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Nicotinamide Mononucleotide (NMN) soon to be available as a supplement

nmn sinclair sirtuin nad

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#31 airplanepeanuts

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Posted 25 March 2016 - 12:15 AM

It's available here for an insane price: http://www.supersmar...ide-10-mg--0674

 

Is there any good reasons to believe it's worth to try at that cost?



#32 Bryan_S

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Posted 09 April 2016 - 04:16 AM

This one looks like the real deal http://www.amazon.co...60174931&sr=8-1

 

They were anounced through businesswire http://www.businessw...nt-Specialized 

 

This went through normal business channels so I think its the real deal. Just a little pricy for my wallet! 


Edited by Bryan_S, 09 April 2016 - 04:16 AM.


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#33 Grim Reaper

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Posted 09 April 2016 - 04:21 AM

Thanks! They even have free shipping!



#34 Bryan_S

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Posted 09 April 2016 - 05:45 PM

And a free trip around the world . . . Maybe if you live in Japan you can spend like there's no tomorrow.

 

"Based in Tokyo, Japan, Shinkowa Pharmaceutical Co., Ltd. (http://shinkowapharma.com/) is a pharmaceutical company that has developed and sells dietary supplements and cosmetics in Japan with the vision of beautiful life and comfortable life for the future. The brand name, Mirailabo, is only available produces to focus on anti-aging care."



#35 playground

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Posted 25 July 2016 - 06:26 AM

And a free trip around the world . . . Maybe if you live in Japan you can spend like there's no tomorrow.

 

"Based in Tokyo, Japan, Shinkowa Pharmaceutical Co., Ltd. (http://shinkowapharma.com/) is a pharmaceutical company that has developed and sells dietary supplements and cosmetics in Japan with the vision of beautiful life and comfortable life for the future. The brand name, Mirailabo, is only available produces to focus on anti-aging care."

 

that should read:  "with the vision of vast profits and a prosperous retirement for the company executives"
 


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#36 richard hnry

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Posted 23 November 2016 - 05:33 AM

https://www.scienced...51210124557.htm This article nicotinamide mononucleotide is dangerous. It is highly toxic to neurons.
  • Informative x 2
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#37 richard hnry

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Posted 23 November 2016 - 05:41 AM

http://www.scienceda...51210124557.htm This article says thatnicotinamide mononucleotide is dangerous. It is highly toxic to neurons.



#38 Bryan_S

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Posted 23 November 2016 - 04:07 PM

Here is the full article its open access

http://www.cell.com/...1247(15)01347-9



#39 Anthony_Loera

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Posted 23 November 2016 - 07:30 PM

Wallarian Degeneration Syndrome...? 

 

...requires pro-degenerative protein SARM1...

 

I suppose if you are not healthy and have both the syndrome and SARM1 protein... you don't take many B Vitamins at all.

 

A

 


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#40 Thell

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Posted 23 November 2016 - 11:42 PM

https://www.scienced...51210124557.htm This article nicotinamide mononucleotide is dangerous. It is highly toxic to neurons.

 

Neither the article or study state or even insinuate that nicotinamide mononucleotide is dangerous or that it itself is toxic to neurons.

 

 

... This research showed that NMN initiates axon degeneration both in neurons in lab cultures and in zebrafish models of acute injury and neurotoxicity.

Building on the earlier work, the current study demonstrates that NMN in injured axons works together with SARM1, a protein involved in the innate immune system -- the body's first line of defence against potential pathogens -- that plays a key role in axon degeneration, and kicks off a chain reaction leading to toxic levels of calcium and axon fragmentation.

 

One thing to keep in mind is that this degeneration of injured cells is required prior to microglia doing its job. Even in the zebrafish the degeneration is required prior to regeneration. If there are injured axons I want them them isolated, broken down and cleaned out as quickly and efficiently as possible with the least swelling so the newly generated neuronal cells can quickly migrate and be utilized. It seems the researchers at Conforti Lab made an effort to report findings rather than conclusions.


