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Does NR Get Broken Down into N+R or Is It Stable?

nicotinamide riboside niagen d-ribose nicotinamaide

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#31 stefan_001

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Posted 22 October 2017 - 05:01 PM

Enjoy the ribose:
Glycation with D-ribose induces protein to misfold rapidly and form globular amyloid-like aggregations which play an important role in cytotoxicity to neural cells. Treatment with D-ribose decreased cell viability and induced more AGE accumulation in cells. Intraperitoneal injection, oral administration and tail intravenous injection of D-ribose caused impairment of spatial learning and memory ability in animals, along with Abeta; deposition, tau hyperphosphorylation and glia activation, one of the key pathological features. The involved mechanisms were also studied.
http://www.alzheimer...1070-1/fulltext
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#32 Michael

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Posted 22 October 2017 - 05:20 PM

 

 

Let's keep things simple and just look at N, R, and NAD. And let's say you have a gram of N+R available in cells and you add a gram of N'R' orally (where N' and R' are labeled with a deuterium atom or C13 atom). So when the cells finish their work, they have 50% NAD+ and 50% NAD''+. That is, half have no label and half are double labeled, while none are single labeled. But this isn't what they saw.

 
Your analysis here only makes sense in isolated cells, and with a static NAD+ pool. Rather, some NR is passing through the liver on its way to to other sites, and present in the cell at any moment as other parts of the "NAD+ metabolome," as they document: some is still present as NR in the cell; all NR that is eventually incorporated intact into NAD+ has to first pass through NMN; some will pass back from NMN to NR; and all of it that is present in NADP(H) was present previously in NAD+. Moreover, simple hydrolysis of NR as the sole source of single-labeled NAM ignores its production by enzymatic breakdown from NAD+ into NAM+ ADPR.
 
You are also still assuming that NR is synthesized de novo in mammals from NAM + R, for which there is currently no evidence. As far as we know now, the only way NR is present in mammalian cells is from the diet/supplements or from NMN breakdown. It's not even known how it's produced in yeast, and the most likely pathway is as part of a fermentative biosynthetic reaction, which isn't likely to translate to mammalian cells.
 
 You have attempted to muddy the waters, but the bottom line is that the data do not show that labeled NR is absorbed intact as the authors claim. In fact, Fig. 5d shows that the peak of plasma NAM is far greater with NR than with NAM by itself (which is likely because the NAM peak from NAM dosing was very sharp and they didn't catch the peak). This is consistent with slow digestion of NR to NAM + ribose. Worse for the argument that NR is better than N+R is Fig. 5b which shows the AUC for NAM produced NAD+ is only about 10% less than for NR (and not significantly different).

Rather, you have attempted to present an analysis that relies on paying no attention to 99% of the dirt actually present in the water ;) . Mice have tissue NAD+ concentrations ranging from 200-800 µmol/kg, depending on the tissue (humans average 300 μmol/kg), vs. a half‐life of ≈10 h in mouse liver in vivo. Based on the steady-state pool and the amounts of tryptophan and NAM required to avoid deficiency, less than 1% of total body NAD+ is replaced from dietary sources daily: the vast majority of tissue NAD+ and NAM present at any given moment is just constantly recycled, predominantly via the appropriately-named salvage pathway.(1)
 
No one is disputing that some significant amount of oral NR is broken down into NAM. But your assertion that it's entirely thus degraded is inconsistent with multiple lines of evidence, as already delineated. The large, delayed NAM peak doubtless comes in part from intestinal hydrolysis — but it also results from the metabolic use of NR-derived NAD+ by PARPs or sirtuins, which cleaves NAD+ and generates NAM and ADP-ribose as products:
 

nrendo.2015.117-f1.jpg

 

Source: Physiological and pathophysiological roles of NAMPT and NAD metabolism

 
So single-labeled NAM comes partially from intestinal NR hydrolysis, but also from NAD+ that is derived directly from NR absorbed intact. At the instant that NR-derived (double-labeled) NAD+ is  actually used for these purposes, you get single-labeled NAM and single-labeled ADP-ribose out  the other end. And then that single-labeled NAM then gets salvaged to synthesizesingle-lableled NMN and single-labeled NAD+ in turn.
 
