192 replies to this topic

[stefan_001]

 

 

 

Any ideas why Revgentics sells a bottle of 50mg of NMN for $38, whereas Alive By Nature sells 125 mg for $45 according to able but Amazon sells it for $86, K-to Go 125 mg for $40 and Gene 125 mg for $40?

If NMN turns out to be as effective as NR then Chromodex's patents won't matter, which should push the prices of both NR and NMN over time.

NMN is 31% heavier than NR. So NMN needs to be 31% cheaper than NR.

 

 

The study uses a lot of relative graphs but the IV graphs in 2.7 do clearly show a larger relative impact on NAD levels from NR with a big difference for muscle. And if you look at the circulating NAM you could also speculate that more NR gets processed inline with the higher relative NAD levels. Considering that equal amount of NMN and NR were injected and that NMN is heavier that makes sense. But the difference in weight doesnt account for the difference of NAD levels in muscle. In elder people muscle atrophy is an important factor so NR is clearly doing a much much better job there.

 

Overall I would say that NR is double effective at the same dose.

 

 

 

The charts clearly do not show NR twice as effective at the same dose.  Oral NR shows slightly more effect in liver, while oral NMN shows more in kidney.    

 

As the authors point out, it is in muscle they see a difference.  

 

Obviously, that is important. 

 

But again, this is very small, single dosages in healthy animals, that did cut off at 135 minutes.

 

We don't know what the results will be for humans, or, the larger doses that we are all taking over months.

 

 

Which graphs are you looking at? In the IV (and probably sublingual use) graphs there is a clear difference also in kidney I would say area under the curve >1.5x better in case of NR. In muscle the difference is more like a factor 5 x. Circulating NAM in IV is closer to each other, it would have been great to have values in a table but looking closely NR circulating NAM is definetely higher. For oral use the difference in circulating NAM is clearly higher for NR >1.5x. Given the step difference for impact on muscle I stick to my "average" 2 x effectiveness difference. Probably its even more relative effectiveness on health as the difference likely also applies to heart muscle.

 

Edited by stefan_001, 21 March 2018 - 01:00 PM.

[MikeDC]

Almost all mice studies so far have flaws. Tremmall study had a bad NAD+ data points at 120 minutes where NAD+ elevation was almost zero compared to hour 6. While this study showed NAD+ was significantly elevated at 135 minutes.

As I said before the golden standard is clinical trials. If clinical trials show NR and NMN is much more effective at improving health than NAM, then these mice studies are wrong.

[MikeDC]

Any ideas why Revgentics sells a bottle of 50mg of NMN for $38, whereas Alive By Nature sells 125 mg for $45 according to able but Amazon sells it for $86, K-to Go 125 mg for $40 and Gene 125 mg for $40?

If NMN turns out to be as effective as NR then Chromodex's patents won't matter, which should push the prices of both NR and NMN over time.

NMN is 31% heavier than NR. So NMN needs to be 31% cheaper than NR.

The study uses a lot of relative graphs but the IV graphs in 2.7 do clearly show a larger relative impact on NAD levels from NR with a big difference for muscle. And if you look at the circulating NAM you could also speculate that more NR gets processed inline with the higher relative NAD levels. Considering that equal amount of NMN and NR were injected and that NMN is heavier that makes sense. But the difference in weight doesnt account for the difference of NAD levels in muscle. In elder people muscle atrophy is an important factor so NR is clearly doing a much much better job there.

Overall I would say that NR is double effective at the same dose.

The charts clearly do not show NR twice as effective at the same dose. Oral NR shows slightly more effect in liver, while oral NMN shows more in kidney.

As the authors point out, it is in muscle they see a difference.

Obviously, that is important.

But again, this is very small, single dosages in healthy animals, that did cut off at 135 minutes.

We don't know what the results will be for humans, or, the larger doses that we are all taking over months.

Which graphs are you looking at? In the IV (and probably sublingual use) graphs there is a clear difference also in kidney I would say area under the curve >1.5x better in case of NR. In muscle the difference is more like a factor 5 x. Circulating NAM in IV is closer to each other, it would have been great to have values in a table but looking closely NR circulating NAM is definetely higher. For oral use the difference in circulating NAM is clearly higher for NR >1.5x. Given the step difference for impact on muscle I stick to my "average" 2 x effectiveness difference. Probably its even more relative effectiveness on health as the difference likely also applies to heart muscle.

