2255 replies to this topic

[Tom Andre F. (ex shinobi)]

 

 

I think this is a distortion of the study. The mice were fed for a period of 6 weeks with NR starting at an age of 24 months. The fact that this short treatment, at such late age results in life extension is quite impressive in my opinion.

 

Yes but most studies on lifespan does the same and this is why I think they should have included a calorie restriction group. But still 4% is small and its also why i think they didnt even gave this %.. Its significant yes but you cant call that impressive. Even they mention a "slightly increased lifespan".

 

But knowing what we all discussed here a few pages ago, the solution is more in an holistic approach: NR + pterostilbene + honokiol..

 

(Also they seems to probably made a mistake somewhere since their result in the text does not match their chart (around 140 / 150 days more in the graph 6G))

 

[stefan_001]

 

I think this is a distortion of the study. The mice were fed for a period of 6 weeks with NR starting at an age of 24 months. The fact that this short treatment, at such late age results in life extension is quite impressive in my opinion.

Yes but most studies on lifespan does the same and this is why I think they should have included a calorie restriction group. But still 4% is small and its also why i think they didnt even gave this %.. Its significant yes but you cant call that impressive. Even they mention a "slightly increased lifespan".

 

But knowing what we all discussed here a few pages ago, the solution is more in an holistic approach: NR + pterostilbene + honokiol..

 

(Also they seems to probably made a mistake somewhere since their result in the text does not match their chart (around 140 / 150 days more in the graph 6G))

 

It says in the text:

 

NR treatment of C57BL/6J mice slightly increased lifespan (chow diet, mean 829 ± 12.0; NR, mean 868 ± 12.4 days

 

so a life extension of 39 days. I think its impressive. The treatment took place at age 24 months = 728 days. So you could also say that the remaining life was 140 days versus 101 days  = 39% extension of the remaining life and that with only 6 weeks of treatment. I dont see a mistake in the charts as the text is mean value.

 

Edited by stefan_001, 17 June 2016 - 10:05 PM.

[Tom Andre F. (ex shinobi)]

 

 

I think this is a distortion of the study. The mice were fed for a period of 6 weeks with NR starting at an age of 24 months. The fact that this short treatment, at such late age results in life extension is quite impressive in my opinion.

Yes but most studies on lifespan does the same and this is why I think they should have included a calorie restriction group. But still 4% is small and its also why i think they didnt even gave this %.. Its significant yes but you cant call that impressive. Even they mention a "slightly increased lifespan".

 

But knowing what we all discussed here a few pages ago, the solution is more in an holistic approach: NR + pterostilbene + honokiol..

 

(Also they seems to probably made a mistake somewhere since their result in the text does not match their chart (around 140 / 150 days more in the graph 6G))

 

It says in the text:

 

NR treatment of C57BL/6J mice slightly increased lifespan (chow diet, mean 829 ± 12.0; NR, mean 868 ± 12.4 days

 

so a life extension of 39 days. I think its impressive. The treatment took place at age 24 months = 728 days. So you could also say that the remaining life was 140 days versus 101 days  = 39% extension of the remaining life and that with only 6 weeks of treatment. I dont see a mistake in the charts as the text is mean value.

 

 

 

ah yes sorry its what I said previously both mean and max lifespan : around 4 to 5% increase (max about 970 versus 1020). They started at exactly 700 days.
 

EDIT: if you take only the remaining time then its: mean = 30% increase with NR and for max lifespan = 18% increase with NR.. More fair result but not a single study does that, they usually start treatment late or at middle age and take the global result

Edited by Tom Andre F. (ex shinobi), 17 June 2016 - 10:22 PM.

[Harkijn]

 

 

 

I think this is a distortion of the study. The mice were fed for a period of 6 weeks with NR starting at an age of 24 months. The fact that this short treatment, at such late age results in life extension is quite impressive in my opinion.

