2255 replies to this topic

[Tom Andre F. (ex shinobi)]

 

I don't know this Daryl and haven't seen the study. Niacin (NA) is cheap, Nicotinamide (NAM) is also, Nicotinamide mononucleotide (NMN) is not, at least the real stuff. There's no way I could take the Niacin in the quantities I'd need. Plus there is chance of liver damage longterm in the higher quantities. "Niacin’s safety record is equally impressive. However, a brief foray into the use of very-slow-release niacin preparations in the 1980s taught us an important lesson: niacin is very safe, if the liver is exposed to it for only a few hours at a time. Niacin is, after all, just vitamin B3. However, 24-hour, day-after-day exposure to niacin over an extended period can be toxic to the liver. Thus, the very-slow-release niacin preparations that yielded sustained, high blood levels of niacin caused liver toxicity in 10-20% of people who used these preparations in the 1980s. Unfortunately, this learning experience left some physicians fearful of recommending niacin to their patients. For this reason, very-slow-release niacin should be avoided."

 

 

A few things:

 

1. The fear of liver damage is unwarranted unless you have an existing liver problem and/or you take high dosages of slow release niacin for a long period of time. The use of immediate release Niacin is a pretty 'safe' bet.

 

2. The flush effect is not permanent. You can slowly build up to higher levels without flushing. Personally, I can take two grams of niacin at once without flushing (unless I drink something hot with it). When I first began supplementation, I would get a nasty flush at 50mg.

 

3. If you can handle the flush and you seem to flat line while trying to build up to a higher dosage, you can take aspirin about 30 minutes prior to niacin and not flush at all. I do suggest you make note of the aspirin / NAD cycle synergy that Darryl has mentioned in the past.

 

thank you for the report !

 

There is positive synergy at high doses. I don't have the links handy, but you can probably find them pretty quickly with the search function. I believe the aspirin dosage is higher than one should take long term due to side affects, but can be mitigated by using a different form of it.

 

its probably due to the fact I read the flush is due to PGD2.

 

omega 3 seems to reduce it : http://www.ncbi.nlm....les/PMC3308705/

 

also aspirin works to remove PGD2.. Same for quercetin

 

Instead of aspirin I use willow bark that also showed increased mitochondria respiratory chain

 

EDIT: for more reading about the flush, here is a good article, they covered the topic : http://www.life-enha...-to-your-health

 

Could be interesting to know if the release of PGD2 decrease over time of niacin due to its anti inflammatory effect. A long term follow up study would be most welcome

Edited by Tom Andre F. (ex shinobi), 27 June 2016 - 06:12 PM.

[Bryan_S]

 

Hi Bryan,

 

lets reply into 3 points, no big deal :

 

1/ the tissues and their specific kinases: Problem is NR can only use the NRK1/2 or being converted by hydrolisis into Nam directly. 

 

2/ About dosage and possible issue: it will not be 20 times more as you state, since NR count actually for half its weight since you have to remove the ribose part. 

 

3/ Ribose in the human body cells : owns pool for ribose as confirmed by this study: Generation, release and uptake of the NAD precursor nicotinic acid riboside by human cells : http://www.jbc.org/c...664458.full.pdf

 

So to conclude: What I want is stop aging as much as possible, and use NR will not be able to do the job properly, its mostly misleading to market it as the ultimate NAD+ booster since it just not. Im sorry for your rosacea condition problem, but I try here to be the more scientist as possible and work with only fact no feeling. I swear I would love NR would be that great, but I dont see it as the case. Now what is funny, is that NR come on the market, people claim its the best precursor and when you doubt about it, they want you to proof it.. Its funny since normally this is the opposite that have to happen

about my own dosage: I believe 50mg is enough to give enough NAD+ precursor, but I do not count for NAD+ precursor as the best strategy to increase NAD+/NADH ratio anymore > get a therapeutic effect, especially on the long run that we do not have. Still B3s are vitamins means essential but in a certain dosage. The high dose for both NR or Na is still a risk that people should be aware and take or not.

 

Best precursor however would be NaR but no one is selling it yet.
 

 

 

We’ve been down this road before. Everyone eventually picks a horse and defends their choice. I’ve supported discussion on every NAD precursor and have attempted to help give them their props. I’ve worked hard to be fair to all of them. As I’ve mentioned every precursor has own tissue specificity. We can’t change the mechanics/biochemistry It boils to to the epigenetic’s of each tissue and that status can change when under stress or during injury. Then outside this not everything is that specific, we have secondary utilization paths. So for example I take my Niacin but some of that Niacin is later exported to other tissues as Nicotinamide Riboside (NR). And incidentally (NR) seems to be the precursor path shared across tissues when injury and repair is needed.

 

What I find interesting is we keep revisiting the same argument of which precursor is best.

Are Other Precursors as Effective in Increasing NAD+ as NR?

 

So upon entry into the cell is the precursor a sirtuin activator or a sirtuin inhibitor? We’ve touted the CR benefits before so I won’t make a this post about that. We know (NR) as a sirtuin activator. So any argument about it being hydrolyzed into NAM is outweighed by the results that continue to point to this. If a significant amount of (NR) were being transformed into (NAM) we would’t see these results.

I’ve searched and can’t find anything terribly convincing to say Niacin (Na) is a potent sirtuin activator. I have found research saying its likely not an inhibitor. The lack of search results tells me it hasn’t really been studied.

 

Now we can’t say the same about Nicotinamide (NAM) and as far back as 2007 the rumblings of sirtuin inhibition began.

https://www.scienced...70208131737.htm

 

But all these precursors don’t live in a vacuum and all of them eventually become Nicotinamide. So whats up with that? Eventually no matter what you take the end result is the same it ends up on the Nicotinamide pile to be recycled. I believe the inhibition of the sirtuin’s is like a signal, saying the cell has what it needs and it puts the breaks on the sirtuin’s and ramps down NAD+ production in response.

 

You guys all seem to want to shift the NAD/NADH ratios or find the NQO1 or AMPK Activators. We also went for awhile discussing beta-lapachone while everyone was calling it off topic.

 

You guys also seem to be ignoring the elephant in the room which is CD38. No matter what NAD precursor you embrace you have this monster in the shadows destroying or minimizing our NAD+ boosting efforts. In this context is shifting the NAD/NADH ratios going to help, is activating NQO1 or stimulating AMPK going to offset the damage inflicted by CD38? I don’t think so.

 

​So we have 2 opposing forces NAD production and CD38 NAD destruction. If pseudohypoxia and NAD depletion are what finally do us in I think this is the focus of aging. Thats why NAD+ repletion is the subject of so many papers.