It would be interesting to see a NMN study that monitors NAD+ for up to 15 hours.

[able]

The authors have all the numbers, and say nothing about a difference in NAD+ boosting for anything other than SKELETAL muscle.

 

Heart is not the same as skeletal muscle, which is what they are looking at here.

 

 

 

[stefan_001]

The authors have all the numbers, and say nothing about a difference in NAD+ boosting for anything other than SKELETAL muscle.

 

Heart is not the same as skeletal muscle, which is what they are looking at here.

 

well I think you can see the kidney graph, pretty obvious. For the muscle graph I am happy it looks this way and not the other way around - do you think its likely that NR will be more effective in hearth muscle or would you put your money on NMN?

Attached Files

•  kidney.JPG   33.5KB   0 downloads

[able]

Yes, as I have said NUMEROUS times, in this study, at this dosage, NR appears more effective (or maybe faster)  at elevating Nad+ in skeletal muscle.

 

Do you really think that is the same as Heart?  So now you are with Mike, trying to imagine possibilities in every bit of research, rather than just interpreting what it says?

 

I notice you posted the kidney graphs for IP, which is not what ANYONE on this forum does.  Why didn't you post the image for kidney graphs for ORAL, where NMN appears to be slightly more effective?  Cherry picking.    

 

Really, using these charts that show the relative contribution of labeled nad to the total, and pointing out minute differences is just silly and meaningless.  The authors didn't mention a difference (besides skeletal muscle) , because it is in the noise.

Edited by able, 21 March 2018 - 02:39 PM.

[stefan_001]

Yes, as I have said NUMEROUS times, in this study, at this dosage, NR appears more effective (or maybe faster)  at elevating Nad+ in skeletal muscle.

 

Do you really think that is the same as Heart?  So now you are with Mike, trying to imagine possibilities in every bit of research, rather than just interpreting what it says?

 

I notice you posted the kidney graphs for IP, which is not what ANYONE on this forum does.  Why didn't you post the image for kidney graphs for ORAL, where NMN appears to be slightly more effective?  Cherry picking.  

 

That is what I wrote "IV" in my post which in my "imagination" is representative for sublingual use which I also wrote in the same message. You are tiring, you think everything that is written here is about share holder interest and so on. You are not commenting the circulating NAM graph in the oral use case, what does that difference tell, happy to hear your imagination or as you write "just interpret what it says"?

 

And yes I think that a good chance that NR has similar effect on heart muscle, if you look in the NRK expression you will see those are at similar levels

Edited by stefan_001, 21 March 2018 - 02:56 PM.

[able]

 

The authors have all the numbers, and say nothing about a difference in NAD+ boosting for anything other than SKELETAL muscle.

 

Heart is not the same as skeletal muscle, which is what they are looking at here.

 

well I think you can see the kidney graph, pretty obvious. For the muscle graph I am happy it looks this way and not the other way around - do you think its likely that NR will be more effective in hearth muscle or would you put your money on NMN?

 

 

I don't see any mention of IV in THIS post - is what I was referring to.  You "cherry picked" a chart for IV usage to try and show NR is superior, which isn't relative to oral capsules that everyone here is interested in.

 

You and Mike claimed the study shows NR twice as effective as NMN at boosting NAD+.

 

I said it seems to be for Skeletal muscle only, and other tissues seem about the same.

 

I have been talking about for oral supplements only.

 

Agree that IP or sublingual does look a lot more beneficial after this study.

Edited by able, 21 March 2018 - 03:53 PM.

[stefan_001]

 

 

The authors have all the numbers, and say nothing about a difference in NAD+ boosting for anything other than SKELETAL muscle.

 

Heart is not the same as skeletal muscle, which is what they are looking at here.

 

well I think you can see the kidney graph, pretty obvious. For the muscle graph I am happy it looks this way and not the other way around - do you think its likely that NR will be more effective in hearth muscle or would you put your money on NMN?

 

 

I don't see any mention of IV in THIS post - is what I was referring to.  You "cherry picked" a chart for IV usage to try and show NR is superior, which isn't relative to oral capsules that everyone here is interested in.

