2255 replies to this topic

[Harkijn]

I will also order the book. Speaking of refreshing the basics, perhaps you have already come across this useful summary:

http://www.lifeexten...ifespan/Page-01

[Bryan_S]

Nicotinamide Riboside Modulates Cardiac Electrophysiology: A Novel Therapeutic Approach for Brugada Syndrome

Seminar

https://events.uiowa...90#.WOQXF1KZMcg

 

Sorry I didn't see this sooner but there is a Seminar later today at the UNIVERSITY OF IOWA.

[Bryan_S]

Commercializing longevity, Dr Lindsay Wu NASA iTech 360 competition

 

Remember the article "Scientists unveil a giant leap for anti-aging" then this was picked up and republished a multitude of times. Here we reach into its roots and we'll start with some interview transcripts.

 

http://www.abc.net.a...pts/1709_wu.pdf

 

http://www.abc.net.a...s/1709_unsw.pdf

 

"In terms of its relevance to ageing: this same molecule has been shown to restore metabolism, eyesight, mitochondrial function in mice, and a very closely related compound called nicotinamide riboside, which does the same thing, extends overall lifespan in mice. Also see this comprehensive paper on the various pathologies of old age that were treated with the same compound."

 

So regarding the playing field between Nicotinamide Mononucleotide and Nicotinamide Riboside, I extracted and highlighted the above statement to make a point, all things being equal it's going to come down to the spin machine.

 

Now if you look thru their materials you will find Professor Sinclair, and Dr. Wu are co-founders and shareholders in MetroBiotech, and a related company, Liberty Biosecurity. So let's keep in mind Prof David Sinclair is very adept at winding up the media machine and NAD repletion is the ship he wants to captain. I can see where all the misnomers are coming from, I work in the media, and these pieces are being sensationalized. We just have to realize NAD precursors appear to be drugs to the uninitiated and are being framed as such. So, to put it mildly, there has been a media blast in progress, and maybe it's been a bit overhyped.

 

So in a war between NMN and NR, it might be who can capture and hold the media's attention. MetroBiotech, and a related company, Liberty Biosecurity are at the core of much of this and driving the recent media blast.

 

Sinclair discusses http://science.scien.../6331/1312.full

 

Here is a short list of recent media:

Dr Lindsay Wu

http://www.abc.net.a...16/s4625416.htm

http://www.abc.net.a...16/s4641652.htm

http://www.abc.net.a...ng-drug/8382788

https://www.scienced...70323141340.htm

 

Prof David Sinclair

http://www.abc.net.a...ies/4485468.htm

https://hms.harvard....mysteries-aging

http://newsroom.unsw...can-be-reversed

http://www.trunews.c...als-in-6-months

https://clinicalnews...an-be-reversed/

 

 

Here is a short list of companies commercializing longevity.

http://www.nature.co...bt.3108_T1.html

Edited by Bryan_S, 05 April 2017 - 03:58 PM.
grammar

[Bryan_S]

Elysium's Motion to Dismiss

https://www.right-of...tion-to-Dismiss

 

This might seem a bit off-topic but this drama could affect us all. Some of you are keeping abreast of the lawsuit others could care less. Personally I'd like to see both companies come out of this without damaging each another or the supply chain we all enjoy today.

 

What I didn't know is Elysium grabbed some key personnel from CromaDex and it appears the employees had transmitted ChromaDex trade secrets and confidential information to Elysium without ChromaDex’s knowledge or consent. So there might be more to this than we thought. The parties are looking at a 5-10 day trial to be held in July 2018. So lets all hope they mediate this long before trial.

 

https://media.wix.co...7fdb8c66a63.pdf

 

https://www.right-of-assembly.org

[bluemoon]

  So let's keep in mind Prof David Sinclair is very adept at winding up the media machine and NAD repletion is the ship he wants to captain. I can see where all the misnomers are coming from, I work in the media, and these pieces are being sensationalized. We just have to realize NAD precursors appear to be drugs to the uninitiated and are being framed as such. So, to put it mildly, there has been a media blast in progress, and maybe it's been a bit overhyped.

 

So in a war between NMN and NR, it might be who can capture and hold the media's attention.  

