167 replies to this topic

[bluemoon]

Yeah, MikeDC has stock in ChromaDex as if we didnn't know that.   He posts as Mike on the yahoo discussion thread about ChromaDex. But it isn't like he is a plant for the company who will sway people reading his posts. 

[MikeDC]

I already said before that I own CDXC. So does many other people who posts here. It would be hard not to buy the stock after one gets great results from Niagen.

[Ibbz]

I'm not really sure the reason why a second thread was created on the exact same question, when the other thread is less than half way down the page and no one has responded to Michael's comments - 

 

http://www.longecity...r-is-it-stable/

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.

 

(Bolding mine)

 

 

Edited by Ibbz, 18 September 2017 - 01:04 AM.

[stefan_001]

According this study in autistic chlidren ribose consumption leads to increases in:

"The Ribose group had significant improvements in ribose-5-phosphate, NADH, ATP, and folic acid"
http://go.galegroup....ymousEntry=true

So it confirms more energy but increase in NADH and therefore it alters the NAD+/NADH ratio and as result turns off SIRTs. So good for gym but bad for aging. Turnbuckle you encourage people to consume large amounts of ribose, I think its time you support that with some kind of study results.

The study did not specify that the ratio of NAD+/NADH was altered either way. You made that assumption and if you're going to make definitive statements, the burden of proof is on you. The study was looking at finite levels of NADH as one of the markers of autism metabolism and as such, that is what the study reported on. The study did not report on changes of NAD+ or the ratio as that is not what they were looking for. If assumptions are what we are looking for, it is more likely that NAD+ increased also. Of course what many are missing is that simple increases in NAD+ are of no consequence if not utilized in beneficial NAD+ metabolism. Biology is more complex than just simply increasing finite amounts of NAD+.

The burden of proof is on the recommending party to use large amounts of ribose, not the other way around. That is right, this study indicates it raises NADH. Measured by hard science and the raise by itself is harmfull. You ASSUME it raises NAD+ relatively more but you have not found a single study showing that or any hard evidence. So the factual situation is that hard science shows NADH goes up versus a bunch of guys on a forum claim that NAD+ goes up even more. My take is that the authors in the autism study did not measure it because they only measured key indicators of factors they thought would change. Really can you show even one theoretical pathway how it raises NAD+?

Edited by stefan_001, 18 September 2017 - 04:51 AM.

[Turnbuckle]

 

I'm not really sure the reason why a second thread was created on the exact same question, when the other thread is less than half way down the page and no one has responded to Michael's comments - 

 

http://www.longecity...r-is-it-stable/

 

You are also still assuming that NR is synthesized de novo in mammals from NAM + R, for which there is currently no evidence. 

 

(Bolding mine)

 

 

 

Sorry that I didn't respond at the time. I had other things to do than argue a tiny point. He made that argument to save his claim that some NR must actually be absorbed without having been first digested, but it doesn't change the reality that most (if not all) of it is indeed digested. The presence of a large amount of single labeled vs double labeled NAD derived from double labeled NR--ten times as much--proves that.  In any case, cells readily make NAD+ out of nicotinamide and ribose. NR in the diet is not required.

 

"However, once administered to cells, NAM is rapidly converted to NAD+ and, therefore, the cellular concentration of NAM decreases rapidly while that of NAD+ increases...."  https://www.ncbi.nlm...pubmed/28417163

Edited by Turnbuckle, 18 September 2017 - 10:46 AM.

[MikeDC]

We know NAM get converted to NAD+. Show us how NAM is converted to NR. NAM doesn't need NRK1 to convert to NAD+

[Turnbuckle]

We know NAM get converted to NAD+. Show us how NAM is converted to NR. NAM doesn't need NRK1 to convert to NAD+

 

 

Show us how only 5% of the double labeled NR ended up as double labeled NAD+. And no hand waving.