 

Oh please check #322 to which you replied and I wrote: "Which graphs are you looking at? In the IV (and probably sublingual use) graphs there is a clear difference also in kidney I would say area under the curve >1.5x better in case of NR"

 

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.

 

well that is all relative, probably should not have written about that. Anyways the fun part is that in any company with that level of holding you get straight answers when you write to CxOs :-)

[able]

 

Yes, as I have said NUMEROUS times, in this study, at this dosage, NR appears more effective (or maybe faster)  at elevating Nad+ in skeletal muscle.

 

Do you really think that is the same as Heart?  So now you are with Mike, trying to imagine possibilities in every bit of research, rather than just interpreting what it says?

 

I notice you posted the kidney graphs for IP, which is not what ANYONE on this forum does.  Why didn't you post the image for kidney graphs for ORAL, where NMN appears to be slightly more effective?  Cherry picking.  

 

 You are not commenting the circulating NAM graph in the oral use case, what does that difference tell, happy to hear your imagination or as you write "just interpret what it says"?

 

 

Several studies suggest NR is utilized for NAD+  in the liver to a greater degree than NMN.  This study also shows a slightly higher  increase in Liver NAD+ with NR vs NMN.

 

Elevating liver NAD+ is not difficult.  As you know, Tramell shows all the precursors are effective at that.  NA is the fastest, while NAM elevates NAD+ the most, mg per mg.

 

This study says NR and NMN increase NAD+ in the liver, which is excreted as NAM for use throughout the body:

"Other tissues, in contrast, relied almost exclusively on circulating NAM made by the liver. Liver synthesis of NAD and excretion of NAM occurred even when serum NAM was elevated by co-infusion of tryptophan and NAM; thus, liver constitutively produces NAM to support NAD synthesis throughout the rest of the body"

 

The slightly larger increase in liver NAD+  from NR would then result in the slightly larger increase in circulating NAM you are pointing out.

 

I actually think that is an argument for NMN, not NR,  as I believe it is preferable to reach other tissues, not be relegated to liver NAD+.

 

Where does the NMN go that is not used in liver is a good question.  

 

I haven’t seen anything to suggest NMN  is somehow trapped and pissed away.

 

In fact, this study shows NMN remains in the body longer than NAM.  

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

 

So, yes, this study found NR was more easily detected in muscle, and slightly more in liver NAD and then NAM.   

 

That doesn’t indicate the NMN is somehow “wasted” or not effective.

Edited by able, 21 March 2018 - 07:19 PM.

[Michael]

You guys appear to be misinterpreting Fig. 2.7e in the Thesis. You're reading it as if it shows the level of NAD+, or NAD+ boost, resulting from administration of IV and oral NR and NMN — which is not what it shows. What it shows is what percentage of the NAD+ in the tissue at time of measure is derived from pre-existing or late-salvage NAD+ (M+0), or directly from parent supplement (M+2), or from NAM derived from early metabolism of supplement (M+1). None of that tells you the actual level of NAD+ in the tissue is at that time— just the fractional breakdown of what's there. I haven't read the paper, but I don't see anywhere where actual levels of NAD+ following supplementation are given.

[MikeDC]

Yes, as I have said NUMEROUS times, in this study, at this dosage, NR appears more effective (or maybe faster) at elevating Nad+ in skeletal muscle.

Do you really think that is the same as Heart? So now you are with Mike, trying to imagine possibilities in every bit of research, rather than just interpreting what it says?

I notice you posted the kidney graphs for IP, which is not what ANYONE on this forum does. Why didn't you post the image for kidney graphs for ORAL, where NMN appears to be slightly more effective? Cherry picking.

You are not commenting the circulating NAM graph in the oral use case, what does that difference tell, happy to hear your imagination or as you write "just interpret what it says"?

Several studies suggest NR is utilized for NAD+ in the liver to a greater degree than NMN. This study also shows a slightly higher increase in Liver NAD+ with NR vs NMN.

Elevating liver NAD+ is not difficult. As you know, Tramell shows all the precursors are effective at that. NA is the fastest, while NAM elevates NAD+ the most, mg per mg.