Your proposed scenario also, again, relies on the existence of an endogenous pathway for NR synthesis from NAM + R in mammalian cells, in the face of no suggestion anywhere in the NAD+ literature that such a pathway even might exist.
 
Reference
1: Fessel JP, Oldham WM. Pyridine Dinucleotides from Molecules to Man. Antioxid Redox Signal. 2017 Jul 25. doi: 10.1089/ars.2017.7120. [Epub ahead of print] PubMed PMID: 28635300.


Edited by Michael, 22 October 2017 - 05:25 PM.

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#33 Nate-2004

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Posted 22 October 2017 - 05:37 PM

Enjoy the ribose:
Glycation with D-ribose induces protein to misfold rapidly and form globular amyloid-like aggregations which play an important role in cytotoxicity to neural cells. Treatment with D-ribose decreased cell viability and induced more AGE accumulation in cells. Intraperitoneal injection, oral administration and tail intravenous injection of D-ribose caused impairment of spatial learning and memory ability in animals, along with Abeta; deposition, tau hyperphosphorylation and glia activation, one of the key pathological features. The involved mechanisms were also studied.
http://www.alzheimer...1070-1/fulltext

 

What if taking NAM with D-Ribose negates this problem quoted above? See below quote. There's no mention of NAM in that study.

 

 

 

Prior to adding ribose, I never liked nicotinamide as I felt off taking it. Now I suspect that was the drain on the body's meager ribose reserves.

 

If you look at the rodent results of NAM vs NR, the AUC NAD+ results are about the same, but the peak of NR is higher, likely because the ribose is supplied at the same time and cells don't have to manufacture it. With N+R the peak should be far higher and quicker, as there is no time delay compared to NR, which is something of a slow release product.

 

Michael has a really good point, but if a significant amount of NR is broken down into NAM+R (as we all seem to be agreeing on) then if the above question and Turnbuckle's point is not the case, we're still dealing with the glycation problem of ribose when we take NR.

 

By the way I also take 3g of glycine every night for quality sleep, this counters glycation as well and is known to reverse some of what is mentioned in your quote.

 

less than 1% of total body NAD+ is replaced from dietary sources daily: the vast majority of tissue NAD+ and NAM present at any given moment is just constantly recycled, predominantly via the appropriately-named salvage pathway.(1)

 

Yes but this is hampered by the age related increase of CD38 and possibly other factors.


Edited by Nate-2004, 22 October 2017 - 05:45 PM.

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#34 stefan_001

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Posted 22 October 2017 - 05:44 PM

Enjoy the ribose:
Glycation with D-ribose induces protein to misfold rapidly and form globular amyloid-like aggregations which play an important role in cytotoxicity to neural cells. Treatment with D-ribose decreased cell viability and induced more AGE accumulation in cells. Intraperitoneal injection, oral administration and tail intravenous injection of D-ribose caused impairment of spatial learning and memory ability in animals, along with Abeta; deposition, tau hyperphosphorylation and glia activation, one of the key pathological features. The involved mechanisms were also studied.
http://www.alzheimer...1070-1/fulltext


What if taking NAM with D-Ribose negates this problem quoted above? See below quote. There's no mention of NAM in that study.


Prior to adding ribose, I never liked nicotinamide as I felt off taking it. Now I suspect that was the drain on the body's meager ribose reserves.

If you look at the rodent results of NAM vs NR, the AUC NAD+ results are about the same, but the peak of NR is higher, likely because the ribose is supplied at the same time and cells don't have to manufacture it. With N+R the peak should be far higher and quicker, as there is no time delay compared to NR, which is something of a slow release product.


Michael has a really good point, but if a significant amount of NR is broken down into NAM+R (as we all seem to be agreeing on) then if the above question and Turnbuckle's point is not the case, we're still dealing with the glycation problem of ribose.


By the way I also take 3g of glycine every night for quality sleep, this counters glycation as well and is known to reverse some of what is mentioned in your quote.

Absolutely Nate probably negates it 100% and more. Thats why I wrote enjoy the ribose.

#35 Nate-2004

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Posted 22 October 2017 - 05:48 PM

Absolutely Nate probably negates it 100% and more. Thats why I wrote enjoy the ribose.

