2255 replies to this topic

[stefan_001]

These off-topic and other ratings are getting boring and are demotivating. I am going to spend my "off-topic" time elsewhere for a while. Have fun, I will limit myself to reading.

Edited by stefan_001, 11 November 2016 - 03:22 PM.

[Harkijn]

Brian, can you perhaps persuade Longecity to give authorization for  the off-topic rating exclusively to you in your function as moderator? That would necessitate all users who think a post irrelevant to make themselves known, explain  and refer to a thread where they think it should have been posted. The way this rating is used at present is simply extremely unkind and discouraging.

[Thell]

Brian, can you perhaps persuade Longecity to give authorization for  the off-topic rating exclusively to you in your function as moderator? That would necessitate all users who think a post irrelevant to make themselves known, explain  and refer to a thread where they think it should have been posted. The way this rating is used at present is simply extremely unkind and discouraging.

 

I believe the quality of this thread has gone downhill recently. So do others if the ratings are to be believed. In Bryan's own words from just a few days ago '... people please rank the posts.' If there is any question as to what the topic is then I highlight a few points from the original post.

 

1. This thread encompasses the latest articles on Nicotinamide Riboside, NAD boosting, clinical updates and emerging studies all aimed at the medical uses of the NAD precursors.
2. In the past we've seen some complaints as we explore and discuss some of the parallel topics and your voices have been noted. Personally I'm not totally Nicotinamide Riboside centric and comments on related current and past NAD precursor studies are welcome but lets keep the topic conversation along the lines of NAD boosting to be true to our readers. Being that we've accumulated a treasure trove of NAD medical articles and studies over the last year many visit this thread to find the latest released publications on this topic and we'll stay true to that focus.

Personally, I take this to mean that the posts not adding to this are indeed off-topic. If no one speaks up by using the ratings then things will end up like in the last thread and if people need to 'qualify' the ratings they give with yet another off-topic post saying the mentioned post is off topic then things get out of hand and we still end up with a thread that doesn't follow the topic.

 

Having said that, this post itself is off-topic (for which I apologize) and I'd mark it as such or I'd rate as agree/disagree and move on happily , knowing I've given feedback to future readers/posters without filling up the inbox of the 77 other followers of this thread. 

[Harkijn]

 

Brian, can you perhaps persuade Longecity to give authorization for  the off-topic rating exclusively to you in your function as moderator? That would necessitate all users who think a post irrelevant to make themselves known, explain  and refer to a thread where they think it should have been posted. The way this rating is used at present is simply extremely unkind and discouraging.

 

I believe the quality of this thread has gone downhill recently. So do others if the ratings are to be believed. 

 

Why believe the ratings? That's the point here! For the rest I agree: posts should be relevant to the topic However if people want to preserve the quality of the thread why don't they come out and make their case? Bryan is perfectly able to decide what is off-topic and to refer peolpe to other threads.

 

 

 

 

 

[Kevnzworld]

SENS have weighed in on NR supplementation with their own analysis of the mouse research on NMN (Posted 23rd November 2015):

http://sens.org/rese...ng-mitochondria

Thanks for finding that. I agree Michael Rae only looked at NR thru the lens of Sinclair's research and possibly only NR venders who have been plagiarizing David Sinclair's work on NMN. Its time to unhitch the Sinclair's caboose form the Nicotinamide Riboside train, its an utter embarrassment.

Rae OMITTED or Failed to find research by:
Anthony A. Sauve WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY
Charles Brenner University of Iowa and Dartmouth
Leonard Guarente Massachusetts Institute of Technology
and a host of many other key researchers and their postdoctoral students who are to numerous to mention. In fact David Sinclair is one of Leonard Guarente's postdoctoral researchers.

