2255 replies to this topic

[Nate-2004]

 Also to be honest I take Pterostilbene which is claimed to be more bioactive than Resveratrol but I'm considering dropping that from my regiment. 

 

Why?

 

I'm taking it still but I know now that it doesn't activate SIRT1 as claimed according to the study I linked to earlier from this thread to another thread. I'm taking it in hopes that it will help with Essential Tremor in some way. It probably won't but I just wonder if it will prevent further degeneration or reverse it in larger doses. I doubt it. I've been trying everything I can to no avail.

[bluemoon]

 

 

"I'm curious what people think about the difference between publications about resveratrol and publications on NR" Whats the question again? Resveratrol studies abound  

 

 

In the past ten years since Sinclair's mouse study made a splash on the front of the New York Times, I have seen only a few resveratrol studies in humans. One showed up to 1500 mg a day was safe over a few weeks. Another showed no weight loss among 11  obese men (and 11 on a placebo) but only given 100 mg a day. Sinclair said last year that hundreds of mg of resveratrol were necessary. A third study showed some amount of resveratrol was somewhat detrimental to elite athletes.

 

There must have been more studies (none that I remember grabbing headlines),  but why are we expecting human NR studies after the compound has been well known a much shorter time?    

[Bryan_S]

blue moon, I picked up on the NR story after Brenner's 2004 publication. I guess its more closely studied today because it directly effects NAD+ levels. Also David Sinclair's Sirtris didn't do so well and GlaxoSmithKline shut down the enterprise so interest in these activator compounds has waned.

 

I look more to the body of evidence that NAD+ increases is where the heath benefits are and consequently study funding. So using the NAD precursors has proven to be more of a direct path to get the desired result which is higher NAD levels.

 

Nate-2004, Is this the study?

http://www.ncbi.nlm....pubmed/21982274

Edited by Bryan_S, 03 July 2016 - 02:54 PM.

[Nate-2004]

Nate-2004, Is this the study?

http://www.ncbi.nlm....pubmed/21982274

 

That's the one.

[lumia]

I know this thread is for more bleeding-edge topics and not for mundane ones, but I'd still need to ask this question: do you count NR in your Vitamin B3 consumption, on top of nicotinic acid and nicotinamide?

[tunt01]

I know this thread is for more bleeding-edge topics and not for mundane ones, but I'd still need to ask this question: do you count NR in your Vitamin B3 consumption, on top of nicotinic acid and nicotinamide?

 

I think you should count all sources of B3, as a general rule of thumb.  However, the RDI for B3 is something like 15-20 mg per day (lower if you are a woman, higher if you are a man), such that any supplementation blows past this requirement.

[Bryan_S]

 

I know this thread is for more bleeding-edge topics and not for mundane ones, but I'd still need to ask this question: do you count NR in your Vitamin B3 consumption, on top of nicotinic acid and nicotinamide?

 

I think you should count all sources of B3, as a general rule of thumb.  However, the RDI for B3 is something like 15-20 mg per day (lower if you are a woman, higher if you are a man), such that any supplementation blows past this requirement.

 

 

I cut my consumption @ 3 grams when I was taking (NR 1000mg) and (Nam 2000mg) today I've dropped back to 1000mg total of just (NR). I would always count them together and not exceed the maximum recommended dose. (for Nam that is around 3 grams) Even at 3 grams per day I advised my doctor so he could watch my blood work.

 

Safety assessment of nicotinamide riboside, a form of vitamin B3

 

Nicotinamide pharmacokinetics in patients.

 

Safety of high-dose nicotinamide: a review.

 

There are many more studies on (Nam). Its been studies for decades. If you are mixing (Na) Niacin I would likely scale back even lower because it taxes the liver. In fact if you have liver or kidney problems I would seek the advice of a physician before undertaking any  gram doses of B3.

Edited by Bryan_S, 05 July 2016 - 02:15 AM.

[lumia]

 

 

I know this thread is for more bleeding-edge topics and not for mundane ones, but I'd still need to ask this question: do you count NR in your Vitamin B3 consumption, on top of nicotinic acid and nicotinamide?

 

I think you should count all sources of B3, as a general rule of thumb.  However, the RDI for B3 is something like 15-20 mg per day (lower if you are a woman, higher if you are a man), such that any supplementation blows past this requirement.