This study says NR and NMN increase NAD+ in the liver, which is excreted as NAM for use throughout the body:
"Other tissues, in contrast, relied almost exclusively on circulating NAM made by the liver. Liver synthesis of NAD and excretion of NAM occurred even when serum NAM was elevated by co-infusion of tryptophan and NAM; thus, liver constitutively produces NAM to support NAD synthesis throughout the rest of the body"

The slightly larger increase in liver NAD+ from NR would then result in the slightly larger increase in circulating NAM you are pointing out.

I actually think that is an argument for NMN, not NR, as I believe it is preferable to reach other tissues, not be relegated to liver NAD+.

Where does the NMN go that is not used in liver is a good question.

I haven’t seen anything to suggest NMN is somehow trapped and pissed away.

In fact, this study shows NMN remains in the body longer than NAM.
"β-Nicotinamide Mononucleotide, an Anti-Aging Candidate Compound, Is Retained in the Body for Longer than Nicotinamide in Rats"

So, yes, this study found NR was more easily detected in muscle, and slightly more in liver NAD and then NAM.

That doesn’t indicate the NMN is somehow “wasted” or not effective.

We will need an NMN study that tracks NAD+ to 15 hours to know if NMN is wasted or not.

[MikeDC]

You guys appear to be misinterpreting Fig. 2.7e in the Thesis. You're reading it as if it shows the level of NAD+, or NAD+ boost, resulting from administration of IV and oral NR and NMN — which is not what it shows. What it shows is what percentage of the NAD+ in the tissue at time of measure is derived from pre-existing or late-salvage NAD+ (M+0), or directly from parent supplement (M+2), or from NAM derived from early metabolism of supplement (M+1). None of that tells you the actual level of NAD+ in the tissue is at that time— just the fractional breakdown of what's there. I haven't read the paper, but I don't see anywhere where actual levels of NAD+ following supplementation are given.

You are correct. But we do get a sense of NAD+ contribution from precursors.

[able]

You guys appear to be misinterpreting Fig. 2.7e in the Thesis. You're reading it as if it shows the level of NAD+, or NAD+ boost, resulting from administration of IV and oral NR and NMN — which is not what it shows. What it shows is what percentage of the NAD+ in the tissue at time of measure is derived from pre-existing or late-salvage NAD+ (M+0), or directly from parent supplement (M+2), or from NAM derived from early metabolism of supplement (M+1). None of that tells you the actual level of NAD+ in the tissue is at that time— just the fractional breakdown of what's there. I haven't read the paper, but I don't see anywhere where actual levels of NAD+ following supplementation are given.

 

 

Yes, thanks Michael.  I understand that it shows the RELATIVE amount of M+1 or M+2 of NAD, and not the absolute amount.

 

Stefan also mentioned relative and I'm sure also understands that.

 

I just didn't dwell on that detail as things are getting confused.  

 

I also don't see anywhere that they point to the change in absolute level.

 

As they are measuring over a short period, I thought it likely that the relative amount of labelled NAD+ detected gives a fair indication of the contribution NR/NMN has made to the NAD+ pool.   

 

Is there a plausible scenario that the relative quantity of labelled NAD+ is not a valid indicator of total NAD?

[stefan_001]

 

 You are not commenting the circulating NAM graph in the oral use case, what does that difference tell, happy to hear your imagination or as you write "just interpret what it says"?

 

Several studies suggest NR is utilized for NAD+  in the liver to a greater degree than NMN.  This study also shows a slightly higher  increase in Liver NAD+ with NR vs NMN.

 

Elevating liver NAD+ is not difficult.  As you know, Tramell shows all the precursors are effective at that.  NA is the fastest, while NAM elevates NAD+ the most, mg per mg.

 

This study says NR and NMN increase NAD+ in the liver, which is excreted as NAM for use throughout the body:

"Other tissues, in contrast, relied almost exclusively on circulating NAM made by the liver. Liver synthesis of NAD and excretion of NAM occurred even when serum NAM was elevated by co-infusion of tryptophan and NAM; thus, liver constitutively produces NAM to support NAD synthesis throughout the rest of the body"

 

The slightly larger increase in liver NAD+  from NR would then result in the slightly larger increase in circulating NAM you are pointing out.

 

I actually think that is an argument for NMN, not NR,  as I believe it is preferable to reach other tissues, not be relegated to liver NAD+.

