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Could low NAD+ the main reason for Osteoporosis?

osteoporosis

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#1 Evan Yang

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Posted 23 August 2017 - 01:10 PM


Calcium and hormone supplementation (Estrogen and DHEA) helps. But none of them shows effectiveness large enough to explain the whole bone loss for old people. Now we are seeing more and more papers showing NAD+ dependent Sirt1 as very important to maintain bone density. So NAD+ precursors such as Nicotinamide Riboside or NMN could be very effective against bone loss. 

 

https://www.ncbi.nlm...pubmed/27378422

 

https://www.ncbi.nlm...medov//26287518

 

https://www.ncbi.nlm...pubmed/25377437

 

https://www.ncbi.nlm...pubmed/25002589

 

https://www.ncbi.nlm...pubmed/23276927


Edited by Evan Yang, 23 August 2017 - 01:21 PM.

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#2 Fafner55

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Posted 23 August 2017 - 01:17 PM

Senolytics, like dasatinib, also show good results in reversing age-related bone loss.

 

“Targeting cellular senescence prevents age-related bone loss in mice” (2017) https://www.nature.c...ll/nm.4385.html

.... The beneficial effects of targeting senescent cells were due to lower bone resorption with either maintained (trabecular) or higher (cortical) bone formation as compared to vehicle-treated mice. In vitro studies demonstrated that senescent-cell conditioned medium impaired osteoblast mineralization and enhanced osteoclast-progenitor survival, leading to increased osteoclastogenesis. Collectively, these data establish a causal role for senescent cells in bone loss with aging, and demonstrate that targeting these cells has both anti-resorptive and anabolic effects on bone. Given that eliminating senescent cells and/or inhibiting their proinflammatory secretome also improves cardiovascular function4, enhances insulin sensitivity3, and reduces frailty7, targeting this fundamental mechanism to prevent age-related bone loss suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.


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#3 Evan Yang

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Posted 23 August 2017 - 01:28 PM

 

Senolytics, like dasatinib, also show good results in reversing age-related bone loss.

 

“Targeting cellular senescence prevents age-related bone loss in mice” (2017) https://www.nature.c...ll/nm.4385.html

.... The beneficial effects of targeting senescent cells were due to lower bone resorption with either maintained (trabecular) or higher (cortical) bone formation as compared to vehicle-treated mice. In vitro studies demonstrated that senescent-cell conditioned medium impaired osteoblast mineralization and enhanced osteoclast-progenitor survival, leading to increased osteoclastogenesis. Collectively, these data establish a causal role for senescent cells in bone loss with aging, and demonstrate that targeting these cells has both anti-resorptive and anabolic effects on bone. Given that eliminating senescent cells and/or inhibiting their proinflammatory secretome also improves cardiovascular function4, enhances insulin sensitivity3, and reduces frailty7, targeting this fundamental mechanism to prevent age-related bone loss suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.

 

 

One way senescent cells cause damage is proinflammatory secretome which depletes NAD+ of normal cells. Supplementing NAD+ precursors from middle life also prevents cells becoming scenescent and even rescue senescent cells. So NAD+ precursors should be first line of therapy. Any remaining scenecent cells then can be eliminated with senolytics. 


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#4 Benko

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Posted 23 August 2017 - 04:53 PM

Mr. Yang,

 

Do you have any financial interest in NR?  And if so, what?

 

 


Edited by Benko, 23 August 2017 - 04:53 PM.

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#5 Harkijn

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Posted 23 August 2017 - 05:33 PM

Benko, please note that Evan only mentions Nad precursors. These are many: tryptophan, aspartic acid, NMN, NR and perhaps even good old Nicotinamide to a little extent.


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#6 Evan Yang

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Posted 23 August 2017 - 05:53 PM

Mr. Yang,

 

Do you have any financial interest in NR?  And if so, what?

 

I have been taking Niagen and believe it is the best anti aging drug at this time. I want people to be aware of its benefits.


Benko, please note that Evan only mentions Nad precursors. These are many: tryptophan, aspartic acid, NMN, NR and perhaps even good old Nicotinamide to a little extent.

 

Niacin is another one. 


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#7 Harkijn

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Posted 23 August 2017 - 06:05 PM

 

Mr. Yang,

 

Do you have any financial interest in NR?  And if so, what?