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#41 richard hnry

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Posted 24 November 2016 - 02:20 AM

 

https://www.scienced...51210124557.htm This article nicotinamide mononucleotide is dangerous. It is highly toxic to neurons.

 

Neither the article or study state or even insinuate that nicotinamide mononucleotide is dangerous or that it itself is toxic to neurons.

 

 

... This research showed that NMN initiates axon degeneration both in neurons in lab cultures and in zebrafish models of acute injury and neurotoxicity.

Building on the earlier work, the current study demonstrates that NMN in injured axons works together with SARM1, a protein involved in the innate immune system -- the body's first line of defence against potential pathogens -- that plays a key role in axon degeneration, and kicks off a chain reaction leading to toxic levels of calcium and axon fragmentation.

 

One thing to keep in mind is that this degeneration of injured cells is required prior to microglia doing its job. Even in the zebrafish the degeneration is required prior to regeneration. If there are injured axons I want them them isolated, broken down and cleaned out as quickly and efficiently as possible with the least swelling so the newly generated neuronal cells can quickly migrate and be utilized. It seems the researchers at Conforti Lab made an effort to report findings rather than conclusions.

 

 



#42 richard hnry

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Posted 24 November 2016 - 02:35 AM

 

https://www.scienced...51210124557.htm This article nicotinamide mononucleotide is dangerous. It is highly toxic to neurons.

 

Neither the article or study state or even insinuate that nicotinamide mononucleotide is dangerous or that it itself is toxic to neurons.

 

 

... This research showed that NMN initiates axon degeneration both in neurons in lab cultures and in zebrafish models of acute injury and neurotoxicity.

Building on the earlier work, the current study demonstrates that NMN in injured axons works together with SARM1, a protein involved in the innate immune system -- the body's first line of defence against potential pathogens -- that plays a key role in axon degeneration, and kicks off a chain reaction leading to toxic levels of calcium and axon fragmentation.

 

One thing to keep in mind is that this degeneration of injured cells is required prior to microglia doing its job. Even in the zebrafish the degeneration is required prior to regeneration. If there are injured axons I want them them isolated, broken down and cleaned out as quickly and efficiently as possible with the least swelling so the newly generated neuronal cells can quickly migrate and be utilized. It seems the researchers at Conforti Lab made an effort to report findings rather than conclusions.

 

 

You are kidding right? The report clearly states that NMN degenerates neurons.  There is no other way to interpret it. In fact after axon degeneration within the neuron it  kicks off a chain reaction leading to toxic levels of calcium and axon fragmentation.  It is impossible to think that toxic levels of calcium and axon fragmentation are a good thing.  What they at are saying is that NMN is a precursor to NAD and that is good but it can also trigger destruction and damage to neurons resulting in a number of neurological diseases like PD, MS or Huntington's.  Take NMN at your own risk as it looks way too risky to me.


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#43 Bryan_S

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Posted 24 November 2016 - 07:51 PM

You are kidding right? The report clearly states that NMN degenerates neurons.  There is no other way to interpret it. In fact after axon degeneration within the neuron it  kicks off a chain reaction leading to toxic levels of calcium and axon fragmentation.  It is impossible to think that toxic levels of calcium and axon fragmentation are a good thing.  What they at are saying is that NMN is a precursor to NAD and that is good but it can also trigger destruction and damage to neurons resulting in a number of neurological diseases like PD, MS or Huntington's.  Take NMN at your own risk as it looks way too risky to me.

 

 

You do know what an Axotomy is don't you? They cut the axon off. Fragmentation of the cell is the natural result of such a severe injury.


Edited by Bryan_S, 24 November 2016 - 07:52 PM.

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#44 Anthony_Loera

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Posted 25 November 2016 - 04:02 PM

 

 

https://www.scienced...51210124557.htm This article nicotinamide mononucleotide is dangerous. It is highly toxic to neurons.

 

Neither the article or study state or even insinuate that nicotinamide mononucleotide is dangerous or that it itself is toxic to neurons.

