326 replies to this topic

[MikeDC]

Quote from this very recently released study:

https://www.scienced...550413118301220

"Whether or not NMN is taken up by a transporter is currently the subject of debate (Mills et al., 2016; Ratajczak et al., 2016). Brenner, Canto´ and colleagues argue that NMN is not taken up quickly enough to invoke the presence of a transporter and that both NAD+ and NMN undergo extracellular degradation to generate permeable precursors that can be taken up by cells (Ratajczak et al., 2016). On the other hand, Imai argues that this is likely a cell-type-specific phenomenon and that some cell types can rapidly take up NMN (Mills et al., 2016). If so, the identification of the putative transporter will help resolve the debate and help identify which cell types and tissues are able to transport NMN across the plasma membrane. Additional studies with isotopically labeled NAD+ precursors to trace the uptake and metabolism of these molecules should help answer these questions."

Mills et al., 2016 said nothing about some cells can rapidly take up NMN. It is not the speed that is relevant, it is the percentage of NMN that can get into cells before degradation or flushed into urine. A previous study comparing NR and NMN on cells in a dish showed NR and NMN yields similar results. But this study doesn’t translate into a living body because NMN can get flushed out in urine while NMN in a dish has no escape route. The Mills et al., 2016 study demonstrated that only a small percentage of NMN gets into cells since 300mg/kg NMN only raised NAD+ in liver and muscles by 14% for a short period of time. This compares with 185mg/kg NR raising NAD+ in liver and muscles by 100% for a much longer period of time. You can augue forever about how NR gets broken down or not, but NR is effective at raising NAD+ in all tissues tested while NMN is much less effective. A recentl study on NAM showed that NAM does not increase NAD+ in tissues or blood long term. Many people taking Niagen have found NR to be effective for many years without losing effectiveness long term. This is in agreement with the observation that many people who took NAM and Niacin for many years without obvious anti aging results started to see great anti aging results after starting NR. What counts is the end results. It is nice to know exactly how NR achieves the anti aging results, but it is more important to know it works.

Mikedc-"Mills et al., 2016 said nothing about some cells can rapidly take up NMN"

wrong... direct quote from Mills et al, 2016:

"NMN was quickly utilized to synthesize NAD+ in tissues"






Mikedc- "the percentage of NMN that can get into cells before degradation or flushed into urine."



You keep making this claim that NMN is "flushed out in urine", which I have never seen any basis for, other than your imagination.

In fact, this study shows NMN is retained in the body far longer than NAM:

"β-Nicotinamide Mononucleotide, an Anti-Aging Candidate Compound, Is Retained in the Body for Longer than Nicotinamide in Rats"

Also you admit NR -> NMN-> NAD+, yes? But somehow, you imagine that exogenous NMN has no effictient route and gets flushed away, but exogenous NR -> NMN and THAT NMN is somehow different, and doesn't "get flushed away"? Why do you believe this?





Mikedc - "The Mills et al., 2016 study demonstrated that only a small percentage of NMN gets into cells since 300mg/kg NMN only raised NAD+ in liver and muscles by 14% for a short period of time"

Yes, mice fed NMN for 1 year, HALF THEIR LIFE, saw increase NAD+ of 14% in the muscle.

I'm sure you know what homeostasis is.

The Elysium study showed NR elevated NAD+ in liver an impressive 90% at one month, which decreased to 40% at three months. You would have to test for 30 years in humans to have a valid comparison. As you know, in mice, there is also NO comparable 12 month study with NR. You keep comparing apples and oranges.

“NMN was quickly utilized to synthesize NAD” this sentence does not describe the experimental data.
The data shows only a small fraction of NMN entered cells and converted to NAD+. The efficiency is 6400% less than NR for area under the curve.

[MikeDC]

http://m.jbc.org/con...83/10/6367.full

This paper shows NAD+ can be effectively transported into cells. So NAD+ doesn’t need to degrade to NAM and NMN to enter cells.
This explains why NAD+ IV has been proven effective. It also explains why NR is so effective even though bioavailability is poor.