Yes but most studies on lifespan does the same and this is why I think they should have included a calorie restriction group. But still 4% is small and its also why i think they didnt even gave this %.. Its significant yes but you cant call that impressive. Even they mention a "slightly increased lifespan".

 

But knowing what we all discussed here a few pages ago, the solution is more in an holistic approach: NR + pterostilbene + honokiol..

 

(Also they seems to probably made a mistake somewhere since their result in the text does not match their chart (around 140 / 150 days more in the graph 6G))

 

It says in the text:

 

NR treatment of C57BL/6J mice slightly increased lifespan (chow diet, mean 829 ± 12.0; NR, mean 868 ± 12.4 days

 

so a life extension of 39 days. I think its impressive. The treatment took place at age 24 months = 728 days. So you could also say that the remaining life was 140 days versus 101 days  = 39% extension of the remaining life and that with only 6 weeks of treatment. I dont see a mistake in the charts as the text is mean value.

 

 

 

ah yes sorry its what I said previously both mean and max lifespan : around 4 to 5% increase (max about 970 versus 1020). They started at exactly 700 days.
 

EDIT: if you take only the remaining time then its: mean = 30% increase with NR and for max lifespan = 18% increase with NR.. More fair result but not a single study does that, they usually start treatment late or at middle age and take the global result

 

Perhaps of more practical importance than healthspan and lifespan is the regeneration in stem cells. This aged mammal read through the study to find out the amount of NR used, but couldn't find it. Did I overlook it? The researchers speak of repletion, did they mean NR ad libitum?

[Harkijn]

 

 

Biosensor reveals multiple sources for mitochondrial NAD+

Science  17 Jun 2016:

Xiaolu A. Cambronne1,*, Melissa L. Stewart1, DongHo Kim1, Amber M. Jones-Brunette2, Rory K. Morgan3, David L. Farrens2, Michael S. Cohen3,*, Richard H. Goodman1

http://science.scien...t/352/6292/1474

 

Abstract

 

Nicotinamide adenine dinucleotide (NAD+) is an essential substrate for sirtuins and poly(adenosine diphosphate–ribose) polymerases (PARPs), which are NAD+-consuming enzymes localized in the nucleus, cytosol, and mitochondria. Fluctuations in NAD+ concentrations within these subcellular compartments are thought to regulate the activity of NAD+-consuming enzymes; however, the challenge in measuring compartmentalized NAD+ in cells has precluded direct evidence for this type of regulation. We describe the development of a genetically encoded fluorescent biosensor for directly monitoring free NAD+ concentrations in subcellular compartments. We found that the concentrations of free NAD+ in the nucleus, cytoplasm, and mitochondria approximate the Michaelis constants for sirtuins and PARPs in their respective compartments. Systematic depletion of enzymes that catalyze the final step of NAD+ biosynthesis revealed cell-specific mechanisms for maintaining mitochondrial NAD+ concentrations.

 

Those who only read the abstracts of the studies posted by Bryan : this time read the full text. It contains photographs of NAD+. For me, being able to see it turns it from an abstraction to a reality...

I also learned from this research that every cell has three NAD+pools and that the mitochondrial pool can fall back on the cytoplasmic pool in case of shortage. The researchers do not know how the NAD is being transported from A to B. I hope this is discovered soon, because perhaps this process, too, can perhaps be tweaked to youthful functioning?

 

SIRT1 as well as SIRT6 (as I understand it the two most important sirtuins for aging) are located in the nucleus so I expect they will use the nuclear NAD+pool. If the NAD+pool is low, as in aging, it is not exclusively the availability of NAD+ which limits SIRT activity but also the effectiveness or lack thereof of the replenishment from the cytoplasmic NAD+pool.  Just suppose someone activates SIRT1 (by taking a cold bath or supplementing resveratrol) this would use a lot of NAD+ and then SIRT6 would kind of idle until the replenishment mechanism delivers. My speculation, of course. Thoughts?

