326 replies to this topic

[stefan_001]

For those that doubt NMN is not on Chromadex radar:
http://www.freepaten...17/0296564.html

[TMNMK]

relatedly, it's always funny to me on these boards when I hear someone say "Aha, they must be making a different salt to get around the patent!"

Oh lordy, if a patent got out the door without a "or salt thereof" someone would most certainly find themselves in a new career.

[stefan_001]

relatedly, it's always funny to me on these boards when I hear someone say "Aha, they must be making a different salt to get around the patent!"
Oh lordy, if a patent got out the door without a "or salt thereof" someone would most certainly find themselves in a new career.

Sounds you have experience in chemistry and IPR! There are quite a few discussions about the Chromadex - Elysium Health clash. At least I am not able to piece together Elysium's plan for NR beyond trying to strong arm Chromadex into a better deal or then make their own version of NR. Would you have a view on that....as it seems the folks that wrote up the IPR havent started a new career recently....?

Edited by stefan_001, 17 November 2017 - 08:58 AM.

[TMNMK]

 

relatedly, it's always funny to me on these boards when I hear someone say "Aha, they must be making a different salt to get around the patent!"
Oh lordy, if a patent got out the door without a "or salt thereof" someone would most certainly find themselves in a new career.

Sounds you have experience in chemistry and IPR! There are quite a few discussions about the Chromadex - Elysium Health clash. At least I am not able to piece together Elysium's plan for NR beyond trying to strong arm Chromadex into a better deal or then make their own version of NR. Would you have a view on that....as it seems the folks that wrote up the IPR havent started a new career recently....?

 

 

Some, but unfortunately I have nothing substantive on that from the business angle. You know as much as I do if not more. Suffice to say at the end of the day it is good news for everyone if companies are fighting over it. 

[Invicta Immortalem]

Anyone tried the product from BuckyLabs?

It seems the cheapest product on the market currently at 9.32 $/g.

[able]

Anyone tried the product from BuckyLabs?

It seems the cheapest product on the market currently at 9.32 $/g.

 

Looks like someone had labels printed out on a cheap home printer, then had their 9 year old glue them on with elmers glue in their garage.   

 

Don't see anything that says it was mfg in a GMP facility.

 

I don't like slamming a brand just because they are inexpensive, but that is not exactly confidence inspiring.

[Invicta Immortalem]

I will post here their CoA - it is from a Chinese lab, made in 2016.

 

I'm not saying it is 100% fake, but it has to be verified in a trustworthy lab (like Intertek etc).

 

On the other side, BuckyLabs (and his owner Mr. Darren Moore) has done a pretty good job in manufacturing the Carbon 60 olive oil solution (fullerene).

 

I hope that BuckyLabs will give us a more reliable CoA, otherwise I will contact Intertek myself for testing the stuff.

Attached Files

•  NicotinamideMononucleotide-COA chinese.jpg   224.35KB   1 downloads

Edited by Invicta Immortalem, 10 December 2017 - 07:00 PM.

[Invicta Immortalem]

LE: Alive by Nature has just released NMN pure at 6,12$/g, with a strong lab CoA.

 

I think that this product has an interesting price and launch the options for supplementing consecutive or combined NMN + NR.

[LawrenceW]

LE: Alive by Nature has just released NMN pure at 6,12$/g, with a strong lab CoA.

 

I think that this product has an interesting price and launch the options for supplementing consecutive or combined NMN + NR.

 

I have been taking NMN for the better part of 2 years and I personally will not take any that is less than 98% pure. Apparently that last step of getting over 98% is very tricky.

[Invicta Immortalem]

 

LE: Alive by Nature has just released NMN pure at 6,12$/g, with a strong lab CoA.

 

I think that this product has an interesting price and launch the options for supplementing consecutive or combined NMN + NR.

 

I have been taking NMN for the better part of 2 years and I personally will not take any that is less than 98% pure. Apparently that last step of getting over 98% is very tricky.

 

 

Now, that we compare providers, it looks that RevGenetics provide NMN with 99.20% purity at 12,65$/g and Alive by Nature provide NMN with 99.88% at 6.12$/g.