[Nate-2004]

Ignoring Mike DC's posts, as everyone should do at this point, thanks for that answer Lawrence et. al. I thought that might be why NMN may be more advantageous than NR at least theoretically. I agree we need several years more research on it (and frankly an abolishment of the patent system) to get anymore details about the answers to this question. I'm still taking some HPN NR these days and have reported my experience on the experiences thread, but I trust unbiased published research independently funded by someone other than patent holders like Chromadex.

 

Side note, if there's anything that Mike DC has demonstrated on this board it is three things: 1) He's a Chromadex shill. 2) It takes less than half the number of posts to develop a negative reputation on this board, which is funny. 3) I'm pretty sure he's the troll who's been randomly marking everyone's posts as ill informed in pretty much every part of this forum.

Edited by Nate-2004, 18 March 2018 - 06:02 PM.

[MikeDC]

Ignoring Mike DC's posts, as everyone should do at this point, thanks for that answer Lawrence et. al. I thought that might be why NMN may be more advantageous than NR at least theoretically. I agree we need several years more research on it (and frankly an abolishment of the patent system) to get anymore details about the answers to this question. I'm still taking some HPN NR these days and have reported my experience on the experiences thread, but I trust unbiased published research independently funded by someone other than patent holders like Chromadex.

Side note, if there's anything that Mike DC has demonstrated on this board it is three things: 1) He's a Chromadex shill. 2) It takes less than half the number of posts to develop a negative reputation on this board, which is funny. 3) I'm pretty sure he's the troll who's been randomly marking everyone's posts as ill informed in pretty much every part of this forum.

Ignore my posts? I am the only one that can make sense with data. You guys are twisting data.

[able]

“NMN was quickly utilized to synthesize NAD” this sentence does not describe the experimental data.
The data shows only a small fraction of NMN entered cells and converted to NAD+. The efficiency is 6400% less than NR for area under the curve.

 
 
NO.  
 
Again, you are comparing 1 YEAR in a mouse, vs a very short time period in humans.  (we don't really know exactly, as you refuse to link to the studies you are using)
 
The data DOES show very clearly, that NMN raised NAD+ in MUSCLE in 10 minutes  - much faster than any studies on NR.

Edited by Michael, 19 May 2018 - 06:45 PM.
trim quotes

[MikeDC]

“NMN was quickly utilized to synthesize NAD” this sentence does not describe the experimental data.
The data shows only a small fraction of NMN entered cells and converted to NAD+. The efficiency is 6400% less than NR for area under the curve.

NO.

Again, you are comparing 1 YEAR in a mouse, vs a very short time period in humans. (we don't really know exactly, as you refuse to link to the studies you are using)

The data DOES show very clearly, that NMN raised NAD+ in MUSCLE in 10 minutes - much faster than any studies on NR.

First speed doesn’t matter. What matters is the total area under the curve. Second, even though NAD+ peaked at hour 6 for NR, the NAD+ raised at shorter time frames are comparable to NMN. The amount of NAD+ raised by NMN is negligible under the NR curve.

Edited by Michael, 19 May 2018 - 06:49 PM.
clean quotes

[MikeDC]

I challenge the NMN camp to show a human study at 250mg dose that can raise NAD+ by even 5%. Most likely it will be undetectable.

[LawrenceW]

Moderator.

 

When I got back to my computer I was all excited to see a vast number of responses to this thread waiting for me to read.  Imagine my disappointment when the vast majority turned out to be NR rants from Mike DC.

 

The title of this thread is:  

nicotinamide mononucleotide (NMN)

 

Please remove every single NR rant by MikeDC from this thread.

 

Thank you.

 

Lawrence

Edited by LawrenceW, 18 March 2018 - 10:19 PM.