 

 

 

Here is what David Sinclair said in the  March 23 Science Daily article after the writer explained that "Human trials of NMN therapy will begin within six months."

 

"This is the closest we are to a safe and effective anti-ageing drug that's perhaps only three to five years away from being on the market if the trials go well," says Sinclair, who maintains a lab at UNSW in Sydney.

 

So Sinclair is clearly saying the drug that he and his team are developing is not just NMN but is based on it and/or incorporates it. In 2014, he spoke of maybe combining NR, metformin, rapamycin, etc into one pill. That would apparently require extensive testing and FDA approval for the U.S. market. 

 

At any rate, Sinclair hasn't been misframing NMN as a drug from everything I've read and heard.

Edited by bluemoon, 05 April 2017 - 07:23 PM.

[Heisok]

If Chromadex breached the contract with the Elysium company, then there are very specific remedies either by the specific contract, or under contract law. Simple as that. There seems to be a discussion in one of your links that Elysium might not have consulted an Attorney, so they could have done something which was not "allowed" under the current contract.

First, they could now walk away from the contract without any further obligation.

Second, they could now renegotiate the agreement.

Third, they could sue for damages, and the legal system would help them recover what they were owed -- although it would take some time, and the resolution would not occur until there there was a lot more clarity about what they were in fact owed.

 

Now they also say that Elysium's CEO is a Harvard Business School graduate in Finance, and might not have known the law. What is the the CEO's position? Like some kids today say in a disingenuous apology "My Bad" Give me a break,an undergraduate in Finance from any school would be taught enough contract law that the very basic concepts involved in enforcing a contract would be obvious. Elysium tried to strong arm Chromadex into giving them what they want. Has it helped our retail pricing competition? The competition bringing prices down looks timely to me. Did Elysium hurt their business long-term with their move? Perhaps, as I can buy Niagen and Pterostilbine from many sources. 

 

Sorry for throwing my 2 cents out and following off topic.

MY BAD

 

 

Elysium's Motion to Dismiss

https://www.right-of...tion-to-Dismiss

 

This might seem a bit off-topic but this drama could affect us all. Some of you are keeping abreast of the lawsuit others could care less. Personally I'd like to see both companies come out of this without damaging each another or the supply chain we all enjoy today.

 

What I didn't know is Elysium grabbed some key personnel from CromaDex and it appears the employees had transmitted ChromaDex trade secrets and confidential information to Elysium without ChromaDex’s knowledge or consent. So there might be more to this than we thought. The parties are looking at a 5-10 day trial to be held in July 2018. So lets all hope they mediate this long before trial.

 

https://media.wix.co...7fdb8c66a63.pdf

 

https://www.right-of-assembly.org

 

 

[Heisok]

Thanks Harkijin. Some will argue that it is "only" mice, but these 2 things are what I want from life! But, Contrary to some, I will even  settle for enhanced healthspan.

 

"nicotinamide riboside, a form of vitamin B3, resulted in both increased lifespan and enhanced healthspan."

 

I will also order the book. Speaking of refreshing the basics, perhaps you have already come across this useful summary:

http://www.lifeexten...ifespan/Page-01

 

Edited by Heisok, 05 April 2017 - 08:12 PM.

[bluemoon]

  Elysium tried to strong arm Chromadex into giving them what they want. Has it helped our retail pricing competition? The competition bringing prices down looks timely to me. Did Elysium hurt their business long-term with their move? Perhaps, as I can buy Niagen and Pterostilbine from many sources. 

 

 

 

  Personally I'd like to see both companies come out of this without damaging each another or the supply chain we all enjoy today.

 

 

 

First, I'm glad Bryan_S linked to this interesting blog post. As the writer noted, we don't have enough information to know how this will play out. My suspicion when I first learned of the lawsuit and stated so on this thread was that Elysium was playing hardball and that it was doing so without much risk to its market position. 

 

Second, maybe one or both companies will be damaged in some way but the supply chain of NR wouldn't be disrupted no matter what the outcome, Even if ChromaDex went bankrupt somehow, another company would buy them out or at leas buy the patents and start selling NR itself. 