 

Though, I am surprised that Fractal Health did not reply A. Loera's Intertek test with their own (no FH CoA by now).
 

Maybe, after the market is stabilizing, we can make a gross-selling group deal with the most reliable provider, like we did with HPN for NR.

[able]

 

 

LE: Alive by Nature has just released NMN pure at 6,12$/g, with a strong lab CoA.

 

I think that this product has an interesting price and launch the options for supplementing consecutive or combined NMN + NR.

 

I have been taking NMN for the better part of 2 years and I personally will not take any that is less than 98% pure. Apparently that last step of getting over 98% is very tricky.

 

 

Now, that we compare providers, it looks that RevGenetics provide NMN with 99.20% purity at 12,65$/g and Alive by Nature provide NMN with 99.88% at 6.12$/g.

 

Though, I am surprised that Fractal Health did not reply A. Loera's Intertek test with their own (no FH CoA by now).
 

Maybe, after the market is stabilizing, we can make a gross-selling group deal with the most reliable provider, like we did with HPN for NR.

 

 

Last February,  Anthony tested the Fractal Health NMN  at Intertek, and found it was something like 5 mg of NMN instead of the 125 claimed. (In the first review of this product)

 

https://www.amazon.c.../dp/B01MRVUAWU/

 

Subsequently, they listed a new NMN product with  pterostilbene.  Fractal did send for testing at Intertek in April, and  shows 99% purity. (in the images they included in the product listing)

 

https://www.amazon.c.../dp/B071CSK7VJ/

 

Is 30 capsules of 250 mg NMN and 250 mg ptero for $59.

 

So if the 99% purity is valid, seems a lot better than their previous NMN, and not  much more than Elysium Basis.

 

One concern is, we don't know if the sample they sent to Intertek for testing is actually what is in the bottle, or just a good sample that was diluted after testing.

 

Guess someone would have to send a sample directly from a bottle, as Anthony did, to be sure.

Edited by able, 11 December 2017 - 06:47 AM.

[Ron H]

I started reading this forum to help me decide how to boost my cellular NAD⁺ levels in a safe, reliable and affordable way.

 

At first, the answer seemed simple: go for something NR-based.

 

Guarente's group recently reported that NRPT (NR + pterostilbene) increases NAD⁺ levels in humans in a safe and sustainable way¹, and e.g. Elysium Basis (essentially NRPT) is produced in facilities that meet FDA requirements and undergoes 'rigorous third-party purity testing' (see https://www.elysiumhealth.com/basis). A year's supply costs a bit less than $500 (https://www.elysiumh...om/product-plan ).

 

Nevertheless, LawrenceW's remark that he (and everybody else in his group) experienced dramatic improvements while taking NMN and no effects when taking NR got me worried. I am aware that LawrenceW's experience is anecdotal, but still, it's the best we've got.

 

The difference between experienced (and measured) effects of NMN vs NR made me wonder if measuring blood NAD⁺ levels gives sufficient information.

 

If you look at Figure 1 from the study by Trammell et al², you can see that NMN is a direct precursor of NAD⁺, whereas there are two options for NR: it either goes to NAD⁺ (via NMN), or it goes to Nam. Nam, in turn, is either further metabolized and excreted, or it is used to salvage NAD⁺ (via NMN). Remarkably, as mentioned in the Trammell paper, the enzyme (NAMPT) involved in this latter process declines with age.

 

 Figure 1.docx   50.87KB   6 downloads

 

This means that when someone takes NMN this will result in increased NAD⁺ levels, whereas some who takes NR will have increased NAD⁺ levels AND increased Nam levels. In fact, this is what Trammell and colleagues find, as you can see in their Figure 2 (I pasted part of this Figure below).

 

 Figure 2.docx   83.65KB   6 downloads

 

Increased Nam levels will shift the equilibrium NAD⁺ <-> Nam to the left (see Fig. 1), that is, it will inhibit the consumption of NAD⁺ by NAD⁺ consuming enzymes.

 

In other words, NMN is expected to increase NAD⁺ levels, whereas NR is expected to increase NAD⁺ levels together with the levels of a substance (Nam) that will inhibit the consumption of NAD⁺ by NAD⁺ consuming enzymes.

