Niacinamide Retards/Reverses Aging And Physiological Decline

haidut

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Yet another study on the beneficial effects of raising NAD levels, and unlike other recent studies this one is not sponsored by ChromaDex. This study used nicotinamide mononucleotide (NMN), and human studies have shown that niacinamide is equally effective as NMN in raising NAD levels. Also, as @tyw pointed out a few times, niacinamide is a SIRT inhibitor while NMN and nicotinamide ribodise (NR) are activators. This SIRT inhibition activity may give niacinamide an edge especially as an anti-cancer nutrient since SIRT inhibitors lower fatty acid oxidation (FAO).
Anyways, the study used life-long supplementation with NMN and used two doses - a HED of 8mg/kg and 16mg/kg. The lower dose (HED 8mg/kg) was more effective in increasing respirtation and physical activity, while the higher dose was more effective for reversing insulin resistance, weight gain and improving bone mineral density.

Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice
"...In this study, we demonstrate that long-term administration of NMN is capable of mitigating age-associated physiological decline in regular chow-fed wild-type mice. We found that a 12 month-long NMN administration 1) is well-tolerated without any obvious deleterious effects, 2) suppresses age-associated body weight gain, 3) enhances food intake, oxygen consumption, energy expenditure, and physical activity, 4) improves insulin sensitivity and plasma lipid profile, independent of its effect on body weight, and 5) improves eye function, bone density, and myeloid-lymphoid composition. NMN administration was also able to prevent age-associated gene expression changes in a tissue-dependent manner and enhance mitochondrial respiratory capability in skeletal muscle. In addition to the already reported effects of short-term NMN administration on various pathological conditions (Caton et al., 2011; Gomes et al., 2013; Long et al., 2015; Stein and Imai, 2014; Yamamoto et al., 2014; Yoshino et al., 2011), this pleiotropic effect of long-term NMN administration opens a new avenue to develop effective anti-aging interventions using key NAD+ intermediates, such as NMN."

"...It should be noted that NMN administration did not generate any obvious toxicity, serious side effects, or increased mortality rate throughout the 12 month-long intervention period, suggesting the long-term safety of NMN. Nonetheless, an optimal dose of NMN to maximize its efficacy appears to differ depending on physiological functions. For example, whereas the effects of NMN on body weight gain, insulin sensitivity, tear production, and bone mineral density were dose-dependent, 100 mg/kg/day of NMN improved oxygen consumption, energy expenditure, and physical activity better than 300 mg/kg/day. For rod and cone photoreceptor function, both doses had similar effects. Indeed, we found that expression of Ox2r and Prdm13, two downstream genes in the SIRT1-mediated signaling pathway in the hypothalamus, exhibited significant decreases in the hypothalami of 300 mg/kg/day NMN-treated mice (our preliminary finding), which could partly explain some of the observed differences in the effects of NMN, particularly those on physical activity, between two tested doses. Additionally, the extent of age-dependent NAD+ decline or NMN uptake in each tissue or organ might determine an optimal dose of NMN to restore each physiological function. Given that 100 mg/kg/day of NMN was able to mitigate most age-associated physiological declines in mice, an equivalent surface area dose for humans would be ~8 mg/kg/day (Freireich et al., 1966), providing hope to translate our findings to humans."

"...In conclusion, our long-term NMN administration study provides compelling support to an effective anti-aging intervention using NMN, a key NAD+ intermediate. Given that NMN is contained in a variety of food sources such as vegetables, fruits and meat, it will be of great interest to translate our study from mice to humans and examine whether this endogenous compound, NMN, is also an effective intervention that prevents age-associated physiological decline in humans."
 
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aguilaroja

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Excuse me if this is duplication. This is a recent review by Yoshino & colleagues.

NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. - PubMed - NCBI

“Research on the biology of NAD+ has been gaining momentum, providing many critical insights into the pathogenesis of age-associated functional decline and diseases. In particular, two key NAD+ intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years. Supplementing these NAD+ intermediates has shown preventive and therapeutic effects, ameliorating age-associated pathophysiologies and disease conditions.”

“NMN has also been reported to improve mitochondrial function in various metabolic organs, including skeletal muscle…, liver…, heart…, and eyes.…”

“Recent studies have suggested that NMN improves numerous neuronal functions in the brain. NMN administration improves cognition and memory in mouse and rat models of Alzheimer’s disease.… NMN protects neurons from cell death after ischemia…or intracerebral hemorrhage….

“NR improves liver health in a variety of contexts. It potently reduces fat accumulation through a mechanism that involves induction of the mitochondrial unfolded protein response.… It further reduces inflammation at least in part through decreased activity of the NLRP3 inflammasome and lessens the development of fibrosis”

“Like NMN, NR has further been reported to have a number of intriguing benefits in the nervous system. One of the first studies to examine the effects of NR in vivo revealed a striking improvement in the progression of Alzheimer’s disease pathology in the Tg2576 model of the disease.… NR has been shown to prevent noise-induced hearing loss and neurite retraction from hair cells in the inner ear.… NR also protects against diabetic and chemotherapy-induced neuropathy in mice….”
 

