LONGECITY

Nicotinamide Riboside thread moderated by the threadstarter.

This is still the Nicotinamide Riboside Current News and Updates thread we've all grown to know. 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.

This thread will continue as before. This thread was started and is supported by NR users and is a tool for those in our community investigating the topic of Nicotinamide Riboside.

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.

If we go to far off topic on an offshoot I'm going to ask that you continue that new topic on a adjacent thread when asked so as to not dilute our primary topic. Along these lines LongeCity administrators felt I should begin to moderate this thread and here we are.

Please feel free to reference our earlier posts here Nicotinamide Riboside Current News and Updates

I've created a Channel on YouTube called NAD Repletion for content related to this thread as it becomes available.

Synthesis of an oligonucleotide with a nicotinamide mononucleotide residue and its molecular recognition in DNA helices

http://pubs.rsc.org/...4a#!divAbstract

Can we use the epigenetic bioactivity of caloric restriction and phytochemicals to promote healthy ageing?

Being that the topic of Nicotinamide Riboside is directly connected to the NAD dependent sirtuin activators and this is all wrapped around epigenetic's and aging this article is a must read by those who are trying to grasp the interdependent relationship. This is an offshoot topic of NAD boosting with direct references to Nicotinamide Riboside.

http://www.researchg..._healthy_ageing

In 2011, the Centers for Disease Control and Prevention reported that half of Americans are using food supplements, intended to provide them with nutrients that they believe they consume in insufficient quantities. Dietary supplements were repeatedly said to be unnecessary if one eats a balanced diet but within the booming “silver economy”, sales of vitamins, minerals and supplements totalled nearly $23 billion in the US last year (Euro monitor International). Seventy eight “antioxidant” supplements trials including 296 707 participants were reviewed by the Cochrane Database System Review. It was concluded that beta-carotene and vitamin E supplements, instead of promoting longevity, were increasing mortality and so may high doses of vitamin A. Several nutrition interventions with or without edible phytochemicals, fasting regimens, and food supplements have now been tried to prevent the development of many different types of tumors. Most were known as antioxidants and are now repurposed because they were shown to change the epigenome. Epigenetic marks are enzymatic tags deposited on the genome which do not change the DNA sequence but change gene expression. They are reversible and epigenetic dietary interventions are thus suggested for the prevention of ageing, ageing related diseases and for breaking the vicious circle of the trans-generational epigenetic inheritance of the metabolic disorders. It is a pressing issue because more and more children are exposed to parents' obesity and are at risk of developing type 2 diabetes. Why is it relevant to propose epigenetic “Nutricures” to prevent diseases linked with ageing? To answer this question we produce this review, whose scope is to underline the importance of the nutritional contribution for a correct functioning of epigenetics. Almost all chromatin-modifying enzymes utilize co-factors, which are crucial metabolites for core metabolism pathways. Because the cellular concentrations of these metabolites fluctuate as a function of the metabolic status of the cell, the activity of most epigenetic enzymes depends on the cell metabolism and thus nutrition. Through one selected representative example, sirtuins, and their metabolic co-factor, nicotinamide, we illustrate the nutrition and epigenetic connections. Then we describe the epigenetic activities of some polyphenols. Finally we underline that with globalization there is a continuing trend changing the variety of food items that we consume. Each may have bioactive effects that may combine with additional epigenetic effects of pollutants such as pesticides. We plead likewise that because they are bioactive, “Nutricures” and food supplements should undergo better evaluation before marketing.

Short list of Parallel publications

http://www.ncbi.nlm....les/PMC3873820/

http://online.lieber...9/ars.2012.4600

http://www.clinicale.../content/7/1/33

NAD in Skin: Therapeutic Approaches for Niacin

http://www.researchg...ches_for_Niacin

Full-Text made available Oct 15, 2015

This article provides more background on the cancer fighting effects of NAD BOOSTING.

"Abstract: The maintenance and regulation of cellular NAD(P)(H ) content and its influence on cell function involves many metabolic pathways, some of which remain poorly understood. Niacin deficiency in humans, which leads to low NAD status, causes sun sensitivity in skin, indicative of deficiencies in responding to UV damage. Animal models of nia-cin deficiency demonstrate genomic instability and increased cancer development in sensitive tissues including skin. Cell culture models of niacin deficiency have allowed the identification of NAD-dependent signaling events critical in early skin carcinogenesis. Niacin restriction in immortalized keratinocytes leads to an increased expression and activity of NADPH oxidase resulting in an accumulation of ROS, providing a potential survival mechanism as has been shown to oc-cur in cancer cells. Niacin deficient keratinocytes are more sensitive to photodamage, as both poly(ADP-ribose) polym-erases and Sirtuins are inhibited by the unavailability of their substrate, NAD+, leading to unrepaired DNA damage upon photodamage and a subsequent increase in cell death. Furthermore, the identification of the nicotinic acid receptor in hu-man skin keratinocytes provides a further link to niacin’s role as a potential skin cancer prevention agent and suggests the nicotinic acid receptor as a potential target for skin cancer prevention agents. The new roles for niacin as a modulator of differentiation and photo-immune suppression and niacin status as a critical resistance factor for UV damaged skin cells are reviewed here." 

The human NAD metabolome: Functions, metabolism and compartmentalization

http://www.tandfonli...38.2015.1028612

Published online: 02 Apr 2015

Abstract "The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD+ and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intraand extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools."