 

So as the moderator its my job to keep this topic which is about Nicotinamide Riboside (NR) and NAD+ repletion/boosting on target. This (NR) is where the research is focusing, not Niacin. I certainly don’t see convincing evidence Niacin (Na) is better than Nicotinamide Riboside (NR) from a publication standpoint and the research certainly doesn’t speak to this point.

 

Our audience likes a good debate and all we can do is repeat the published science. From my perspective Niacin (Na) isn’t receiving enough research now that all these new cellular mechanisms need defining. Nicotinamide Riboside (NR) on the other hand is attracting a ton of research and these are the metabolic questions of the day and this is where the money is going. I’m sorry this is the current reality.

 

So I always leave it up to the reader which precursor to pick. Right now the science community is huddled around Nicotinamide Riboside (NR) so this is what I’m reporting. It gives us all something to consider and hang our comments.  If Niacin is the jewel that needs recognition convince the academia to put more research into it.

 

So I’ll say again show me Niacin (Na) is better at raising NAD levels because this is the bottom line and what I asked you for.

[Steve H]

CD38 is regulated by the NF-KB pathway as shown in numerous research papers and resources including here:

http://www.bu.edu/nf...s/target-genes/

I strongly suggest you all review the numerous Senolytic and Senescent cells papers relating to SASP if you have not done so already, you will understand hopefully then how CD38 can be dealt with. Sinclair talks about inflammation being the likely culprit in its upregulation in the CD38 destroys NAD paper and again its importance is noted here:

 

http://www.cell.com/...43?showall=true

http://www.cell.com/...4131(16)30224-8

 

So we can either target the CD38 directly or ideally the source of that which is the chronic inflammation being caused to significant extent by SASP from accumulating Senescent cells. Senolytics that is systemically effective could reduce that senescent cell burden and reduce CD38 and other inflammatory signalls. This is why my hypothesis is that Senolytics is a suitable therapy for dealing with this problem and seeing as I am running a research project focused on senolytics I can quite easily add NAD/NADH ratio, NK-FB and CD38 metrics to the study to confirm that. The Sinclair paper practically spells out the association between inflammation and NAD decline so I am keen to confirm that. 

This is probably why Reason at fight aging thinks messing around with precursors instead of addressing the source of the dysfunction is unlikely to lead to much utility. 

https://www.fightagi...eotide-in-japan

And yes he talks about Nicotinamide mononucleotide here but he has said similar about other precursors for NAD. 

 

CD38 and its upstream regulators are the problem here in my view.

[stefan_001]

 

 

 

 

 

 

Hi Bryan,

 

lets reply into 3 points, no big deal :

 

1/ the tissues and their specific kinases: Problem is NR can only use the NRK1/2 or being converted by hydrolisis into Nam directly. So yes its ok for brain cells but not for kidney, liver, lung, pancreas, and placenta.. So make for instance your study about NAD+ boosting for the liver useless in this topic. NR will not improve your liver condition via NAD+. Not possible. This is also confirmed by this vivo study where they fed mice with NR: http://www.cell.com/...4131(12)00192-1 the only effect you will get using NR for the liver is due to hydrolisis into Nam that will use the normal Nampt pathway. Thats it. Since liver own preiss handler pathway, Na is a much better candidate and this is also confirmed in the study.

And to finish with the brain cells part, I want to refer to point 3 below

 

So Tom you would then say these researchers have falsified their study wrt fatty liver disease ? or then your statement is wrong?

 

Orally administration of nicotinamide riboside, a natural NAD+ precursor, completely corrected these NAFLD phenotypes induced by NAD+ deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes.

http://www.ncbi.nlm....pubmed/27174364

Edited by stefan_001, 27 June 2016 - 09:10 PM.

[niner]

 

George church gives the following figure for NR on his slides:
 

Nicotinamide $1600/g 0.5g/kg = $50k/day

http://crispr-congre...resentation.pdf

 

Church is referring to NMN (Nicotinamide Mononucleotide), not NR (Nicotinamide Riboside).

 

At least it might be possible to find NMN somewhere priced by the milligram that would make Church's slide technically correct, but it is revoltingly disingenuous, given that NMN is amenable to bulk synthesis.  It's probably not scaled for HED either.

Edited by niner, 27 June 2016 - 10:26 PM.

[Steve H]

Niner no doubt it is but his approach with TFAM is still good in my view. I want permanent solutions to problems not taking drugs constantly to try and shore up a failing system. Hence I favour reducation of systemic inflamation which as I have refferenced contributes to rising CD38 and other signalling factors that effect NAD.

 

[Tom Andre F. (ex shinobi)]

 

 

So Tom you would then say these researchers have falsified their study wrt fatty liver disease ? or then your statement is wrong?

 

Orally administration of nicotinamide riboside, a natural NAD+ precursor, completely corrected these NAFLD phenotypes induced by NAD+ deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes.

http://www.ncbi.nlm....pubmed/27174364

 

 

No I would say you have to read the full study :

 

"Our work highlights the therapeutic value of NR in NAFLD. In fact, other NAD+ substrates such as nicotinamide, was also shown to be able to prevent fatty liver and fibrosis."

 

So if this chinese study is your ultimate source to say NR is a good candidate fo treat liver, then you should use Nam instead of NR, its cheaper as they concluded: These results provide the first evidence that aging-associated NAD⁺ deficiency is a critical risk factor for NAFLD, and suggest that supplement of NAD⁺ substrates (enjoy how they do not specify NR) may be a promising therapeutic strategy to prevent and treat NAFLD.

 

The study is poorly conducted, they did not monitored NRK and does not explain how NR could give positive result. And it seems mainly again because Nam fragment and some "detectable" (very very low)) level  of NRK2 already mentioned in the study I previously quoted: http://www.ncbi.nlm....les/PMC3616313/ where you see Na was better candidate to boost NAD+ in liver than NR.

 

Furthermore, and to connect the dots here, this chinese study also mentioned to use their dosage and protocol, and its huge: 400mg/kg/day

 

And by the way, none of the above is "my statement", its what mention the studies and also the link Bryan quoted: http://www.ncbi.nlm....51433/table/T1/

 

For Bryan answer, I will have to reply tommorow.

 

Cheers

 

Edited by Tom Andre F. (ex shinobi), 27 June 2016 - 11:42 PM.

[Bryan_S]

Inflammation, Inflammation and Inflammation have been a focus of mine and I haven't seen anything to change this notion. CD38 is the monster in the shadows and the more we understand it, the closer we get to stemming our NAD loss.

 

As I look at the picture its impossible to see if any of the NAD salvage mechanisms are at fault because of this CD38 sponge depleting or hampering its build up. Let's push past this vail and see if the machine is broken before we start editing our DNA or flood our bodies with inhibitors to stem a pathway we don't understand. The way I look at it, as long as we have this looming NAD depletion problem the old-timers can't take enough NAD precursors to maintain youthful levels for any extended time. So if some are criticizing the NAD repletion approach and are looking for something better, I think that there is a better way but in the mean time I'm not giving up my (NR) until its proved I don't need it. So i'm not saying NAD+ Repletion it a waste because I think when the boat is sinking every cup full of water removed and dumped overboard still helps the boat stay afloat longer. It does however look like we're just forestalling the inevitable and I give the critics that. 