[stefan_001]

 

 

 

 

 

 

It says in the text:

 

NR treatment of C57BL/6J mice slightly increased lifespan (chow diet, mean 829 ± 12.0; NR, mean 868 ± 12.4 days

 

so a life extension of 39 days. I think its impressive. The treatment took place at age 24 months = 728 days. So you could also say that the remaining life was 140 days versus 101 days  = 39% extension of the remaining life and that with only 6 weeks of treatment. I dont see a mistake in the charts as the text is mean value.
 

 

ah yes sorry its what I said previously both mean and max lifespan : around 4 to 5% increase (max about 970 versus 1020). They started at exactly 700 days.
 

EDIT: if you take only the remaining time then its: mean = 30% increase with NR and for max lifespan = 18% increase with NR.. More fair result but not a single study does that, they usually start treatment late or at middle age and take the global result

 

Perhaps of more practical importance than healthspan and lifespan is the regeneration in stem cells. This aged mammal read through the study to find out the amount of NR used, but couldn't find it. Did I overlook it? The researchers speak of repletion, did they mean NR ad libitum?

 

 

In this article the human equivalent dose was calculated, very high:

 

http://www.timelessl...-complications/

Edited by stefan_001, 19 June 2016 - 07:28 PM.

[stefan_001]

 

Those who only read the abstracts of the studies posted by Bryan : this time read the full text. It contains photographs of NAD+. For me, being able to see it turns it from an abstraction to a reality...

 

 

I also learned from this research that every cell has three NAD+pools and that the mitochondrial pool can fall back on the cytoplasmic pool in case of shortage. The researchers do not know how the NAD is being transported from A to B. I hope this is discovered soon, because perhaps this process, too, can perhaps be tweaked to youthful functioning?

 

SIRT1 as well as SIRT6 (as I understand it the two most important sirtuins for aging) are located in the nucleus so I expect they will use the nuclear NAD+pool. If the NAD+pool is low, as in aging, it is not exclusively the availability of NAD+ which limits SIRT activity but also the effectiveness or lack thereof of the replenishment from the cytoplasmic NAD+pool.  Just suppose someone activates SIRT1 (by taking a cold bath or supplementing resveratrol) this would use a lot of NAD+ and then SIRT6 would kind of idle until the replenishment mechanism delivers. My speculation, of course. Thoughts?

 

 

I see this situation the same way, even somewhat broader. There are several processes competing for a shrinking NAD+ pool so depending on the situation one process or another runs short with some deteriorating effect as result. All together a downward spiral...well I guess thats what aging is. So in my view filling the NAD+ pool is the basis and then ontop we can stimulate processes that in turn hopefully have repair and re-generative effects which hopefully would lead to a systematic recovery or at least stop/slow the system from sliding further.

Edited by stefan_001, 19 June 2016 - 08:03 PM.

[Harkijn]

 

 

Those who only read the abstracts of the studies posted by Bryan : this time read the full text. It contains photographs of NAD+. For me, being able to see it turns it from an abstraction to a reality...

 

 

I also learned from this research that every cell has three NAD+pools and that the mitochondrial pool can fall back on the cytoplasmic pool in case of shortage. The researchers do not know how the NAD is being transported from A to B. I hope this is discovered soon, because perhaps this process, too, can perhaps be tweaked to youthful functioning?

 

SIRT1 as well as SIRT6 (as I understand it the two most important sirtuins for aging) are located in the nucleus so I expect they will use the nuclear NAD+pool. If the NAD+pool is low, as in aging, it is not exclusively the availability of NAD+ which limits SIRT activity but also the effectiveness or lack thereof of the replenishment from the cytoplasmic NAD+pool.  Just suppose someone activates SIRT1 (by taking a cold bath or supplementing resveratrol) this would use a lot of NAD+ and then SIRT6 would kind of idle until the replenishment mechanism delivers. My speculation, of course. Thoughts?