 

 

... This research showed that NMN initiates axon degeneration both in neurons in lab cultures and in zebrafish models of acute injury and neurotoxicity.

Building on the earlier work, the current study demonstrates that NMN in injured axons works together with SARM1, a protein involved in the innate immune system -- the body's first line of defence against potential pathogens -- that plays a key role in axon degeneration, and kicks off a chain reaction leading to toxic levels of calcium and axon fragmentation.

 

One thing to keep in mind is that this degeneration of injured cells is required prior to microglia doing its job. Even in the zebrafish the degeneration is required prior to regeneration. If there are injured axons I want them them isolated, broken down and cleaned out as quickly and efficiently as possible with the least swelling so the newly generated neuronal cells can quickly migrate and be utilized. It seems the researchers at Conforti Lab made an effort to report findings rather than conclusions.

 

 

 

I totally agree with this Thell:

"If there are injured axons I want them them isolated, broken down and cleaned out as quickly and efficiently as possible with the least swelling so the newly generated neuronal cells can quickly migrate and be utilized."

 

 

So basically, in the study they injure the Axons, then wait to see what happens... 

 

"we found a marked increase in Ca2+levels in distal injured axons starting 2–3 hr after axotomy..."

"This Ca2+ rise just preceded the appearance of morphological damage and axon integrity was lost 10–25 min after Ca2+ started to increase"

 

But now it appears SARM1 is the real culprit... for the axon cleanup:

 

"We tested this possibility by adding NMN to transected Sarm1−/− axons and found that they remained intact for at least 4 days, even in the presence of high concentrations of exogenous NMN, which we even tested up to 5 mM (data not shown). In contrast, FK866-protected wild-type neurites degenerate within 3 hr when exposed to concentrations of NMN 200-fold lower. Thus, NMN requires SARM1 to induce axon degeneration."

 

And just for kicks... 

SARM1 the real cleanup culprit is found in another study as well...

http://science.scien...8/6233/453.full

 

From the study...

"SARM1 must function after injury to promote degeneration"

 

 

My non-scientific conclusion:

Damn you SARM1, you are acting like a parent telling his kid to clean up the mess in his room... geezz

 

Attached File  SARM1 Damnitall.jpg   37.38KB   2 downloads

 

 

IMHO after reading Thells summary and the study, It looks like NR and NMN are fine to take.


Edited by Anthony_Loera, 25 November 2016 - 04:24 PM.

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#45 Thell

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Posted 25 November 2016 - 07:38 PM

 

 

https://www.scienced...51210124557.htm This article nicotinamide mononucleotide is dangerous. It is highly toxic to neurons.

 

Neither the article or study state or even insinuate that nicotinamide mononucleotide is dangerous or that it itself is toxic to neurons.

 

 

... This research showed that NMN initiates axon degeneration both in neurons in lab cultures and in zebrafish models of acute injury and neurotoxicity.

Building on the earlier work, the current study demonstrates that NMN in injured axons works together with SARM1, a protein involved in the innate immune system -- the body's first line of defence against potential pathogens -- that plays a key role in axon degeneration, and kicks off a chain reaction leading to toxic levels of calcium and axon fragmentation.

 

One thing to keep in mind is that this degeneration of injured cells is required prior to microglia doing its job. Even in the zebrafish the degeneration is required prior to regeneration. If there are injured axons I want them them isolated, broken down and cleaned out as quickly and efficiently as possible with the least swelling so the newly generated neuronal cells can quickly migrate and be utilized. It seems the researchers at Conforti Lab made an effort to report findings rather than conclusions.

 

 

You are kidding right? The report clearly states that NMN degenerates neurons.  There is no other way to interpret it. In fact after axon degeneration within the neuron it  kicks off a chain reaction leading to toxic levels of calcium and axon fragmentation.  It is impossible to think that toxic levels of calcium and axon fragmentation are a good thing.  What they at are saying is that NMN is a precursor to NAD and that is good but it can also trigger destruction and damage to neurons resulting in a number of neurological diseases like PD, MS or Huntington's.  Take NMN at your own risk as it looks way too risky to me.