 

Where does the NMN go that is not used in liver is a good question.  

 

I haven’t seen anything to suggest NMN  is somehow trapped and pissed away.

 

In fact, this study shows NMN remains in the body longer than NAM.  

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

 

So, yes, this study found NR was more easily detected in muscle, and slightly more in liver NAD and then NAM.   

 

That doesn’t indicate the NMN is somehow “wasted” or not effective.

 

When you look at the IV graphs in figure 2.7d you can see that NMN is never detected to be in circulation even after the infusion of NMN. In fact is shows that NMN is converted to NR as that increases in circulation after NMN infusion. So I find your theory that NMN is preferable to reach other tissues unlikely. Combine that with the graphs that show the increases in tissue NAD in the IV case really points to less effectiveness of NMN. My speculation is that the reason we see some increase in NAD+ in the muscle case for NMN infusion is because the NR goes a bit up in circulation and that enters the muscle.

 

Moreover if you look in figure 2.5. you can see that muscle is slow in using NAM to elevate NAD so that supports the point that NR is able to boost NAD in muscle because it goes into circulation and reaches the muscle and NMN does not. So NMN is converted into something, my guess NAM and NR and does nothing or little by itself.

 

(The paper says this about NAD fluxes: Mouse tissues vary markedly in NAD fluxes and turnover rates, with liver, lung, spleen, and small intestine having a turnover half-time faster than any of the tested cultured cell lines, and skeletal muscle slower)

 

Edited by stefan_001, 21 March 2018 - 09:46 PM.

[able]

 

 

 You are not commenting the circulating NAM graph in the oral use case, what does that difference tell, happy to hear your imagination or as you write "just interpret what it says"?

 

Several studies suggest NR is utilized for NAD+  in the liver to a greater degree than NMN.  This study also shows a slightly higher  increase in Liver NAD+ with NR vs NMN.

 

Elevating liver NAD+ is not difficult.  As you know, Tramell shows all the precursors are effective at that.  NA is the fastest, while NAM elevates NAD+ the most, mg per mg.

 

This study says NR and NMN increase NAD+ in the liver, which is excreted as NAM for use throughout the body:

"Other tissues, in contrast, relied almost exclusively on circulating NAM made by the liver. Liver synthesis of NAD and excretion of NAM occurred even when serum NAM was elevated by co-infusion of tryptophan and NAM; thus, liver constitutively produces NAM to support NAD synthesis throughout the rest of the body"

 

The slightly larger increase in liver NAD+  from NR would then result in the slightly larger increase in circulating NAM you are pointing out.

 

I actually think that is an argument for NMN, not NR,  as I believe it is preferable to reach other tissues, not be relegated to liver NAD+.

 

Where does the NMN go that is not used in liver is a good question.  

 

I haven’t seen anything to suggest NMN  is somehow trapped and pissed away.

 

In fact, this study shows NMN remains in the body longer than NAM.  

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

 

So, yes, this study found NR was more easily detected in muscle, and slightly more in liver NAD and then NAM.   

 

That doesn’t indicate the NMN is somehow “wasted” or not effective.

 

When you look at the IV graphs in figure 2.7d you can see that NMN is never detected to be in circulation even after the infusion of NMN. In fact is shows that NMN is converted to NR as that increases in circulation after NMN infusion. So I find your theory that NMN is preferable to reach other tissues unlikely. Combine that with the graphs that show the increases in tissue NAD in the IV case really points to less effectiveness of NMN. My speculation is that the reason we see some increase in NAD+ in the muscle case for NMN infusion is because the NR goes a bit up in circulation and that enters the muscle.

 

Moreover if you look in figure 2.5. you can see that muscle is slow in using NAM to elevate NAD so that supports the point that NR is able to boost NAD in muscle because it goes into circulation and NMN does not. So NMN is converted into something, my guess NAM and NR and does nothing or little by itself.

 

 

Yes, it is a bit puzzling that NMN injection does not increase circulating NMN.  That contradicts several other studies that find otherwise.  I don't know if it has to do with dosage, timing, collection methods, or what.

 

However, in previous studies where NR was not detected in bloodstream, Trammel, you and Mike were certain that was due to NR being so quickly utilized.

