nuwu

Nicotinamide Mononucleotide (NMN)

10 posts in this topic

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NAD+ directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.

https://pubmed.ncbi.nlm.nih.gov/28336669/

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Treatment with NAD(+) inhibited experimental autoimmune encephalomyelitis by activating AMPK/SIRT1 signaling pathway and modulating Th1/Th17 immune responses in mice

https://pubmed.ncbi.nlm.nih.gov/27500459/

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After 18-month-old mice were treated with NMN for two months, their capillary density was restored to levels typically seen in young mice, and they experienced a 56 to 80 percent improvement in endurance. Beneficial effects were also seen in mice up to 32 months of age (comparable to humans in their 80s).

https://news.mit.edu/2018/study-suggests-method-boost-growth-blood-vessels-muscle-0322

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We found that neurovascular coupling responses were significantly impaired in aged mice. NMN supplementation rescued NVC responses by increasing endothelial NO-mediated vasodilation, which was associated with significantly improved spatial working memory and gait coordination.

https://www.sciencedirect.com/science/article/pii/S221323171930240X

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Last, the concept proposed that aging is the process in which biological robustness gradually alters and eventually breaks down according to a functional hierarchy determined by the susceptibility to systemic NAD+ biosynthesis. In other words, the cascade of robustness breakdown triggered by a decrease in systemic NAD+ biosynthesis and the resultant functional defects in susceptible organs and tissues is the central process of aging.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516857/

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Numerous studies have demonstrated that boosting NAD+ levels increases insulin sensitivity, reverses mitochondrial dysfunction, and extends lifespan. [...] Taken orally, NMN is rapidly absorbed and converted to NAD+. [...] NMN is naturally found in small amounts in fruits and vegetables such as avocados, broccoli, cabbage, edamame, and cucumbers17 [...] NMN levels fall with age, and aging itself has also been shown to significantly compromise the body’s conversion of NMN to NAD+.26

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238909/

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The problem with taking this supplement is you'll never know if it's working. You'll have to take it for 30 years.


How is this post just me acting out my ego in the usual ways? Is this post just me venting and justifying my selfishness? Are the things you are posting in alignment with principles of higher consciousness and higher stages of ego development? Are you acting in a mature or immature way? Are you being selfish or selfless in your communication? Are you acting like a monkey or like a God-like being?

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@integral this is also what i used to think, but since trying it i quickly experienced raise in energy levels and well-beings. i dont feel like its over stimulating or anything. a bit similar to taking creatine supplements as a vegan. i had been taking various forms of B3 supplements (nicotinic acid, nicotinamide, inositol hexanicotinate) and still experienced a difference

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Twenty-five postmenopausal women with prediabetes based on criteria proposed by the American Diabetes Association(12) who were overweight or obese completed this study; 12 were randomized to the placebo group and 13 to the NMN group (250 mg/day; Oriental Yeast Co., Ltd., Tokyo, Japan)

[...]

Muscle insulin sensitivity, assessed as the rate of insulin-stimulated glucose disposal per kg of fat-free mass during the clamp procedure, was 25±7% greater after than before 10 weeks of NMN supplementation (p<0.01), but was not different after than before placebo treatment (Fig. 2A).

[...]

This randomized, placebo-controlled, double-blind trial demonstrates that 10 weeks of NMN supplementation increases muscle insulin signaling (increased insulin-stimulated phosphorylated AKT and mTOR) and muscle insulin sensitivity (increased insulin-stimulated glucose disposal rate expressed per kg fat-free mass) in postmenopausal women with prediabetes who are overweight or obese. This improvement in muscle insulin sensitivity is clinically relevant and is similar to the improvement observed after ~10% weight loss (19) and after 12 weeks of treatment with the insulin sensitizing agent troglitazone(20) in people with obesity.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550608/

f-feels worth randomly sharing. obviously i could be cherry picking studies, do your own research!

there is also an alternative compound called nicotinamide riboside (NR) which is patented, and appears less effective despite greater marketing and financial pressures (but i havent tried). https://novoslabs.com/nmn-vs-nr-is-nmn-better-than-nr/

Edited by nuwu

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These are all in-vitro and in-vivo studies. The hysteria with NMN that people like David Sinclair have started is not based on human outcome data. These things are being sold as miracle supplements and are becoming a multibillion dollar fad. 

Most mechanisms fail once we get to human RCTs. Only about 3% of mechanisms survive Phase 1  and 2 clinical trials in humans. And that does not account for the mechanisms that do not even get considered because they seem so whacky. 