DennisX

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The HED conversation is x0.162. Thus 100mg/kg/day for rats is 16.2mg/kg/day for humans.
 

haidut

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Excuse me if this is duplication. This is a recent review by Yoshino & colleagues.

NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. - PubMed - NCBI

“Research on the biology of NAD+ has been gaining momentum, providing many critical insights into the pathogenesis of age-associated functional decline and diseases. In particular, two key NAD+ intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years. Supplementing these NAD+ intermediates has shown preventive and therapeutic effects, ameliorating age-associated pathophysiologies and disease conditions.”

“NMN has also been reported to improve mitochondrial function in various metabolic organs, including skeletal muscle…, liver…, heart…, and eyes.…”

“Recent studies have suggested that NMN improves numerous neuronal functions in the brain. NMN administration improves cognition and memory in mouse and rat models of Alzheimer’s disease.… NMN protects neurons from cell death after ischemia…or intracerebral hemorrhage….

“NR improves liver health in a variety of contexts. It potently reduces fat accumulation through a mechanism that involves induction of the mitochondrial unfolded protein response.… It further reduces inflammation at least in part through decreased activity of the NLRP3 inflammasome and lessens the development of fibrosis”

“Like NMN, NR has further been reported to have a number of intriguing benefits in the nervous system. One of the first studies to examine the effects of NR in vivo revealed a striking improvement in the progression of Alzheimer’s disease pathology in the Tg2576 model of the disease.… NR has been shown to prevent noise-induced hearing loss and neurite retraction from hair cells in the inner ear.… NR also protects against diabetic and chemotherapy-induced neuropathy in mice….”

Thanks, I don't think it has been posted yet and it definitely complement this thread if somebody wants to see a comparison among the 3 widely used NAD precursors.
 

haidut

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The HED conversation is x0.162. Thus 100mg/kg/day for rats is 16.2mg/kg/day for humans.

Those were mice, so an additional division of 2 needs to be done. They say themselves in the study (see second quote) that the 100mg/kg dose is equivalent to 8mg/kg for a human.
 

Giocondi

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How on earth is one able to take such a small dose accurately? Most pills are 500mg and the powders, like the one from bulk supplements are 100 milligrams per 1/16 tsp!
 

Ulysses

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Those were mice, so an additional division of 2 needs to be done. They say themselves in the study (see second quote) that the 100mg/kg dose is equivalent to 8mg/kg for a human.
How rigorous is this conversion?
 

haidut

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How rigorous is this conversion?

I don't know how rigorous but that is the currently used formula. The currently accepted conversion regimen is based on BSA and the scalling factor for rats to humans is 1/6 of the rat dose and for mice is 1/12. So, 1/12 is exactly 1/2 of 1/6. In other words, if a study says a dose for rat would be 6mg/kg, the HED would be 1mg/kg and if it was a mouse the HED would be 0.5mg/kg.
 

WayneSmith

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So if I weigh 80 kg then it would be 640 mg per day? I have a two month NMN supply being shipped. I guess it will be more like less than one month now. Does this HED calculation have a built in safety margin which skews the result? I read somewhere that the body in charge of working this stuff out for initial climical trials errs toward caution. I think it was a tenfold decrease to be safe but that can't be right, right?

I was thinking about taking Niagen AND NMN as they have different bioavailabity to the various organs and might be complimentary. Should I halve each dose? I think the maximum effect with Niagen is achieved with 300 mg per day. Some kind of spillover effect stores away surplus NR. Also heard Niacin has high demand for other Methyl groups or you risk a crash in energy. Double the Niagen dose I think. B vitamin mix? Is this only an issue for Niagen or NMN too? Vitamin C supplements helpful? Somebody suggested them too.
 

Texon

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So if I weigh 80 kg then it would be 640 mg per day? I have a two month NMN supply being shipped. I guess it will be more like less than one month now. Does this HED calculation have a built in safety margin which skews the result? I read somewhere that the body in charge of working this stuff out for initial climical trials errs toward caution. I think it was a tenfold decrease to be safe but that can't be right, right?

I was thinking about taking Niagen AND NMN as they have different bioavailabity to the various organs and might be complimentary. Should I halve each dose? I think the maximum effect with Niagen is achieved with 300 mg per day. Some kind of spillover effect stores away surplus NR. Also heard Niacin has high demand for other Methyl groups or you risk a crash in energy. Double the Niagen dose I think. B vitamin mix? Is this only an issue for Niagen or NMN too? Vitamin C supplements helpful? Somebody suggested them too.