 

I have been taking Niagen and believe it is the best anti aging drug at this time. I want people to be aware of it. 

 

 

In that case Benko's question still stands, with a little refrasing: do you have any financial interest in Niagen?

Thanks for clarifying!


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#8 Evan Yang

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Posted 23 August 2017 - 06:53 PM

I can tell you i am not related to ChromaDex. 


This is NR area. Why do you guys harassing people for mentioning NR?


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#9 Benko

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Posted 23 August 2017 - 07:18 PM

I can tell you i am not related to ChromaDex. 


This is NR area. Why do you guys harassing people for mentioning NR?

 

You are behaving (including choice of words) the way someone who is making money off of this would behave.  Your behavior is not that of a benevolent person simply offering advise.  And I say that as someone who takes NR and is tempted to invest.

 

Also as someone else pointed out, a recent screen name was banned for similar behavior and your screen name started 2 days after that person was banned.  The powers that be here really should see if you have the same IP address as that person.
 

 

 


Edited by Benko, 23 August 2017 - 07:19 PM.

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#10 Benko

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Posted 23 August 2017 - 07:21 PM

To the person rating all these questions as timewasting, don't read it then.


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#11 mrkosh1

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Posted 24 August 2017 - 12:27 AM

 

 

Senolytics, like dasatinib, also show good results in reversing age-related bone loss.

 

“Targeting cellular senescence prevents age-related bone loss in mice” (2017) https://www.nature.c...ll/nm.4385.html

.... The beneficial effects of targeting senescent cells were due to lower bone resorption with either maintained (trabecular) or higher (cortical) bone formation as compared to vehicle-treated mice. In vitro studies demonstrated that senescent-cell conditioned medium impaired osteoblast mineralization and enhanced osteoclast-progenitor survival, leading to increased osteoclastogenesis. Collectively, these data establish a causal role for senescent cells in bone loss with aging, and demonstrate that targeting these cells has both anti-resorptive and anabolic effects on bone. Given that eliminating senescent cells and/or inhibiting their proinflammatory secretome also improves cardiovascular function4, enhances insulin sensitivity3, and reduces frailty7, targeting this fundamental mechanism to prevent age-related bone loss suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.

 

 

One way senescent cells cause damage is proinflammatory secretome which depletes NAD+ of normal cells. Supplementing NAD+ precursors from middle life also prevents cells becoming scenescent and even rescue senescent cells. So NAD+ precursors should be first line of therapy. Any remaining scenecent cells then can be eliminated with senolytics. 

 

 

I totally agree. Keeping NAD+ levels high induces all sorts of positive changes such as activtating the SIRT genes, protecting stem cells, inducing the production of natural antioxidants via the NRF2 pathway, and activating telomerase via PGC1A. 

 

The NR hate on this forum is becoming outrageous. I think it stems from certain people who want to NMN to become a prescription drug costing thousands of dollars. The truth is that NMN must be transformed into NR before it can pass through the cell membrane. NMN is therefore an inferior supplement. 


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#12 mrkosh1

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Posted 24 August 2017 - 12:31 AM

 

I can tell you i am not related to ChromaDex. 


This is NR area. Why do you guys harassing people for mentioning NR?

 

You are behaving (including choice of words) the way someone who is making money off of this would behave.  Your behavior is not that of a benevolent person simply offering advise.  And I say that as someone who takes NR and is tempted to invest.

 

Also as someone else pointed out, a recent screen name was banned for similar behavior and your screen name started 2 days after that person was banned.  The powers that be here really should see if you have the same IP address as that person.
 

 

 

I find nothing wrong with his posts. I agree with them. Your behavior is inappropriate, IMO. 


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#13 Michael

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Posted 29 August 2017 - 03:08 AM

To get back to the original subject:

While it's true that Ca deficiency and estrogen decline can't explain all of the age-related risk of osteo, NAD+ decline clearly can't be the main factor. Osteoporosis begins earlier, proceeds more quickly, and is far more severe in women than in men, yet the decline with age of NAD+ is substantially more steep in men than in women (correlation between age and NAD+ levels r =-0.706 vs. -0.537, respectively, at least in sun-protected skin, which is the only place for which we have gender-specific human data(1)). In C57BL/6J mice, liver NAD+ levels at 23–24 months of age are non-significantly higher in males than females (≈0.65 vs. 0.60 nmol/mg protein, respectively).(2)
 

The NR hate on this forum is becoming outrageous. I think it stems from certain people who want to NMN to become a prescription drug costing thousands of dollars.