 

 

I cut my consumption @ 3 grams when I was taking (NR 1000mg) and (Nam 2000mg) today I've dropped back to 1000mg total of just (NR). I would always count them together and not exceed the maximum recommended dose. (for Nam that is around 3 grams) Even at 3 grams per day I advised my doctor so he could watch my blood work.

 

Safety assessment of nicotinamide riboside, a form of vitamin B3

 

Nicotinamide pharmacokinetics in patients.

 

Safety of high-dose nicotinamide: a review.

 

There are many more studies on (Nam). Its been studies for decades. If you are mixing (Na) Niacin I would likely scale back even lower because it taxes the liver. In fact if you have liver or kidney problems I would seek the advice of a physician before undertaking any  gram doses of B3.

 

 

Thank you; I'll take that in mind just in case. My current dosage is low--250mg NR and 40mg NA, but since I'm going to add 500mg of NA (as Slo-Niacin), I've to be sure I'm not overdoing stuff.

 

[Ethic]

Avoid slow-release Niacin! Be a MAN, take the pure thing and deal with it! (Caution: stereotypes)

[Logic]

Bryan I am glad you spotted the Quercetin and CD38 connection I was going to cite that today. A number of Senolytic studies reduce SASP significantly which improves healthspan, we know that SASP contains our friend CD38 in increasing amounts (Campisi et al) along with other chemockines and cytokines eg, IL6, TGF-b, TNF-a and other NF-KB associated signals. So for me I find the NAD and inflammation connection compelling and combined with the Sinclair data the connection becomes even more obvious. 

So I have recommended we monitor NAD, NAD/NADH ratio, CD38 and NF-KB as additional metrics in our research program. I suspect Aubrey is correct and if we reduce CD38 levels by removing SASP we might see the NAD levels "bounce" back up as the CD38 is not destroying it. 

http://www.ncbi.nlm....pubmed/27304511
http://diabetes.diab...ntent/62/4/1084

Ultimately Quercetin, ABT737, Venetoclax and so on give us useful insights into aging and indeed could reveal the link between NAD/NADH and inflammation and clearly show us how a large part of aging occurs. Of course these drugs are not a full on therapeutic answer as they all exhibit "selectiveness" on cell types effected. However the good news is companies like Osiin Biotechnology and Unity are developing drugs and therapies that have much wider mutli cell application, this will allow us to systemically treat inflammation and potentially restore NAD system wide. The closest we have come to seeing this in practice is the Barker studies which used a genetic trigger to kill P16 cells system wide, the results were impressive. 

http://www.nature.co...ature10600.html
http://www.ncbi.nlm....pubmed/26840489

 

 

I don't know if these effects are upstream or downstream of CD38 Steve but felt you should be aware of :

 

An extract of the fern Polypodium leucotomos (Difur) modulates Th1/Th2 cytokines balance in vitro and appears to exhibit anti-angiogenic activities in vivo: pathogenic relationships and therapeutic implications.

 

In the present study we show the capacity of an extract of the fern Polypodium leucotomos (PLE) to partially inhibit the production of cytokines showing a Th1 pattern (IL-2, IFN-gamma and TNF-alpha) in human PHA-stimulated peripheral blood mononuclear cells. The percentage of inhibition was 24% for IL-2, 72% for INF-gamma and 53% for TNF-alpha. With regard to Th2 cytokines, the addition of PLE resulted in a significant increase (33%) in IL-10 production. Surprisingly, the production of the inflammatory cytokine IL-6 was completely abolished (100% inhibition) by PLE at all doses tested...

http://www.ncbi.nlm....pubmed/10928072

[Logic]

 

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.

 

 

The thread:

http://www.longecity...effective-dose/

 

Ascorbic acid attenuates aspirin-induced gastric damage: role of inducible nitric oxide synthase.

http://www.longecity...ndpost&p=750581

http://www.longecity...ndpost&p=768925

[Bryan_S]

Study finds boosting SIRT1 may prevent and treat Osteoporosis

http://www.timelessl...t-osteoporosis/

 

Our friend finds another research thread in the search. I'm convinced this person is a lurker here or is one of our main contributors on LongeCity.

 

http://www.sciencedi...006291X16311081

[Bryan_S]

An Educational Article on the Business of Selling Nicotinamide Riboside

https://www.fightagi...amide-riboside/

 

A less than stellar view of the market space.

 

This top article was preceded by this next article.