Here are some basic NR searches based on:
|| Cornell University || Dartmouth || University of Iowa || Massachusetts Institute of Technology || Washington University || University of Copenhagen || National Institutes of Health || Scripps || Spinal Cord || Neuron || Cockayne Syndrome || Mitochondria || Biogenesis || Sirtuin SIRT || Cancer || Once you know the players or have read one paper and have pulled some keywords you turn up more study reading than you could cover in a week.

Since David Sinclair is associated with Harvard I wanted to see if their NR research is being confused with David Sinclair's work by our current venders. See || Harvard ||

For the most part I'd say no, however I do see some non-study articles mentioning both NR and Harvard and if you poke deeper into the links there is some vague vender associations. One term has bothered me which I think is misleading "fountain of youth" But I don't think David Sinclair ever mentioned it in describing Nicotinamide Riboside or promoted it as such. So to find an association to these claims I ran || David Sinclair Harvard with fountain of youth. || to see what vender turned up. I found one who was almost exclusive in these claims but I refrain from mentioning them because I've challenged them on their claims before. So the association of "fountain of youth," "David Sinclair," AND "Harvard" with Nicotinamide Riboside is the domain of one vender in particular. Sure wish my brand of NR did all that. This is the sort of stuff that warps the public perception and the expectation of the NR molecule. Its over the top marketing period. "Niagen Origins Niagen is a nutritional supplement that was discovered as recently as late 2013 by Dr. David Sinclair of Harvard Medical School whilst performing clinical research on mice." This is so far from the truth it makes me laugh and it gets reproduced as a cut and past misnomer time after time. What isn't true confuses the public and this is at the core of the SENS NR review and in the end ChromaDex isn't policing there own venders by letting this LIE continue.

There is the possibility that Sinclair is allowing the the use of his name in the NR advertising in which case this doesn't bother him but a false hood is still growing.

I just hate when reviewers examine and comment on a field of research with only a cursory glance into what first appeared in their google browser. In this case an advertiser who has jumbled up the facts and has portrayed it origins incorrectly. From his review its obvious Michael Rae either didn't bother to find more research pointing to Nicotinamide Riboside than David Sinclair's work on NMN, Niagen vender claims or he intentionally omitted a plethora of NR research to reach his conclusion. Now I don't believe he omitted anything intentionally but I'd have to grade his review on the NR topic as an F for his research effort. I'm speculating he found the aforementioned vender claims and immediately called foul without checking further. I'm kind of disappointed to hear he is a research assistant at the SENS Foundation because its obvious he isn't an unbiased researcher and was quickly opinionated and stopped reading.

This is why I have such a strong opinion about not reading venders marketing claims. Sure they condense a lot of material and you get it fast but they do it in a loose fashion. Who are you going to believe the guy with a Bachelor of Arts in Marketing or someone from our esteemed list above?

I just did an open Nicotinamide Riboside search and could see your standard BS vender claims but there was one bonafide NIH research paper that appeared on page one. I repeated the search with one extra word to exclude the venders "nicotinamide riboside scholarly" and that cleaned up the whole picture.

Some one should point him here. LOL
http://www.longecity...ws-and-updates/

Michael Rae is biased. He only believes in CR as an anti aging protocol. He dismisses research that doesn't fit his world view.
The study that showed that diabetic people on Metformin outlived non diabetics being one example.
He has not read or studied the research on NR/NAD .

[Kevnzworld]

I've been a long time lurker on this thread, I get email updates for every post and I've followed this topic closely.
I want to give Kudo's to Bryan. What he's doing isn't easy. I for one get annoyed with those that continually try to hijack the thread with their own pet topics. He's done a fair and necessary job as moderator.
Start your own thread topic f you don't like Bryan's focus.
I've been taking 500 mg per day in divided doses. I altered my intake to 250mg twice a day after watching Bryan's interview.
Ok, all that being said I'll go back to reading to the updates unless I have something useful to add......