[TMNMK]

We could go on and on about NR vs NMN and get all emotional about it but the reality is that what we say here will not make much of a difference until we have more data directly comparing the two. I think in five or ten years we'll know more, but who wants to wait that long when we can listen to our bodies and let that speak for itself. So I take both. NMN is vastly more expensive so I only take about 100-150mg NMN each day whereas generally I take greater than 1g/day NR. I added NMN into my regimen (which is simply D3, NR, NMN) only maybe three or four months ago, I haven't noticed any difference between the time that I was strictly taking NR versus taking both. I still feel amazing! But I continue to take the NMN because there is some debate about differences in tissue distribution and why not right? NR definitely has an excellent safety profile and I would would imagine that NMN does as well (at least we know that LawrenceW is still alive to talk about it). I've debated ceasing NR for a month or two in order to see if NMN does its job but unfortunately at such small doses I'm afraid such a test would not tell me much, my guess is that I would cease getting the tangible benefits that I do from NR and would not be able to attribute this to efficacy given the vast difference in molar quantities being taken. Furthermore, NMN ~334 mol/g whereas NR is ~255 mol/g, which means that for each milligram of NR you take, you'd have to take ~1.3mg NMN so not only is NMN immensely more expensive but you would have to take significantly more of it to reasonably compare the two. In summary, for me personally I'm absolutely NOT going to stop taking NR (that is now a permanent part of my life!) and I may or may not continue with NMN but I'm pretty sure it won't hurt to keep it around (and it may be reaching some types of cells that NR may not be reaching).

 

Oh and MikeDC, I love that you are passionate about NR because I am too! But that does not mean that I am dispassionate about NMN and nor should any other scientifically-minded individual be. The entire NAD metabolome (that I am sure we have not yet fully elucidated) is fascinating and biology has a way of surprising even the most informed among us. So let it play out, it is enjoyable to be surprised!

Edited by TMNMK, 19 March 2018 - 11:53 AM.

[MikeDC]

1. Can you tell us how much you pay for 100 mg of NMN?

2. I think NR and NMN is dangerous because when the two molecules interact, they annihilate upon impact and release gamma rays. Gamma rays = bad. That's all according to MikeDC

Take as much NMN as you want. But don’t post false information to lure others to take it. Let’s stop the discussion until some human data becomes available for NMN.

[bluemoon]

 Thanks for the responses.

[LawrenceW]

Stefan_001

 

Before you edited your post you posted  "I bought 0,25% of Chromadex shares for the fun of it, nothing else."   CDXC is currently trading at $5.05 per share with a market cap of $270M.  Your 0.25% shareholding is worth over $660,000 at today's price.  That hardly makes you an unbiased supporter of NR.

[stefan_001]

Remember I read this study some time ago, seems more relevant now that NMN does not seem to be effective in muscle to raise NAD:

 

However, NMN protection was absent in hearts perfused without glucose (i.e. with palmitate as respiratory substrate). In isolated cardiomyocytes, NMN induced rapid and large-scale cytosolic acidification (fluorescent pH reporter), with increased glycolytic flux (Seahorse XF) yielding lactate (LC-MS/MS based metabolomics). Glycolysis requires NAD+ and is known to be beneficial during hypoxia. As such, our data suggest that protection afforded by an NMN-induced elevation in NAD+ may simply be due to glycolytic stimulation rather than SIRT1 activation. Consistent with this, western blot for acetyl-lysine (as a surrogate for in-situ sirtuin activity) showed that NMN drove protein deacetylation in mitochondrial and nuclear compartments, but not in cytosol where cardiac SIRT1 is located. We conclude the benefit of NMN in IR and potentially other disease states is mediated via stimulation of glycolysis. Caution is thus urged, in the human therapeutic use of NAD+ boosting dietary supplements.

https://www.scienced...891584917310316

Edited by stefan_001, 21 March 2018 - 06:51 PM.