 

http://www.wired.com...-drug-yeah-fda/

 

But the first one to appear this morning was this article.

 

http://www.totalheal...e-Riboside.html

 

So it appears they all borrowed upon each other or set the stage.

Edited by Bryan_S, 07 July 2016 - 01:59 AM.

[Harkijn]

My sunny view on these articles: If even Reason who has been stuck in a rut for years decrying any approach other than his own, seems to give Guarente a little credit, then the paradigms are truly shifting! The third article seems to me a fair and balanced account for beginners. Yesterday a friend asked me how he could read up quickly on NR. I'll mail him the link to this article.

Curious BTW that life elongation can be  achieved by tryptophan restriction, the very nutrient essential for de novo synthesis of NR...

[stefan_001]

An Educational Article on the Business of Selling Nicotinamide Riboside

https://www.fightagi...amide-riboside/

 

A less than stellar view of the market space.

 

This top article was preceded by this next article.

 

http://www.wired.com...-drug-yeah-fda/

 

But the first one to appear this morning was this article.

 

http://www.totalheal...e-Riboside.html

 

So it appears they all borrowed upon each other or set the stage.

 

I think it is time to step away from the CR comparison. My bold view it that CR may slow aging somewhat but that we NR/NMN as basis we can somewhat reverse aging of certain parts of the body. I think that is also evidenced by the study results coming out and posted here. CR seems a path with finite upside.

Edited by stefan_001, 07 July 2016 - 07:57 AM.

[Anthony_Loera]

An Educational Article on the Business of Selling Nicotinamide Riboside

https://www.fightagi...amide-riboside/

 

A less than stellar view of the market space.

 

This top article was preceded by this next article.

 

http://www.wired.com...-drug-yeah-fda/

 

But the first one to appear this morning was this article.

 

http://www.totalheal...e-Riboside.html

 

So it appears they all borrowed upon each other or set the stage.

 

From the article:

"But another company, ChromaDex, actually is interested in getting FDA approval for NR right now. It wouldn't be an anti-aging drug - again, aging isn't a disease - but would instead get approved to treat a rare, genetic disease in kids called Cockayne syndrome. The point? While ChromaDex is waiting for that approval, it makes and sells raw NR to several companies, who repackage the supplement and sell it under their own brands - including, yes, Elysium."

 

From the recent facebook marketing link I clicked on:

https://blogs.scient...-aging-nad-fad/

"Elysium isn't the only pterostilbene vendor. In fact, ChromaDex also offers pterostilbene for supplements separately from Niagen."

 

Uhm... Chromadex owns and manufacturers Niagen and sells it to Elysium... why obfuscate the facts? 

 

A

[Steve H]

I think I will wait until a proper direct genetic solution arrives rather than waste my money on supplements I am yet to see concrete evidence work in humans. Sure some mouse studies are interesting and I work in mouse testing so I know that translation is not always a given. I will take the supplement vendors advice in the article and wait. Certainly not interested in paying the ridiculous prices these companies charge for things I can source directly from my suppliers at factory cost especially given the human data is not reliable at this time. 

 

As I have previously said I think there is more mileage with tackling the root of the problem eg, NFKB, CD38 and chronic inflammation via senolytics and other robust approaches. I will collect NAD/NADH data in our current study and we will soon find out if reducing CD38 allows the NAD/NADH ratio to bounce back, that is what is really important here, that ratio is critical. 

[Tom Andre F. (ex shinobi)]

 

An Educational Article on the Business of Selling Nicotinamide Riboside

https://www.fightagi...amide-riboside/

 

A less than stellar view of the market space.

 

This top article was preceded by this next article.

 

http://www.wired.com...-drug-yeah-fda/

 

But the first one to appear this morning was this article.

 

http://www.totalheal...e-Riboside.html

 

So it appears they all borrowed upon each other or set the stage.

 

From the article:

"But another company, ChromaDex, actually is interested in getting FDA approval for NR right now. It wouldn't be an anti-aging drug - again, aging isn't a disease - but would instead get approved to treat a rare, genetic disease in kids called Cockayne syndrome. The point? While ChromaDex is waiting for that approval, it makes and sells raw NR to several companies, who repackage the supplement and sell it under their own brands - including, yes, Elysium."

 

From the recent facebook marketing link I clicked on:

https://blogs.scient...-aging-nad-fad/

"Elysium isn't the only pterostilbene vendor. In fact, ChromaDex also offers pterostilbene for supplements separately from Niagen."