 

Oh I thought you were being sarcastic. So we're all in agreement that Ribose is not a problem because NAM uses it to make NR? That's the only reason I can think of that NAM could negate the effects described in this study you posted.


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#36 stefan_001

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Posted 22 October 2017 - 05:54 PM

Absolutely Nate probably negates it 100% and more. Thats why I wrote enjoy the ribose.


Oh I thought you were being sarcastic. So we're all in agreement that Ribose is not a problem because NAM uses it to make NR? That's the only reason I can think of that NAM could negate the effects described in this study you posted.
I agree I am not sarcastic, cynical is the better wording. Sorry about that. Michael's post reflects what I think too. For me ribose is a more harmfull form of glucose which I moderate as well. I posted the link as warning thats all. Do with it as you want. Exception to this is if you certain heart condition where the harmfull is overshadowed by the specific positive effects.

Edited by stefan_001, 22 October 2017 - 06:03 PM.

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#37 Turnbuckle

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Posted 22 October 2017 - 07:59 PM

Theoretical handwaving aside, the following points are clear from the data in the papers above--

 

1. The areas under the NAD+/time curves for NAM and NR are not substantially different. Fig. 5.b. NR is being sold for the brief peak over NAM, but there is no evidence of its health importance over the overall NAD+ levels.

 

2. The area under the NAM curve is actually higher for NR than it is for NAM. Fig. 5.d, indicating extensive breakdown of NR.

 

3. Virtually zero double labeled NAD was found in muscle tissue and only a little in the liver, indicating that NR is extensively broken down prior to forming NAD. So if it gets past the stomach, then it is broken down in the liver. Figs. 6c and 6d.  Which is the same conclusion that can be drawn from point 2.

 

4. The endogenous production of NR in the body is not addressed, but that it can be synthesized in mammals is known, as it appears in milk, and unlabeled NR was found in the blood of experimental mice along with double labeled NR, indicating mammals have an endogenous source of NR. Fig. 6h.

 

5. The availability of ribose is a bottle neck for NAD+ resynthesis in athletes.

 

Taken together, these points suggest that NAM and NR take the same path to NAD+, and that NAM + ribose (N+R) should be superior to NAM, and likely superior to NR.

 

 


Edited by Turnbuckle, 22 October 2017 - 08:51 PM.

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#38 Nate-2004

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Posted 23 October 2017 - 02:15 PM

Is there any definitive proof anywhere that NAM essentially "mops up" ribose?



#39 able

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Posted 23 October 2017 - 04:31 PM

Is there any definitive proof anywhere that NAM essentially "mops up" ribose?

 

That is the question.  

 

 

I believe our bodies must create NR somehow.  It really does seem most is broken down during digestion, and doesn’t circulate at detectable levels.  Yet it does exist in our bodies for a reason.  But that doesn't prove it must come from N + R.

 

It seems like it would be a very simple experiment to feed rats labeled N and R, then check liver and plasma NAD+ to see.

 

If it does show N + R combine in vivo, Chromadex and Elysium stock would be worthless.

 

So why would all those nobel prize winners and smart investors climb on board such a fragile ship?

 

But in looking further at the experiment on Nampt muscle knockout mice, I’m trying to understand if the double labelled NR shows ribose and NAM must combine in vivo. Or maybe I'm missing something, idk.

 

 

chart 6F shows that 100 minutes after gavage of NR, both control and Mnko mice have nearly as much N+1 NR as N+2 NR.

 

How does that N+1 NR get there, if not from NR digested to NAM, then combined with unlabeled Ribose?


Edited by able, 23 October 2017 - 04:34 PM.

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#40 Kirito

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Posted 23 October 2017 - 05:33 PM

One thing that's easily overlooked - CD38 degrades not only NAD, but also NMN. And the byproduct released is NAM. Since NR is metabolized into NMN, the effect of CD38 could at least partially explain a portion of the NAM spike.


Edited by Kirito, 23 October 2017 - 05:34 PM.

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#41 stefan_001

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Posted 23 October 2017 - 05:37 PM

Is there any definitive proof anywhere that NAM essentially "mops up" ribose?