 

SASP sounds like a step in the right direction I'll read more. I'd like to see us arrive at something that is treatable rather than supplement the problem. However I think a combination of approaches might be in the cards before a cure is found and that might be to inhibit CD38 somewhere upstream where the problem originates rather than attack CD38 head on. Then NAD repletion can moderate our levels, should we need it, without its production being so easily destroyed. If we can address that than the CR sirtuin's get what they need and maybe we don't have to worry so much about activating them because that issue will take care of itself as will a number of others with restored NAD levels.  JMHO

[Steve H]

Right so first practical step is our mouse lab running Senolytics testing can run metrics for CD38 and NAD. We are looking at various SASP markers anyway and TGF-beta which is another downstream consequence of Nf-KB signalling as is CD38. So if we see a reduction of inflammation and an increase in NAD in the tissues tested we are onto a winner. 

You may also find these papers about Senolytics interesting in relation to the chronic inflammation SASP and Senescent cells cause.
 

Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL. (2013) Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest. 2013 Mar;123(3):966-72.

Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, Palmer AK, Ikeno Y, Hubbard GB, Lenburg M, O'Hara SP, LaRusso NF, Miller JD, Roos CM, Verzosa GC, LeBrasseur NK, Wren JD, Farr JN, Khosla S, Stout MB, McGowan SJ, Fuhrmann-Stroissnig H, Gurkar AU, Zhao J, Colangelo D, Dorronsoro A, Ling YY, Barghouthy AS, Navarro DC, Sano T, Robbins PD, Niedernhofer LJ, Kirkland JL. (2015) The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell.  Aug;14(4):644-58.

Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010). The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression. Annual Review of Pathology, 5, 99–118.

Freund, A., Orjalo, A. V., Desprez, P.-Y., & Campisi, J. (2010). Inflammatory Networks during Cellular Senescence: Causes and Consequences. Trends in Molecular Medicine, 16(5), 238–246.

Baker,van Deursen Kirkland et al (2011) Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders, Nature 479, 232–236

Baker, van Deursen et al (2016) Naturally occurring p16Ink4a-positive cells shorten healthy lifespan nature 16932

Roos, Zhu, Tchkonia, Kirkland et al (2016) Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice DOI: 10.1111/acel.12458

[stefan_001]

 

 

 

So Tom you would then say these researchers have falsified their study wrt fatty liver disease ? or then your statement is wrong?

 

Orally administration of nicotinamide riboside, a natural NAD+ precursor, completely corrected these NAFLD phenotypes induced by NAD+ deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes.

http://www.ncbi.nlm....pubmed/27174364

 

 

No I would say you have to read the full study :

 

"Our work highlights the therapeutic value of NR in NAFLD. In fact, other NAD+ substrates such as nicotinamide, was also shown to be able to prevent fatty liver and fibrosis."

 

So if this chinese study is your ultimate source to say NR is a good candidate fo treat liver, then you should use Nam instead of NR, its cheaper as they concluded: These results provide the first evidence that aging-associated NAD⁺ deficiency is a critical risk factor for NAFLD, and suggest that supplement of NAD⁺ substrates (enjoy how they do not specify NR) may be a promising therapeutic strategy to prevent and treat NAFLD.

 

The study is poorly conducted, they did not monitored NRK and does not explain how NR could give positive result. And it seems mainly again because Nam fragment and some "detectable" (very very low)) level  of NRK2 already mentioned in the study I previously quoted: http://www.ncbi.nlm....les/PMC3616313/ where you see Na was better candidate to boost NAD+ in liver than NR.

 

Furthermore, and to connect the dots here, this chinese study also mentioned to use their dosage and protocol, and its huge: 400mg/kg/day

 

And by the way, none of the above is "my statement", its what mention the studies and also the link Bryan quoted: http://www.ncbi.nlm....51433/table/T1/

 

For Bryan answer, I will have to reply tommorow.

 

Cheers

 

 

Hi Tom you miss the point entirely. NR did have a positive impact on NAD+ in the liver and appeared to improve the health as opposed to your statement:

"NR will not improve your liver condition via NAD+. Not possible."

Even the study you refer too shows that in case of chronic NR administration you get a nice NAD+ boost in the liver: I attached the graph for you.

 

Your statements is wrong. NR supplementation DOES increase NAD+ and have a postitive health impact on your liver. People that would believe you and stop taking  NR will likelly be worse off.

Attached Files

•  liverfig5.JPG   18.23KB   2 downloads

Edited by stefan_001, 28 June 2016 - 05:59 AM.

[Tom Andre F. (ex shinobi)]

 

 

 

 

So Tom you would then say these researchers have falsified their study wrt fatty liver disease ? or then your statement is wrong?

 

Orally administration of nicotinamide riboside, a natural NAD+ precursor, completely corrected these NAFLD phenotypes induced by NAD+ deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes.

http://www.ncbi.nlm....pubmed/27174364

 

 

No I would say you have to read the full study :

 

"Our work highlights the therapeutic value of NR in NAFLD. In fact, other NAD+ substrates such as nicotinamide, was also shown to be able to prevent fatty liver and fibrosis."

 

So if this chinese study is your ultimate source to say NR is a good candidate fo treat liver, then you should use Nam instead of NR, its cheaper as they concluded: These results provide the first evidence that aging-associated NAD⁺ deficiency is a critical risk factor for NAFLD, and suggest that supplement of NAD⁺ substrates (enjoy how they do not specify NR) may be a promising therapeutic strategy to prevent and treat NAFLD.

 

The study is poorly conducted, they did not monitored NRK and does not explain how NR could give positive result. And it seems mainly again because Nam fragment and some "detectable" (very very low)) level  of NRK2 already mentioned in the study I previously quoted: http://www.ncbi.nlm....les/PMC3616313/ where you see Na was better candidate to boost NAD+ in liver than NR.

 

Furthermore, and to connect the dots here, this chinese study also mentioned to use their dosage and protocol, and its huge: 400mg/kg/day

 

And by the way, none of the above is "my statement", its what mention the studies and also the link Bryan quoted: http://www.ncbi.nlm....51433/table/T1/

 

For Bryan answer, I will have to reply tommorow.

 

Cheers

 

 

Hi Tom you miss the point entirely. NR did have a positive impact on NAD+ in the liver and appeared to improve the health as opposed to your statement:

"NR will not improve your liver condition via NAD+. Not possible."