@haidut @Koveras Guys I just got through watching Joe Rogan podcast #1234 where he interviews David Sinclair the Harvard genetics researcher about anti-aging and genetic engineering topics.


So Sinclair specifically says he takes a gram of NMN in the morning, metformin at night and a statin since he was 20 because he inherited bad cholesterol genes from his Ashkenazi Jewish ancestors.

Aside from practicing caloric restriction and moderate weightlifting and interval running, that's about it. He says his energy is great and he looks like he's 30 instead of nearly 50. Oh...only one cup of coffee per day because of the energy he gets from NMN. And, I almost forgot, he has taken resveratrol for about 10 years. The whole podcast is fascinating. I would love comments?
 
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pepsi

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@haidut @Koveras Guys I just got through watching Joe Rogan podcast #1234 where he interviews David Sinclair the Harvard genetics researcher about anti-aging and genetic engineering topics.


So Sinclair specifically says he takes a gram of NMN in the morning, metformin at night and a statin since he was 20 because he inherited bad cholesterol genes from his Ashkenazi Jewish ancestors.

Aside from practicing caloric restriction and moderate weightlifting and interval running, that's about it. He says his energy is great and he looks like he's 30 instead of nearly 50. Oh...only one cup of coffee per day because of the energy he gets from NMN. And, I almost forgot, he has taken resveratrol for about 10 years. The whole podcast is fascinating. I would love comments?

Wow ,this guy looks way better than the bullet proof guy Dave Asprey , so I guess fasting is better than paleo,
 

Texon

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Wow ,this guy looks way better than the bullet proof guy Dave Asprey , so I guess fasting is better than paleo,
Yeah and he takes metformin, resveratrol, and a statin, none of which are "Peaty" in the least.
 
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jb116

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@haidut @Koveras Guys I just got through watching Joe Rogan podcast #1234 where he interviews David Sinclair the Harvard genetics researcher about anti-aging and genetic engineering topics.


So Sinclair specifically says he takes a gram of NMN in the morning, metformin at night and a statin since he was 20 because he inherited bad cholesterol genes from his Ashkenazi Jewish ancestors.

Aside from practicing caloric restriction and moderate weightlifting and interval running, that's about it. He says his energy is great and he looks like he's 30 instead of nearly 50. Oh...only one cup of coffee per day because of the energy he gets from NMN. And, I almost forgot, he has taken resveratrol for about 10 years. The whole podcast is fascinating. I would love comments?
How and why is the verdict on SIRT so polarized?? Most say activating it is a path to longevity. But the Peat perspective is that it promotes cancer.
 

Texon

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How and why is the verdict on SIRT so polarized?? Most say activating it is a path to longevity. But the Peat perspective is that it promotes cancer.
Weird isn't it that niacinamide inhibits it and NR enhances it.
 
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jb116

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Weird isn't it that niacinamide inhibits it and NR enhances it.
Yes, that aspect also boggles the mind.
I can live with that difference though at the end of the day.
But the polarization of opinions regarding SIRT, just truly boggles the mind.
 
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LeeLemonoil

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There is a massive thread on longecity where they try to optimize mitos by stimulating fusion and fission alternately by supps. Stearin avid for fusion mostly and Niacinamide-Riboside for fission.
They don’t take niagen though but seem to be convinced that taking niacinamide along with ribose forms the niagen-comping within the cells.

I’ve read all about Haiduts and others stance on SIRT inhibition by Niacinamide, and I still can’t wrap my mind around this either. There is too much data atoms suggesting Sirr activation to be „beneficial“
 

ddjd

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has anyone tried taking NMN and want to share their experience?
 

lampofred

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@haidut @Koveras Guys I just got through watching Joe Rogan podcast #1234 where he interviews David Sinclair the Harvard genetics researcher about anti-aging and genetic engineering topics.


So Sinclair specifically says he takes a gram of NMN in the morning, metformin at night and a statin since he was 20 because he inherited bad cholesterol genes from his Ashkenazi Jewish ancestors.

Aside from practicing caloric restriction and moderate weightlifting and interval running, that's about it. He says his energy is great and he looks like he's 30 instead of nearly 50. Oh...only one cup of coffee per day because of the energy he gets from NMN. And, I almost forgot, he has taken resveratrol for about 10 years. The whole podcast is fascinating. I would love comments?

My 2 cents: everything he is doing powerfully reduces inflammation (calorie restriction, reservatol), and statins and metformin raise adrenaline while keeping serotonin low. But these all work by increasing cortisol. Having high cortisol is better than being inflamed, but at best, high cortisol/low inflammation prevents degeneration. It doesn't induce regeneration, which requires glucose oxidation/CO2/progesterone/GABA. Peat's work is aimed at increasing our youthful regenerative capacity, and doesn't stop at just trying to avoid degeneration.
 
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