That is the question.


I believe our bodies must create NR somehow. It really does seem most is broken down during digestion, and doesn’t circulate at detectable levels. Yet it does exist in our bodies for a reason. But that doesn't prove it must come from N + R.


It seems like it would be a very simple experiment to feed rats labeled N and R, then check liver and plasma NAD+ to see.


If it does show N + R combine in vivo, Chromadex and Elysium stock would be worthless.


So why would all those nobel prize winners and smart investors climb on board such a fragile ship?


But in looking further at the experiment on Nampt muscle knockout mice, I’m trying to understand if the double labelled NR shows ribose and NAM must combine in vivo. Or maybe I'm missing something, idk.



chart 6F shows that 100 minutes after gavage of NR, both control and Mnko mice have nearly as much N+1 NR as N+2 NR.


How does that N+1 NR get there, if not from NR digested to NAM, then combined with unlabeled Ribose?

6F is liver graph

#42 able

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Posted 23 October 2017 - 06:05 PM

 

 

Is there any definitive proof anywhere that NAM essentially "mops up" ribose?


That is the question.


I believe our bodies must create NR somehow. It really does seem most is broken down during digestion, and doesn’t circulate at detectable levels. Yet it does exist in our bodies for a reason. But that doesn't prove it must come from N + R.

It seems like it would be a very simple experiment to feed rats labeled N and R, then check liver and plasma NAD+ to see.

If it does show N + R combine in vivo, Chromadex and Elysium stock would be worthless.

So why would all those nobel prize winners and smart investors climb on board such a fragile ship?

But in looking further at the experiment on Nampt muscle knockout mice, I’m trying to understand if the double labelled NR shows ribose and NAM must combine in vivo. Or maybe I'm missing something, idk.


chart 6F shows that 100 minutes after gavage of NR, both control and Mnko mice have nearly as much N+1 NR as N+2 NR.

How does that N+1 NR get there, if not from NR digested to NAM, then combined with unlabeled Ribose?

6F is liver graph

 

 

Yes.

 

How does single label NR get to the liver 100 minutes after ingesting double labeled NR?

 

Is it:  NR -> NAM, then combine with existing ribose, to form single label NR in the liver?

 

I have no chemistry/biology background, so apologize if that is a silly, impossible explanation.


Edited by able, 23 October 2017 - 06:10 PM.


#43 stefan_001

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Posted 23 October 2017 - 06:20 PM

 

 

 

Is there any definitive proof anywhere that NAM essentially "mops up" ribose?


That is the question.

I believe our bodies must create NR somehow. It really does seem most is broken down during digestion, and doesn’t circulate at detectable levels. Yet it does exist in our bodies for a reason. But that doesn't prove it must come from N + R. [...]
 
chart 6F shows that 100 minutes after gavage of NR, both control and [Nampt muscle knockout] mice have nearly as much N+1 NR as N+2 NR.

How does that N+1 NR get there, if not from NR digested to NAM, then combined with unlabeled Ribose?

 


6F is liver graph
 
Yes.
 
How does single label NR get to the liver 100 minutes after ingesting double labeled NR?
 
Is it:  NR -> NAM, then combine with existing ribose, to form single label NR in the liver?
 
I have no chemistry/biology background, so apologize if that is a silly, impossible explanation.

 
Ah ok, I thought the comment was about why those graphs show the same. Michael had a good post describing it bit earlier in the thread.


Edited by Michael, 23 October 2017 - 06:41 PM.
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#44 Michael

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Posted 23 October 2017 - 06:30 PM

Theoretical handwaving aside,

 
Straightforward mapping out of known biochemistry is hardly "Theoretical handwaving." OTOH, continuously and stridently asserting the existence of a biosynthetic pathway that has nowhere been posited in the scientific literature doesn't even rise to the level of theoretical handwaving.
  
Turnbuckle wrote: the following points are clear from the data in the papers above--

1. The areas under the NAD+/time curves for NAM and NR are not substantially different. Fig. 5b. NR is being sold for the brief peak over NAM, but there is no evidence of its health importance over the overall NAD+ levels.