 

Now in this study,  NMN is not found in bloodstream - but you don't consider it possible the NMN is converted to NAD+ quickly (as it IS one step closer to NAD than NR).  

 

Now,  you are now certain that means the NMN is wasted?

Edited by able, 21 March 2018 - 09:46 PM.

[stefan_001]

@able If NMN is converted quickly to NAD then where is the NAD? The only place where it is observed somewhat after 5 minutes is in the kidney.

 

I dont trust the measurements in the oral consumption case as I wrote earlier I would suspect that the NR (and for that matter NMN) that does enter the bloodstream to be much more gradual than in the IV case. The Trammel measurements were hourly so yes NR is utilized much faster on that time scale. In this study they noted 3 minute halflife in blood.

 

I like the infusion experiment because it show what happens when NR and NMN enter the bloodstream. Like I wrote in the other thread I am not sure either how much NR makes it into circulation through the oral route. We know some does but I am hedging my bets by taking 50% of my daily NR sublingual method.

 

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.

[stefan_001]

 

You guys appear to be misinterpreting Fig. 2.7e in the Thesis. You're reading it as if it shows the level of NAD+, or NAD+ boost, resulting from administration of IV and oral NR and NMN — which is not what it shows. What it shows is what percentage of the NAD+ in the tissue at time of measure is derived from pre-existing or late-salvage NAD+ (M+0), or directly from parent supplement (M+2), or from NAM derived from early metabolism of supplement (M+1). None of that tells you the actual level of NAD+ in the tissue is at that time— just the fractional breakdown of what's there. I haven't read the paper, but I don't see anywhere where actual levels of NAD+ following supplementation are given.

You are correct. But we do get a sense of NAD+ contribution from precursors.

 

 

Its an indication of NAD boost. I dont think the pre-cursers influence the "steady state" NAD so if the relative portion of steady state NAD is lower that means total NAD is higher. Given that multiple studies have shown that NR & NMN administration increases NAD I think its reasonable to make the conclusion its indicative of NAD boost size.
 

Edited by stefan_001, 21 March 2018 - 10:51 PM.

[stefan_001]

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?

 

No, the study says:

"In contrast, extrahepatic tissues displayed minimal M+2 NAD (Figure 2.7e), suggesting that orally delivered NR and NMN are converted into NAM before reaching the systemic circulation. IV injection of NR or NMN, on the other hand, resulted in substantial M+2 NAD in both liver and kidney"

 

So in oral use they raise NAD in the liver but the rest of the body relies on picking up NAM from the bloodstream that is secreted by the liver. But from the Wasu study we know that at least NR supplementation does result in more NR circulation (see Michael's comment in "sublingual" thread).

Edited by stefan_001, 22 March 2018 - 11:10 AM.

[LawrenceW]

Please allow me to ask the question differently.  Are NMN and NR supplementation simply mechanisms of increasing the amount of NAD+ in our bodies by way of providing more NAM for the NAD+ to be converted from?

Edited by LawrenceW, 22 March 2018 - 11:36 AM.

[stefan_001]

Please allow me to ask the question differently.  Are NMN and NR supplementation simply mechanisms of increasing the amount of NAD+ in our bodies by way of providing more NAM for the NAD+ to be converted from?

 

Well that has been the debate for some time. These pre-cursors, when they make it to the bloodstream, can increase NAD in cells via a different pathway and hence can help cells in trouble. It is also believed small amounts can be enough to save cells like axons.

 

That is why in these debates there is so much focus on whether these pre-cursors make it into circulation. The liver clearly benefits and a healthy liver likely has body wide effects. Apart from that various studies have shown that NR is more effective in raising NAD in the blood than simply consuming NAM which would indicate NR works different than just raising NAM in the blood.

 

Sublingual use seems to be a more sure way to get NR into circulation thus making it do more than simply raising NAM in the blood (which is not the case -> Wasu study mentioned several times).

 

For NMN I find it peculiar that even with IV it doesnt get to circulation. Unfortunately most here see comment through the lense of people having financial interests instead of wondering what is going on.
 

[LawrenceW]

Stefan.

 

Why do you say "For NMN I find it peculiar that even with IV it doesnt get to circulation." 

 

When from the Liu Abstract.