Even the study you refer too shows that in case of chronic NR administration you get a nice NAD+ boost in the liver: I attached the graph for you.

 

Your statements is wrong. NR supplementation DOES increase NAD+ and have a postitive health impact on your liver. People that would believe you and stop taking  NR will likelly be worse off.

 

 

Hi Stefan,

 

nope! I cant agree sorry. The chronic consumption graph that you point out is actually just enough significant: 0,08 for control to about 0,11mmol for the NR group and this result was achieved using MASSIVE dosage: 400mg/kg/day

 

You can achieve this result very likely using normal Nam and such dosage you will likely develop toxicity or sides. Here the chronic brings the result from 0,26 to about 0,11

 

I work with fact, not with feeling, so people that would believe you and continue taking NR will likelly see no result in liver using normal dosage.

 

If you want to proof Im wrong you have to do 2 things: show me normal dosage works (not such high and dangerous one, see Nam toxicity report), show me better result compared to Nam, because otherwize its pointless, purely.
 

[Bryan_S]

 

Right so first practical step is our mouse lab running Senolytics testing can run metrics for CD38 and NAD. We are looking at various SASP markers anyway and TGF-beta which is another downstream consequence of Nf-KB signalling as is CD38. So if we see a reduction of inflammation and an increase in NAD in the tissues tested we are onto a winner.

 

Steve H,

 

I have to ask have you read the latest papers on NAD+Repletion and what happened to senescent cells?  Restoring stem cells — all you need is NAD+

 

NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice

 

Senolytics has been a topic of great interest to many of us here. Especially from the standpoint of the inflammation senescent cells contribute. However now that results have been seen in improving their metabolism with NAD+ (reference above) this whole engrained idea of the Hayflick limit may have been pushed a few cell divisions further down the line (reference above). This make's some of us question if killing off our senescent cells might be premature if they can be restored to a functional status. (reference above) It appears once NAD+ levels are restored even what we thought was a hopeless situation now appears to be reversible enabling us to rejuvenate stem cells and extend lifespan in mice.

 

I mention this because as your group writes their mission statement some of the game pieces are being re-thought. Project Summary Senolytics Phase 1 Our humble group isn't on the forefront of chasing these leads down and picking the research projects but it appears the landscape is changing rapidly and with it the targets with the most beneficial information to uncover like this CD38 we spoke of.   

 

Edited by Bryan_S, 29 June 2016 - 06:43 AM.
More references added fromsciencemag.org, Cell.com and wikipedia

[stefan_001]

 

 

 

 

 

So Tom you would then say these researchers have falsified their study wrt fatty liver disease ? or then your statement is wrong?

 

Orally administration of nicotinamide riboside, a natural NAD+ precursor, completely corrected these NAFLD phenotypes induced by NAD+ deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes.

http://www.ncbi.nlm....pubmed/27174364

 

 

No I would say you have to read the full study :

 

"Our work highlights the therapeutic value of NR in NAFLD. In fact, other NAD+ substrates such as nicotinamide, was also shown to be able to prevent fatty liver and fibrosis."

 

So if this chinese study is your ultimate source to say NR is a good candidate fo treat liver, then you should use Nam instead of NR, its cheaper as they concluded: These results provide the first evidence that aging-associated NAD⁺ deficiency is a critical risk factor for NAFLD, and suggest that supplement of NAD⁺ substrates (enjoy how they do not specify NR) may be a promising therapeutic strategy to prevent and treat NAFLD.

 

The study is poorly conducted, they did not monitored NRK and does not explain how NR could give positive result. And it seems mainly again because Nam fragment and some "detectable" (very very low)) level  of NRK2 already mentioned in the study I previously quoted: http://www.ncbi.nlm....les/PMC3616313/ where you see Na was better candidate to boost NAD+ in liver than NR.

 

Furthermore, and to connect the dots here, this chinese study also mentioned to use their dosage and protocol, and its huge: 400mg/kg/day

 

And by the way, none of the above is "my statement", its what mention the studies and also the link Bryan quoted: http://www.ncbi.nlm....51433/table/T1/

 

For Bryan answer, I will have to reply tommorow.

 

Cheers

 

 

Hi Tom you miss the point entirely. NR did have a positive impact on NAD+ in the liver and appeared to improve the health as opposed to your statement:

"NR will not improve your liver condition via NAD+. Not possible."

Even the study you refer too shows that in case of chronic NR administration you get a nice NAD+ boost in the liver: I attached the graph for you.

 

Your statements is wrong. NR supplementation DOES increase NAD+ and have a postitive health impact on your liver. People that would believe you and stop taking  NR will likelly be worse off.

 

 

Hi Stefan,

 

nope! I cant agree sorry. The chronic consumption graph that you point out is actually just enough significant: 0,08 for control to about 0,11mmol for the NR group and this result was achieved using MASSIVE dosage: 400mg/kg/day

 

You can achieve this result very likely using normal Nam and such dosage you will likely develop toxicity or sides. Here the chronic brings the result from 0,26 to about 0,11

 

I work with fact, not with feeling, so people that would believe you and continue taking NR will likelly see no result in liver using normal dosage.

 

If you want to proof Im wrong you have to do 2 things: show me normal dosage works (not such high and dangerous one, see Nam toxicity report), show me better result compared to Nam, because otherwize its pointless, purely.
 

 

 

Of course you don't agree and you are free to think or believe what ever you want but similarly so are others. Some views:

 

1) the researchers in these studies target therapeutic effect. Meaning they apply doses to cure/improve a disease. This is very different to what I am interested in which is maintaining health so I don't need an equivalent large NAD+ boost as needed to overcome disease.

 

2) Its comical you point out that 400mg / kg / day is high dosing for NR while in the graph that you cite continuously as example that NA is effective the dosing is also 400mg / kg / day:  http://www.cell.com/...4131(12)00192-1 figure 1 D 

 

3) specifically about nonalcoholic fatty liver disease I think NR is quite an interesting track as there is no standard treatment / medication today. 

 

4) The doses of 400mg/kg/day translates into 2.1 gram / day for a human weighing 70kg. I would not say its of the charts. Cost wise, as we talk disease medication application, its not bad either with about 10-15USD cost per day. 

 

5) From the Chromadex study: http://www.timelessl...clinical-study/ we know that concentration levels in the blood peak below 1 gram / day dosing. So while there is no proof for me this implies that similar NAD+ raising effects can be reached at lower levels. 

 

6) As you are a believer in NA I searched PUBMED studies using Niacin supplementation for NAFLD (NAM is the amide of Niacin).  Surprise they use high dosing and the results are not better than the NR study. For example in this study:

http://www.ncbi.nlm....pubmed/24356885

the dosing is:

"Based on the diet intake, we estimate that rats consumed 0.1 g and 0.2 g niacin per day"

with rats weighing about 250gram that would translate into a dose for a 70kg human of 3,5g-7gram / day which is far higher than NR dosing. 