 

Uhm... Chromadex owns and manufacturers Niagen and sells it to Elysium... why obfuscate the facts? 

 

A

 

 

And from : http://www.wired.com...-drug-yeah-fda/

 

"To boost future demand, ChromaDex has set up 70 research agreements with universities or research institutes to study nicotinamide riboside, putting up money and supplying scientists with the compound"

 

I understand now why we see more data about NR to boost NAD+ more than any others B3, especially nicotinic acid or nicotinic acid riboside, even when the tissue targeted is not ideal for NR... And also why they almost never used others B3 as control and play more with dosage. Its not good for the marketing I guess

 

And also why we miss data about its effect on homocysteine etc in the opposite
 

Edited by Tom Andre F. (ex shinobi), 07 July 2016 - 01:57 PM.

[tunt01]

My sunny view on these articles: If even Reason who has been stuck in a rut for years decrying any approach other than his own, seems to give Guarente a little credit, then the paradigms are truly shifting! 

 

Could not agree more.  It's like there is this perfectionist caucus in the longevity community that lives at the altar of Aubrey De Grey and anything else is sacreligious.  Calico?  They're doing it wrong - they need to do it like SENS.  Guarante/Sinclair?  They are just tweaking metabolism and not really fundamentally addressing aging/lifespan.  Or worse, they're just trying to make money.

 

In the last 2-3 years, I think there has been some real interesting and fundamental insight into what the sirtuins and NAD/NADH ratio is doing in the body/mitochondria.  Whether or not that only helps a small group of Cockanye patients or more broadly alzheimer/diabetes patients, only time will tell.  I understand it's important to make calculated bets on how the science will play out over time and everyone is welcome to their own opinion.

 

But for god's sake, can people let the human trials and studies play out over 4-5 years before convicting Lenny Guarente as a supplement huckster?  I find it infuriating.

 

I think it is time to step away from the CR comparison. My bold view it that CR may slow aging somewhat but that we NR/NMN as basis we can somewhat reverse aging of certain parts of the body. I think that is also evidenced by the study results coming out and posted here. CR seems a path with finite upside.

 

 

 

NR/SIRT1 activation is in many ways an attempt to be a CR mimetic.  It's likely to fall short of CR itself, but I wouldn't discard the CR comparison.

[stefan_001]

 

 

I think it is time to step away from the CR comparison. My bold view it that CR may slow aging somewhat but that we NR/NMN as basis we can somewhat reverse aging of certain parts of the body. I think that is also evidenced by the study results coming out and posted here. CR seems a path with finite upside.

 

 

 

NR/SIRT1 activation is in many ways an attempt to be a CR mimetic.  It's likely to fall short of CR itself, but I wouldn't discard the CR comparison.

 

 

Well lets take this study as example:

Activation of SIRT3 by the NAD+ Precursor Nicotinamide Riboside Protects from Noise-Induced Hearing Loss

http://www.cell.com/...4131(14)00500-2

• •The NAD+ precursor NR prevents noise-induced hearing loss
• •NR can be administered after acoustic trauma to prevent hearing loss
• •Prevention of noise-induced hearing loss by NAD+ and NR is dependent upon SIRT3
• •NAD+ and NR prevent noise-induced neurite retraction in the cochlea

 

So you are saying if I dont eat before noise overload or after I damage my hearing my ears will be fine?

 

Or perhaps we should just tell these kids with Cockayne syndrom to go on a diet because CR has the same effect?

 

NIH and ChromaDex Announce Material Cooperative Research and Development Agreement to Study the Effects of ChromaDex’s NIAGEN® Nicotinamide Riboside on Cockayne Syndrome and Ataxia Telangiectasia

http://investors.chr...icle&ID=2113486

Edited by stefan_001, 07 July 2016 - 02:46 PM.

[Tom Andre F. (ex shinobi)]

 

 

 

I think it is time to step away from the CR comparison. My bold view it that CR may slow aging somewhat but that we NR/NMN as basis we can somewhat reverse aging of certain parts of the body. I think that is also evidenced by the study results coming out and posted here. CR seems a path with finite upside.

 

 

 

NR/SIRT1 activation is in many ways an attempt to be a CR mimetic.  It's likely to fall short of CR itself, but I wouldn't discard the CR comparison.