 
You may be right about this: as I've emphasized before, there are (separate) studies showing many of the effects of NR and NMN seem to be recapitulated with NAM. We certainly could use a lot more comparative effectiveness studies, and also studies in different tissues and at different ages.

Turnbuckle wrote: 2. The area under the NAM curve is actually higher for NR than it is for NAM.Fig. 5d indicating extensive breakdown of NR.
 
No one is arguing that there isn't extensive breakdown (including metabolic breakdown). The question is where it goes and what it does along the way.

Turnbuckle wrote: 3. Virtually zero double labeled NAD was found in muscle tissue and only a little in the liver, indicating that NR is extensively broken down prior to forming NAD.
 
That doesn't follow, for reasons given.
 
Turnbuckle wrote: So if it gets past the stomach, then it is broken down in the liver. Figs. 6c and 6d. Which is the same conclusion that can be drawn from point 2.
 
No: again, while it's straightforwardly "broken down" (hydrolyzed) in the gut, the way it's "broken down" in the liver is by metabolism to NAD+ and then recycling of the NAM into the "NAD+ metabolome" (and separate use of the ADP-ribosyl moieties).
 
Turnbuckle wrote: 4. The endogenous production of NR in the body is not addressed, but that it can be synthesized in mammals is known, as it appears in milk, and unlabeled NR was found in the blood of experimental mice along with double labeled NR, indicating mammals have an endogenous source of NR. Fig. 6h.
 
As has been pointed out before, it can form from endogenously by CD73 action on NMN (this is how circulating NMN gets into cells), and may also be in milk as a result of microbes present therein, or microbes if the cattle are fed brewers' grain. None of this entails mammalian synthesis of NR from NAM + R (or mammalian "synthesis" in the ordinary sense at all).
 
Turnbuckle wrote: The availability of ribose is a bottle neck for NAD+ resynthesis in athletes.
 
That study does not show any such thing. It shows that R is required for salvage of IMP back to ADP and thence ATP: R is nowhere implicated in limiting NAD+ resynthesis. And NR is a nucleoside, not a nucleotide.
 
Turnbuckle wrote: Taken together, these points suggest that NAM and NR take the same path to NAD+, and that NAM + ribose (N+R) should be superior to NAM, and likely superior to NR.
 
Positive evidence would be nice. And being clear that this is a mechanistic speculation based on a biochemical pathway that no one but you posits even exists, instead of proclaiming it as if it were a known fact, would seem to be simple transparency.
 

Is there any definitive proof anywhere that NAM essentially "mops up" ribose?

If there were, that would be preliminary evidence for mammalian synthesis of NR from NAM + R. There is no such evidence.
 

It seems like it would be a very simple experiment to feed rats labeled N and R, then check liver and plasma NAD+ to see.

Yup. An even easier first step would be to test for it in cells. But since AFAICS no one in the NAD+ biochemistry world believes there is such a pathway, I doubt anyone will test for one.
 

url=https://www.ncbi.nlm...igure/F6/]chart6F[/url] shows that 100 minutes after gavage of NR, both control and Mnko mice have nearly as much N+1 NR as N+2 NR.

How does that N+1 NR get there, if not from NR digested to NAM, then combined with unlabeled Ribose?

N'R'' --> N'MN'' --> N'AD'' --[Sirtuins or PARPs here]--> NAM' + ADPR''

NAM' [from above reaction] ---> N'AD  --[CD38 or CD73 here] --> N'MN --[CD73 here]--> N'R

Edited by Michael, 23 October 2017 - 07:15 PM.
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#45 able

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Posted 23 October 2017 - 06:38 PM

N'R'' --> N'MN'' --> N'AD'' --[Sirtuins or PARPs here]--> NAM' + ADPR''

NAM' [from above reaction] ---> N'AD  --[CD38 or CD73 here] --> N'MN --[CD73 here]--> N'R

 

 

I understand that pathway.  I was kind of wondering if there was some shorter path.  

 

It just seems strange that so much double labeled NR has been through NAD+ twice already at 100 minutes, yet other studies show no increase in NAD+ by 100 minutes in similar dosages  with mice.

 

But I guess that just shows the constant turnover of NAD+ in liver.

 

 


 


Edited by able, 23 October 2017 - 07:32 PM.