 

Finally you wrote:

"If you want to proof I am wrong you have to do 2 things: show me normal dosage works (not such high and dangerous one, see Nam toxicity report), show me better result compared to Nam, because otherwize its pointless, purely"

 

So why dont you post here some studies that demonstrate any positive effect of your low dose recommendations of NA? You said use 50mg right? Well thats a factor 100 lower than the study above? 

 

Edited by stefan_001, 28 June 2016 - 08:15 AM.

[Tom Andre F. (ex shinobi)]

 

 

Of course you don't agree and you are free to think or believe what ever you want but similarly so are others. Some views:

 

1) the researchers in these studies target therapeutic effect. Meaning they apply doses to cure/improve a disease. This is very different to what I am interested in which is maintaining health so I don't need an equivalent large NAD+ boost as needed to overcome disease.

 

2) Its comical you point out that 400mg / kg / day is high dosing for NR while in the graph that you cite continuously as example that NA is effective the dosing is also 400mg / kg / day:  http://www.cell.com/...4131(12)00192-1 figure 1 D 

 

3) specifically about nonalcoholic fatty liver disease I think NR is quite an interesting track as there is no standard treatment / medication today. 

 

4) The doses of 400mg/kg/day translates into 2.1 gram / day for a human weighing 70kg. I would not say its of the charts. Cost wise, as we talk disease medication application, its not bad either with about 10-15USD cost per day. 

 

5) From the Chromadex study: http://www.timelessl...clinical-study/ we know that concentration levels in the blood peak below 1 gram / day dosing. So while there is no proof for me this implies that similar NAD+ raising effects can be reached at lower levels. 

 

6) As you are a believer in NA I searched PUBMED studies using Niacin supplementation for NAFLD (NAM is the amide of Niacin).  Surprise they use high dosing and the results are not better than the NR study. For example in this study:

http://www.ncbi.nlm....pubmed/24356885

the dosing is:

"Based on the diet intake, we estimate that rats consumed 0.1 g and 0.2 g niacin per day"

with rats weighing about 250gram that would translate into a dose for a 70kg human of 3,5g-7gram / day which is far higher than NR dosing. 

 

Finally you wrote:

"If you want to proof I am wrong you have to do 2 things: show me normal dosage works (not such high and dangerous one, see Nam toxicity report), show me better result compared to Nam, because otherwize its pointless, purely"

 

So why dont you post here some studies that demonstrate any positive effect of your low dose recommendations of NA? You said use 50mg right? Well thats a factor 100 lower than the study above? 

 

 

 

Stefan.. I see lot of emotive behaviour here and will pass on that. Moreover, I can also understand you still dont get the full pathway. Important are only facts not what one believe or not.

 

What part you dont understand in: "liver (especially as studied in human) does not owns NRK (or very few only if not significant in some mice), but owns preiss handler pathway" ?

 

you also mention another study while you have a direct comparison where you see Na to boost NAD+ much better (more significant result) versus NR  using same dosage.

 

And to answer to "why dont you post here some studies that demonstrate any positive effect of your low dose recommendations of NA? You said use 50mg right? Well thats a factor 100 lower than the study above?"

 

its very simple: because same reason as you dont use high dose NR: "I am interested in which is maintaining health so I don't need an equivalent large NAD+ boost as needed to overcome disease."

 

Why I use Na over NR ? because 1/ the preiss handler pathway is more present in human tissue and because (and here only is my speculation that you can discuss or not, but based on the facts in previous post that I will not loose time to repeat)

 

2/ Na will not be converted directly into Nam (this is the opposite) unlike NR, and I dont want to saturate much on the long run Nampt

3/ Na will also be converted into NaR that use same NRK pathway as NR

4/Nam released, due to NAD+ increased, will also be converted in a certain way to NR already

 

[Black Fox]

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

[stefan_001]

 

 

 

Of course you don't agree and you are free to think or believe what ever you want but similarly so are others. Some views:

 

1) the researchers in these studies target therapeutic effect. Meaning they apply doses to cure/improve a disease. This is very different to what I am interested in which is maintaining health so I don't need an equivalent large NAD+ boost as needed to overcome disease.

 

2) Its comical you point out that 400mg / kg / day is high dosing for NR while in the graph that you cite continuously as example that NA is effective the dosing is also 400mg / kg / day:  http://www.cell.com/...4131(12)00192-1 figure 1 D 

 

3) specifically about nonalcoholic fatty liver disease I think NR is quite an interesting track as there is no standard treatment / medication today. 

 

4) The doses of 400mg/kg/day translates into 2.1 gram / day for a human weighing 70kg. I would not say its of the charts. Cost wise, as we talk disease medication application, its not bad either with about 10-15USD cost per day. 

 

5) From the Chromadex study: http://www.timelessl...clinical-study/ we know that concentration levels in the blood peak below 1 gram / day dosing. So while there is no proof for me this implies that similar NAD+ raising effects can be reached at lower levels. 

 

6) As you are a believer in NA I searched PUBMED studies using Niacin supplementation for NAFLD (NAM is the amide of Niacin).  Surprise they use high dosing and the results are not better than the NR study. For example in this study:

http://www.ncbi.nlm....pubmed/24356885

the dosing is:

"Based on the diet intake, we estimate that rats consumed 0.1 g and 0.2 g niacin per day"

with rats weighing about 250gram that would translate into a dose for a 70kg human of 3,5g-7gram / day which is far higher than NR dosing. 

 

Finally you wrote:

"If you want to proof I am wrong you have to do 2 things: show me normal dosage works (not such high and dangerous one, see Nam toxicity report), show me better result compared to Nam, because otherwize its pointless, purely"

 

So why dont you post here some studies that demonstrate any positive effect of your low dose recommendations of NA? You said use 50mg right? Well thats a factor 100 lower than the study above? 

 

 

 

Stefan.. I see lot of emotive behaviour here and will pass on that. Moreover, I can also understand you still dont get the full pathway. Important are only facts not what one believe or not.

 

What part you dont understand in: "liver (especially as studied in human) does not owns NRK (or very few only if not significant in some mice), but owns preiss handler pathway" ?

 

you also mention another study while you have a direct comparison where you see Na to boost NAD+ much better (more significant result) versus NR  using same dosage.

 

And to answer to "why dont you post here some studies that demonstrate any positive effect of your low dose recommendations of NA? You said use 50mg right? Well thats a factor 100 lower than the study above?"

 

its very simple: because same reason as you dont use high dose NR: "I am interested in which is maintaining health so I don't need an equivalent large NAD+ boost as needed to overcome disease."