 

If my reasoning is correct, this would be a big vote in favor of the use of NMN over that of NR. This brings us back to the issue of safety, reliability and affordability – of NMN in this case. The suppliers mentioned by Invicta Immortalem look promising, but I prefer to wait for one to come up with e.g. NSF certification, as Alivebynature promises. I am also curious to see the soon-to-be-released human clinical NR studies that Stefan_001 mentioned.

 

References

1. Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study Dellinger RW, Roel Santos S, Morris M, Evans M, Alminana D, Guarente L & Marcotulli E. npj Aging and Mechanisms of Disease 3, Article number 17 (2017) https://www.nature.c...hor-information Creative Commons license: http://creativecommo...icenses/by/4.0/
2. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Trammell SAJ, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, & Brenner C. Nature Communications 7, Article number 12948 (2016) https://www.nature.c...les/ncomms12948 ) Creative Commons license: http://creativecommo...icenses/by/4.0/

 

 

 

Edited by Ron H, 11 January 2018 - 04:01 PM.

[Michael]

LawrenceW's remark that he (and everybody else in his group) experienced dramatic improvements while taking NMN and no effects when taking NR got me worried. I am aware that LawrenceW's experience is anecdotal, but still, it's the best we've got.

No, it's not the best we've got: it's the worst we've got. The best we've got is controlled human trials and well-done animal studies.
 

The difference between experienced (and measured) effects of NMN vs NR made me wonder if measuring blood NAD⁺ levels gives sufficient information.
 
If you look at Figure 1 from the study by Trammell et al², you can see that NMN is a direct precursor of NAD⁺, whereas there are two options for NR: it either goes to NAD⁺ (via NMN), or it goes to Nam. Nam, in turn, is either further metabolized and excreted, or it is used to salvage NAD⁺ (via NMN). Remarkably, as mentioned in the Trammell paper, the enzyme (NAMPT) involved in this latter process declines with age.

This means that when someone takes NMN this will result in increased NAD⁺ levels, whereas some who takes NR will have increased NAD⁺ levels AND increased Nam levels.

That doesn't follow. Supplementing with NMN will raise NAM levels just as taking NR does, for the same principal reason: after they are converted to NAD+, NAD+ is consumed by PARPs, sirtuins, et al, an ddegraded to NAM. Indeed, NR goes to NAM precisely through NMN:

 

 

 

[able]

Wouldn't anything that increases NAD+  also increase NAM downstream?

 

It sounds like Ron H is talking about the initial path of NR and NMN to NAD+.

 

How much NR and NMN get digested to NAM first?

 

The most recent review talks about this:

 

NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR 

 

 

 

"a substantial fraction of orally administered NR is likely converted into nicotinamide by first-pass metabolism in the liver or by hydrolysis in the blood circulation before its uptake into other tissues in vivo (Figure 2) "

 

they also theorize some NMN may also go thru NAM before NAD+:

 

"Similarly, NMN may be subjected to first-pass meta- bolism or converted into NR by ectonucleotidases and then de- grades into nicotinamide before uptake (Figure 2). "

 

Maybe I don't understand that entirely, but it sounds to me like they believe  substantial fraction of NR goes thru NAM.  And some NMN may also.  But currently we don't have any idea what the percentages are.

 

 

 

 

 

 

[Ron H]

I am new to this forum, and I haven't managed to neatly quote comments made by other users and then put my own comment below.  So here goes the 'dirty way':

 

Michael said that 'The best we've got is controlled human trials and well-done animal studies.' 

In general terms I agree with that (of course), but I am not aware of any published outcomes of controlled human trials. If you are, I would be more than happy if you would share them with us. Regarding animals studies, they are valuable as a first step, but we never know if what is true for mice also holds true for humans until human trials are done. 

 

Michael also said '... Indeed, NR goes to NAM precisely through NMN'.  The point I was trying to make is that apart from the NR->NMN->NAD-> Nam pathway, there is also a direct NR->Nam route (at least according to Fig. 1 I attached), i.e. in your figure there seems to be an arrow missing that goes directly from NR or to Nam. That means that x% of NR gets converted into Nam through NAD, and(100-x)% of NR is directly converted into Nam without passing through NAD.