 

"We also showed that intravenous, but not oral administration of NR or NMN delivered intact molecules to multiple tissues."

[able]

Stefan.

 

Why do you say "For NMN I find it peculiar that even with IV it doesnt get to circulation." 

 

When from the Liu Abstract.

 

"We also showed that intravenous, but not oral administration of NR or NMN delivered intact molecules to multiple tissues."

 

Is it because, at this small dosage, the NMN makes its way quickly into tissues and none REMAINS in blood circulation at high enough levels to be detected?

 

We know from other studies using higher dosages that IP and oral NMN is found in blood circulation (and muscle).

 

For NR, we know that higher dosage used in UWash human pharmacodynamics trial study that oral NR is found in blood circulation, but not with the smaller dosages used here.

 

Is this simply a matter of too low a dosage?   Perhaps this study gives some indication of the preferential use of small dosages of NR/NMN, but not what happens when higher dosages are used?

Edited by able, 22 March 2018 - 01:18 PM.

[stefan_001]

Stefan.

 

Why do you say "For NMN I find it peculiar that even with IV it doesnt get to circulation." 

 

When from the Liu Abstract.

 

"We also showed that intravenous, but not oral administration of NR or NMN delivered intact molecules to multiple tissues."

 

please have a look at the attached graph (2.7 figure)

Attached Files

•  NMNcirculation.JPG   37.58KB   0 downloads

[able]

 

Stefan.

 

Why do you say "For NMN I find it peculiar that even with IV it doesnt get to circulation." 

 

When from the Liu Abstract.

 

"We also showed that intravenous, but not oral administration of NR or NMN delivered intact molecules to multiple tissues."

 

please have a look at the attached graph (2.7 figure)

 

 

 

Yes, clearly at this small dosage NMN doesn't REMAIN in circulation.   But clearly it also GETS to circulation, hence it's rapid appearance in tissues throughout the body.

Edited by able, 22 March 2018 - 01:30 PM.

[MikeDC]

Stefan.

Why do you say "For NMN I find it peculiar that even with IV it doesnt get to circulation."

When from the Liu Abstract.

"We also showed that intravenous, but not oral administration of NR or NMN delivered intact molecules to multiple tissues."

please have a look at the attached graph (2.7 figure)

The study also showed base levels of NR in circulation is much higher than NMN. This contradict previous studies that show NMN is higher at base level. Maybe they didn’t have an efficient methods to measure NR before. This may also mean that NR is the preferred precursor in the body to transfer NAD+ from liver to other organs.

Edited by MikeDC, 22 March 2018 - 01:36 PM.

[LawrenceW]

Does the graph show that NR remains in circulation whereas NMN is no longer in circulation as it has reached its destination?

[LawrenceW]

Are we trying to ascribe / theorize magical attributes to NR and NMN or is it simply that both contribute NAM to our systems which in turn raises NAD+ levels?

 

With NMN having the higher molecular weight, would a gram of NR contribute more NAM than a gram of NMN?

Edited by LawrenceW, 22 March 2018 - 02:35 PM.

[stefan_001]

 

 

Stefan.

 

Why do you say "For NMN I find it peculiar that even with IV it doesnt get to circulation." 

 

When from the Liu Abstract.

 

"We also showed that intravenous, but not oral administration of NR or NMN delivered intact molecules to multiple tissues."

 

please have a look at the attached graph (2.7 figure)

 

 

 

Yes, clearly at this small dosage NMN doesn't REMAIN in circulation.   But clearly it also GETS to circulation, hence it's rapid appearance in tissues throughout the body.

 

 

We had this discussion before. After 5 minutes all NMN is gone but only in the kidney NAD is up. Where is the NMN? Floating around as NR and NAM?

 

Does the graph show that NR remains in circulation whereas NMN is no longer in circulation as it has reached its destination?

 

Same answer as above. The only place NAD has gone up after 5 mintues is in the Kidney. So NMN is gone but where?
 

See attached graph.

Attached Files

•  NMN2.JPG   60.02KB   0 downloads

Edited by stefan_001, 22 March 2018 - 02:58 PM.

[LawrenceW]

The Mills study, http://www.cell.com/...6)30495-8.pdf, showed that NMN raised NAD+ levels in the liver, skeletal muscle and cortex.