#46 Nate-2004

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Posted 23 October 2017 - 07:07 PM

Can we use our connection with Ichor to test this and get some kind of answer? I think it would save people a lot of money and time to know once and for all what is true.


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#47 stefan_001

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Posted 23 October 2017 - 08:05 PM

Can we use our connection with Ichor to test this and get some kind of answer? I think it would save people a lot of money and time to know once and for all what is true.

Nate I dont get this obsession. There are far more usefull research targets. For example it appears we hit a ceiling in increasing NAD+ with NR at certain dosing levels and at later age we may dip under "the limit" despite the boosting. How can we go beyond that? Combining with milk thistle and/or quercetin? Other comibinations? I am experimenting with both.

http://www.mdpi.com/...-6643/9/10/1086

Edited by stefan_001, 23 October 2017 - 08:08 PM.

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#48 Turnbuckle

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Posted 23 October 2017 - 09:27 PM

Turnbuckle wrote: 4. The endogenous production of NR in the body is not addressed, but that it can be synthesized in mammals is known, as it appears in milk, and unlabeled NR was found in the blood of experimental mice along with double labeled NR, indicating mammals have an endogenous source of NR. Fig. 6h.
 
As has been pointed out before, it can form from endogenously by CD73 action on NMN (this is how circulating NMN gets into cells), and may also be in milk as a result of microbes present therein, or microbes if the cattle are fed brewers' grain. None of this entails mammalian synthesis of NR from NAM + R (or mammalian "synthesis" in the ordinary sense at all).

 

 

 

Yes, it does appear that both NR and NAM are going the same route, first forming NMN and then NAD+. In the rodent trials, NAM and NMN are increased with both NR and NAM as shown in Fig. 5, and from there NMN (from NAM in both cases) goes to either NAD+ or NR. With NAM the rate is limited by the availability of ribose. Thus the ribose in NR is the only real advantage, but that is also a disadvantage as NR has to be broken down first, resulting in a big time delay (and the elimination of most double labeled NAD). Thus N+R will be superior.


Edited by Turnbuckle, 23 October 2017 - 09:43 PM.

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#49 Nate-2004

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Posted 25 October 2017 - 01:37 PM

What if NR is injected intramuscularly or subcutaneously? I realize it's not stable for long in water but you could mix it just before injection. Or perhaps sublingually or using DMSO? Some have even tried snorting it. I probably mocked them for that but now I'm seeing that there's a good reason for going that route of administration.


Edited by Nate-2004, 25 October 2017 - 01:37 PM.


#50 Harkijn

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Posted 26 October 2017 - 02:59 PM

What if NR is injected intramuscularly or subcutaneously? I realize it's not stable for long in water but you could mix it just before injection. Or perhaps sublingually or using DMSO? Some have even tried snorting it. I probably mocked them for that but now I'm seeing that there's a good reason for going that route of administration.

Please reread post #44 carefully. It says all about this subject that is known so far. Don't let yourself be guided by speculations and assertions and happily go on taking your NR capsules orally.


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#51 MikeDC

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Posted 26 October 2017 - 04:08 PM

https://www.ncbi.nlm...mentation sirt1

“We treated mice with NAM (100 mg/kg/day) and normal chow for 8 weeks. Strikingly, NAM induced glucose intolerance and skeletal muscle lipid accumulation in nonobese mice. NAM impaired mitochondrial respiration capacity and energy production in skeletal muscle,”

If NR is broken down to Nicotinamide, We would not have seen the beneficial effects on insulin sensitivity. Nicotinamide reduces insulin sensitivity.

Edited by MikeDC, 26 October 2017 - 04:12 PM.

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#52 MikeDC

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Posted 26 October 2017 - 04:27 PM

Increasing NAD+ in skeleton muscle does not increase oxidation capacity in the muscle. There is more to NR and NMN supplement than we currently understand. If you think you can get good results from N+R, do it. But don’t try to fool other people into this nonsense and so they won’t get the benefits from NR.

https://www.ncbi.nlm...ubmed/25411251/

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#53 Nate-2004

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Posted 26 October 2017 - 05:29 PM

 

What if NR is injected intramuscularly or subcutaneously? I realize it's not stable for long in water but you could mix it just before injection. Or perhaps sublingually or using DMSO? Some have even tried snorting it. I probably mocked them for that but now I'm seeing that there's a good reason for going that route of administration.