 

I hope this also answers part of your comments, able. Regrettably I don't have full access to the paper you quoted, because it looks quite interesting. And you are quite right that we don't know the percentage of NR that is directly converted into Nam without passing through NAD - thanks for pointing that out. 

Edited by Ron H, 11 January 2018 - 07:38 PM.

[stefan_001]

NAM:

 

However, once administered to cells, NAM is rapidly converted to NAD+ and, therefore, the cellular concentration of NAM decreases rapidly while that of NAD+ increases. The result would be an inhibition of SIRT1 for a limited duration, followed by an increase in the activity.

https://link.springe...0018-017-2527-8

 

[Ron H]

NAM:

 

However, once administered to cells, NAM is rapidly converted to NAD+ and, therefore, the cellular concentration of NAM decreases rapidly while that of NAD+ increases. The result would be an inhibition of SIRT1 for a limited duration, followed by an increase in the activity.

https://link.springe...0018-017-2527-8

Interesting, stefan_001, but I'm not sure if this is applicable to humans taking NMN or NR.

 

First, seeing the abstract, I get the impression that the authors are talking about cells in culture because they are mentioning NAM administered to cells (again, I don't have access to the full paper). If you artificially increase intracellular NAM, part of it will be methylated and further metabolized away from NAD+; another part will be converted to NAD+, via NMN. Over time NAD+ levels will increase, NAM levels will decrease, and e.g. SIRT1 will be activated.

 

If, on the other hand, you increase intracellular NMN levels (be it through direct NMN administration or through NR administration), you will decrease the amount of NAM that is converted to NMN (and hence to NAD+) and increase the amount that is methylated and catabolized. NMN or NR administration by itself will already lead to increased NAD+ levels, and in that sense it does not really matter where the NAD+ comes from. What does matter is the relative NAM concentration, i.e. whether it is decreased (as in the paper you quote) or whether it is elevated (as in the Trammel paper I mentioned in my first post).

 

Increased NAD+ and decreased NAM levels will stimulate NAD+ consuming enzymes, but if you increase NAD+ levels and NAM levels at the same time the effect will be a lot less – if any.

[stefan_001]

"Accordingly, the NAD+/NADH ratio was significantly increased (Figure 2B), and the ratio between acetylated and total FOXO1, a direct target of Sirt1, was clearly reduced (Figure 2C) in skeletal muscle of NR-treated versus vehicle-treated Sco2KOKI and WT animals"

http://www.sciencedi...550413114001648

[Michael]

 

 

Ron H wrote: LawrenceW's remark that he (and everybody else in his group) experienced dramatic improvements while taking NMN and no effects when taking NR got me worried. I am aware that LawrenceW's experience is anecdotal, but still, it's the best we've got.

No, it's not the best we've got: it's the worst we've got. The best we've got is controlled human trials and well-done animal studies.

In general terms I agree with that (of course), but I am not aware of any published outcomes of controlled human trials. If you are, I would be more than happy if you would share them with us. Regarding animals studies, they are valuable as a first step, but we never know if what is true for mice also holds true for humans until human trials are done.

If by "outcomes" you mean hard outcomes, you're right, of course. Still, the human trial data and animal exp'ts in normal, otherwise-healthy aging rodents are still better evidence than anecdotal non-evidence.
 
Additionally, while I have no direct knowledge of him or his motivations, it bears bearing in mind that LawrenceW came out of nowhere, with no prior contact with our community, to announce that he and his fellow participants were getting miraculous results with a product that was only potentially affordably available through his organization — an organization with some extremely sketchy scientific information, laughable parodies of patent applications, and that solicits "“accredited” investors (that have the appropriate health to participate) looking to assess [their proprietary supplement and company] for possible investment into [their] Reg D 506c SEC registered offering" to participate in their "trial," which in turn requires participants to pay for both their supply of the test agent and for diagnostic testing to include some of the more expensive analytes.
 

 

 

Ron H wrote: NMN is a direct precursor of NAD⁺, whereas there are two options for NR: it either goes to NAD⁺ (via NMN), or it goes to Nam. Nam, in turn, is either further metabolized and excreted, or it is used to salvage NAD⁺ (via NMN). Remarkably, as mentioned in the Trammell paper, the enzyme (NAMPT) involved in this latter process declines with age.