 

 

 

 

[Bryan_S]

CNIO: Centro Nacional de Investigaciones Oncológicas

 

Some researchers are leveraging their research.

 

http://www.cnio.es/a...tion Office.pdf

"Public-private partnerships are potent tools for the valorisation of research results whereby scientific knowledge gets converted into diagnostic and therapeutic products and services. Valorisation of CNIO’s research results through alliances with industry is not just about ‘ money ’, but also about the impact that can be created for the public benefit and, in particular, for cancer patients. In 2016, a project based on the  findings of CNIO scientists that boosting levels with nicotinamide riboside ( NR ) prevented and abolished aggressive tumor formation received nearly 1 Mio in funding from the MINECO Retos-Colaboración programme. The project was focussed on the development of a new NR-based therapy that could be used for Hepatocellular Carcinoma and other tumors."

 

http://www.cnio.es/a...unior Group.pdf

 

A CNIO team discovers that a derivative of vitamin B3 prevents liver cancer in mice

You guys will remember https://www.cnio.es/...-cancer-in-mice

http://www.cell.com/...4)00392-4?cc=y=

 

Edited by Bryan_S, 06 April 2017 - 12:50 AM.

[soulprogrammer]

NAD+ in DNA repair and mitochondrial maintenance

Deborah L. Croteaua , Evandro Fei Fanga , Hilde Nilsenb , and Vilhelm A. Bohra

a Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA; b Institute of Clinical Medicine, University of Oslo and Akershus University Hospital Lørenskog, Norway ARTICLE HISTORY Received 21 December 2016;

Accepted 15 January 2017 KEYWORDS Aging; DNA repair; mitochondria; NAD; sirtuins

 

http://www.tandfonli...needAccess=true

 

Is the above paper already discussed here? Seems important and similar to Sinclair's finding that NAD+ repair DNA damage, now using NR instead of NMN.

[Fafner55]

More support that a sufficient quantity of NR induces mitophagy and DNA repair.

 

"NAD+ in DNA repair and mitochondrial maintenance" (2017) http://www.tandfonline.com/doi/full/10.1080/15384101.2017.1285631

Edited by Fafner55, 07 April 2017 - 11:51 AM.

[soulprogrammer]

@Fafner, I really enjoyed reading your experiments using high doses of NR to induce mitophagy. But how do you quantify or measure mitophagy? And any update on your experiments? How do you feel now after so long your last mitophagy experiment? Any plan to conduct more experiment?

Edited by soulprogrammer, 07 April 2017 - 12:25 PM.

[Fafner55]

@Fafner, I really enjoyed reading your experiments using high doses of NR to induce mitophagy. But how do you quantify or measure mitophagy? And any update on your experiments? How do you feel now after so long your last mitophagy experiment? Any plan to conduct more experiment?

 

After reading many overly optimistic self assessments on this forum, I am hesitant to make statements that are not well supported.  That caveat said, I do feel that there are persistent benefits from my five 6 day treatments with large doses of NR to my skeletal muscle, which has responded well to light exercise. Subjectively, I haven't been this toned since my 20's.  I am 61.

[soulprogrammer]

interesting video lecture about anti-aging research

 

https://www.youtube....h?v=5zHyUI13NDg

 

and interesting crowd funding website for longevity

 

https://www.lifespan.io

 

Edited by soulprogrammer, 07 April 2017 - 02:19 PM.

[bluemoon]

 

 

After reading many overly optimistic self assessments on this forum, I am hesitant to make statements that are not well supported.  That caveat said, I do feel that there are persistent benefits from my five 6 day treatments with large doses of NR to my skeletal muscle, which has responded well to light exercise. Subjectively, I haven't been this toned since my 20's.  I am 61.

 

 

How large a dose?

[Fafner55]

 

 

 

After reading many overly optimistic self assessments on this forum, I am hesitant to make statements that are not well supported.  That caveat said, I do feel that there are persistent benefits from my five 6 day treatments with large doses of NR to my skeletal muscle, which has responded well to light exercise. Subjectively, I haven't been this toned since my 20's.  I am 61.

 

 

How large a dose?