Come now. Cite a single instance of "NR hate." NR caution? NR skepticism? Sure.
 
References
1: Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. doi: 10.1371/journal.pone.0042357. Epub 2012 Jul 27. PubMed PMID: 22848760; PubMed Central PMCID: PMC3407129.
 
2: Mitchell SJ, Madrigal-Matute J, Scheibye-Knudsen M, Fang E, Aon M, González-Reyes JA, Cortassa S, Kaushik S, Gonzalez-Freire M, Patel B, Wahl D, Ali A, Calvo-Rubio M, Burón MI, Guiterrez V, Ward TM, Palacios HH, Cai H, Frederick DW, Hine C, Broeskamp F, Habering L, Dawson J, Beasley TM, Wan J, Ikeno Y, Hubbard G, Becker KG, Zhang Y, Bohr VA, Longo DL, Navas P, Ferrucci L, Sinclair DA, Cohen P, Egan JM, Mitchell JR, Baur JA, Allison DB, Anson RM, Villalba JM, Madeo F, Cuervo AM, Pearson KJ, Ingram DK, Bernier M, de Cabo R. Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice. Cell Metab. 2016 Jun 14;23(6):1093-1112. doi: 10.1016/j.cmet.2016.05.027. PubMed PMID: 27304509; PubMed Central PMCID: PMC4911707.


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#14 stefan_001

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Posted 29 August 2017 - 09:03 PM

 

The NR hate on this forum is becoming outrageous. I think it stems from certain people who want to NMN to become a prescription drug costing thousands of dollars.


Come now. Cite a single instance of "NR hate." NR caution? NR skepticism? Sure.
 

 

I do believe that the skeptics here are eager to accept non supportive results without exposing them to the same scrutiny. I think the discussion around this study was a proof of that:

 

9: Kourtzidis IA, Stoupas AT, Gioris IS, Veskoukis AS, Margaritelis NV, Tsantarliotou M, Taitzoglou I, Vrabas IS, Paschalis V, Kyparos A, Nikolaidis MG. The NAD(+) precursor nicotinamide riboside decreases exercise performance in rats. J Int Soc Sports Nutr. 2016 Aug 2;13:32. doi: 10.1186/s12970-016-0143-x. eCollection 2016. PubMed PMID: 27489522; PubMed Central PMCID: PMC4971637.

 


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#15 mrkosh1

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Posted 30 August 2017 - 01:33 AM

A great example of the NR hate is how the factual information NMN absolutely without a doubt must be converted into NR before being transported through the cell membrane. I had to argue this issue and posted the thesis that provided the data. That thesis clearly showed that NR is directly transported into cells while NMN is slowly converted to NR extracellularly. A number of users on this forum seemed to forget that information. Additionally, there seems to be a general trend to promote NMN as something unique or special when it's clearly inferior due to the much slower conversion/transport process.

 

I sincerely believe that there are elements on this forum who would like to see NMN declared a pharmaceutical drug and NR restricted in the same way that pyradoximine was banned. Right now, there is zero reason for anyone to buy NMN (unless it is some exotic form that is modified so it doesn't need to be converted to NR) when NR is already available. Anyone who promotes NMN over NR -- unless new studies refute what was provided in the thesis -- is very likely to have an agenda. I also think some of them could have a financial interest in NMN.

 

I'm taking NR right now and have had very good results. The last thing I want to see happen is it taken off the market so NMN can be given a fancy name (perhaps Naduppla) and be sold by prescription for $500 dollars a bottle. No one would pay for such a perscription if they could go on Amazon and buy a bottle of NR for $50 or less. 


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#16 YOLF

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Posted 30 August 2017 - 03:17 AM

I can tell you i am not related to ChromaDex. 


This is NR area. Why do you guys harassing people for mentioning NR?

I think NR has it's own social media mafia. It's got some benefits, but is it worth the level of attention that it gets? I think that attention reinforces consumer behavior that is only good for the producers of Niagen as it leaves consumers feeling like the stuff is a silver bullet against the whole spectrum of aging and all they need to take for it. No monotherapy can really hold a candle to the wind of a well researched supplement regimen and recent supplements have shown that synergies multiply benefits.