This means that when someone takes NMN this will result in increased NAD⁺ levels, whereas some who takes NR will have increased NAD⁺ levels AND increased Nam levels.

That doesn't follow. Supplementing with NMN will raise NAM levels just as taking NR does, for the same principal reason: after they are converted to NAD+, NAD+ is consumed by PARPs, sirtuins, et al, an ddegraded to NAM. Indeed, NR goes to NAM precisely through NMN:

 

The point I was trying to make is that apart from the NR->NMN->NAD-> Nam pathway, there is also a direct NR->Nam route (at least according to Fig. 1 I attached), i.e. in your figure there seems to be an arrow missing that goes directly from NR or to Nam. That means that x% of NR gets converted into Nam through NAD, and(100-x)% of NR is directly converted into Nam without passing through NAD+

Sure — I did say "the principle way." The point I was trying to make was that both supplements will lead to NAM production via their production of NAD+.  Before replying to you, I did invest what was probably an excessive amount of time trying to find data on the relative use of NR by NRKs vs. by PNP in mammalian cells at normal physiologic NR concentration and/or after supplementation — or at least, the relative Kms of the two reactions — and came up empty-handed.
 
In any case, there's an argument to be made that the distinction won't play out in vivo, particularly intracellularly. Remember (or know ye!), the best evidence — particularly after PMID 27725675, whose thoroughness impresses me — is that NMN has to be converted to NR outside of the cell prior to cellular uptake, and then reconverted to NMN via the same NRK-dependent mechanism as "primary" NR does. So at least inside the cell, the production of NAM should be the same from both supplements. Extracellular NAD+ production from NMN via eNAMPT would not have this problem, tho' whether such extracellular production is beneficial or not is not clear to me.
 
Curiously, however, in cell culture, NR elevated both intracellular NAD+ and NAM levels much more than equimolar NMN:
 

 

Figure 4 | Extracellular NMN dephosphorylates to NR. Nat Commun. 2016 Oct 11;7:13103. doi: 10.1038/ncomms13103.

 
Further complicating matters, it appears possible that more NR is degraded into NAM in circulation — see their suggestive Supplementary Fig. 4. However, this is in medium alone or serum-supplemented medium, and therefore doesn't capture the effects of CD73 or eNAMPT.

Edited by Michael, 14 January 2018 - 10:36 PM.

[Ron H]

Hello Michael,

 

I understand that you are suspicious of LawrenceW's contributions to this forum, but the possibility remains that he is sincere and that his experiences are real. He may have a commercial interest, but so do Sinclair and Brenner. Be it as it may, I agree with you that his experiences are anecdotal and should be regarded with caution.

 

Regarding the science, maybe I should start by rephrasing my original statements: in my opinion, if you want to define a cell's potential to activate NAD-consuming enzymes (with the concomitant production of Nam) one should not just consider NAD levels, but also the NAD/Nam ratio.

 

You are absolutely right when you say that inside the cell the production of NAM should be the same from NMN and NR since NMN needs to be converted to NR outside of the cell prior to uptake. My original comment that NMN should be better than NR because some NR is directly converted to Nam whereas all NMN is converted to NAD is therefore invalid.

 

Nevertheless, the paper by Brenner's group you mentioned ('the Ratajczak paper', PMID 27725675) provided me with some other ammunition in favor of NMN over NR. To be clear, I am not in favor of one compound or the other. I just want to decide, based on available data and with the help of this forum, if one is better than the other.

 

First, there is the matter of stability of NR vs NMN in serum.

 

According to Ratajczak's data, some 66% of NR incubated in serum disappears in 1 hour, whereas NMN is stable under these conditions. The observation that NR is partially converted into Nam does not tell me much: if you compare the counts in their Figs 8e and 8g, you can see that only some 5% of NR is converted into Nam. This may still be a lot under their experimental conditions (high doses and short incubation times, and suggested by their supplementary Fig. 4c), but I wonder how this translates to humans taking low doses of NMN or NR once or twice daily.