 

 

My posts on upgrading mitochondria with NR appear on another thread, beginning at

http://www.longecity...ndpost&p=791908

 

[mrkosh1]

Here are my thoughts on the current situation.

 

1) The only way that Sinclair could produce an NMN "drug" or supplement (with NMN alone) that would be more effective at increasing NAD+ levels is if he were able to produce a modified NMN molecule that could slip through the outer cell membrane without having to be first converted to NR. Maybe I'm missing something, but I don't see a single paper about such a modified form of NMN.

 

2) If there is no special form of NMN being developed that slips through the outer cell membrane without first being converted to NR, any anti-aging "cocktail" of supplements might as well just use NR rather than NMN. For such a drug cocktail, I think the primary two gene pathways (I'm not exactly sure what to call this) that should be studied are CD38 and NQO1. For example, Sulforaphane activates NQO1 as well as R-Alpha Lipoic Acid. Due to R-Alpha Lipoic Acid having a VERY long track record and overall good safety profile (sulforaphane isn't even commonly available yet), I think a combo of NR and R-ALA should be tested in animals and humans, ASAP. If more of the spent NADH is being converted to NAD+, then the overall level of NAD+ should be higher and SIRT 1-7 and PARP should be expressed to greater degrees.

 

3) Let's pray that Sinclair doesn't somehow figure out a way to get NR restricted so that a prescription is required to obtain it. The benefits of NR seem to be so far ranging and the safey issues relatively small (I'm not saying there are none) that it should certainly be allowed as a supplement. For goodness sakes, I'd say aspirin is more dangerous than NR.

 

 

[albedo]

NAD+ in DNA repair and mitochondrial maintenance

Deborah L. Croteaua , Evandro Fei Fanga , Hilde Nilsenb , and Vilhelm A. Bohra

a Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA; b Institute of Clinical Medicine, University of Oslo and Akershus University Hospital Lørenskog, Norway ARTICLE HISTORY Received 21 December 2016;

Accepted 15 January 2017 KEYWORDS Aging; DNA repair; mitochondria; NAD; sirtuins

 

http://www.tandfonli...needAccess=true

 

Is the above paper already discussed here? Seems important and similar to Sinclair's finding that NAD+ repair DNA damage, now using NR instead of NMN.

"...To test whether increased NADC might ameliorate some of the features noted above we activate the NADC/SIRT1 pathway using 3 strategies: NADC supplementation with an NADC precursor nicotinamide riboside (NR), PARP1 inhibition with olaparib or SIRT1 activation by SRT1720. Consistently, all 3 treatments improved the mitochondrial phenotypes, and decreased PARylation..."

[Nate-2004]

Here are my thoughts on the current situation.

 

1) The only way that Sinclair could produce an NMN "drug" or supplement (with NMN alone) that would be more effective at increasing NAD+ levels is if he were able to produce a modified NMN molecule that could slip through the outer cell membrane without having to be first converted to NR. Maybe I'm missing something, but I don't see a single paper about such a modified form of NMN.

 

2) If there is no special form of NMN being developed that slips through the outer cell membrane without first being converted to NR, any anti-aging "cocktail" of supplements might as well just use NR rather than NMN. For such a drug cocktail, I think the primary two gene pathways (I'm not exactly sure what to call this) that should be studied are CD38 and NQO1. For example, Sulforaphane activates NQO1 as well as R-Alpha Lipoic Acid. Due to R-Alpha Lipoic Acid having a VERY long track record and overall good safety profile (sulforaphane isn't even commonly available yet), I think a combo of NR and R-ALA should be tested in animals and humans, ASAP. If more of the spent NADH is being converted to NAD+, then the overall level of NAD+ should be higher and SIRT 1-7 and PARP should be expressed to greater degrees.

 

3) Let's pray that Sinclair doesn't somehow figure out a way to get NR restricted so that a prescription is required to obtain it. The benefits of NR seem to be so far ranging and the safey issues relatively small (I'm not saying there are none) that it should certainly be allowed as a supplement. For goodness sakes, I'd say aspirin is more dangerous than NR.

 

What if NR is just broken down into Nicotinamide and Riboside in the gut though? Is there any solid proof that it isn't?