[shadowhawk]

From my stack.  I take a small glass of this every day and it gives me a real boost,

NAD+ May Contribute to Longer Telomeres
NAD+ Promotes DNA Repair
NAD+ Modulates Immune-Cell Signaling
NAD+ Induces Energy-Intensive Enzymes
NAD+ Promotes Chromosome Stability
NAD+ Is a Neurotransmitter
NAD+ Activates Sirtuins 1-7
NAD+ Supports Energy Production
 
     Pau D' Arco Bark Milk
Here's the science The anti-aging, anti-inflammatory, anti-oxidant and anti-cancer benefits of a compound called “Nicotinamide Adenine Dinucleotide” (NAD).  A compound called “beta-lapachone” can massively increase levels of NAD, and that this pricey chemical can actually be quite inexpensively obtained via a pau d' arco tree bark tea from the Peruvian jungles.
How?
Follow this recipe:
-Mix 1-2 teaspoons of pau d' arco tree bark with 4-8 ounces of warm water and allow it to sit overnight for 10-12 hours.
-In a good blender for 2-3 minutes, blend the water and soaked bark with fats, which will form liposomes that can increase absorption of the beta-lapachone from the tea. For fats, you can use ghee, brain octane oil , coconut oil, olive oil, fish oil or full fat coconut milk The best solution, aside from a special krill oil formulation that is not yet available on the market, is simply a half teaspoon of organic, non-GMO sunflower lecithin, which contains good amounts of phosphatidylcholine, an excellent way to make phospholipids.

-For even more absorption, add 1-2 teaspoons of organic turmeric powder to this mixture.
1800 mg betaine and the hydrogen peroxide two drops of 35%.
-Strain after blending.

You can then use the resulting foamy white bark “milk” as an ingredient in smoothies or shakes, or you can drink it straight.


Experiments on mice by Professor Sinclair and his team showed that after just a week of being fed NMN - NAD dissolved in their drinking water, the cells of ageing mice were indistinguishable from those of young mice. Their muscles looked and behaved like those of a young mouse, too.

In human terms, it was the equivalent of a 60-year-old’s cells and muscles transforming into those of a 20-year-old.

[MikeDC]

From my stack. I take a small glass of this every day and it gives me a real boost ...

Pau D' Arco Bark Milk
Here's the science The anti-aging, anti-inflammatory, anti-oxidant and anti-cancer benefits of a compound called “Nicotinamide Adenine Dinucleotide” (NAD). A compound called “beta-lapachone” can massively increase levels of NAD, and that this pricey chemical can actually be quite inexpensively obtained via a pau d' arco tree bark tea from the Peruvian jungles.

There is no solid evidence that beta-lapachone increases NAD+. On the contrary it depletes NAD+.

“β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion”

Edited by Michael, 19 May 2018 - 06:56 PM.
trim quotes

[able]

 

You can argue what you want but these findings pose questions wrt NMN. If the results were the other way around I would dump all my chromadex shares at opening of the market. Perhaps NMN can have other usefull roles but for the tissues studied here there is no reason to take it over NR, quite the opposite.

 

You can argue what you want also and cherry pick the parts you like.  

 

But if you believed ALL of this study, you would have sold all of your Chromadex stock 2 days ago when you notice that none of the oral NR makes it to bloodstream and is no better than NAM.

 

Of course neither one of us believe that one data point is 100% accurate and applies to all oral NR intake.

 

But you want to pick and choose the parts that seem to benefit Chromadex share price as gospel, and ignore others.

 

For the "tissues studied here", ORAL NMN was roughly equal to NR, except for skeletal muscle, where NR seems to result in  slightly increased quantity of labeled NAD+.  

 

You want to say that barely noticeable blip in the chart proves NR is superior to NMN. 

 

Edited by able, 22 March 2018 - 02:55 AM.

[Michael]

As Lawrence correctly notes, this whole discussion of RevGen NR is off-topic in an NMN thread; unless anyone objects, I'm going to create a new dedicated thread on that subject and move the relevant posts there.

 

Having received no objections and a couple of approvals, I have now somewhat belatedly created a thread on Suppliers of NMN with posts from this thread.