 

Why I use Na over NR ? because 1/ the preiss handler pathway is more present in human tissue and because (and here only is my speculation that you can discuss or not, but based on the facts in previous post that I will not loose time to repeat)

 

2/ Na will not be converted directly into Nam (this is the opposite) unlike NR, and I dont want to saturate much on the long run Nampt

3/ Na will also be converted into NaR that use same NRK pathway as NR

4/Nam released, due to NAD+ increased, will also be converted in a certain way to NR already

 

 

 

Tom there is no emotion here  beyond normal interest and observations so your first statement is misguided. Anyways its not so difficult there are multiple pathways towards NAD, you can see them in the picture attached, that's easier to understand than text. PNP is present in many tissues but NRK1 (and even NRK2 to some level) is also present in the liver, see other figure attached.

 

The problem is that you simply refute multiple studies with experimental date showing "a" NR pathway is effective in the liver whether it takes the NAM route, uses some residual NRK or possibly an unknown route". You then bring up an alternative which you lace with some "speculation" that as you say your self doesnt have either hard experimental results and push that as the superior way to go. So until experimental data appears that proof your assertions its not the time discard another method.

Attached Files

•  pathways.JPG   44.96KB   1 downloads
•  NRK1and2.JPG   33.79KB   1 downloads

Edited by stefan_001, 28 June 2016 - 11:36 AM.

[Tom Andre F. (ex shinobi)]

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

 

You right its also why I would not use much ANY of the B3s : http://www.ncbi.nlm....pubmed/23768418

 

The present study suggests that long-term high nicotinamide intake (e.g. induced by niacin fortification) may be a risk factor for methylation- and insulin resistance-related metabolic abnormalities.

 

If indeed they used high dose, we have to stay careful, especially with Nam accumulation and Nampt decrease over the long run. Even if another unknown mechanism show a possible protective effect in brain (adaptative body response ?) http://www.ncbi.nlm....pubmed/18389009

 

Tom there is no emotion here so your first statement is misguided beyond normal interest. Anyways its not so difficult there are multiple pathways towards NAD, you can see them in the picture attached, that's easier to understand than text. PNP is present in many tissues but NRK1 (and even NRK2 to some level) is also present in the liver, see other figure attached.

 

The problem is that you simply refute multiple studies with experimental date showing "a" NR pathway is effective in the liver whether it takes the NAM route, uses some residual NRK or possibly an unknown route". You then bring up an alternative which you lace with some "speculation" that as you say your self doesnt have either hard experimental results and push that as the superior way to go. So until experimental data appears that proof your assertions its not the time discard another method.

 

 

Stefan, you are in bad faith.. what studies I refute ? I take the result like they are. NR looks a bad candidate knowing the dosage, risk for homocysteine, sirtuins silencing, Nampt consumption etc. Na looks a better candidate to increase NAD+ in liver. And its proven in the study from where you quote the graph, like that its more clear :

 

 

 

so vivo here confirmed the speculation isnt ? I know its hard to say because NR is marketed as THE product, but where are evidences ? When I look at the comparison Na is better and cheaper. There is only the flush effect that some want to avoid in favor of NR, so im still waiting for the data I ignored that show NR is better ? (You also said: "specifically about nonalcoholic fatty liver disease I think NR is quite an interesting track as there is no standard treatment / medication today")

 

I agree with you that we need more experimental data to show one is better however, normally its should be NR that has to proof itself, not the opposite

Edited by Tom Andre F. (ex shinobi), 28 June 2016 - 12:07 PM.

[midas]

Not sure if this is relevant or not!

 

METHODS OF PREPARING NICOTINAMIDE RIBOSIDE AND DERIVATIVES THEREOF

 

http://www.freepaten...16/0168184.html

Edited by midas, 28 June 2016 - 12:24 PM.

[stefan_001]

 

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

 

 

so vivo here confirmed the speculation isnt ? I know its hard to say because NR is marketed as THE product, but where are evidences ? When I look at the comparison Na is better and cheaper. There is only the flush effect that some want to avoid in favor of NR, so im still waiting for the data I ignored that show NR is better ? (You also said: "specifically about nonalcoholic fatty liver disease I think NR is quite an interesting track as there is no standard treatment / medication today")

 

I agree with you that we need more experimental data to show one is better however, normally its should be NR that has to proof itself, not the opposite

 

 

NAFLD study both in rats so good comparison:

NR supplementation:

http://www.ncbi.nlm..../?term=26404765

NA supplementation:

http://www.ncbi.nlm....pubmed/24356885

 

NR dosing about half of NA. NR is better. Show me a study where its the other way around and dont come again with the earlier graph but come with a disease application test.

Edited by stefan_001, 28 June 2016 - 12:31 PM.

[Steve H]

I have to ask have you read the latest papers on NAD+Repletion and what happened to senescent cells.  Restoring stem cells — all you need is NAD+

 

Senolytics has been a topic of great interest to many of us here. Especially from the standpoint of the inflammation they contribute. However now that results have been seen in improving their metabolism with NAD+ this whole engrained idea of the Hayflick limit may have been pushed a few cell divisions further down the line. This make's some of us question if killing off our senescent cells might be premature if they can be restored to a functional status. It appears once NAD+ levels are restored even what we thought was a hopeless situation now appears to be reversible enabling us to rejuvenate stem cells and extend lifespan in mice.

 

I mention this because as your group writes their mission statement some of the game pieces are being re-thought. Project Summary Senolytics Phase 1 Our humble group isn't on the forefront of chasing these leads down and picking the research projects but it appears the landscape is changing rapidly and with it the targets with the most beneficial information to uncover like this CD38 we spoke of.   

 

 

I have read them yes and in my view simply replacing NAD is not a magic bullet and anyone who suggests it is has a simplistic view of the forces involved here. Senolytics addresses the probable root cause of NAD decline which is inflamation and increase of the NF-KB pathway which in turn leads to rising CD38, there is no point addressing CD38 if you are not fixing the rising NF-KB regulating CD38 at the top of the chain. Whilst I have no doubt restoration of NAD levels and NAD ratio is good (the Sinclair data shows it) it isnt the full story and I am focused on getting to the root of the problem which Sinclair himself suggests is chronic inflammation. What may be going on in these experiments is the increased NAD levels are allowing the cells to overcome the deleterous effects of CD38 to a certain point by chanigng the NAD/NADH ratio, thus we see the cells are able to proliferate for longer and indeed are functionally younger. If so it still does not address the root of the problem which is inflammation and the NF-KB pathway which includes CD38.

Now a therapy that addresses the CD38 levels ideally from its source NF-KB should hypothetically help the body restore its own production of NAD by reducing the CD38 on hand to destroy NAD, Senolytics is one possible way to achieve that as the data shows that NF-KB and CD38 are reduced by their action. This is something we can easily demonstrate in our Senolytic program simply testing the NAD/NADH ratio and how if it changes plus NF-KB and CD38 levels and changes post Senolytic treatment.If we are VERY lucky the levels will return to normal simply by removing CD38 but that would need to be demonstrated.
 