[MikeDC]

We know it is not because ChrimaDex's Niagen is a chloride salt of Nicotinamide Riboside in order to stablize it in water. If the broken down version works, why trying to prevent it?

[SearchHorizon]

Most likely, NR is broken down into nicotinamide and ribose in the gut. 

 

Based on various threads, I see one problem with testing NR: we don't have accurate information about a dosing protocol. To make a proper jump from mice experiments (which are scientifically sound) to humans, we need a methodical, verifiable approach. Most of the posts on the NR experience thread relates subjective "feelings."

 

Nonetheless, from what I read, people taking NR seem to experience two things: (1) alertness; and (2) "crash" or sorts after a while. I have tried the nicotinamide and ribose combination, and I have gotten the very same effect. My mom also tried the same combo, with similar results. Interestingly, after an NR crash, there appears to be improvements in her cognition and recall. 

 

What all this suggests is that (assuming NAM + ribose = NR for the moment) that it is possible to cause NAD+ or its precursors to accumulate in one's body through NR administration. Apparently, NAD+ salvage pathways do what they are supposed to do: salvage NAD+. Most likely, it is the overloading of NAD+ (or one of its precursors) that is leading to the reported NR crashes. It is not clear if NR crashes are a bad thing or a good thing. 

 

Edited by SearchHorizon, 09 April 2017 - 12:53 PM.

[MikeDC]

Most likely, NR is broken down into nicotinamide and ribose in the gut.

Based on various threads, I see one problem with testing NR: we don't have accurate information about a dosing protocol. To make a proper jump from mice experiments (which are scientifically sound) to humans, we need a methodical, verifiable approach. Most of the posts on the NR experience thread relates subjective "feelings."

Nonetheless, from what I read, people taking NR seem to experience two things: (1) alertness; and (2) "crash" or sorts after a while. I have tried the nicotinamide and ribose combination, and I have gotten the very same effect. My mom also tried the same combo, with similar results. Interestingly, after an NR crash, there appears to be improvements in her cognition and recall.

What all this suggests is that (assuming NAM + ribose = NR for the moment) that it is possible to cause NAD+ or its precursors to accumulate in one's body through NR administration. Apparently, NAD+ salvage pathways do what they are supposed to do: salvage NAD+. Most likely, it is the overloading of NAD+ (or one of its precursors) that is leading to the reported NR crashes. It is not clear if NR crashes are a bad thing or a good thing.

Two human trials have proved that 250mg can increase NAD+ significantly like 40%. Depending on the age 250 mg to 500 mg is a good range to stay with. Going much higher is asking for trouble.
The results of Niagen are not feelings. It is real hard data. You post is more like a feeling than real scientific argument.

[Nate-2004]

Most likely, NR is broken down into nicotinamide and ribose in the gut. 

 

Based on various threads, I see one problem with testing NR: we don't have accurate information about a dosing protocol. To make a proper jump from mice experiments (which are scientifically sound) to humans, we need a methodical, verifiable approach. Most of the posts on the NR experience thread relates subjective "feelings."

 

Nonetheless, from what I read, people taking NR seem to experience two things: (1) alertness; and (2) "crash" or sorts after a while. I have tried the nicotinamide and ribose combination, and I have gotten the very same effect. My mom also tried the same combo, with similar results. Interestingly, after an NR crash, there appears to be improvements in her cognition and recall. 

 

What all this suggests is that (assuming NAM + ribose = NR for the moment) that it is possible to cause NAD+ or its precursors to accumulate in one's body through NR administration. Apparently, NAD+ salvage pathways do what they are supposed to do: salvage NAD+. Most likely, it is the overloading of NAD+ (or one of its precursors) that is leading to the reported NR crashes. It is not clear if NR crashes are a bad thing or a good thing. 

 

Well from what I understand, the whole end goal is activating SIRT. Right? Not specifically NAD+, but activating SIRT and giving it their food right? If I'm understanding correctly. Mimicking the effects of fasting. If nicotinamide inhibits SIRT that's a problem. I think the question of whether it remains whole until conversion in the cell is a very important one to answer. Like, the most important one next to the question of whether SIRT is activated.