 

 

Well lets take this study as example:

Activation of SIRT3 by the NAD+ Precursor Nicotinamide Riboside Protects from Noise-Induced Hearing Loss

http://www.cell.com/...4131(14)00500-2

• •The NAD+ precursor NR prevents noise-induced hearing loss
• •NR can be administered after acoustic trauma to prevent hearing loss
• •Prevention of noise-induced hearing loss by NAD+ and NR is dependent upon SIRT3
• •NAD+ and NR prevent noise-induced neurite retraction in the cochlea

 

So you are saying if I dont eat before noise overload or after I damage my hearing my ears will be fine?

 

 

http://www.ncbi.nlm....es/PMC3759555/ Maintaining good hearing: Calorie restriction, Sirt3, and glutathione

 

http://www.ncbi.nlm....pubmed/20298166 Effects of caloric restriction on age-related hearing loss in rodents and rhesus monkeys.

 

[tunt01]

 

Well lets take this study as example:

Activation of SIRT3 by the NAD+ Precursor Nicotinamide Riboside Protects from Noise-Induced Hearing Loss

http://www.cell.com/...4131(14)00500-2

• •The NAD+ precursor NR prevents noise-induced hearing loss
• •NR can be administered after acoustic trauma to prevent hearing loss
• •Prevention of noise-induced hearing loss by NAD+ and NR is dependent upon SIRT3
• •NAD+ and NR prevent noise-induced neurite retraction in the cochlea

 

So you are saying if I dont eat before noise overload or after I damage my hearing my ears will be fine?

 

 

I'm not going to sit here and write out a treatment plan for noise overload/cochlear damage, a specific exposure/condition I've spent little more than 5 minutes of time thinking about or looking at.

 

There is a fundamental nature of NR increasing the NAD+/NADH ratio, the conserved nature of Sirtuins in mediating repair, increased mitochondrial function, and the requirements of sirtuins for mediating (at least some of) the benefits of Calorie Restriction.

 

 

Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-related Hearing Loss under Caloric Restriction

Caloric restriction (CR) extends the lifespan and healthspan of a variety of species, and slows the progression of age-related hearing loss (AHL), a common age-related disorder associated with oxidative stress. Here we report that CR reduces oxidative DNA damage in multiple tissues and prevents AHL in wild-type mice, but fails to modify these phenotypes in mice lacking the mitochondrial deacetylase Sirt3, a member of the sirtuin family. In response to CR, Sirt3 directly deacetylates and activates mitochondrial isocitrate dehydrogenase 2 (Idh2), leading to increased NADPH levels and an increased ratio of reduced to oxidized glutathione in mitochondria. In cultured cells, overexpression of Sirt3 and/or Idh2 increases NADPH levels and protects from oxidative stress-induced cell death. Therefore, our findings identify Sirt3 as an essential player in enhancing the mitochondrial glutathione antioxidant defense system during CR, and suggest that Sirt3-dependent mitochondrial adaptations may be a central mechanism of aging retardation in mammals.

 

See Figure 2

 

I'm not 100% sure where the maximum benefits lies right now between SIRT1 and SIRT3 or the tradeoffs between activating either or both.

 

But I think anyone who wants to completely disregard the comparison of CR to NR/SIRT activiation, because it's obviously guiding part of Guarente/Sinclair's thought process over the years and CR is directly used as a comparison in several of these papers.

 

I think it's incumbent upon people to show where it falls short, and I share Tom's concern over Homocysteine and lack of Nam comparisons in the ongoing research.  But to that end, we might have a better understanding of the benefits of NR/Sirt activation and the narrowness of where it is applicable rather than throwing everything out at once and declaring Guarente/Sinclair/ChromaDex/ et al to be a bunch of supplement pill pushers with ulterior motives.

 

It's the totality of throwing out everything Chromadex/Elysium are doing that irritates me, rather than the nuanced, intellectual argument (which I don't buy 100%) that at least some people like Tom are respectfully and thoughtfully making.

 

IDK.  I still have 10 more NAD/SIRT papers to get through until I am up to speed where Bryan/Tom are.  But that is my off the cuff view at this point.

Edited by prophets, 07 July 2016 - 02:56 PM.