Please reread post #44 carefully. It says all about this subject that is known so far. Don't let yourself be guided by speculations and assertions and happily go on taking your NR capsules orally.

 

 

So after having re-read that I'm guessing there's no answer to this question?


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#54 MikeDC

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Posted 26 October 2017 - 05:35 PM

What if NR is injected intramuscularly or subcutaneously? I realize it's not stable for long in water but you could mix it just before injection. Or perhaps sublingually or using DMSO? Some have even tried snorting it. I probably mocked them for that but now I'm seeing that there's a good reason for going that route of administration.

Please reread post #44 carefully. It says all about this subject that is known so far. Don't let yourself be guided by speculations and assertions and happily go on taking your NR capsules orally.

So after having re-read that I'm guessing there's no answer to this question?

If you inject NR or NMN, it will definitely make it more available to organs other than liver.
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#55 Nate-2004

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Posted 26 October 2017 - 06:25 PM

First off, this is my thread, it's not "pointless" or "time wasting" to ask this essential question with regards to administration in light of this debate. Seriously, jeez.

 

I also do not think this is an "obsession" if it's hotly debated and a concern for all involved. We're either wasting our time with N+R or we're wasting our money with NR. Personally I'd like to know which and no question unanswered should be dismissed out of hand as being something not worth investigation, especially a question about a substance everyone into this site has been excited and hopeful about in one way or another for the past 3 or 4 years.

 


Edited by Nate-2004, 26 October 2017 - 06:26 PM.

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#56 MikeDC

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Posted 26 October 2017 - 06:57 PM

It might make sense to question the authenticity if Niagen is just another plant based supplement and with no clinical trials and detailed scientific studies. Do you really think all the top scientists who have been fascinated by NR and fighting over to study it are faking it when N+R can do the same?
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#57 Harkijn

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Posted 27 October 2017 - 06:55 AM

Harkijn said:

 

 

 

Please reread post #44 carefully. It says all about this subject that is known so far. Don't let yourself be guided by speculations and assertions and happily go on taking your NR capsules orally.

 

 

Nate said:

 

So after having re-read that I'm guessing there's no answer to this question?

 

 

 

Harkijn: No, at the moment there are no definitive scientific answers to your original question and also not to the deeper liying question of  at what places and moments it is metabolized.



#58 Nate-2004

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Posted 03 November 2017 - 05:02 PM

Another relevant bit posted on Alive By Nature regarding how NR doesn't even make it past the liver:

 

http://alivebynature.com/about-niagen/

 

Pretty sure I'm on my last bottle of NR at this point. Might be good to just wait and see or start injecting it IM or going sublingual. Is there anything in terms of ideal vehicles that would improve sublingual administration absorption? What's the molecular weight of NR?

 

 

 


Edited by Nate-2004, 03 November 2017 - 05:21 PM.

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#59 stefan_001

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Posted 03 November 2017 - 06:30 PM

Alivebynature conveniently bypasses the fact that Trammel unfortunately only did his first measurements at the 1 hour time point so we dont know if NR would show a similar fast behavior as NMN inside the first hour.Similarly the NMN study they reference did not do the hourly followup measurements so we dont know whether in the NMN behaves like NR on longer time scale.

 

Overall all these reasonings bypass the transcient behavior and try to make conclusions at a momentary view at arbitrary time point after ingestion. Typically this time point is >1h. To truly understand we woulld need realtime measurements.


Edited by stefan_001, 03 November 2017 - 06:35 PM.

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#60 able

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Posted 03 November 2017 - 07:02 PM

It does seem like conjecture on what pathways these different metabolites take.

 

To me, it seems the double labelled experiments provide most valid clues.

 

1 thing I've realized - Measuring increase in liver NAD+ is likely only one of many important measures.

 

It does bother me that the liver seems to filter NR out of the bloodstream so likely has a very brief period it might be effective outside the liver.

 

But NR does have many proven health benefits, whatever the pathways.

 

 


Edited by able, 03 November 2017 - 07:05 PM.






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