 

 

No Richard, I wasn't kidding; I was being sincere. The line of research that you happened upon is attempting to shed light on the processes of ion channel immunity responses. The innate immunity system is so amazingly complex that little is known regarding the particular trigger/response mechanisms. Thankfully, the constituents of the NAD cycle are getting put under the microscope (so to say) and findings like this are being published. I, for one, want to know exactly how NR and NMN supplementation will influence neuroregeneration and thank you for bringing it to the attention of the thread.

 

Anyhow, I personally believe we will find that NAD, or rather the balance of the constituents in the NAD cycle (particularly the salvage pathways) plays a crucial role in signalling for inflammation. Both good and bad! Research is already being published regarding NAMPT inhibition and inflammation response. This provides a hint as to why possible use of NAMPT inhibitor FK866 could result in some of the same benefits as is believed to exist in the WldS mouse.

 

Excerpt(emphasis mine)

Discovery of the Wlds mouse

During their investigations into the role of recruited myelomonocytic cells in WD of mouse peripheral nerve, M. C. Brown, V. H. Perry and their colleagues discovered, quite serendipitously, a spontaneous mutation in the C57Bl/6 line of mice supplied originally by Harlan-Olac (Lunn et al. 1989). The mutant mice show no readily discernible phenotype and they breed easily. What distinguishes these mice is that WD is significantly delayed and protracted after axotomy. Thus, the distal portion of cut axons and their motor nerve terminals remain morphologically intact for as long as 2 weeks. Remarkably, the isolated distal axons are still capable of conducting action potentials, and neuromuscular synapses continue to release neurotransmitter and recycle synaptic vesicles for several days, despite being disconnected from their cell bodies (Tsao et al. 1994; Ribchester et al. 1995). Both sensory and motor axons are delayed in their degeneration, and the mutation also delays WD in the central nervous system, for example following section of the optic nerve (Perry et al. 1990a; Ludwin & Bisby, 1992). The Wlds phenotype appears to be an age-dependent phenomenon, however; mice over 4 months of age appear to revert to the WD pattern of a wild-type (Perry et al. 1992; Tsao et al. 1994; Ribchester et al. 1995; Gillingwater et al. 2000; T. H. Gillingwater, D. Thompson, M. P. Coleman & R. R. Ribchester, manuscript in preparation; but see Crawford et al. 1995).

→ source (external link)

 

How awesome would it be to have and retain that ability?! And how can we get it? We can't yet; we haven't even identified the players. Quoting large blocks of text sucks, but it helps make the point so well that I can't resist...

 

Neurotraumaand Inflammation: CNS and PNS Responses

Excerpt

 

After a traumatic lesion, the axon becomes separated into two segments: a proximal segment that remains in contact with the cell soma and a distal segment that becomes separated from the neuron cell body. The distal nerve stump undergoes a cascade of events called WD [4, 105], while the proximal stump begins to be prepared for axon regeneration. WD is initiated within 24 to 48 h by the entry of calcium into the axoplasm, leading to activation of proteases, such as calpains, that promote axoplasm disintegration [106, 107]. Soon after this, macrophages are attracted to the site of injury and, together with SC, initiate intense phagocytosis and removal of the degenerating axon and myelin debris. Almost immediately after injury, Schwann cells in the distal stump of the nerve begin the process of differentiation and modify their gene expression [108] by decreasing myelin protein expression and start to express genes related to regeneration, such as c-Jun and growth-associated protein 43 (GAP-43), neurotrophic factors, neuregulins, and their receptors [17]. In addition, Schwann cells start to proliferate and migrate to form specialized cellular columns, referred to as Bands of Büngner, that act as a guide pathway for growing axons [17]. Inside these bands, Schwann cells support the growth potential of injured neurons by releasing basal lamina components such as laminin and type IV collagen [109–114]. When SC contacts the regenerating axons, the process of remyelination is started [115].
 