 

 

I see this situation the same way, even somewhat broader. There are several processes competing for a shrinking NAD+ pool so depending on the situation one process or another runs short with some deteriorating effect as result. All together a downward spiral...well I guess thats what aging is. So in my view filling the NAD+ pool is the basis and then ontop we can stimulate processes that in turn hopefully have repair and re-generative effects which hopefully would lead to a systematic recovery or at least stop/slow the system from sliding further.

 

Yes, and then there still is this other slightly creepy side: NAD+ destroyal. Schultz and Sinclair in this very recent article 

http://www.cell.com/...4131(16)30244-3

put the blame fair and square on CD38 and point out that quercetin and apigenin are useful inhibitors, but I think they also wonder if the age related extra activity of CD38 perhaps serves a useful health purpose.

 

Edit: punctuation improved....

Edited by harkijn, 20 June 2016 - 04:03 PM.

[stefan_001]

 

 

 

Those who only read the abstracts of the studies posted by Bryan : this time read the full text. It contains photographs of NAD+. For me, being able to see it turns it from an abstraction to a reality...

 

 

I also learned from this research that every cell has three NAD+pools and that the mitochondrial pool can fall back on the cytoplasmic pool in case of shortage. The researchers do not know how the NAD is being transported from A to B. I hope this is discovered soon, because perhaps this process, too, can perhaps be tweaked to youthful functioning?

 

SIRT1 as well as SIRT6 (as I understand it the two most important sirtuins for aging) are located in the nucleus so I expect they will use the nuclear NAD+pool. If the NAD+pool is low, as in aging, it is not exclusively the availability of NAD+ which limits SIRT activity but also the effectiveness or lack thereof of the replenishment from the cytoplasmic NAD+pool.  Just suppose someone activates SIRT1 (by taking a cold bath or supplementing resveratrol) this would use a lot of NAD+ and then SIRT6 would kind of idle until the replenishment mechanism delivers. My speculation, of course. Thoughts?

 

 

I see this situation the same way, even somewhat broader. There are several processes competing for a shrinking NAD+ pool so depending on the situation one process or another runs short with some deteriorating effect as result. All together a downward spiral...well I guess thats what aging is. So in my view filling the NAD+ pool is the basis and then ontop we can stimulate processes that in turn hopefully have repair and re-generative effects which hopefully would lead to a systematic recovery or at least stop/slow the system from sliding further.

 

Yes, and then there still is this other slightly creepy side: NAD+ destroyal. Schultz and Sinclair in this very recent article 

http://www.cell.com/...4131(16)30244-3

put the blame fair and square on CD38 and point out that quercetin and apigenin are useful inhibitors, but I think they also wonder if the age related extra activity of CD38 perhaps serves a useful health purpose.

 

Edit: punctuation improved....

 

 

I am not going to touch CD38, first I will ride the NR train till the end. So far its still good, well over a year in and improvement trend holds. Wrt Sinclair I always have the feeling that he is somewhat irked about NR because it is not his and is coming up with other possible solutions to re-claim the throne.....

Edited by stefan_001, 20 June 2016 - 04:51 PM.

[Nate-2004]

 

 

Yes, and then there still is this other slightly creepy side: NAD+ destroyal. Schultz and Sinclair in this very recent article 

 

 

 

 

 

http://www.cell.com/...4131(16)30244-3

put the blame fair and square on CD38 and point out that quercetin and apigenin are useful inhibitors, but I think they also wonder if the age related extra activity of CD38 perhaps serves a useful health purpose.

 

Edit: punctuation improved....

 

I am not going to touch CD38, first I will ride the NR train till the end. So far its still good, well over a year in and improvement trend holds. Wrt Sinclair I always have the feeling that he is somewhat irked about NR because it is not his and is coming up with other possible solutions to re-claim the throne.....