 

As for NR being produced in cells--

 

NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5'-nucleotidases (5'-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro. Similar to their counterpart from yeast, Sdt1, the human 5'-NTs require high (millimolar) concentrations of nicotinamide mononucleotide or NAMN for efficient catalysis. Overexpression of FLAG-tagged CN-II and CN-III in HEK293 and HepG2 cells resulted in the formation and release of NAR. However, NAR accumulation in the culture medium of these cells was only detectable under conditions that led to increased NAMN production from nicotinic acid. The amount of NAR released from cells engineered for increased NAMN production was sufficient to maintain viability of surrounding cells unable to use any other NAD precursor. Moreover, we found that untransfected HeLa cells produce and release sufficient amounts of NAR and NR under normal culture conditions. Collectively, our results indicate that cytosolic 5'-NTs participate in the conversion of NAD precursors and establish NR and NAR as integral constituents of human NAD metabolism. In addition, they point to the possibility that different cell types might facilitate each other's NAD supply by providing alternative precursors.

 

https://www.ncbi.nlm...pubmed/26385918

 

 

Edited by Turnbuckle, 18 September 2017 - 11:07 AM.

[MikeDC]

First there is existing NAD+ recycling. Second is NR may have been recycled many times after converting to NAD+.

After all we are not real NAD+ scientists, we are just guessing. I would like to see a few papers published challenging the NR story with bulletproof experiments. Otherwise, your argument is conspiracy theory at best. In the mean time, I am happy to buy NR and improving my health.

[Turnbuckle]

First there is existing NAD+ recycling. Second is NR may have been recycled many times after converting to NAD+.

After all we are not real NAD+ scientists, we are just guessing. I would like to see a few papers published challenging the NR story with bulletproof experiments. Otherwise, your argument is conspiracy theory at best. In the mean time, I am happy to buy NR and improving my health.

 

 

Conspiracy theory at best? We are all just guessing? And in the meantime you will continue to "buy NR and improving my health"? That's some fine arguments.

[stefan_001]

 

We know NAM get converted to NAD+. Show us how NAM is converted to NR. NAM doesn't need NRK1 to convert to NAD+

 

 

Show us how only 5% of the double labeled NR ended up as double labeled NAD+. And no hand waving.

 

As for NR being produced in cells--

 

NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5'-nucleotidases (5'-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro. Similar to their counterpart from yeast, Sdt1, the human 5'-NTs require high (millimolar) concentrations of nicotinamide mononucleotide or NAMN for efficient catalysis. Overexpression of FLAG-tagged CN-II and CN-III in HEK293 and HepG2 cells resulted in the formation and release of NAR. However, NAR accumulation in the culture medium of these cells was only detectable under conditions that led to increased NAMN production from nicotinic acid. The amount of NAR released from cells engineered for increased NAMN production was sufficient to maintain viability of surrounding cells unable to use any other NAD precursor. Moreover, we found that untransfected HeLa cells produce and release sufficient amounts of NAR and NR under normal culture conditions. Collectively, our results indicate that cytosolic 5'-NTs participate in the conversion of NAD precursors and establish NR and NAR as integral constituents of human NAD metabolism. In addition, they point to the possibility that different cell types might facilitate each other's NAD supply by providing alternative precursors.

 

https://www.ncbi.nlm...pubmed/26385918

 

 

 

I read the paper and what I read is essentially that human cytosolic 5′-nucleotidases may aid the conversion of NMN into NR inside the cell. And that certain cells types can release NAD+ precursers for other cells. Morever the study says:

"However, the levels of the produced riboside were rather low (∼1.2–1.5 μm). To test whether such low concentrations would be sufficient to support cell survival, we incubated HepG2 cells in the presence of FK866 and low concentrations of NR or NAR (10−9–10−4 m). As can be inferred from Fig. 6D, low micromolar concentrations of either riboside were sufficient to maintain cell viability."

 

So I conclude two things. Firstly this supports that NR circulates. Secondly that even if only a small amount of oral ingested NR goes into circulation intact it can have a meaningful health impact.

 

All in all this study supports the use of NR as oral supplement. Didnt find anything that support use of N and R separately.