 

I could make the case that oral NMN is stable in plasma and that orally ingested NMN will lead to levels of circulating NMN that are much higher than the levels of circulating NR in the case of equimolar orally ingested NR. In addition, CD73 might serve as a specific 'NMN receptor' that produces high levels of NR close to the cell; much of this NR may be taken up by the cell before factors present in plasma would have a chance to convert NR into Nam and whatever else it may be converted to. Thus, NMN would be better at boosting intracellular NR levels than NR itself when levels of circulating NR are low.

 

Ratajczak's suggestion that NR may be circulating in a cell-associated form in animals with a lifetime of hours may be correct and thus change the picture, but at present this is not backed by any direct experimental data.

 

Second, there is the matter of CD73.

 

A general line of reasoning, at least by people posting in this forum, is that NR is better than NMN at boosting NAD+ synthesis, simply because NMN needs to be converted by CD73 to NR before it can enter the cell, whereas NR itself enters the cell directly. In fact, this seems to be corroborated by most head-to-head comparisons of NR and NMN in the Ratajczak paper. Such comparisons are shown in Figs 2d and e, 4, 5e, 6a (controls), 7 and 8a.

However, there are a few caveats here:

• First, it should be kept in mind that in Figs 1-7 very high NR concentrations are used and that therefore the cells' equilibrative nucleoside transporters (ENTs) may be saturated. This would mask any advantage that a local increase in NR concentration through NMN dephosphorylation by CD73 might have.
• The cell lines used in Figures 2 and 4 have low levels of CD73:
  • In Figure 2 3T3 cells are used. Apparently, only some 3% of NIH/3T3 cells express CD73 (see Fig. 3 of ref. 1)
  • In Figure 4 HepG2 cells are used. In human liver, alternative splicing of the NTE5E gene (encoding CD73) leads to two transcripts: NT5E-1 encoding functional CD73, and NT5E-2 encoding an inactive form of CD73 that lacks 5′-nucleotidase activity and that promotes degradation of active CD73². Relative to the normal human liver, the expression levels of the NT5E-2 transcript are increased by one to two orders of magnitude in the HepG2 cell line, whereas NT5E-1 levels are decreased (see Fig. 3 of ref. 2).
• In Figs 5 and 6 hepatocytes from WT or NRK1KO mice are used, but the cells were grown under serum-free conditions. Again, the absence of serum and concomitant very high NR concentrations might mask any advantage that a local increase in NR concentration through NMN dephosphorylation by CD73 might have.
• In Figs 7 and 8 whole animals are used. The mouse strain used in this study is a derivative of the C57BL strain and, for what it's worth, in a comparative study the livers of C57BL mice were shown to contain significantly less CD73 protein- and mRNA levels than another strain³. Nevertheless, I find it striking that in Figure 7 of the Ratajczak paper only in kidney the effects of NR and NMN are indistinguishable, and that CD73 levels in this organ are clearly higher than in the other tissues (cf. their supplementary Fig. 3a). In Figure 8 10-fold lower doses of NR and NMN are used and here the advantage of NR over NMN disappears.

 

Taken together, I think that the conclusion that NR is better than NMN at boosting NAD+ synthesis is only true when dealing with very high NR concentrations and low CD73 levels. I find it premature to conclude that NR would be better than NMN at raising tissue NAD+ levels in humans taking low doses of NR or NMN.

 

References

1. Murine Embryonic Fibroblast Cell Lines Differentiate into Three Mesenchymal Lineages to Different Extents: New Models to Investigate Differentiation Processes. Dastagir K, Reimers K, Lazaridis A, Jahn S, Maurer V, Strauß S, Dastagir N, Radtke C, Kampmann A, Bucan V, and Vogt PM. Cell Reprogram. 2014; 16(4): 241–252.
2. Alternative splicing of human NT5E in cirrhosis and hepatocellular carcinoma produces a negative regulator of ecto-5′-nucleotidase (CD73). Snider NT, Altshuler PJ, Wan S, Welling TH, Cavalcoli J, Omarya MB. Mol Biol Cell. 2014; 25(25): 4024–4033.
3. CD73 (ecto-5'-nucleotidase) hepatocyte levels differ across mouse strains and contribute to mallory-denk body formation. Snider NT, Griggs NW, Singla A, Moons DS, Weerasinghe SV, Lok AS, Ruan C, Burant CF, Conjeevaram HS, Omary MB. Hepatology. 2013;58(5):1790-800.