 

I similarly think it would make sense to move all the recent discussion of comparative pharmacodynamics of NR and NMN sparked by the Liu thesis into the existing thread on NAD+ increase from oral intake of NR and NMN. What do y'all think?

[able]

 

As Lawrence correctly notes, this whole discussion of RevGen NR is off-topic in an NMN thread; unless anyone objects, I'm going to create a new dedicated thread on that subject and move the relevant posts there.

 

Having received no objections and a couple of approvals, I have now somewhat belatedly created a thread on Suppliers of NMN with posts from this thread.

 

I similarly think it would make sense to move all the recent discussion of comparative pharmacodynamics of NR and NMN sparked by the Liu thesis into the existing thread on NAD+ increase from oral intake of NR and NMN. What do y'all think?

 

 

Sure, combining this Liu thesis with the NAD+ increase thread seems a great fit.  

 

But I'm confused - are you moving all other posts from here to "suppliers of NMN" and this thread goes away?

 

So there would be no thread for general discussion of NMN, like personal experiences, dosages used, and such?  

 

Why not a personal experiences with NMN thread, like there is with NR?

 

I would really dislike having no dedicated place to discuss NMN, at least partially shielded from the constant barrage from NR fans.

Edited by able, 22 March 2018 - 03:41 AM.

[stefan_001]

 

 

You can argue what you want but these findings pose questions wrt NMN. If the results were the other way around I would dump all my chromadex shares at opening of the market. Perhaps NMN can have other usefull roles but for the tissues studied here there is no reason to take it over NR, quite the opposite.

 

You can argue what you want also and cherry pick the parts you like.  

 

But if you believed ALL of this study, you would have sold all of your Chromadex stock 2 days ago when you notice that none of the oral NR makes it to bloodstream and is no better than NAM.

 

Of course neither one of us believe that one data point is 100% accurate and applies to all oral NR intake.

 

But you want to pick and choose the parts that seem to benefit Chromadex share price as gospel, and ignore others.

 

For the "tissues studied here", ORAL NMN was roughly equal to NR, except for skeletal muscle, where NR seems to result in  slightly increased quantity of labeled NAD+.  

 

You want to say that barely noticeable blip in the chart proves NR is superior to NMN. 

 

 

Sure we will see what future studies say. I my view, this study is positive for NR shareholder:

- clear difference in behavior compared to NMN. As the investment case is about "healthy aging" and frailty in elderly that is an important aspect. Its a good outcome that NR impacts muscle NAD strongly versus NMN

- It kinda helps to put in a worst case scenario.for NR. The study shows NR does circulate (although that was already known as Michael points out in the sublingual thread). Sublingual administration is not a big issue in my view, people will do that to stay healthy longer.

 

Its already known that NR is a very effective pre-cursor to raise NAD in blood despite open topics about first pass metabolism so in that way this study does not improve or worsen that.

 

But is an NMN thread so better to move the debate elsewhere.
 

Edited by stefan_001, 22 March 2018 - 08:01 AM.

[LawrenceW]

Does the Liu thesis confirm that both NMN and NR are delivery vehicles to get NAM to the liver where it is converted to NAD+ ready for distribution to the body?

Edited by LawrenceW, 22 March 2018 - 10:56 AM.

[Michael]

 

 

As Lawrence correctly notes, this whole discussion of RevGen NR is off-topic in an NMN thread; unless anyone objects, I'm going to create a new dedicated thread on that subject and move the relevant posts there.

 
Having received no objections and a couple of approvals, I have now somewhat belatedly created a thread on Suppliers of NMN with posts from this thread.
 
I similarly think it would make sense to move all the recent discussion of comparative pharmacodynamics of NR and NMN sparked by the Liu thesis into the existing thread on NAD+ increase from oral intake of NR and NMN. What do y'all think?

 

 
Sure, combining this Liu thesis with the NAD+ increase thread seems a great fit.  
 
But I'm confused - are you moving all other posts from here to "suppliers of NMN" and this thread goes away?
 