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#17 YOLF

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Posted 30 August 2017 - 03:21 AM

A great example of the NR hate is how the factual information NMN absolutely without a doubt must be converted into NR before being transported through the cell membrane. I had to argue this issue and posted the thesis that provided the data. That thesis clearly showed that NR is directly transported into cells while NMN is slowly converted to NR extracellularly. A number of users on this forum seemed to forget that information. Additionally, there seems to be a general trend to promote NMN as something unique or special when it's clearly inferior due to the much slower conversion/transport process.

 

I sincerely believe that there are elements on this forum who would like to see NMN declared a pharmaceutical drug and NR restricted in the same way that pyradoximine was banned. Right now, there is zero reason for anyone to buy NMN (unless it is some exotic form that is modified so it doesn't need to be converted to NR) when NR is already available. Anyone who promotes NMN over NR -- unless new studies refute what was provided in the thesis -- is very likely to have an agenda. I also think some of them could have a financial interest in NMN.

 

I'm taking NR right now and have had very good results. The last thing I want to see happen is it taken off the market so NMN can be given a fancy name (perhaps Naduppla) and be sold by prescription for $500 dollars a bottle. No one would pay for such a perscription if they could go on Amazon and buy a bottle of NR for $50 or less. 

Sometimes slower is better... my question is do the benefits of NR persistence from NMN outperform acute administration of NR? How fast is it used and is some of it available whenever needed?


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#18 Harkijn

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Posted 30 August 2017 - 06:51 AM

Sometimes slower is better... my question is do the benefits of NR persistence from NMN outperform acute administration of NR? How fast is it used and is some of it available whenever needed?

 

 

 

The  opposite may also turn out to be true. There has been one study(I forget which) that concluded that NMN raised NAD+ surprisingly quickly after ingestion, while NR is thought to peak after about 8 hours. Maybe there is a future for both compounds....


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#19 mrkosh1

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Posted 30 August 2017 - 12:10 PM

 

A great example of the NR hate is how the factual information NMN absolutely without a doubt must be converted into NR before being transported through the cell membrane. I had to argue this issue and posted the thesis that provided the data. That thesis clearly showed that NR is directly transported into cells while NMN is slowly converted to NR extracellularly. A number of users on this forum seemed to forget that information. Additionally, there seems to be a general trend to promote NMN as something unique or special when it's clearly inferior due to the much slower conversion/transport process.

 

I sincerely believe that there are elements on this forum who would like to see NMN declared a pharmaceutical drug and NR restricted in the same way that pyradoximine was banned. Right now, there is zero reason for anyone to buy NMN (unless it is some exotic form that is modified so it doesn't need to be converted to NR) when NR is already available. Anyone who promotes NMN over NR -- unless new studies refute what was provided in the thesis -- is very likely to have an agenda. I also think some of them could have a financial interest in NMN.

 

I'm taking NR right now and have had very good results. The last thing I want to see happen is it taken off the market so NMN can be given a fancy name (perhaps Naduppla) and be sold by prescription for $500 dollars a bottle. No one would pay for such a perscription if they could go on Amazon and buy a bottle of NR for $50 or less. 

Sometimes slower is better... my question is do the benefits of NR persistence from NMN outperform acute administration of NR? How fast is it used and is some of it available whenever needed?

 

 

Even if there were some benefit to a slower trickle of NR entering the cell after being converted from NMN, I'd rather take an over the counter time released version of NR (at current prices or lower) than a $500 dollar prescription of NMN after NR is legally declared to violate someone's patents and banned. 


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#20 Michael

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Posted 30 August 2017 - 02:30 PM

 

 

A great example of the NR hate is how the factual information NMN absolutely without a doubt must be converted into NR before being transported through the cell membrane. I had to argue this issue and posted the thesis that provided the data. That thesis clearly showed that NR is directly transported into cells while NMN is slowly converted to NR extracellularly. A number of users on this forum seemed to forget that information. Additionally, there seems to be a general trend to promote NMN as something unique or special when it's clearly inferior due to the much slower conversion/transport process.
 