Edited by stefan_001, 18 September 2017 - 03:36 PM.

[MikeDC]

Good find. But NR needs to go through NMN to become NAD+.
Maybe this is a mechanism to limit the NMN concentration in cells. I posted a paper before that shows high levels of NMN is toxic.

[Nate-2004]

Mike definitely has stock in CDXC. His rep here is -136 and it's almost like he's striving to break some kind of negative record. I do think we are lacking proof on both sides, there is no good research showing N+R results in a boost in NAD+ and there is no research showing NR is absorbed intact and is fully bioavailable, and in fact there is some evidence which Turnbuckle pointed to, that indicates it is not.

 

At this point it's just wait and see. I sold all my stock when it went back up to 4.5 the other day. I am suspicious of the fact that they have still not revealed the results of their recent studies. I am not expecting the best results.

[Harkijn]

Point well taken, Nate (at least by me, perhaps not by two other posters  ). Perhaps it is time to return to one of the thread starter's questions: What are the experiences of   Ribose and NAM  takers? How does it feel? Does it help you in any way? Please post!

[MikeDC]

Point well taken, Nate (at least by me, perhaps not by two other posters ). Perhaps it is time to return to one of the thread starter's questions: What are the experiences of Ribose and NAM takers? How does it feel? Does it help you in any way? Please post!

No cheating by alternating Niagen and N+R. Stop Niagen for 30 days at least. Then start the test. I can tell if it works with N+R by how my skin feels. But I will have to stop Niagen for probably 6 month. I am not willing to do that. Better find some people who never used Niagen.

Edited by MikeDC, 18 September 2017 - 06:38 PM.

[stefan_001]

Mike definitely has stock in CDXC. His rep here is -136 and it's almost like he's striving to break some kind of negative record. I do think we are lacking proof on both sides, there is no good research showing N+R results in a boost in NAD+ and there is no research showing NR is absorbed intact and is fully bioavailable, and in fact there is some evidence which Turnbuckle pointed to, that indicates it is not.

 

At this point it's just wait and see. I sold all my stock when it went back up to 4.5 the other day. I am suspicious of the fact that they have still not revealed the results of their recent studies. I am not expecting the best results.

 

Hi Nate, I think the statement that "there is no good research showing N+R results in a boost in NAD+" should be there is NO research showing N+R results in a boost in NAD+". Can you poiny to any research that even hints at ribose being rate limiting for N conversion to NMN or having any role at all?
 

[MikeDC]

We know N boosts NAD+. So N+R will definitely boosts NAD+. The question is "is N+R the same as NR".

[stefan_001]

We know N boosts NAD+. So N+R will definitely boosts NAD+. The question is "is N+R the same as NR".

 

indeed correct, I should have written it differently. N boosts NAD+, but there is no research that shows a role for R boosting in relation to NAM pathways

Edited by stefan_001, 19 September 2017 - 03:55 PM.

[Turnbuckle]

 

Mike definitely has stock in CDXC. His rep here is -136 and it's almost like he's striving to break some kind of negative record. I do think we are lacking proof on both sides, there is no good research showing N+R results in a boost in NAD+ and there is no research showing NR is absorbed intact and is fully bioavailable, and in fact there is some evidence which Turnbuckle pointed to, that indicates it is not.

 

At this point it's just wait and see. I sold all my stock when it went back up to 4.5 the other day. I am suspicious of the fact that they have still not revealed the results of their recent studies. I am not expecting the best results.

 

Hi Nate, I think the statement that "there is no good research showing N+R results in a boost in NAD+" should be there is NO research showing N+R results in a boost in NAD+". Can you poiny to any research that even hints at ribose being rate limiting for N conversion to NMN or having any role at all?
 

 

 

 

Considering that N by itself increases NAD+ by half as much as NR (according to the NR researchers/vendors themselves), that indicates N+R must also increase NAD+ by at least half as much, unless you want to make the argument that ribose somehow suppresses NAD+. 