So there would be no thread for general discussion of NMN, like personal experiences, dosages used, and such?  
 
Why not a personal experiences with NMN thread, like there is with NR?
 
I would really dislike having no dedicated place to discuss NMN, at least partially shielded from the constant barrage from NR fans.

 

I'm all for people setting up a thread for personal experiences with NMN: that way, people interested in dueling anecdotes could corral the discussion there, without it interfering with discussion of actual science .

 

I'm certainly not trying to make this thread go away; I am, however, trying to get extended discussions on specific topics grouped together where they can be found, rather than simultaneously scattered in multiple threads and half-lost in a giant omnibus thread.

 

Similarly, I just moved several posts about sublingual use into the existing thread on that subject.

Edited by Michael, 22 March 2018 - 04:52 PM.

[LawrenceW]

NMN personal experience thread can be viewed at http://www.longecity...erience-thread/

[hav]

Remember I read this study some time ago, seems more relevant now that NMN does not seem to be effective in muscle to raise NAD:

 

However, NMN protection was absent in hearts perfused without glucose

 

  ...

 

Caution is thus urged, in the human therapeutic use of NAD+ boosting dietary supplements.

https://www.scienced...891584917310316

 

Not sure the general caution expressed regarding dietary oral ingestion of any NAD+ boosting supplement is fair since the study administered NMN (not NAD+) by "perfusion" which I take it was by direct injection into the bloodstream just ahead of the heart.

 

Howard

[TRUGAN]

So 1000 mg of NR might be a better dose now?

 

https://www.nature.c...467-018-03421-7

 

I've been taking the recommended 250mg dose without any noticeable benefits. I'm trying to decide now if I should step it up to 500mg of NR and maybe 500mg of NMN or just 1000mg of NR.

 

I thought that I read in another study that 500mg of NR didnt do any better than 250mg. Taking 1000mg of NR is going to be expensive.

 

 

 

[MikeDC]

So 1000 mg of NR might be a better dose now?

https://www.nature.c...467-018-03421-7

I've been taking the recommended 250mg dose without any noticeable benefits. I'm trying to decide now if I should step it up to 500mg of NR and maybe 500mg of NMN or just 1000mg of NR.

I thought that I read in another study that 500mg of NR didnt do any better than 250mg. Taking 1000mg of NR is going to be expensive.

It depends on each person. Most people get good benefits at 250mg. Some don’t feel anything at 250mg. These people should take 500mg.

[able]

But then is there a reason to take NMN sublingualy when I can take NR sublingually and for quite a bit less money?

 

The alivebynature powder is $69 for 12 grams.

 

Revgenetics is the only pure NR I have found, and it is quite a bit more $.  I've used that and NMN powder. Not enough to tell if their is a difference for me.

 

Niagen at $30 for a  7.5 gram bottle is less $ per Mg if you don't mind opening capsules and taking the fillers.

[Michael]

With the permission of parties involved, it seems merited to split off a thread dedicated to intranasal NMN/NR delivery.

[able]

I'd bet Sinclair has a well defined pathway to big $$$$.

 

One of his companies was granted this patent in March, for NMN derivatives:

 

https://patents.just...9919003#history

 

And that most recent mouse study used NMN in combination with H2s.

 

He's probably holding off on publishing the results from the study with humans until he has all his ducks lined up and products ready to go.

[stefan_001]

I'd bet Sinclair has a well defined pathway to big $$$$.

 

One of his companies was granted this patent in March, for NMN derivatives:

 

https://patents.just...9919003#history

 

And that most recent mouse study used NMN in combination with H2s.

 

He's probably holding off on publishing the results from the study with humans until he has all his ducks lined up and products ready to go.

 

Absolutely he could go for a combination product, but he will be significantly exposed to parties like ABN who just sell them as separate items. I remember that derivatives IPR but that seems to have a long road ahead of it.

[TMNMK]

With the permission of parties involved, it seems merited to split off a thread dedicated to intranasal NMN/NR delivery.

 

I'm good with that Michael