[stefan_001]

I've been a long time lurker on this thread, I get email updates for every post and I've followed this topic closely.
I want to give Kudo's to Bryan. What he's doing isn't easy. I for one get annoyed with those that continually try to hijack the thread with their own pet topics. He's done a fair and necessary job as moderator.
Start your own thread topic f you don't like Bryan's focus.
I've been taking 500 mg per day in divided doses. I altered my intake to 250mg twice a day after watching Bryan's interview.
Ok, all that being said I'll go back to reading to the updates unless I have something useful to add......

 

I said I would take a break from this thread but this one I cannot really let go past. So you are lurking, dont contribute to the research, hypothesis making or trying to formulate a conclusion but yet seem to assume the right to be annoyed about people that contribute items you dont like? Wow it really seems I made the correct conclusion to stop spending time on this.

[tunt01]

Michael Rae is biased. He only believes in CR as an anti aging protocol. He dismisses research that doesn't fit his world view.

The study that showed that diabetic people on Metformin outlived non diabetics being one example.
He has not read or studied the research on NR/NAD .

 

 

 

Michael Rae is certainly very opinionated.  He has a very strong view of CR vs. "everything else", but he seems pretty data driven.  His opinions aren't without merit.  In a message forum full of incomplete information and an Internet full of hucksters pushing supplements, I think his thought process is excellent, even if he seems somewhat close minded on non-CR interventions given the high threshold of "proof" he seems to require.

 

 

That metformin study has been called into question for its statistical validity and Michael Rae noted this here.

 

 

Michael Rae has written on the NR/NAD phenomenon and you can read some of his (dated) remarks here.  It'd be interesting to see if he had updated thoughts and was following some of the more recent publications like Zhang, Auwerx (2016), et. al. that seem to indicate life extension properties.

 

 

Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., & Luan, P. et al. (2016). NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science, 352(6292), 1436-1443. doi:10.1126/science.aaf2693

[Bryan_S]

Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration

http://onlinelibrary.../hep.28912/full

Authors

Sarmistha Mukherjee,

Karthikeyani Chellappa,

Andrea Moffitt,

Joan Ndungu,

Ryan W. Dellinger,

James G. Davis,

Beamon Agarwal,

Joseph A. Baur

Accepted manuscript online: 3 November 2016Full publication history

DOI: 10.1002/hep.28912View/save citation

Cited by: 0 articlesCitation tools

Abstract

 

The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. To distinguish the role of hepatocyte NAD levels from any systemic effects of NR, we generated mice overexpressing Nicotinamide phosphoribosyltransferase (Nampt), a rate-limiting enzyme for NAD synthesis, specifically in the liver. Nampt overexpressing mice were mildly hyperglycemic at baseline and, similarly to the mice treated with NR, exhibited enhanced liver regeneration and reduced steatosis following partial hepatectomy. Conversely, mice lacking Nampt in hepatocytes exhibited impaired regenerative capacity that was completely rescued by administering NR.

 

Conclusion: NAD availability is limiting during liver regeneration and supplementation with precursors such as NR may be therapeutic in settings of acute liver injury.

[Harkijn]

 

Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration

http://onlinelibrary.../hep.28912/full

Authors

Sarmistha Mukherjee,

Karthikeyani Chellappa,

Andrea Moffitt,

Joan Ndungu,

Ryan W. Dellinger,

James G. Davis,

Beamon Agarwal,

Joseph A. Baur

Accepted manuscript online: 3 November 2016Full publication history

DOI: 10.1002/hep.28912View/save citation

Cited by: 0 articlesCitation tools

Abstract

 

The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. To distinguish the role of hepatocyte NAD levels from any systemic effects of NR, we generated mice overexpressing Nicotinamide phosphoribosyltransferase (Nampt), a rate-limiting enzyme for NAD synthesis, specifically in the liver. Nampt overexpressing mice were mildly hyperglycemic at baseline and, similarly to the mice treated with NR, exhibited enhanced liver regeneration and reduced steatosis following partial hepatectomy. Conversely, mice lacking Nampt in hepatocytes exhibited impaired regenerative capacity that was completely rescued by administering NR.