[stefan_001]

 

 

Well lets take this study as example:

Activation of SIRT3 by the NAD+ Precursor Nicotinamide Riboside Protects from Noise-Induced Hearing Loss

http://www.cell.com/...4131(14)00500-2

• •The NAD+ precursor NR prevents noise-induced hearing loss
• •NR can be administered after acoustic trauma to prevent hearing loss
• •Prevention of noise-induced hearing loss by NAD+ and NR is dependent upon SIRT3
• •NAD+ and NR prevent noise-induced neurite retraction in the cochlea

 

So you are saying if I dont eat before noise overload or after I damage my hearing my ears will be fine?

 

 

I'm not going to sit here and write out a treatment plan for noise overload/cochlear damage, a specific exposure/condition I've spent little more than 5 minutes of time thinking about or looking at.

 

There is a fundamental nature of NR increasing the NAD+/NADH ratio, the conserved nature of Sirtuins in mediating repair, increased mitochondrial function, and the requirements of sirtuins for mediating (at least some of) the benefits of Calorie Restriction.

 

 

 

 

I'm not 100% sure where the maximum benefits lies right now between SIRT1 and SIRT3 or the tradeoffs between activating either or both.

 

But I think anyone who wants to completely disregard the comparison of CR to NR/SIRT activiation, because it's obviously guiding part of Guarente/Sinclair's thought process over the years and CR is directly used as a comparison in several of these papers.

 

I think it's incumbent upon people to show where it falls short, and I share Tom's concern over Homocysteine and lack of Nam comparisons in the ongoing research.  But to that end, we might have a better understanding of the benefits of NR/Sirt activation and the narrowness of where it is applicable rather than throwing everything out at once and declaring Guarente/Sinclair/ChromaDex/ et al to be a bunch of supplement pill pushers with ulterior motives.

 

It's the totality of throwing out everything Chromadex/Elysium are doing that irritates me, rather than the nuanced, intellectual argument (which I don't buy 100%) that at least some people like Tom are respectfully and thoughtfully making.

 

IDK.  I still have 10 more NAD/SIRT papers to get through until I am up to speed where Bryan/Tom are.  But that is my off the cuff view at this point.

 

 

I think you take my reply too literal. CR is great and has shown mechanisms of anti-aging. At the same time it has been around now for decades and has not led to specific treatments that can treat health conditions in the population at large. Its obvious to me at least that NR has changed the status quo and allows a more direct and immediate intervention. Personally I believe that a combination of both and couple more can help us forward a long way. 

 

And perhaps to still add that NR may not and is unlikely the final solution but it is available TODAY. For example my parents who are in there late 70s are using it and have definitely improved and are more active. My mom already eats so little that the notion of CR is simply nonsense.

Edited by stefan_001, 07 July 2016 - 03:35 PM.

[Tom Andre F. (ex shinobi)]

Stefan, I think we still need CR as control group in studies as it is not same as for usage, but to understand a certain mechanism. So I would add always CR AND nicotinic acid / nicotinic acid riboside (not Nam since already proven to be less potent than NA and shut sirt) : http://www.ncbi.nlm....les/PMC3616313/

 

in this study,

 

they explained the reason why they used NR instead of NA, and I let you take your own conclusion:

 

"The administration of NAD⁺ precursors, mostly in the form of nicotinic acid (NA), has long been known to promote beneficial effects on blood lipid and cholesterol profiles and even to induce short-term improvement of type 2 diabetes (Karpe and Frayn, 2004). Unfortunately, NA treatment often leads to severe flushing, resulting in poor patient compliance (Bogan and Brenner, 2008). These side effects are mediated by the binding of NA to the GPR109A receptor (Benyo et al., 2005). We hence became interested in the possible therapeutic use of alternative NAD⁺ precursors that do not activate GPR109A."

 

So purely, they admit NR wouldnt be superior to NA but since the later can induce flush then they moved for ONLY NR

 

they are maybe not aware that :

 

• the flush effect disappear after regular use and can be none if started at low dose
• activate GPR109A is a beneficial anti inflammatory pathway
• there is some form of niacin that are flush free http://www.iherb.com...-Capsules/37900 (extended release niacin, do not confuse with slow release preparation).

So they just not used nicotinic acid (niacin) as control. Fine, it was probably one of those sponsored chromadex studies ?

 

However since its not that black they found interesting things such as:

 

We also tested whether the increase in NAD⁺ would be concomitant to changes in other NAD⁺ metabolites. Strikingly, NADH and nicotinamide (NAM) levels were largely diminished in muscles from NR-fed mice

 

that mean modulate positively the NAD/NADH ratio and then probably turn off some nAD+ ase consuming enzyme as some speculated here. This is an interesting part.