Another target is NQO1 which regulates the NAD=NADH ratio.

 

I highly recommend Anti-Aging firewalls NAD 5 part series here for those of you who have not read it:
 

http://www.anti-agin...he-nad-world-2/

 

[Tom Andre F. (ex shinobi)]

 

 

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

 

 

so vivo here confirmed the speculation isnt ? I know its hard to say because NR is marketed as THE product, but where are evidences ? When I look at the comparison Na is better and cheaper. There is only the flush effect that some want to avoid in favor of NR, so im still waiting for the data I ignored that show NR is better ? (You also said: "specifically about nonalcoholic fatty liver disease I think NR is quite an interesting track as there is no standard treatment / medication today")

 

I agree with you that we need more experimental data to show one is better however, normally its should be NR that has to proof itself, not the opposite

 

 

NAFLD study both in rats so good comparison:

NR supplementation:

http://www.ncbi.nlm..../?term=26404765

NA supplementation:

http://www.ncbi.nlm....pubmed/24356885

 

NR dosing about half of NA. NR is better. Show me a study where its the other way around and dont come again with the earlier graph but come with a disease application test.

 

 

Nope you cant conclude that, not possible. So you dont work with facts. You can speculate but then it has to be based on facts at least. In a standard very high dosage, Na ranked better than NR. If you want to show NR is better, then try to use species with more NRK1/2 and play with dosage versus Na. Else, its pointless.

 

Also, you will most likely use Nam metabolite to get your result that I would avoid like you avoid any fact that does not suit you such as sirt silencing, nampt leakage, homocysteine etc and love to bring differents study using different dosage to match your goal etc. Sorry im done with you

 

Good news is at least everyone can choose what they do with their body and use as supplement

 

 

Edited by Tom Andre F. (ex shinobi), 28 June 2016 - 12:55 PM.

[ROBST3R]

Hi i found a good article about apigenin.

Think this should be taken in combination with NR?

http://herbnutrition...tracts/apigenin

Edited by ROBST3R, 28 June 2016 - 01:12 PM.

[stefan_001]

 

 

 

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

 

 

so vivo here confirmed the speculation isnt ? I know its hard to say because NR is marketed as THE product, but where are evidences ? When I look at the comparison Na is better and cheaper. There is only the flush effect that some want to avoid in favor of NR, so im still waiting for the data I ignored that show NR is better ? (You also said: "specifically about nonalcoholic fatty liver disease I think NR is quite an interesting track as there is no standard treatment / medication today")

 

I agree with you that we need more experimental data to show one is better however, normally its should be NR that has to proof itself, not the opposite

 

 

NAFLD study both in rats so good comparison:

NR supplementation:

http://www.ncbi.nlm..../?term=26404765

NA supplementation:

http://www.ncbi.nlm....pubmed/24356885

 

NR dosing about half of NA. NR is better. Show me a study where its the other way around and dont come again with the earlier graph but come with a disease application test.

 

 

Nope you cant conclude that, not possible. So you dont work with facts. You can speculate but then it has to be based on facts at least. In a standard very high dosage, Na ranked better than NR. If you want to show NR is better, then try to use species with more NRK1/2 and play with dosage versus Na. Else, its pointless.

 

Also, you will most likely use Nam metabolite to get your result that I would avoid like you avoid any fact that does not suit you such as sirt silencing, nampt leakage, homocysteine etc and love to bring differents study using different dosage to match your goal etc. Sorry im done with you

 

Good news is at least everyone can choose what they do with their body and use as supplement

 

 

Reality is cell metabolism is complicated, one single parameter/measurement doesn't determine the entire outcome. You asked for comparison so you got one. These studies are facts, same species, same disease. 

Edited by stefan_001, 28 June 2016 - 01:19 PM.

[Nate-2004]

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

 

This is disconcerting. In reading all these arguments between Tom, Stefan and Bryan I concluded that Na was just as useful in some ways as NR and so I figured why not take them together. I didn't know that Na raised homocysteine levels though, that's not good at all for aging. Does NR raise homocysteine? What can be done to counter this effect? Anything?

 

What is so "dangerous and irresponsible" about my posts lately? Just asking questions, jeez.

 

Also Tom seems to be suggesting that NR inhibits Sirtuins? I was under the impression that the exact opposite is the case.

Edited by Nate-2004, 28 June 2016 - 03:58 PM.

[mikeinnaples]

 

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

 

This is disconcerting. In reading all these arguments between Tom, Stefan and Bryan I concluded that Na was just as useful in some ways as NR and so I figured why not take them together. I didn't know that Na raised homocysteine levels though, that's not good at all for aging. Does NR raise homocysteine? What can be done to counter this effect? Anything?

 

What is so "dangerous and irresponsible" about my posts lately? Just asking questions, jeez.

 

Also Tom seems to be suggesting that NR inhibits Sirtuins? I was under the impression that the exact opposite is the case.

 

 

The homocysteine issue was picked apart in another long running thread on this board. Personally, I have kept mine in check with sublingual methyl-b12 and TMG
 

[mikeinnaples]

 

 

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

 

 

so vivo here confirmed the speculation isnt ? I know its hard to say because NR is marketed as THE product, but where are evidences ? When I look at the comparison Na is better and cheaper. There is only the flush effect that some want to avoid in favor of NR, so im still waiting for the data I ignored that show NR is better ? (You also said: "specifically about nonalcoholic fatty liver disease I think NR is quite an interesting track as there is no standard treatment / medication today")

 

I agree with you that we need more experimental data to show one is better however, normally its should be NR that has to proof itself, not the opposite

 

 

NAFLD study both in rats so good comparison:

NR supplementation:

http://www.ncbi.nlm..../?term=26404765

NA supplementation:

http://www.ncbi.nlm....pubmed/24356885

 

NR dosing about half of NA. NR is better. Show me a study where its the other way around and dont come again with the earlier graph but come with a disease application test.

 

 

NR is all together better I agree, though NA is better in certain tissues.

 

The price point is grossly different between the two though, and that is something to consider. Like some others, I think there is benefit in taking both as well as exploring the NQ01 route.

 

[stefan_001]

 

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

 

This is disconcerting. In reading all these arguments between Tom, Stefan and Bryan I concluded that Na was just as useful in some ways as NR and so I figured why not take them together. I didn't know that Na raised homocysteine levels though, that's not good at all for aging. Does NR raise homocysteine? What can be done to counter this effect? Anything?

 

What is so "dangerous and irresponsible" about my posts lately? Just asking questions, jeez.