I sincerely believe that there are elements on this forum who would like to see NMN declared a pharmaceutical drug and NR restricted in the same way that pyradoximine was banned. Right now, there is zero reason for anyone to buy NMN (unless it is some exotic form that is modified so it doesn't need to be converted to NR) when NR is already available. Anyone who promotes NMN over NR -- unless new studies refute what was provided in the thesis -- is very likely to have an agenda. I also think some of them could have a financial interest in NMN.
 
I'm taking NR right now and have had very good results. The last thing I want to see happen is it taken off the market so NMN can be given a fancy name (perhaps Naduppla) and be sold by prescription for $500 dollars a bottle. No one would pay for such a perscription if they could go on Amazon and buy a bottle of NR for $50 or less.

Sometimes slower is better... my question is do the benefits of NR persistence from NMN outperform acute administration of NR? How fast is it used and is some of it available whenever needed?

 

 
Even if there were some benefit to a slower trickle of NR entering the cell after being converted from NMN, I'd rather take an over the counter time released version of NR (at current prices or lower) than a $500 dollar prescription of NMN after NR is legally declared to violate someone's patents and banned.

You're entitled to your preference. But don't confuse your preference and financial ease with the science — and don't drag the discussion down into ad hominem against anyone who disagrees with you.


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#21 Michael

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Posted 30 August 2017 - 02:40 PM

I do believe that the skeptics here are eager to accept non supportive results without exposing them to the same scrutiny. I think the discussion around this study was a proof of that:
 
9: Kourtzidis IA, Stoupas AT, Gioris IS, Veskoukis AS, Margaritelis NV, Tsantarliotou M, Taitzoglou I, Vrabas IS, Paschalis V, Kyparos A, Nikolaidis MG. The NAD(+) precursor nicotinamide riboside decreases exercise performance in rats. J Int Soc Sports Nutr. 2016 Aug 2;13:32. doi: 10.1186/s12970-016-0143-x. eCollection 2016. PubMed PMID: 27489522; PubMed Central PMCID: PMC4971637.

 
This study was discussed quite extensively and in detail; I don't think it got any less scrutiny than any other NR study that got more than a single post's notice.
 

I can tell you i am not related to ChromaDex. 

This is NR area. Why do you guys harassing people for mentioning NR?

 
No one is being harassed for mentioning NR. Certain Posters are being called out for engaging in incessant, aggressive, one-sided boosterism.
 
Remember, in any case that the NR forum is for discussion of NR, not as a special "safe space" zone for the  NR cheerleading squad.
 

A great example of the NR hate is how the factual information NMN absolutely without a doubt must be converted into NR before being transported through the cell membrane.

 
How exactly does that constitute "NR hate?"


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#22 Harkijn

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Posted 30 August 2017 - 03:24 PM

Let me repeat here what I mentioned in another NR thread: dr. Brenner recently compared NMN with NR in a number of respects. Though NR came out better, dr. B. is not at all negative about NMN.

I call on everyone to take a few deep breaths and reflect on the relative importance of whatever we say on these threads. NMN and/or NR will find their way whatever we say about them  :-)


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#23 Heisok

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Posted 30 August 2017 - 11:49 PM

Harkjin, I agree that NMN and/or NR will find their way.

 

I will say however, that for those seeking health benefit information, these threads are very important. The majority who get to view them, and gain actionable information, far surpass any cheerleading or questioning by posters which takes place. Your comments, and those of others matter.


Edited by Heisok, 30 August 2017 - 11:50 PM.


#24 mrkosh1

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Posted 31 August 2017 - 01:10 AM

 

Even if there were some benefit to a slower trickle of NR entering the cell after being converted from NMN, I'd rather take an over the counter time released version of NR (at current prices or lower) than a $500 dollar prescription of NMN after NR is legally declared to violate someone's patents and banned.


You're entitled to your preference. But don't confuse your preference and financial ease with the science — and don't drag the discussion down into ad hominem against anyone who disagrees with you.

 

If we are discussing the science of getting NAD+ precursors through the cell membrane to boost the NAD+ to NADH ratio for SIRT activation (among other intracellular benefits that result) then the hard science that has been performed (such as in the extremely detailed thesis paper I'll be happy to post a link to yet again if that is what it takes)  which proves NR can pass directly into cells while NMN must be more slowly converted into NR before penetrating. I'm more than willing to add three caveats here: 
 
1) I'm talking about NR vs. NMN when it comes to getting the precursor into the interior of the cell to boost the NAD+ to NADH ratio. If there are purely extracellular benefits of these substances -- that have nothing to do with getting them through the membrane -- then NMN could very well be equal or superior to NR. 
 