 

 

I've been constantly pushing for an explanation of *why* NAD+ falls with age, then someone finally answers the question with a prime suspect (that being a rise in CD38 with age). I don't know of any correlations with problems associated with the drinking of chamomile tea or eating celery or anything of the sort. I don't see what it could hurt to take apigenin in addition to NR, reducing CD38 seems to be the logical way to go. We had less CD38 at age 25, I wonder how much of it is inhibited (and to what levels) with apigenin.  I'm going to try this with my remaining two bottles of NR, I have the apigenin on the way should be here today.  I'll let you know if I notice anything new.

 

Getting to the root of why CD38 is on the rise with age is certainly a worthwhile pursuit. I doubt it serves some useful purpose though, it could be linked back to inflammation, which I will also be tackling by attempting to increase certain gut bacteria such as Akkermansia and Christensenellaceae using Glutamine, N-A-G and FOS. See this thread for details.

Edited by Nate-2004, 20 June 2016 - 06:00 PM.

[Bryan_S]

Coenzyme protects against diabetes complications in mice

The Pharmaceutical Journal17 JUN 2016

 

http://www.pharmaceu...0201250.article

 

We'e already seen the main study but the article is making it rounds through the community.

 

Courtesy of Charles Brenner

 

Nicotinamide riboside (NR) improves intraepidermal nerve fibre density, helping to fight prediabetic polyneuropathy in mice given normal chow (NC), a high fat diet (HFD) and HFD plus streptozotocin (toxic to pancreatic beta cells)

 

Around half of people with diabetes will experience peripheral neuropathy, for which there is currently no treatment. 

 

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme crucial to cell metabolism. Recent research has suggested that increased NAD+ metabolism may be neuroprotective. To explore this, researchers administered nicotinamide riboside (NR), an NAD+ precursor, to mice with induced prediabetes and type 2 diabetes. 

[amw]

Bryan, has Cromadex considered manufacturing sublingual Niagen? Maybe tablets or strips or drops?

 

Has anyone tried a transdermal application? The MM is about 255, which is good. I know ChromaDex applied for a transdermal patent, so I'll probably whip some up, using phlogel and give it a shot.

[Yajerman]

Chromadex has just been exposed in a huge stock fraud. Stocks are falling; my only concern is whether or not Niagin and or NR will survive past CHromadex.

 

http://seekingalpha....inus-80-percent

[HappyPaul]

Chromadex has just been exposed in a huge stock fraud. Stocks are falling; my only concern is whether or not Niagin and or NR will survive past CHromadex.

 

http://seekingalpha....inus-80-percent

Been following this all day.  I read it this AM and sold because I didn't need the drama.  Still ahead luckily.  

 

I am sold on NR but that does not mean that a great thing like NR can't be tied up in something not too cool.   We will see. 

[Bryan_S]

Chromadex has just been exposed in a huge stock fraud. Stocks are falling; my only concern is whether or not Niagin and or NR will survive past CHromadex.

 

http://seekingalpha....inus-80-percent

 

thats a question in all our minds.

[Supierce]

Chromadex has just been exposed in a huge stock fraud. Stocks are falling; my only concern is whether or not Niagin and or NR will survive past CHromadex.
 
http://seekingalpha....inus-80-percent

 
thats a question in all our minds.

If Chromadex does the manufacturing themselves, the supply may be in jeopardy. If they license the process to others, then those licenses remain valid and production can probably continue. If they become bankrupt, the patent and licenses become a monetary asset.

Edited by Supierce, 21 June 2016 - 01:36 AM.

[Bryan_S]

In my opinion you can't fake the academic study results. These are all peer reviewed studies. These publications aren't the results of a promotions pump and dump scheme. The product appears real and the research interest is growing monthly. ChomaDex entered a new world by moving to the NASDAQ. Now there is the new element of fast money trying to move share price, for better or worse. The tactics are all disgusting to me. 

Edited by Bryan_S, 21 June 2016 - 11:35 AM.

[Heisok]

Deleted after further research.

 

I believe in the products, and I hope that the company makes it through this. Otherwise, the products should be taken up by another.

Edited by Heisok, 21 June 2016 - 04:24 AM.