 

[MikeDC]

NMN or NR is the better NAD+ precursor?

300mg/kg NMN increased NAD+ in liver and muscle by less than 20%.
185mg/kg NR doubled NAD+ in the liver.

My speculation is it doesn’t matter which NAD+ precursor you use, most NAD+ are generated in the liver
And released to blood stream. These NAD+ become precursors for other organs.

Based on this data, NMN is the worst NAD+ precursor.

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Edited by MikeDC, 09 February 2018 - 03:48 PM.

[able]

NMN or NR is the better NAD+ precursor?

300mg/kg NMN increased NAD+ in liver and muscle by less than 20%.
185mg/kg NR doubled NAD+ in the liver.

My speculation is it doesn’t matter which NAD+ precursor you use, most NAD+ are generated in the liver
And released to blood stream. These NAD+ become precursors for other organs.

Based on this data, NMN is the worst NAD+ precursor.

 

So, based on your theory, NA and NAM are the BEST NAD+ precursors?

 

NA is much faster and elevates NAD+ about the same amount as NR.

 

NAM elevates NAD+ in the liver much more (per mg)  than NR or NMN.

 

This is according to the Brenner/Trammel research in humans.

 

https://www.nature.c...12948/figures/5

 

(Chart 5b shows NR elevates NAD+ slightly more than NAM, but the study was deceptive in using molar weight, meaning 255 of NR vs 122 of NAM)

[MikeDC]

I have no doubt Nicotinamide and Niacin are effective NAD+ precursors. But both Nicotinamide and Niacin are not effective Sirtuin activators.
I can give you one example here. A 70 year old physician who has been on slow release Niacin for 5 years and he has stage 2 kidney disease based on blood work. He has never experienced rejuvenating effects from High dose Niacin. But after one year of Niagen, he has improved his health and energy considerably. His stage 2 kidney disease is cured and he plays tennis like a young person.

[MikeDC]

I have a coworker who has diabetes and on metformin. His A1C were consistently near mid 6 range. After 2 weeks of Niagen, his A1C dropped to 5.9. He said if his A1C dropps to normal range in another few weeks, he will buy a big position of CDXC. He had a hip replacement surgery and on sick leave. So I don’t know if it happened not not.

You need Sirt1 activators to normalize insulin sensitivity. NR can do it. But Nicotinamide and Niacin can’t.

[MikeDC]

Everyone knows Nicotinamide causes insulin resistance. I also read Niacin reviews on Amazon that said it causes big insulin resistance on some Niacin users. So large doses of both are bad for health.

https://www.ncbi.nlm...ulin resistance

Niaspan increases insulin resistance in the liver.

“Eight weeks of Niaspan(®) treatment in dyslipidemic patients with metabolic syndrome induce hepatic insulin resistance. The mechanism could involve an accumulation of diacylglycerol and an ”

Edited by MikeDC, 09 February 2018 - 06:20 PM.

[NoodleHead]

Hi there, I've just picked up some Bucky Labs NMN 125mg (30 pills), I plan to take 250mg a day for 2 weeks as a initial test (Split morning and evening). I'm a 36 years old man, maybe a little young to see profound results, but the signs of aging have definitely started to appear! I'm testing with the plan of getting my father (aged 65) to start his own trial.

 

Reading through this thread, there's a lot of interesting information. I'm not going to wade into the NR vs NMN discussion as I don't believe there's enough evidence yet to say anything with certainty. I did try some niagen NR a year ago (250mg a day) and found that it made me feel very toxic with headache after only a week (maybe it was not NR, but it did bear the niagen brand name). 3 doses of NMN in, and I have no side effects as yet.

 

LawrenceW, thanks for sharing your experience! So they seem to have gone straight in with the equivalent rat dose for humans. This strikes me a little reckless, normal procedure is to start low and work up to the effective dose for humans. Which if you convert from the rat dose is about 500mg a day NMN for me as a 73kg human. I would expect that optimum would be found at the 500mg-1g range which would be far less damaging to our wallets, and minimizes any risk.