 

Conclusion: NAD availability is limiting during liver regeneration and supplementation with precursors such as NR may be therapeutic in settings of acute liver injury.

 

Also take a look at the extrapolation to human use by the Timeless Life website. Those who are hoping for age reversal (as against longevity) may find his dosage calculation useful.

Edited by harkijn, 11 November 2016 - 07:30 PM.

[Bryan_S]

ChromaDex Announces the Results of Pre-IND meeting for Nicotinamide Riboside for Cockayne Syndrome

https://globenewswir...e-Syndrome.html

 

 

http://investors.chr...rol-newsarticle

Edited by Bryan_S, 12 November 2016 - 05:28 PM.

[Kevnzworld]

I've been a long time lurker on this thread, I get email updates for every post and I've followed this topic closely.
I want to give Kudo's to Bryan. What he's doing isn't easy. I for one get annoyed with those that continually try to hijack the thread with their own pet topics. He's done a fair and necessary job as moderator.
Start your own thread topic f you don't like Bryan's focus.
I've been taking 500 mg per day in divided doses. I altered my intake to 250mg twice a day after watching Bryan's interview.
Ok, all that being said I'll go back to reading to the updates unless I have something useful to add......

I said I would take a break from this thread but this one I cannot really let go past. So you are lurking, dont contribute to the research, hypothesis making or trying to formulate a conclusion but yet seem to assume the right to be annoyed about people that contribute items you dont like? Wow it really seems I made the correct conclusion to stop spending time on this.

I read every post ( lurker ) because I follow this thread. Every post shows up in my email inbox. I don't like my time wasted with off topic posts ( like this one ). I don't personally contribute unless I have something informative to add. That doesn't make my opinion immaterial.

[Iporuru]

http://www.freepaten...16/0317420.html

 

"It is known that niacinamide (CAS No. 98-92-0) and nicotinamide riboside, which are both NAD+ precursors, can be used to modulate the NAD+ pathway to treat cells for some of the symptoms commonly associated with aging. It is also known that niacinamide can improve the appearance of sallow skin by suppressing glycation. Prior to the present invention, it was not known whether nicotinamide riboside could provide a similar benefit, since it has been demonstrated that niacinamide and nicotinamide riboside impact skin biochemistry differently, namely biochemical pathways related to skin pigmentation, ARE modulation and glycolytic ATP depletion. It has now been discovered that nicotinamide riboside can suppress glycation in skin and reduce yellowness associated with glycation. Surprisingly, it has also been discovered that nicotinamide riboside can reduce skin yellowness in skin exposed to environmental stressors such as cigarette smoke. Without intending to be bound by theory, it is believed that nicotinamide riboside blocks an inflammatory pathway linked to the release of the High Mobility Group Box 1 (“HMGB 1”) in keratinocytes exposed to environmental stressors. HMGB 1 release is known to recruit neutrophils, which in turn are known to release factors such as reactive oxygen species, which participate in the sugar rearrangement/crosslinking reaction associated with glycation."

[Harkijn]

 

I read every post ( lurker ) because I follow this thread. Every post shows up in my email inbox. I don't like my time wasted with off topic posts ( like this one ). I don't personally contribute unless I have something informative to add. 

 

 

 

I do not want to prolong this altercation and the following is sincere advice. I agree that notifications can build up stress.  Therefore in our profiles we can adjust the notification options to, for instance, daily.