[Bryan_S]

I ran a search and found a guy by the name of Chris Drose of Bleecker Street Research behind the stock shorting. Very well orchestrated I might add and he has a number of followers to pounce on thinly traded stocks like Chromadex. We'll see if his accusations carried any criminal wrongdoing as he claims in the days to come.

 

 

 

Edited by Bryan_S, 21 June 2016 - 12:29 PM.

[Yajerman]

Frank L. Jaksch, Founder and CEO, ChromaDex, stated, "The report appears to be a blatant and transparent attempt by a shortseller or shortsellers to profit from an immediate and precipitous decline in the company's share price through the use of an opinion piece published anonymously and laden with misinformation, innuendo and the use of selective historical information. It is also important for investors in ChromaDex and other stakeholders to carefully consider the statement the author made on the last page of his/her editorial attacking the company: 'I am/we are short CDXC. I wrote this article myself, and it expresses my own opinions.'"

Jaksch continued, "ChromaDex is exploring its options in response to this attack." http://finance.yahoo...-224000230.html

 

While the report includes Mr. Jaksch as part of the fraud, there are two factors that do not jive with me.

1. Mr. Jaksch is the founder, so why would he destroy his own company that he started in 1999.

2. The latest large purchase ($5 mil in stock) basically paid out on a  loan they had owed on in order to decrease their expenses. Why would fraudulent people care about paying off loans?

Things will inevitably surface as this goes on. I for one am starting to think this was some sort of ruse to benefit someone or some people. Welcome to public trade I guess.

NR is real in my opinion, so this will more then likely fall to the way side. I own stock (not that much) but I am pretty sure they will bounce back. And if it is a case of attempts to destroy a company then their stock will bounce back fast so now would be a good time to get it while it is low. Just saying.

 

 

[stefan_001]

 

Frank L. Jaksch, Founder and CEO, ChromaDex, stated, "The report appears to be a blatant and transparent attempt by a shortseller or shortsellers to profit from an immediate and precipitous decline in the company's share price through the use of an opinion piece published anonymously and laden with misinformation, innuendo and the use of selective historical information. It is also important for investors in ChromaDex and other stakeholders to carefully consider the statement the author made on the last page of his/her editorial attacking the company: 'I am/we are short CDXC. I wrote this article myself, and it expresses my own opinions.'"

Jaksch continued, "ChromaDex is exploring its options in response to this attack." http://finance.yahoo...-224000230.html

 

While the report includes Mr. Jaksch as part of the fraud, there are two factors that do not jive with me.

1. Mr. Jaksch is the founder, so why would he destroy his own company that he started in 1999.

2. The latest large purchase ($5 mil in stock) basically paid out on a  loan they had owed on in order to decrease their expenses. Why would fraudulent people care about paying off loans?

Things will inevitably surface as this goes on. I for one am starting to think this was some sort of ruse to benefit someone or some people. Welcome to public trade I guess.

NR is real in my opinion, so this will more then likely fall to the way side. I own stock (not that much) but I am pretty sure they will bounce back. And if it is a case of attempts to destroy a company then their stock will bounce back fast so now would be a good time to get it while it is low. Just saying.

 

 

Ofcourse NR is real, it would be one of the largest scientific conspiracies on the planet otherwise.....But then again some believe Neil Armstrong never landed on the moon either........... 

Edited by stefan_001, 21 June 2016 - 02:05 PM.

[Tom Andre F. (ex shinobi)]

there is no point NR would not be legit, we have parallel works done with NMN and knowing NR is just niacinamide with a ribosie, we know it can enter cell.. so its a real direct precursor for NAD+, this is out of discussion. However, im really shock since I really thought chromadex was a stable company and I couldnt even imagin that happened

[Skyguy2005]

 

Researchers link specific enzyme to process of metabolic dysfunction in aging

June 14, 2016

 

Another link in falling NAD levels with aging.