Not saying NMN is useless but it is probably not this superhuman drug it appears to be 

 


“If you find yourself acting to impress others, or avoiding action out of fear of what they might think, you have left the path.” ― Epictetus

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40 minutes ago, Michael569 said:

The hysteria with NMN that people like David Sinclair have started is not based on human outcome data.

the increased lifespan claims are not based on human data, but it seems logical to think any recent discovery will not have such data available after some inevitable delay. we will be blind until the end (unless simulation of artificial cell is possible somehow)

42 minutes ago, Michael569 said:

These things are being sold as miracle supplements and are becoming a multibillion dollar fad. 

not sure but this seems to be the sentiment for NR, where studies showing lack of evidence are sometimes generalized to both. nmn is not patented, thus constructing a socially-engineered fad around is less likely. there still could be biases from scientific reputation among other things, david sinclair has also been advocating for antioxydants that have been shown actually prooxydant in some contexts ( https://pubmed.ncbi.nlm.nih.gov/23793960/ ) without human data for longevity as well (and sometimes evidences of contrary)

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For example, a randomized placebo-controlled clinical trial of NR in humans showed that NR is safe, however, it did not show benefits in the population studied. This clinical trial showed that NR did not improve insulin sensitivity and whole-body glucose metabolism in obese, insulin-resistant men (Dollerup et al., 2018).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172449/

NR might be degraded by gut microbiome into nicotinic acid. unclear for NMN

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Using stable isotope tracing and microbiota-depleted mice, we demonstrate that this bacteria-mediated deamidation contributes substantially to the NAD-boosting effect of oral nicotinamide and nicotinamide riboside supplementation in several tissues.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194078/

1 hour ago, Michael569 said:

Not saying NMN is useless but it is probably not this superhuman drug it appears to be

its definitely possible the hype is exaggerated. i only started this thread based on anecdotal evidence from my own experience after few weeks of use and the observed positive outcomes, despite the fact i used to take nicotinamide supplements, in contrast to studies suggesting there should be no difference

im not attached to any supplements. thank you for providing a balancing viewpoint. nmn is more expensive than other simpler forms of b3, and im not entirely sure its worth recommending or anything. it may vary depending on each individual's metabolism and environment. overall seems like a safe and effective way to burn fiat tokens!

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On 24.8.2022 at 1:13 PM, Michael569 said:

These are all in-vitro and in-vivo studies. The hysteria with NMN that people like David Sinclair have started is not based on human outcome data. These things are being sold as miracle supplements and are becoming a multibillion dollar fad. 

Most mechanisms fail once we get to human RCTs. Only about 3% of mechanisms survive Phase 1  and 2 clinical trials in humans. And that does not account for the mechanisms that do not even get considered because they seem so whacky. 

Not saying NMN is useless but it is probably not this superhuman drug it appears to be 

 

This. 

It's astonishing to me how Harvard professors like Sinclair are somehow not able to reliably integrate the available data in some form of bayesian risk/reward-model. If we have learned anything from our medical history, then it's that in-vitro/in-vivo studies or mechanistical arguments are for the most part highly unreliable, if not dangerous. Many great failures of once highly praised pharmaceutical interventions were rooted in recommendations based on weak evidence and terrible sensemaking - we have fed millions upon millions of patients with drugs, which at the end didn't really show any significant improvement inmortality, while causing deliberating side effects left and right.

NMN could be promising. I will remain agnostic towards it.
However, from all the evidence that is available at the moment - one shouldn't come to any conclusion. I would never recommend this agent for anyone - just wait 5 more years for larger trials and actual human data to come out. 
 


MD. Internal medicine/gastroenterology - Evidence based integral health approaches

"Perhaps all the dragons in our lives are princesses who are only waiting to see us act, just once, with beauty and courage. Perhaps everything that frightens us is, in its deepest essence, something helpless that wants our love."
- Rainer Maria Rilke

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https://youtu.be/YBWQNsWi9lc

https://youtu.be/Zm5ev4X__lE

https://youtu.be/xSdq0jlc4R4

overall, if one has low cancer risks, nmn can be interesting. but there is still issues with degradation in intestine/plasma and down regulation of NAD enzymes. perhaps direct liposomal nad+ supplementation may work around both these but there isn't much studies or brands with purity guarantees

cycloastragenol is potentially another interesting compound to activate telomerase https://pubmed.ncbi.nlm.nih.gov/25095809/ and seems safer cancer-wise https://pubmed.ncbi.nlm.nih.gov/33448320/ (with astragalus extract at least)

 

Edited by nuwu

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Wasn't there a study done where perfectly healthy rats where given chemo-therapy and they lived twice as long? Something to do with that rats all die from cancer so if you poison them with chemo they live longer lol. 

Edited by integral

How is this post just me acting out my ego in the usual ways? Is this post just me venting and justifying my selfishness? Are the things you are posting in alignment with principles of higher consciousness and higher stages of ego development? Are you acting in a mature or immature way? Are you being selfish or selfless in your communication? Are you acting like a monkey or like a God-like being?

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not sure about astragalus extract which is reported toxic at low levels. yet it has been used in chinese medicine for a long time so maybe there is something more to it. (100g of plant contains 200mg of AS-IV according to some random source, concentration of cycloastragenol is much lower)

@integral makes sense considering the replication crisis, and conflicting results on lifetime benefits of nmn. i wish scientists would realize the whole structure of peer-review can be improved in and of itself

@vindicated erudite depends, sublingual relatively works, but both NMN and NR are unstable in bloodstream, unlike NAD+. there are some interesting opinions on reddit (not sure how truthful they are): [1] [2]

the thread on peptides also has interesting things to inject, but there isnt much studies and labs with purity levels that seem adequate for humans (btw i have no idea what im talking about, not sure if that matters)

Edited by nuwu

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