 

Also, I don't experience crashes, but then again I also don't experience all that much in terms of alertness. I do experience more "energy" and mobility whatever that means. Feelings of well being. That's not science though. I don't care if it changes my feelings, I just care if it stops or slows aging via the mechanisms theorized.

Edited by Nate-2004, 09 April 2017 - 02:13 PM.

[MikeDC]

Can you guys at least study some before posting? Studies has shown that Nicotinamide Riboside enters the cells as whole. Sirt1 and other longecity genes are over expressed.

[Harkijn]

Most likely, NR is broken down into nicotinamide and ribose in the gut. 

 

Based on various threads, I see one problem with testing NR: we don't have accurate information about a dosing protocol. To make a proper jump from mice experiments (which are scientifically sound) to humans, we need a methodical, verifiable approach. Most of the posts on the NR experience thread relates subjective "feelings."

 

Nonetheless, from what I read, people taking NR seem to experience two things: (1) alertness; and (2) "crash" or sorts after a while. I have tried the nicotinamide and ribose combination, and I have gotten the very same effect. My mom also tried the same combo, with similar results. Interestingly, after an NR crash, there appears to be improvements in her cognition and recall. 

 

What all this suggests is that (assuming NAM + ribose = NR for the moment) that it is possible to cause NAD+ or its precursors to accumulate in one's body through NR administration. Apparently, NAD+ salvage pathways do what they are supposed to do: salvage NAD+. Most likely, it is the overloading of NAD+ (or one of its precursors) that is leading to the reported NR crashes. It is not clear if NR crashes are a bad thing or a good thing. 

Only very very few people have posted about a 'crash'. And this crash may be as subjective as their feelings of wellbeing. So let's not worry overmuch about too much NAD+ because too little NAD+ is the real problem. Here you find a clear, recent overview:

http://www.cell.com/...4131(15)00266-1

Like you I am looking forward to reliable data on human NRdosing! Some info on that can be found here, though many studies used mice that are not comparable to normal wild type mice:

http://www.timelessl...osing-overview/

[MikeDC]

I have been taking 500 mg a day and have not crashed. But too much Nicotinamide in the body is a concern, so over dosing NR is not advised. People should increase dose gradually to detect any side effects from over dosing. Always start from 125 mg.

[soulprogrammer]

I also have not experience any crash, so as my sister. The crash is probably due to certain people who has some defect in certain gene. There are many papers that state NR enters our bloodstream as a whole, not as NAM+ribose. if NR becomes NAM+ribose, then NR will have exactly the same effect as NAM, which of course is totally not the case.

 

I don't understand why people still want to say NR is NAM+ribose where the fact says otherwise. IF they really think so, just take NAM+ribose and forget about NR. This is a thread about NR. Please start a thread that says "NR is just NAM+ribose", you will find your interested readers there. Here we are only keen on NR!!!

[MikeDC]

I also have not experience any crash, so as my sister. The crash is probably due to certain people who has some defect in certain gene. There are many papers that state NR enters our bloodstream as a whole, not as NAM+ribose. if NR becomes NAM+ribose, then NR will have exactly the same effect as NAM, which of course is totally not the case.

I don't understand why people still want to say NR is NAM+ribose where the fact says otherwise. IF they really think so, just take NAM+ribose and forget about NR. This is a thread about NR. Please start a thread that says "NR is just NAM+ribose", you will find your interested readers there. Here we are only keen on NR!!!

Some people will not accept reality. Niagen works so perfectly that It is a miracle.

[bluemoon]

 

 

 

 

My posts on upgrading mitochondria with NR appear on another thread, beginning at

http://www.longecity...ndpost&p=791908

 

 

Thanks for linking to your self studies. I saw that 'niner' thought dividing the dose by 12 would be in line with the mouse study due to differences in metabolism. I'm curious if you tried a similar study at 4000 mg/12 = 333 mg or maybe 500 mg?  

[midas]

Uhhhhhhhhhhhhhhhhh because you can't patent each individually and sell them as a proprietary blend?

 

MONEY

 

 

NR is not patented, the manufacturing process is...