 

 

So bad they didnt monitored that into other tissue but only in an NR specific tissue (muscle). However they stated that unfortunately: The image reveals that PGC-1a is not detectable by current immunoprecipitation protocols in total white adipose and brain lysates in conditions at which it is detectable in muscle, heart BAT or liver. (that mean that NR was kind of ineffective for others tissue).

 

And as we can see indeed for instance: in brain NR decreased a bit the sirtuins activity but increased it in the muscles. Thats why again we should see NA as control and should never rely on NR to completely help as an NAD+ boosting. We need stronger approach than just precursor, and should consider NA even if less marketed (as pushed by chromadex) and less expensive (so less sexy ?). Furthermore, NR is probably also a methyl consumer, so even if no flush, one would have to take B6, B9 and B12 with it is the case for all B3s

 

EDIT: what was true for niacin in the 1980s study regarding slow release niacin can be true for NR, so caution would be there too about supplementation with it more than twice a day. Again further studies are needed

 

 

 

 

Edited by Tom Andre F. (ex shinobi), 07 July 2016 - 04:32 PM.

[stefan_001]

 

Furthermore, NR is probably also a methyl consumer, so even if no flush, one would have to take B6, B9 and B12 with it is the case for all B3s

 

 

 

Well NR is not niacinamide, its niacinamide(nicotinamide) riboside which means it has already a ribose sugar bonded to it. It cannot not work like niacinamide.

 

the rest I read later..

Edited by stefan_001, 07 July 2016 - 06:17 PM.

[Bryan_S]

I posted "An Educational Article on the Business of Selling Nicotinamide Riboside" to stimulate some conversation and I'm a bit taken by the response. Guys the data is still coming in and already we see groups polarizing around specific opinions. Steve H also has a horse in the race and I do think inflammation is at the heart of the matter and we await his and other supporting studies. We can all agree NAD is central to the reported health benefits and this is at the core of this discussion from hearing loss, anti-aging thru possible anti-cancer results.

 

Tom makes the point that they are not giving the other NAD precursors comparative study. And yes (NA) has "poor patient compliance," but truth be told (Na) has had 70-years of research. If (Na) can produce the same effects as (NR) at similar or increased dosages why haven't researchers outside Brenner's Lab included it as a control? Personally I don't see a conspiracy to withhold comparative study. (Na) has shown to be beneficial and yet the medical community has forsaken it for statins and thrown away its other benefits. But truth in fact it does come down to "poor patient compliance" and we can't gloss over that fact.

 

Still others feel its a money grab by some of our esteemed researchers. We are going to see this spun in so many directions its going to make your head spin. 

 

I do think we can see a comparison to the failed resveratrol days. However resveratrol didn't give rise to increased NAD levels like taking NAD precursors. So I think thats where that comparison ends.

 

Money follows success and thats what we'll see play out from the supplement market thru the academic and medical worlds.

 

If NAD Repletion threatens some well entrenched pharmaceuticals we could also see some push back from them as well.  

 

Bottom line NAD repletion is showing lab results to a number of ailments. We are all keen to see these experiments repeated in humans. So no matter how we chip away at this (NR) will persist now that the score card is saying people will take it, their appears to be no adverse effects, it increases NAD levels and all supporting research says it addresses "some" aspects of aging.

 

I think much of this is dose dependent but thats a discussion for another day.

 

As I've said before I don't think (NR) is the final story. I also won't argue the value of (Na) for those who can endure the flush. It really does come down to patient compliance and thats why I and many others can't take Niacin. I would however stress that that those who take it at therapeutic dosages should have their doctors check their liver enzymes.

 

It's much as I explained in the leaky boat scenario before. We are losing NAD like we've sprung a leak. However lets look at it like a leaky cup which is a better analogy. (NR) or (Na) for that matter are replenishing lost reserves. As we get older the leak gets bigger and the ability to replace lost NAD will eventually become futile. So I don't see simple NAD Repletion as the final answer. I see it as postponing the inevitable. The research path beyond NAD Repletion is to stem the leak and understand the increased destruction of NAD and halt this action. Compounds like Quercetin & Apegenin might retard the CD38 conundrum but this still remains to be seen.

 

Good points and discussion guys.