 

Hopefully buckylabs are selling the real deal. I shall report back soon.

 

 

 

 

[stefan_001]

Hi there, I've just picked up some Bucky Labs NMN 125mg (30 pills), I plan to take 250mg a day for 2 weeks as a initial test (Split morning and evening). I'm a 36 years old man, maybe a little young to see profound results, but the signs of aging have definitely started to appear! I'm testing with the plan of getting my father (aged 65) to start his own trial.

 

Reading through this thread, there's a lot of interesting information. I'm not going to wade into the NR vs NMN discussion as I don't believe there's enough evidence yet to say anything with certainty. I did try some niagen NR a year ago (250mg a day) and found that it made me feel very toxic with headache after only a week (maybe it was not NR, but it did bear the niagen brand name). 3 doses of NMN in, and I have no side effects as yet.

 

LawrenceW, thanks for sharing your experience! So they seem to have gone straight in with the equivalent rat dose for humans. This strikes me a little reckless, normal procedure is to start low and work up to the effective dose for humans. Which if you convert from the rat dose is about 500mg a day NMN for me as a 73kg human. I would expect that optimum would be found at the 500mg-1g range which would be far less damaging to our wallets, and minimizes any risk.

 

Hopefully buckylabs are selling the real deal. I shall report back soon.

 

Never heard of anybody that they got headaches from Niagen. Expensive this NMN product you are promoting, what is the origin?

[stefan_001]

on that note anybody buying this:

https://www.amazon.c...customerReviews

 

would be interesting to hear some experiences.

[NoodleHead]

 

Hi there, I've just picked up some Bucky Labs NMN 125mg (30 pills), I plan to take 250mg a day for 2 weeks as a initial test (Split morning and evening). I'm a 36 years old man, maybe a little young to see profound results, but the signs of aging have definitely started to appear! I'm testing with the plan of getting my father (aged 65) to start his own trial.

 

Reading through this thread, there's a lot of interesting information. I'm not going to wade into the NR vs NMN discussion as I don't believe there's enough evidence yet to say anything with certainty. I did try some niagen NR a year ago (250mg a day) and found that it made me feel very toxic with headache after only a week (maybe it was not NR, but it did bear the niagen brand name). 3 doses of NMN in, and I have no side effects as yet.

 

LawrenceW, thanks for sharing your experience! So they seem to have gone straight in with the equivalent rat dose for humans. This strikes me a little reckless, normal procedure is to start low and work up to the effective dose for humans. Which if you convert from the rat dose is about 500mg a day NMN for me as a 73kg human. I would expect that optimum would be found at the 500mg-1g range which would be far less damaging to our wallets, and minimizes any risk.

 

Hopefully buckylabs are selling the real deal. I shall report back soon.

 

Never heard of anybody that they got headaches from Niagen. Expensive this NMN product you are promoting, what is the origin?

 

 

Hi , yes I've not seen any one else reporting headaches either but I can only tell you what I experienced. There are people who felt worse from NR though on this forum. I'm not promoting any product, I'm just here to tell you how I got on with the first NMN I've acquired. If you read up someone posted that the Bucky labs NMN is from a Chinese lab, there is also a certificate of analysis posted as well. No one has said anything about their experiences with Bucky labs NMN as yet so I thought Id post here for others to read. I may also try the Revgenetics NMN in future too, depends how I get on. I have a history of being quite unlucky with side effects from supplements and medicines so I'm just hoping I can tolerate NMN and that the product is authentic.

[able]

on that note anybody buying this:

https://www.amazon.c...customerReviews

 

would be interesting to hear some experiences.

 

I tried the Alivebynature NMN for 4 weeks.  Personally, I couldn't tell much difference from Niagen myself.    I see a lot more variation in health due to my exercise, sleep, and keto diet, so is often hard for me to point to changes as being from supplements.

 

Over the last month I  have also used a jar of the revegenetics powder with no filler.  I have had a significant improvement in prostate issues (BPH) after a few weeks taking this sublingual.

 

Probably a coincidence.  I don't recall anyone else reporting prostate improvement from NR or NMN, but maybe decreased inflammation?

Edited by able, 11 February 2018 - 08:42 PM.