2) If NMN were modified in some way to directly pass through the cellular membrane without the requirement to be converted to NR, then that could be an amazing pharmaceutical drug since NMN, intercellularly, is a more direct precursor to NAD+ than NR. 
 
3) Someone has mentioned a paper exists that shows NMN producing a health benefit while NR does not. That sure seems strange to me if the benefit comes from increased NAD+ levels. In such a situation, perhaps NMN provided some sort of EXTRACELLULAR benefit that is superior to NR. 
 
Now, I challenge you with the permanent ban of my account to point out one specific case in which I have directly attacked any particular person over this issue with anything more than the statement that I found their behavior inappropriate (which isn't an attack but just a statement of an opinion without name calling or bad behavior). Anyone here can check my post history in this thread and others: I haven't been attacking any specific user. Yes, I'll say in *general* that I think there is a trend to bash NR and promote NMN despite the HARD SCIENCE (at least when it comes to intracellular health benefits) that explains how NR is superior. But I have not called one person a hateful name, used one word of profanity, told "off" anyone, etc. 
 
Moreover, when I discuss my fear of NR being banned due to a legal action claiming it violates someone's patent (like happened with a superior version of vitamin B6 which made the LEF Foundation remove it from their product), I'm in no way mixing my desire for ease of access with the science. NR is superior when it comes to penetrating the membrane and getting inside a cell to boost NAD+. The NAD+ benefit to activate SIRT genes and turn on PARP to repair DNA is the health benefit I'm seeking. If someone else is seeking another extracellular benefit (for all we know NMN might break apart extracellular molecules like glucosepane although I've read no evidence of this) then NMN might be superior. 
 
Everyone in the world has the right to disagree with me. They have the right to say anything they so desire. However, I also have the right to say peacefully and politely that if they claim NMN is better/faster at penetrating the cell wall and boosting NAD+ they are wrong. Multiple papers written by highly qualified PhD's would back me up.


Edited by Michael, 13 November 2017 - 08:41 PM.
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#25 able

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Posted 31 August 2017 - 02:26 AM

If we are discussing the science of getting NAD+ precursors through the cell membrane to boost the NAD+ to NADH ratio for SIRT activation (among other intracellular benefits that result) then the hard science that has been performed (such as in the extremely detailed thesis paper I'll be happy to post a link to yet again if that is what it takes)  which proves NR can pass directly into cells while NMN must be more slowly converted into NR before penetrating. I'm more than willing to add three caveats here: 

 

 

 

1) I'm talking about NR vs. NMN when it comes to getting the precursor into the interior of the cell to boost the NAD+ to NADH ratio. If there are purely extracellular benefits of these substances -- that have nothing to do with getting them through the membrane -- then NMN could very well be equal or superior to NR. 

 

2) If NMN were modified in some way to directly pass through the cellular membrane without the requirement to be converted to NR, then that could be an amazing pharmaceutical drug since NMN, intercellularly, is a more direct precursor to NAD+ than NR. 

 

 

 

 

 

Yes, the Trammell thesis has experiments that seem to prove NR passes the cell membrane and NMN does not.    That MIGHT be important, and might not.

 

Assuming their conclusion is accurate, it  makes little difference if NR is not present in quantity in the blood “knocking on the door” to enter a cell.

 

As Micheal mentioned several times, NR has not been found in the bloodstream.  NMN has.

 

Also, it might not matter if NMN is easily converted to NR before passing thru the cell membrane.

 

Studies show that NMN is rapidly converted in vivo and elevates NAD in many different tissues.  

 

If you don’t believe any of that, I’ll go dig up references, but none of that is new.

 

I have posted this link  a couple times already to a 2011 experiment which concluded NAD+ CAN pass the cell membrane.  If that is so, it MAY render the whole issue moot.

 

 

"eNAD crosses intact the plasma membrane"

 


3) Someone has mentioned a paper exists that shows NMN producing a health benefit while NR does not. That sure seems strange to me if the benefit comes from increased NAD+ levels. In such a situation, perhaps NMN provided some sort of EXTRACELLULAR benefit that is superior to NR. 