 

JMHO

[Supierce]

My take on resveratrol is that after Sirtris' failure and the discrediting of Dipak Das, people thought resveratrol itself was discredited. Far from it. A simple search shows continuing research with very encouraging results:

http://scholar.googl...ratrol&scisbd=1

As far as I know, Sinclair hasn't lost interest in resveratrol at all. He merely wondered why it worked well for some test subjects and not others. NAD+ turned out to be the answer and so here we are.

[bluemoon]

Yes. I don't see why resveratrol has been dismissed including in the Bloomberg article in early 2015 just because there hasn't been a GSK drug on the market. I don't even know if GSK is completely out of the Sirt activating business or not.

 

In late 2014, Sinclair stated during a Q&A in Australia that "Resveratrol is old technology, and we think the NAD approach will be superior." Yet in August 2015, he told a Washington Post reporter that he takes 1000 mg of resveratrol with breakfast each morning.  In April 2015, Guarente said he takes 250 mg of resveratrol along with Elysium Basis.

 

So two of the leading NR/NMN researchers are still taking resveratrol.    

[stefan_001]

Yes. I don't see why resveratrol has been dismissed including in the Bloomberg article in early 2015 just because there hasn't been a GSK drug on the market. I don't even know if GSK is completely out of the Sirt activating business or not.

In late 2014, Sinclair stated during a Q&A in Australia that "Resveratrol is old technology, and we think the NAD approach will be superior." Yet in August 2015, he told a Washington Post reporter that he takes 1000 mg of resveratrol with breakfast each morning. In April 2015, Guarente said he takes 250 mg of resveratrol along with Elysium Basis.

So two of the leading NR/NMN researchers are still taking resveratrol.

Not entirely surprising. Most on this board use more than NR alone in the belief that other factors need to be adressed e.g. Inflamation, extra stimulus for the sirts, anti cancer, anti glycation and so on. With the NAD pool improved via one method or another the rest also gets more meaning. Perhaps it makes sense to have another look at resveratrol too.

[Tom Andre F. (ex shinobi)]

Hi Bryan,

 

 

 

Tom makes the point that they are not giving the other NAD precursors comparative study. And yes (NA) has "poor patient compliance,"

 

As I've said before I don't think (NR) is the final story. I also won't argue the value of (Na) for those who can endure the flush. It really does come down to patient compliance and thats why I and many others can't take Niacin.

 

are you aware the flush disapear after some time of use and allow people to start from very low (20mg for instance) and increase bit by bit the dosage without experiencing any flush ?

 

Second, as I stated, there is flush free niacin that lifextension explained is different than the slow release one, they just linked to a inositol (extended release niacin) ?

 

So if the flush is really your concern, still these informations have to be clearly stated here.

 

 

 

 

but truth be told (Na) has had 70-years of research. If (Na) can produce the same effects as (NR) at similar or increased dosages why haven't researchers outside Brenner's Lab included it as a control? Personally I don't see a conspiracy to withhold comparative study. (Na)

 

 

 

My explanation is more that one: after the buzz from sinclair using NMN intramuscular, people was looking for way to reproduce the experiment and NR was on the same root. So they started to use NR in partnership / as sponsored by chromadex as stated in the article, sounds very logical isnt ?

 

There is no point to just promote as NR as best precursor and to not use NA as control if you just mention the flush as a problem since NR is actually then marketed not as a basic flush NA, just look the hype around it including this topic. We have to rely on facts : is NR the real and best precursor or not ? No evidence so far. And indeed basic flush free niacin or low dosage as starter do not owns patent so.. less interesting ? It still look strange to me sorry

 

As I've said before I don't think (NR) is the final story. I also won't argue the value of (Na) for those who can endure the flush. It really does come down to patient compliance and thats why I and many others can't take Niacin. I would however stress that that those who take it at therapeutic dosages should have their doctors check their liver enzymes.

As far as I know this could happen only in high dosage and using slow release niacin. So do you have others evidence ? please share.

 

For now what I see Bryan is that we dont have any info about that for NR.. no one still monitored that yet, and actually I dont see why it couldnt happen as same range using NR, after all its niacinamide linked to the glucose by a C-N bond half aminal and half acetal (SP3 character) isnt ?

 

I just want make people cautious too due to the recomendation in this topic to use NR quiet frenquently in order to insure the NAD+ does not fall to normal after couple hours and maintain it.

 

Regards (and as always sorry for my english that does not match your level )