[albedo]

Can possibly add to the discussion on cancer (see a couple of pages before this one):

 

"Some tumor cells are known to have a higher capability to synthesize NAD, so we were concerned that giving NMN might increase cancer incidence," Imai said. "But we have not seen any differences in cancer rates between the groups."

https://www.scienced...61027122047.htm

[albedo]

 

Jobs / Job post

Post-doc/Associate Specialist - NAD+ Metabolism

PostDoc Position

Posted on 04 Nov 2016

https://www.research...-NAD_Metabolism

 

 

http://www.universit...nne-switzerland

 

 

Interesting Bryan. I am sure you and others are aware Nestlè (and its branch NIHS) is between the sponsors of the LISP lab of Prof. Auwerx at EPFL which I am following. I am sure you know he was awarded the Marcel Benoist prize which is considered kind of Swiss Nobel Prize. I was at the award ceremony and had a chat with some of the folks;  felt both the momentum and the scientific production is pretty high. In his slides he quoted both the Canto et al work published in Cell on NR and the more recent work on Urolithin A.

[bluemoon]

Any idea what kind of product that Nestle would put NR into? I just read on wiki that they also make medical food. I've wondered the same thing about P&G. 

[Bryan_S]

 

A vitamin could help treat Duchenne muscular dystrophy

http://actu.epfl.ch/...muscular-dystr/

 

NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation

http://stm.sciencema.../8/361/361ra139

 

I didn't see much interest in this publication when albedo and I reviewed it but here is a recent followup article that breaks it down into bit sized pieces.

 

A Vitamin Could Help Treat Duchenne Muscular Dystrophy

Last updated Nov. 14, 2016

http://www.dovemed.c...ular-dystrophy/

"Reversing course with a vitamin: nicotinamide riboside successfully tested on animals"

 

THE MENZIES LAB

Metabolic Diseases and Aging

http://keirmenziesla...ular-dystrophy/

Selected Publications: http://keirmenzieslab.com/research/

Interesting list of NR/NAD/SIRT publications this group is associated with.

Edited by Bryan_S, 15 November 2016 - 03:13 PM.
THE MENSES LAB added

[Bryan_S]

Thesis defense Thursday 1 December 2016 17:00 BCH 1103

New optical tools for non-invasive imaging and quantification of glucose and nicotinamide riboside in living cells and animals

By Aleksandra KONOVALOVA

 

Thesis director : Prof. E. Dubikovskaya

Chemistry and Chemical Engineering doctoral program.

Thesis 7139

 

Accessibility General public

 

Admittance Free

 

In searching ÉCOLE POLYTECHNIQUE FÉDÉRALE DE LAUSANNE EPFL for the thesis I found they've filed a few studies I hadn't seen on nicotinamide riboside. So we have another research source. https://search.epfl....e&origin=header

 

One video also turned up thru their search engine (in French).

http://www.latele.ch/play?i=59670

Une vitamine qui empêche le vieillissement

SCIENCES - 11/05/16

Une vitamine qui empêche le vieillissement des organes : c’est la découverte faite par des chercheurs de l’EPFL. La nicotinamide riboside pourrait donc permettre de vivre mieux et plus longtemps.

[midas]

"Says FDA has indicated it will consider a fast track designation for Nicotinamide Riboside at time of IND submission" (Nicotinamide Riboside for cockayne syndrome)

 

http://www.reuters.c...e/idUSFWN1DC0VQ

 

-----------------------------------------------------------------------------------------------------------------------------

 

Proctor and Gamble file for patent...

 

http://www.freepaten...16/0317419.html

 

-----------------------------------------------------------------------------------------------------------------------------

[Oakman]

...

 

Proctor and Gamble file for patent...

 

http://www.freepaten...16/0317419.html

 

-----------------------------------------------------------------------------------------------------------------------------

 

Briefly read that application and wow, can they really patent so broadly? They cover virtually any topical formulation of NR and other substances possible, in any amount, for any period of time. They also talk about oral supplementation along with the topical. Not sure, but can that be part of the patent as well? Hopefully not, or everyone else selling NR is going to be left high and dry.

 

Anyone a patent expert?

[HappyPaul]

 

...

 

Proctor and Gamble file for patent...