 

Now, I challenge you with the permanent ban of my account to point out one specific case in which I have directly attacked any particular person over this issue with anything more than the statement that I found their behavior inappropriate (which isn't an attack but just a statement of an opinion without name calling or bad behavior). Anyone here can check my post history in this thread and others: I haven't been attacking any specific user. Yes, I'll say in *general* that I think there is a trend to bash NR and promote NMN despite the HARD SCIENCE (at least when it comes to intracellular health benefits) that explains how NR is superior. But I have not called one person a hateful name, used one word of profanity, told "off" anyone, etc. 

 

Moreover, when I discuss my fear of NR being banned due to a legal action claiming it violates someone's patent (like happened with a superior version of vitamin B6 which made the LEF Foundation remove it from their product), I'm in no way mixing my desire for ease of access with the science. NR is superior when it comes to penetrating the membrane and getting inside a cell to boost NAD+. The NAD+ benefit to activate SIRT genes and turn on PARP to repair DNA is the health benefit I'm seeking. If someone else is seeking another extracellular benefit (for all we know NMN might break apart extracellular molecules like glucosepane although I've read no evidence of this) then NMN might be superior. 

 

Everyone in the world has the right to disagree with me. They have the right to say anything they so desire. However, I also have the right to say peacefully and politely that if they claim NMN is better/faster at penetrating the cell wall and boosting NAD+ they are wrong. Multiple papers written by highly qualified PhD's would back me up. 

 

 

 

 

Maybe that was me, posting these two experiments below which seemed to show NMN was successful where NR was not.  

 

Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model

 

Remarkably, NMN administered to FXN-KO mice restores cardiac function to near-normal levels. “

 

 

NAD+ replacement therapy with nicotinamide riboside does not improve cardiac function in a model of mitochondrial heart disease.

 

In conclusion, NAD+ supplementation with NR in the FRDA model of mitochondrial heart disease does not alter SIRT3 activity or improve cardiac function.”

 

 

Obviously different tests.  I posted to see if someone smarter than me could point out how it wasn’t a good comparison. Even if valid, the fact that one works in a disease model doesn’t mean it is “better” overall.  

 

AFAIK, there are few head to head tests.  But I do like to debate the issues from both sides and try to learn.  It’s sometimes hard to do without people getting offended.

 

Overall, I do believe NR is likely to be effective in more situations, but that doesn’t mean it will necessarily be better in every case. 

 

If it was an open and shut case that one  is clearly superior, all those PHD's wouldn't be wasting their time on both molecules 


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#26 jjnz

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Posted 05 September 2017 - 03:14 AM

I have (for unknown reasons) significant osteoporosis. I'm 46/m and most of my t scores are less than -2.5 the worst being -4.5 in hip wards.
I also suffered a long period of strong fatigue. The bone scan was recommended after my endocrinologist browsed over a chest X-ray and noted thin bones.
To cut a Long story short I started taking nr and pterostilbene (along with prunes, boron, vit d vit k (mk4 and mk7) and saw a massive improvement in bone density in 13 months.
Some measures were up 20%, average around 5% which is quite significant.
Happy to supply Dexa scans.
Can't say for sure that it was nr alone but the sirtuin angle was a surprise benefit of something I took to help me with fatigue, basically got me out of bed after a good 8 week stint.
I now know the fatigue was due to inflammation and I now suffer from what I still can't clinically prove is rheumatoid arthritis but it sure looks like it.
Anyway hope this adds some n=1 weight to surtuin activation in humans having an effect on bone density.
The prunes BTW (in rats) slow down osteoclasts I have 8 every morning.
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#27 pauleyphonic

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Posted 05 November 2017 - 04:40 AM

I'm in love with Vitamin K2 since it appears to be crucial in regulating calcium and we tend to be deficient in it.

A study on K2 and osteoporosis: https://www.ncbi.nlm...pubmed/15320745

A video podcast on it: https://blog.bulletp...-bleue-podcast/



#28 recon

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Posted 05 November 2017 - 05:11 AM

I know this may be bad taste to ask in the middle of this heated argument, but where can one source NMN anyways?

There’s an overpriced Revgenetics and most NMN products now uses NR anyways. Even Elysium Basis now uses NR.

EDIT: I just searched it up. Apparently there are quite a few.

Edited by recon, 05 November 2017 - 05:13 AM.






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