Summary

"Nicotinamide adenine dinucleotide (NAD) levels decrease during aging and are involved in age-related metabolic decline. To date, the mechanism responsible for the age-related reduction in NAD has not been elucidated. Here we demonstrate that expression and activity of the NADase CD38 increase with aging and that CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by regulation of SIRT3 activity. We also identified CD38 as the main enzyme involved in the degradation of the NAD precursor nicotinamide mononucleotide (NMN) in vivo, indicating that CD38 has a key role in the modulation of NAD-replacement therapy for aging and metabolic diseases."

 

http://medicalxpress...ysfunction.html

 

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

 

 

What form is it? NAD+/NADH? 

[Nate-2004]

Nobel Laureate Roger Kornberg is on the scientific advisory board so my guess is that ChromaDex's studies have been legit. 

 

But they haven't. Many of the studies Brian has posted look very promising but ChromaDex's "studies", at least the "published" one on a poster from April this year had a very small sample size and no controls.  That's not quality or legit IMO. 

 

That said, ChromaDex only has a license from Dartmouth to manufacture the NR, Dartmouth has the patent. They could easily take it away (if there is some legal language that this behavior is in violation of the license) and give it to someone else. I wouldn't worry about NR's reputation, it stands on its own I think.

Edited by Nate-2004, 21 June 2016 - 03:14 PM.

[Skyguy2005]

 

 

 

Those who only read the abstracts of the studies posted by Bryan : this time read the full text. It contains photographs of NAD+. For me, being able to see it turns it from an abstraction to a reality...

 

 

I also learned from this research that every cell has three NAD+pools and that the mitochondrial pool can fall back on the cytoplasmic pool in case of shortage. The researchers do not know how the NAD is being transported from A to B. I hope this is discovered soon, because perhaps this process, too, can perhaps be tweaked to youthful functioning?

 

SIRT1 as well as SIRT6 (as I understand it the two most important sirtuins for aging) are located in the nucleus so I expect they will use the nuclear NAD+pool. If the NAD+pool is low, as in aging, it is not exclusively the availability of NAD+ which limits SIRT activity but also the effectiveness or lack thereof of the replenishment from the cytoplasmic NAD+pool.  Just suppose someone activates SIRT1 (by taking a cold bath or supplementing resveratrol) this would use a lot of NAD+ and then SIRT6 would kind of idle until the replenishment mechanism delivers. My speculation, of course. Thoughts?

 

 

I see this situation the same way, even somewhat broader. There are several processes competing for a shrinking NAD+ pool so depending on the situation one process or another runs short with some deteriorating effect as result. All together a downward spiral...well I guess thats what aging is. So in my view filling the NAD+ pool is the basis and then ontop we can stimulate processes that in turn hopefully have repair and re-generative effects which hopefully would lead to a systematic recovery or at least stop/slow the system from sliding further.

 

Yes, and then there still is this other slightly creepy side: NAD+ destroyal. Schultz and Sinclair in this very recent article 

http://www.cell.com/...4131(16)30244-3

put the blame fair and square on CD38 and point out that quercetin and apigenin are useful inhibitors, but I think they also wonder if the age related extra activity of CD38 perhaps serves a useful health purpose.

 

Edit: punctuation improved....

 

 

Apigenin Sources: Chamomile, Ginkgo Biloba, Celery, Parsley, Wheat, Spicy Red Peppers 

Quercetin Sources: Capers, Ginkgo Biloba, Red Onions, Dock Leaf, Red Wine, Dill, 

[bluemoon]

 

Nobel Laureate Roger Kornberg is on the scientific advisory board so my guess is that ChromaDex's studies have been legit. 

 

But they haven't. Many of the studies Brian has posted look very promising but ChromaDex's "studies", at least the "published" one on a poster from April this year had a very small sample size and no controls.  That's not quality or legit IMO. 

 

That said, ChromaDex only has a license from Dartmouth to manufacture the NR, Dartmouth has the patent. They could easily take it away (if there is some legal language that this behavior is in violation of the license) and give it to someone else. I wouldn't worry about NR's reputation, it stands on its own I think.