[stefan_001]

I think the statement that "there is no good research showing N+R results in a boost in NAD+" should be there is NO research showing N+R results in a boost in NAD+". Can you poiny to any research that even hints at ribose being rate limiting for N conversion to NMN or having any role at all?

Considering that N by itself increases NAD+ by half as much as NR (according to the NR researchers/vendors themselves), that indicates N+R must also increase NAD+ by at least half as much, unless you want to make the argument that ribose somehow suppresses NAD+.

Not claiming that at all, see the followup post. Ribose is a builing block in ATP and taking it as supplement likely helps ATP production. Thats why you feel more energetic.

Edited by Michael, 22 September 2017 - 04:03 AM.
trim quote

[Nate-2004]

 

Mike definitely has stock in CDXC. His rep here is -136 and it's almost like he's striving to break some kind of negative record. I do think we are lacking proof on both sides, there is no good research showing N+R results in a boost in NAD+ and there is no research showing NR is absorbed intact and is fully bioavailable, and in fact there is some evidence which Turnbuckle pointed to, that indicates it is not.

 

At this point it's just wait and see. I sold all my stock when it went back up to 4.5 the other day. I am suspicious of the fact that they have still not revealed the results of their recent studies. I am not expecting the best results.

 

Hi Nate, I think the statement that "there is no good research showing N+R results in a boost in NAD+" should be there is NO research showing N+R results in a boost in NAD+". Can you poiny to any research that even hints at ribose being rate limiting for N conversion to NMN or having any role at all?
 

 

 

You're right. However there is research showing nictotinamide alone does boost NAD+. There's nothing on +R.

 

EDIT: I hadn't seen the other posts yet saying the same exact thing I just said. However, I will add that nicotinamide has been shown to suppress SIRT1 in vitro and apparently this is not true in vivo, but I don't know how strong the evidence is for the latter and this was one of the major arguments for using NR instead. This was also one of the major arguments for NMN and apparently this molecule, unless, like NR, is injected, will be subject to the same problem.

 

I don't see how NAD+ is anything but a minor issue in aging and the upstream root cause should be the main target of any research so that we can determine why CD38 is on the rise over time. We still have yet to confirm that it's SASP but if it is, then synolitics should take priority over NAD+ boosters and none of this debate or concern matters. Till then, I'll drink my chamomile and assume I may be doing more for NAD+ boosting than the NR.

Edited by Nate-2004, 19 September 2017 - 06:22 PM.

[stefan_001]

.

You're right. However there is research showing nictotinamide alone does boost NAD+. There's nothing on +R.

EDIT: I hadn't seen the other posts yet saying the same exact thing I just said. However, I will add that nicotinamide has been shown to suppress SIRT1 in vitro and apparently this is not true in vivo, but I don't know how strong the evidence is for the latter and this was one of the major arguments for using NR instead. This was also one of the major arguments for NMN and apparently this molecule, unless, like NR, is injected, will be subject to the same problem.

I don't see how NAD+ is anything but a minor issue in aging and the upstream root cause should be the main target of any research so that we can determine why CD38 is on the rise over time. We still have yet to confirm that it's SASP but if it is, then synolitics should take priority over NAD+ boosters and none of this debate or concern matters. Till then, I'll drink my chamomile and assume I may be doing more for NAD+ boosting than the NR.

Hi Nate, agree NAD+ is a "workaround". Senolytics, SASP, CD38 are certainly factors. I am wondering however whether declining NAD+ is actually a systematic problem in human and animal biology. After your body has full grown it passes a certain equilibrium and NAD+ starts to come down and detoriation starts. So perhaps the workaround is the only way to compensate.

[MikeDC]

You are NOT going to remove all inflammation with senolytics. Inflammation is part of us and will always be there. NR has been proven to reverse aging for most users so far. Neglecting NR at your own risk.

Edited by MikeDC, 19 September 2017 - 06:58 PM.