While the distal stump axon disintegrates and provides a permissive microenvironment for regeneration, it also generates signals that target the neuronal cell body, resulting in its change from transmitting to a growth-promoting phenotype. These changes reflect variations in the metabolic activity of neurons, which, as a result, start to produce substances that are important for axonal elongation, initiating the process of axon regeneration from the proximal stump [116]. But, how does inflammation affect the process of axon regeneration? In the injured peripheral nerve, the proinflammatory reaction accelerates the disintegration of nerve fibers but primarily prepares nonneuronal cells (i.e., glial and immune cells) and the distal stump microenvironment to receive newly growing axons. This scenario is best exemplified by the impaired axon regeneration when WD is disturbed [117–120] or when the macrophage response is deficient [18, 72, 85]. Conversely, augmented inflammation seems to improve axon regrowth, not only in injured peripheral nerves [19, 20] but also in the optic nerve, where regeneration barely occurs after trauma [24, 56, 121]. First, inflammation recruits circulating macrophages to efficiently phagocytize damaged myelin, which contains several axonal-growth inhibitors [122–124]. In addition to being involved in myelin clearance, macrophages are important sources of several factors related to promoting axonal regeneration, such as Ocm. They also release large quantities of IL-1β, and its production regulates the generation of nerve-growth factor (NGF) by fibroblasts and Schwann cells [125]. Another important aspect is the role of LIF (leukemia inhibitory factor) for neural regeneration [17]. After injury, LIF is retrogradely transported toward the cell body and induces the expression of regeneration-associated genes such as the activating transcription factor-3 [126] and growth-associated proteins [127, 128], among others [129]. Indeed, mice lacking LIF showed deficient peripheral nerve regeneration after lesion [130]. Although WD-derived inflammation is associated with several beneficial effects for axon elongation, the shutdown of this inflammatory process is also essential for nerve regeneration. Uncontrolled inflammation is the underlying reason for innumerable nerve pathologies, including neuropathic pain [131] and autoimmune diseases, such as Guillain-Barré syndrome [132].



→ source (external link)

 

I think Ca2+ is like spectators with dark glasses and a ball caps on at multiple crime scenes in that we aren't sure just how it gets signaled to come to the scene and at what point does it cross over from being another possibly helpful bystander to a suspected hindrance?

 

If the balance of extracellular NAD substrates is a signaller and Ca2+ is a modulator for inflammation and that inflammation is good in the peripheral but possibly not central systems then what can we do to help the system operate as effeciently as possible? I'd place my bet on the quicker the inflammation response and the faster macrophage (particularly microglia) activation with effective vaso-dilation and constriction(particularly of the BBB) the better; hence supplementation that helps in each of these areas is, to me, a positive. So NR, Resveratrol, Pterostilbene and Curcumin are already headliners here and NMN could be as well.


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#46 ClarkSims

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Posted 28 June 2017 - 12:33 AM

They are selling it now: https://www.revgenet...nucleotide.aspx

And the Sinclair news release:

https://www.scienced...70323141340.htm

 

It seems he has done several studies with nmn. He injected it in this study:

https://www.ncbi.nlm...les/PMC4990541/

NMN (Sigma N3501) was dissolved in PBS and injected i.p. daily 500 mg/kg body weight (Yoshino et al., 2011) for 17 days before sacrifice.

 

 

 



#47 ClarkSims

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Posted 28 June 2017 - 01:40 AM

This is his most publicized study:

https://www.research...uring-aging.pdf

 

Again he used injection:

A week of NMN treatment (500 mg/kg per day intraperitoneally)

 

It seems that he doesn't want to deal with the pharmicology or oral supplementation.

 



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#48 ryukenden

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Posted 29 June 2017 - 10:30 AM

From the posts above, I conclude that NMN is okay for brain and it facilitates clearing injured brain cells. Is that right?

 

I would like to know whether it increases the risks of dementia, Parkinson etc as well?

 

Many thanks


Edited by ryukenden, 29 June 2017 - 10:39 AM.




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