2.49% compared
with 61.32% ± 2.58% in NR and placebo, respectively; change: 1.34% ± 0.50%,
P = 0.02) and increased sleeping metabolic rate. Interestingly,
acetylcarnitine concentrations in skeletal muscle were increased upon NR
(4558 ± 749 compared with 3025 ± 316 pmol/mg dry weight in NR and placebo,
respectively; change: 1533 ± 683 pmol/mg dry weight, P = 0.04) and the
capacity to form acetylcarnitine upon exercise was higher in NR than in
placebo (2.99 ± 0.30 compared with 2.40 ± 0.33 mmol/kg wet weight; change:
0.53 ± 0.21 mmol/kg wet weight, P = 0.01). However, no effects of NR were
found on insulin sensitivity, mitochondrial function, hepatic and
intramyocellular lipid accumulation, cardiac energy status, cardiac ejection
fraction, ambulatory blood pressure, plasma markers of inflammation, or
energy metabolism"
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Short-term NAD+
supplementation prevents hearing loss in mouse models of Cockayne syndrome -
NPJ Aging Mech Dis. 2020 Jan 7;6:1 - "In this study, we
report that NAD+ levels are reduced in the cochlea of CSB m/m mice and that
short-term treatment (10 days) with the NAD+ precursor nicotinamide riboside
(NR), prevents hearing loss, restores outer hair cell loss, and improves
cochlear health in CSB m/m mice. Similar, but more modest effects were observed
in CSA -/- mice. Remarkably, we observed a reduction in synaptic ribbon counts
in the presynaptic zones of inner hair cells in both CSA -/- and CSB m/m mice,
pointing to a converging mechanism for cochlear defects in CS. Ribbon synapses
facilitate rapid and sustained synaptic transmission over long periods of time.
Ribeye, a core protein of synaptic ribbons, possesses an NAD(H) binding pocket
which regulates its activity. Intriguingly, NAD+ supplementation rescues reduced
synaptic ribbon formation in both CSA -/- and CSB m/m mutant cochleae. These
findings provide valuable insight into the mechanism of CS- and ARHL-associated
hearing loss, and suggest a possible intervention" - [Nutra
USA]
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Cardioprotective Effect
of the Mitochondrial Unfolded Protein Response During Chronic Pressure Overload
- J Am Coll Cardiol. 2019 Apr 16;73(14):1795-1806 - " Boosting the UPRmt with
nicotinamide riboside (which augments NAD+ pools) in cardiomyocytes in vitro or
hearts in vivo significantly mitigated the reductions in mitochondrial oxygen
consumption induced by these stresses. In mice subjected to pressure overload,
nicotinamide riboside reduced cardiomyocyte death and contractile dysfunction.
Myocardial tissue from patients with aortic stenosis also showed evidence of
UPRmt activation, which correlated with reduced tissue cardiomyocyte death and
fibrosis and lower plasma levels of biomarkers of cardiac damage
(high-sensitivity troponin T) and dysfunction (N-terminal pro–B-type natriuretic
peptide)." - [Nutra
USA]
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NAD+ supplementation
normalizes key Alzheimer's features and DNA damage responses in a new AD mouse
model with introduced DNA repair deficiency - Proc Natl Acad Sci U S A. 2018
Feb 20 - "NR-treated 3xTgAD/Polβ+/- mice exhibited
reduced DNA damage, neuroinflammation, and apoptosis of hippocampal neurons and
increased activity of SIRT3 in the brain. NR improved cognitive function in
multiple behavioral tests and restored hippocampal synaptic plasticity in 3xTgAD
mice and 3xTgAD/Polβ+/- mice. In general, the deficits between genotypes and the
benefits of NR were greater in 3xTgAD/Polβ+/- mice than in 3xTgAD mice. Our
findings suggest a pivotal role for cellular NAD+ depletion upstream of
neuroinflammation, pTau, DNA damage, synaptic dysfunction, and neuronal
degeneration in AD. Interventions that bolster neuronal NAD+ levels therefore
have therapeutic potential for AD" - [Nutra
USA]
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Nicotinamide riboside,
a form of vitamin B3, protects against excitotoxicity-induced axonal
degeneration - FASEB J. 2017 Aug 21 - "NAD+
depletion is a common phenomenon in neurodegenerative pathologies ... Taken
together, our findings demonstrate that NR is a better neuroprotective agent
than NAD+ in excitotoxicity-induced AxD and that axonal protection involves
defending intracellular NAD+ homeostasis"
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Nicotinamide Riboside
Opposes Type 2 Diabetes and Neuropathy in Mice - Sci Rep. 2016 May
27;6:26933 - "NR improved glucose tolerance, reduced
weight gain, liver damage and the development of hepatic steatosis in
prediabetic mice while protecting against sensory neuropathy. In T2D mice,
NR greatly reduced non-fasting and fasting blood glucose, weight gain and
hepatic steatosis while protecting against diabetic neuropathy. The
neuroprotective effect of NR could not be explained by glycemic control
alone ... Quantitative metabolomics established that hepatic NADP(+) and
NADPH levels were significantly degraded in prediabetes and T2D but were
largely protected when mice were supplemented with NR" - [Nutra
USA]
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