[Turnbuckle]

 

Not claiming that at all, see the followup post. Ribose is a builing block in ATP and taking it as supplement likely helps ATP production. Thats why you feel more energetic.

 

 

The research with double labeled NR produced 54% single labeled NAD+ and 5% double labeled NAD+. This indicates that NR has to be cleaved--either in the intestines or elsewhere--before NAD+ can be made from it. So there is no reason to believe that NR will act any differently than N+R. 

[MikeDC]

You don't really know that. NAD+ recycling turn NAD+ into Nicotinamide. These labled N can combine with unlabeled R to form single labeled NR. Vise versa.

[stefan_001]

You don't really know that. NAD+ recycling turn NAD+ into Nicotinamide. These labled N can combine with unlabeled R to form single labeled NR. Vise versa.

I think Mike has a good point. I was for some time planning to search in the study at what time point they had done the measurement or if they had done a series of time spread measurements.

[Turnbuckle]

You don't really know that. NAD+ recycling turn NAD+ into Nicotinamide. These labled N can combine with unlabeled R to form single labeled NR. Vise versa.

 

 

You just shot yourself in both feet. 

[stefan_001]

You don't really know that. NAD+ recycling turn NAD+ into Nicotinamide. These labled N can combine with unlabeled R to form single labeled NR. Vise versa.

You just shot yourself in both feet.

No he did not. Start from double labelled NR:

NR -> NMN -> NAD->NAM

After that recycling so that can lead to single labelled NR

Edited by stefan_001, 19 September 2017 - 07:42 PM.

[Heisok]

Unlike expressed in another post, This issue is very important for those who are trying to improve their health and those of loved ones now. (including Niki the cat)

 

Some might not have access to NR for location or monetary reasons. There have been many suggestions in posts, and topics of how NR and Nad+ and possible alternatives work and what for. Be it in cells, in organisms, in humans and through personal experiences alone.

 

The debate might not matter to some involved in this thread. In that case, the thread could be allowed to go forward with those trying to get some answers to the original posters questions which included:

 

OP:  "As you can see there, I have detailed my extremely impressive results, using both Nicotinamide Riboside, as well as Nicotinamide + Ribose mixed together. While both have given me very significant results, I am unable to tell which one would be better, hence this thread. "

 

 

Others perhaps: "I don't see how NAD+ is anything but a minor issue in aging and the upstream root cause should be the main target of any research so that we can determine why CD38 is on the rise over time. We still have yet to confirm that it's SASP but if it is, then synolitics should take priority over NAD+ boosters and none of this debate or concern matters"

 

The solution for many of these threads that end up cluttered with off topic posts, circular arguments and whatever else is clouding the great information is to mine the thread by copying posts which seem to contribute and create a document. Will somebody who is coming here to read the information mine the thread. Doubtful. Too many of the [poster/participants are VERY knowledgeable, so perhaps could figure out ways to help the knowledge base. 

Edited by Heisok, 19 September 2017 - 08:05 PM.

[MikeDC]

D-ribose is naturally occurring in all cells. There is no shortage of that. Too much ribose causes excessive glycation and aging! You might get more NAD+, but you will age faster. Does it defeat the purpose?

http://journals.plos...al.pone.0024623

Edited by MikeDC, 19 September 2017 - 08:08 PM.

[stefan_001]

Hi Heisok, if you are suggesting we should let people proclaim something works without evidence then that sounds like a dangerous path. Fact is NR has many reports demonstrating a positive health impact. Morover NR is not about feeling better in a day, the long term benefits you should get after years of use so better think before discarding and using something unproven for years. NAM is a cheaper alternative and probably does something positive. Its available however for decades and been experimented with endlessly. So any true meaningfull anti aging effect would be known. Taking lots of D-Ribose on a gamble, for years, doesnt sound like a plan to me. You could as well take dextrose. Be aware that d-ribose activates insuline and lower glucose levels so people with diabetes watch out and check the recommendations to consume it with food only.

Edited by stefan_001, 19 September 2017 - 08:23 PM.