 

http://www.freepaten...16/0317419.html

 

-----------------------------------------------------------------------------------------------------------------------------

 

Briefly read that application and wow, can they really patent so broadly? They cover virtually any topical formulation of NR and other substances possible, in any amount, for any period of time. They also talk about oral supplementation along with the topical. Not sure, but can that be part of the patent as well? Hopefully not, or everyone else selling NR is going to be left high and dry.

 

Anyone a patent expert?

 

I'm not an expert but I believe there are patent applications preceding this dealing with skin.  The patent I am truly interested in is if Cromadex has one in the drug pipeline for NR treating Neuropathy.  I think they do but not 100% sure.  If this evolves into an drug fighting Neuropothy which is so prevalent with type II diabetes in the US, we are talking billions if not tens of billions. 

[Bryan_S]

 

Proctor and Gamble file for patent...

 

http://www.freepaten...16/0317419.html

 

 

Great find! At the moment NR is only stable as a salt. Do we see a water or emulsive base for NR yet? When this happens watch out. 

[HappyPaul]

For just P&G and NR 24 hits

 

http://www.freepaten...mit=&patents=on

 

For just NR 440 hits 

 

http://www.freepaten...mit=&patents=on

 

 

 

[Nate-2004]

 

 

Proctor and Gamble file for patent...

 

http://www.freepaten...16/0317419.html

 

 

Great find! At the moment NR is only stable as a salt. Do we see a water or emulsive base for NR yet? When this happens watch out. 

 

 

Crossing fingers. The stability degrades after about 6 hrs right? I assume this degrades into nicotinamide and ribose? 

 

I've been using it topically but have to mix it before each application so that it's stable. You can do this with hyaluronic acid water based gel or Cerave lotion which I think is mostly water based.

 

As for patents. I hate them with a passion.

Edited by Nate-2004, 16 November 2016 - 06:51 PM.

[HappyPaul]

This one from P&G published Nov 10 is just NR http://www.freepaten...16178945A1.html

 

WIPO Patent Application WO/2016/178945

Kind Code:

A1

Abstract:

A cosmetic method for reducing glycation rate in skin by topically applying a cosmetic composition that includes an effective amount of nicotinamide riboside to a target portion of skin during a treatment period. The treatment period is sufficient for the nicotinamide ribosidecontaining composition to improve the appearance of sallow-looking skin caused by glycation. In particular, the method enables a reduction in skin yellowness related to glycation.

 

[lost69]

 

 

 

Proctor and Gamble file for patent...

 

http://www.freepaten...16/0317419.html

 

 

Great find! At the moment NR is only stable as a salt. Do we see a water or emulsive base for NR yet? When this happens watch out. 

 

 

Crossing fingers. The stability degrades after about 6 hrs right? I assume this degrades into nicotinamide and ribose? 

 

I've been using it topically but have to mix it before each application so that it's stable. You can do this with hyaluronic acid water based gel or Cerave lotion which I think is mostly water based.

 

As for patents. I hate them with a passion.

 

 

does this work on skin appearance//color?how many 100mg pills do you mix in Cerave lotion and how do you mix?

thanks

[Oakman]

This >  https://patentscope....=PCTDescription

 

describes just about everything in detail related to concocting NR topical compositions (except as noted in the P&G patent of preserving them).

 

And finally (to me anyway) it describes just what good pterostilbene combined with NR is good for, among several other compounds it can be combined with for various purposes.

 

Time to get out the old test tubes and play mad scientist         

 

 

[StanG]

I wonder if supplements like NR in combination with others mentioned in P&G's patent have some of the same benefit to skin cells when taken orally as I already do? Any thoughts?

[Iporuru]

NAD+ supplementation normalises central carbon metabolism in skeletal muscle: a mechanistic insight into the energetic consequences of age-related NAD+ decline

http://www.endocrine.../ea0044P187.htm

 

 

Mechanisms of ageing metabolic decline revealed by targeted metabolomics and energy metabolism in NAD+ depleted skeletal muscle

http://www.endocrine.../ea0044P189.htm