 

 

A small sample size doesn't mean that the study is not legit. It means that it has a small sample size which is usually used to see if a larger study is worth it. 

[Tom Andre F. (ex shinobi)]

I discussed the NAD+/NADH ratio that we also have to control here http://www.longecity...e-2#entry779564

 

But since physiological concentrations of nicotinamide noncompetitively inhibit both Sir2 and SIRT1 in vitro. The degree of inhibition by nicotinamide (IC₅₀< 50 μm) is equal to or better than the most effective known synthetic inhibitors of this class of proteins. It compete with NAD+ sites http://www.jbc.org/c...pe2=tf_ipsecsha

 

And since nicotinamide is a precursor of nicotinic acid, why to not move for this last one ? as speculated here http://www.longecity...erience-thread/

[Skyguy2005]

I discussed the NAD+/NADH ratio that we also have to control here http://www.longecity...e-2#entry779564

 

But since physiological concentrations of nicotinamide noncompetitively inhibit both Sir2 and SIRT1 in vitro. The degree of inhibition by nicotinamide (IC₅₀< 50 μm) is equal to or better than the most effective known synthetic inhibitors of this class of proteins. It compete with NAD+ sites http://www.jbc.org/c...pe2=tf_ipsecsha

 

And since nicotinamide is a precursor of nicotinic acid, why to not move for this last one ? as speculated here http://www.longecity...erience-thread/

 

Personally I find Nicotinic Acid more potent than Nicotinamide Riboside. Anyway Nicotinamide: 

 

Nicotinamide-induced mitophagy: event mediated by high NAD+/NADH ratio and SIRT1 protein activation. 

http://www.jbc.org/c...7/23/19304.full

 

Nicotinamide Forestalls Pathology and Cognitive Decline in Alzheimer Mice: Evidence for Improved Neuronal Bioenergetics and Autophagy Procession

http://www.ncbi.nlm....les/PMC3596471/

 

 

Nicotinamide enhances mitochondria quality through autophagy activation in human cells. 

http://www.ncbi.nlm....ubmed/19473119 

 

So... Contradictions... 

Edited by Skyguy2005, 21 June 2016 - 05:09 PM.

[Tom Andre F. (ex shinobi)]

 

I discussed the NAD+/NADH ratio that we also have to control here http://www.longecity...e-2#entry779564

 

But since physiological concentrations of nicotinamide noncompetitively inhibit both Sir2 and SIRT1 in vitro. The degree of inhibition by nicotinamide (IC₅₀< 50 μm) is equal to or better than the most effective known synthetic inhibitors of this class of proteins. It compete with NAD+ sites http://www.jbc.org/c...pe2=tf_ipsecsha

 

And since nicotinamide is a precursor of nicotinic acid, why to not move for this last one ? as speculated here http://www.longecity...erience-thread/

 

Personally I find Nicotinic Acid more potent than Nicotinamide Riboside. Anyway Nicotinamide: 

 

Nicotinamide-induced mitophagy: event mediated by high NAD+/NADH ratio and SIRT1 protein activation. 

http://www.jbc.org/c...7/23/19304.full

 

Nicotinamide Forestalls Pathology and Cognitive Decline in Alzheimer Mice: Evidence for Improved Neuronal Bioenergetics and Autophagy Procession

http://www.ncbi.nlm....les/PMC3596471/

 

 

Nicotinamide enhances mitochondria quality through autophagy activation in human cells. 

http://www.ncbi.nlm....ubmed/19473119 

 

So... Contradictions... 

 

 

thanks skyguy,

 

I think its not contradictions, its just depend of what part of the loop take the advantage at the end. Im however concerned about it as well as the release of Nam after NAD+ consumption
 

[Smedvick]

http://www.the-japan...cle/0003030620 

Edited by Smedvick, 21 June 2016 - 07:42 PM.