 

Also Tom seems to be suggesting that NR inhibits Sirtuins? I was under the impression that the exact opposite is the case.

 

 

Hi Nate, no idea why you get those flags to your posts - not me.

 

I don't think there is anything wrong with using some NA. Niacin has been used since the 1950s to lower elevated LDL (bad) cholesterol and triglyceride (fat) levels in the blood. So I guess it will not kill you :-) But in those 60 years of usage it appears there have been no miracle anti-aging side effects as surely they would have been noticed by now. What hasn't been discussed lately (but has been mentioned before somewhere in these threads) is why do we have these NR and NMN pathway in our body? There is some speculation that the reason is it allows cells to move "NAD+" between each other so creating a "moveable" NAD+ pool that goes where its needed. Probably this will lead to "misses references" flags but I could imagine that NAD+ need in a cell fluctuates a lot and it doesnt peak in all cells at the same time so a flexible pool may help to meet this peak demand and would be a differentiating aspect from NA.

 

The sirt inhibition comment I dont get either.

Edited by stefan_001, 28 June 2016 - 07:12 PM.

[stefan_001]

 

 

 

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

 

 

so vivo here confirmed the speculation isnt ? I know its hard to say because NR is marketed as THE product, but where are evidences ? When I look at the comparison Na is better and cheaper. There is only the flush effect that some want to avoid in favor of NR, so im still waiting for the data I ignored that show NR is better ? (You also said: "specifically about nonalcoholic fatty liver disease I think NR is quite an interesting track as there is no standard treatment / medication today")

 

I agree with you that we need more experimental data to show one is better however, normally its should be NR that has to proof itself, not the opposite

 

 

NAFLD study both in rats so good comparison:

NR supplementation:

http://www.ncbi.nlm..../?term=26404765

NA supplementation:

http://www.ncbi.nlm....pubmed/24356885

 

NR dosing about half of NA. NR is better. Show me a study where its the other way around and dont come again with the earlier graph but come with a disease application test.

 

 

NR is all together better I agree, though NA is better in certain tissues.

 

The price point is grossly different between the two though, and that is something to consider. Like some others, I think there is benefit in taking both as well as exploring the NQ01 route.

 

 

yes cost is somewhat high, midas posted earlier a new patent application for NR synthesis. I read that and got the impression it will not lead to cheap NR but hopefully more competition will come. Also I believe be more routes/methods to be discovered, another one in addition to what you mentionis the inflammation dampening.

Edited by stefan_001, 28 June 2016 - 07:09 PM.

[Tom Andre F. (ex shinobi)]

 

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

 

This is disconcerting. In reading all these arguments between Tom, Stefan and Bryan I concluded that Na was just as useful in some ways as NR and so I figured why not take them together. I didn't know that Na raised homocysteine levels though, that's not good at all for aging. Does NR raise homocysteine? What can be done to counter this effect? Anything?

 

What is so "dangerous and irresponsible" about my posts lately? Just asking questions, jeez.

 

Also Tom seems to be suggesting that NR inhibits Sirtuins? I was under the impression that the exact opposite is the case.

 

 

Nicotinamide (Nam) a metabolite both direct and indirect of NR is a sirtuin inhibitor in a physiological dosage (thats the main problem) while Na does not convert into Nam directly. Thats why at the beginning of this thread (or the old version, im not sure) we used to advice to add pterostilbene along NR.

 

When NAD+ will increase following NR or Na you will activates sirtuins. So its a loop

 

and as posted all B3s due to the fact they eat methylation are all homocysteine promoter. Thats why you need a complex B6 and B12 along ideally

 

Now why such hype around NR ? because sinclair succeed to rejuvenate muscle mice using NMN as intramuscular injection. So then people speculated that a dietary supplement such as NR could then in turn being transformed into NMN and does the same thing. However as I tried at least to explain its not that easy.

 

Finally, the body does convert Nam into NR as it also converts Na into NaR. Both NR and NaR are part of the human metabolome as stated in a study.

 

 

[Nate-2004]

 

 

Have y'all taken into account the homocysteine levels raise by NA? 'Cuz I suffered it in my own skin, I had one blood test showing 12 for homocysteine and after 3 months and having added too my diet, B12, B6, folic acid , taurine and NAC to lower my homocysteine levels and found myself with 16..... So , I sat and I looked at what I had added apart from all that, yep Niacin 500 mg in the morning with breakfast

http://www.ncbi.nlm....pubmed/11895163

As we all know . High homocysteine means faster shorten of the telomeres , and accelerating the telomeres fraying is no bueno IMHO

 

This is disconcerting. In reading all these arguments between Tom, Stefan and Bryan I concluded that Na was just as useful in some ways as NR and so I figured why not take them together. I didn't know that Na raised homocysteine levels though, that's not good at all for aging. Does NR raise homocysteine? What can be done to counter this effect? Anything?

 

What is so "dangerous and irresponsible" about my posts lately? Just asking questions, jeez.

 

Also Tom seems to be suggesting that NR inhibits Sirtuins? I was under the impression that the exact opposite is the case.

 

 

Nicotinamide (Nam) a metabolite both direct and indirect of NR is a sirtuin inhibitor in a physiological dosage (thats the main problem) while Na does not convert into Nam directly. Thats why at the beginning of this thread (or the old version, im not sure) we used to advice to add pterostilbene along NR.

 

When NAD+ will increase following NR or Na you will activates sirtuins. So its a loop

 

and as posted all B3s due to the fact they eat methylation are all homocysteine promoter. Thats why you need a complex B6 and B12 along ideally

 

Now why such hype around NR ? because sinclair succeed to rejuvenate muscle mice using NMN as intramuscular injection. So then people speculated that a dietary supplement such as NR could then in turn being transformed into NMN and does the same thing. However as I tried at least to explain its not that easy.

 

Finally, the body does convert Nam into NR as it also converts Na into NaR. Both NR and NaR are part of the human metabolome as stated in a study.

 

 

So basically because at the end of the path, after NAD+ is consumed by the very Sirtuins it activates, the resulting output of Nam then deactivates the sirtuins? That makes sense to me.

 

However, pterostilbene does not activate SIRT1 apparently. So that's a problem.

 

I'm still pretty concerned about the homocysteine, as that makes Na not so good compared to NR, unless NR also boosts homocysteine levels? I don't understand what you're saying when you state "all B3s", I assume by that you mean "all B3 vitamin forms" and then you say "eat methylation are all homocysteine promoter", can you rewrite that? I'm confused.

 

Also, why is it that you say "it's not that easy"? I recall in this very thread a ton of references being posted showing that NR does in fact boost NAD+. Whether or not it does it any better than Na is obviously in hot debate here.

Edited by Nate-2004, 28 June 2016 - 07:53 PM.