Conclusions and future perspectives "Recent research has revealed the importance of the regulatory roles of NAD. In fact, some of these pathways have already been targeted for therapeutic treatments of cancer and other diseases. While impressive progress has been made over the last years with regard to NAD-dependent signaling mechanisms, some critical issues have remained unresolved. For example, NAD-dependent signaling uses up an unexpectedly large amount of NAD. Therefore, NAD biosynthesis has to be highly active and needs to be fine-tuned to the actual demands of the cell. However, except for the identification of the principal pathways of NAD biosynthesis and the corresponding enzymes, surprisingly little is known about the mechanisms regulating NAD synthesis and how it influences signaling pathways. Moreover, cellular NAD is compartmentalized in distinct membrane-coated organelles in human cells. Yet, almost nothing is known about whether (and how) NAD enters these organelles or is produced there. In this regard more detailed insights into the interconversions of NAD metabolites will likely facilitate understanding the maintenance of individual NAD pools. It appears as an intriguing possibility that the compartmentalization might represent a means to selectively influence NAD-dependent signaling events. The tremendous medical relevance as well as the broad scientific interest in this field will promote further research into these and other exciting questions regarding NAD biology."

OPINION Caloric restriction mimetics: towards a molecular definition

http://www.scribd.co...1038-2Fnrd4391#

Abstract | Caloric restriction, be it constant or intermittent, is reputed to have health-promoting and lifespan-extending effects. Caloric restriction mimetics (CRMs) are compounds that mimic the biochemical and functional effects of caloric restriction. In this Opinion article, we propose a unifying definition of CRMs as compounds that stimulate autophagy by favouring the deacetylation of cellular proteins. This deacetylation process can be achieved by three classes of compounds that deplete acetyl coenzyme A (AcCoA; the sole donor of acetyl groups), that inhibit acetyl transferases (a group of enzymes that acetylate lysine residues in an array of proteins) or that stimulate the activity of deacetylases and hence reverse the action of acetyl transferases. A unifying definition of CRMs will be important for the continued development of this class of therapeutic agents.

In a date restricted search for any "recent" publications by Leonard Guarente I found one that Google crawled 7-days ago which I hadn't seen before. I also ran a search here on longecity and could not find this study. It was . . . Published Online: December 31, 2013

SIRT1 and other sirtuins in metabolism

http://www.cell.com/...2760(13)00206-3

Boosting hepatic NAD+ prevents and reverses NAFLD in mice

http://www.nature.co...o.2015.175.html

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY   ADVANCE ONLINE PUBLICATION Nature Reviews Gastroenterology & Hepatology advance online publication 20 October 2015;  doi:10.1038/nrgastro.2015.175; doi:10.1038/nrgastro.2015.176; doi:10.1038/nrgastro.2015.177; doi:10.1038/nrgastro.2015.178RESEARCH HIGHLIGHTSIN BRIEFNAFLD

Boosting hepatic NAD+ prevents and reverses NAFLD in miceFew therapies are approved for the treatment of NAFLD. Now, researchers have shown that treatment with nicotinamide riboside, a precursor for NAD+ biosynthesis, can protect mice against the development of diet-induced NAFLD by increasing hepatic NAD+ levels. The treatment also reversed the disease in mice with pre-existing NAFLD. Nicotinamide riboside activated the hepatic mitochondrial unfolded protein response, increasing fatty acid oxidation and mitochondrial complex activity. Original article Gariani, K. et al. Eliciting the mitochondrial unfolded protein response via NAD+ repletion reverses fatty liver disease. Hepatology doi:10.1002/hep.28245

On a seperate note: There could be an interesting NAFLD correlation developing here, researchers have discovered a novel protein that is released as a consequence of fatty liver and this its believed causes pre-diabetes.  http://medicalxpress...e-diabetes.html

A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention

In the NEW ENGLAND JOURNAL of MEDICINE October 22, 2015  Vol. 373 No. 17 issue the findings of "A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention" received some new acknowledgment.

We've reviewed this study here on LongeCity on several occasions. Here are 2-posts.

http://www.longecity...e-6#entry727674

http://www.longecity...e-9#entry739280

Hopefully this issue of sun damage, NAD depletion and DNA repair gains some more momentum as a result. It would be interesting with all the new medical interest surrounding Nicotinamide Riboside and the associated ailments stemming from NAD depletion to see a study published looking at this same condition treated with NR.

October 30th update:

Since this articles appearance in the NEW ENGLAND JOURNAL of MEDICINE October 22nd it has spread like a wild fire across the internet. This (NEJM) publication is beginning to turn the tide and some physicians are now beginning to recommend nicotinamide as a safe and effective means in reducing the rates of new non-melanoma skin cancers. Sadly however the American Medical Association has still not weighed in on the topic. Lets hope they eventually get onboard with this idea of B3 cancer prevention.

Along this logical course of NAD cancer prevention a new class of NAD dependent DNA repair enzyme's have been discovered.

http://phys.org/news...dna-enzyme.html Lets hope the medical "establishment" rallies around the evidence of what's staring them in the face.

Protein acetylation in metabolism—metabolites and cofactors

Published online 27 October 2015

http://www.nature.co...o.2015.181.html

Reversible acetylation was initially described as an epigenetic mechanism regulating DNA accessibility. Since then, this process has emerged as a controller of histone and nonhistone acetylation that integrates key physiological processes such as metabolism, circadian rhythm and cell cycle, along with gene regulation in various organisms. The widespread and reversible nature of acetylation also revitalized interest in the mechanisms that regulate lysine acetyltransferases (KATs) and deacetylases (KDACs) in health and disease. Changes in protein or histone acetylation are especially relevant for many common diseases including obesity, diabetes mellitus, neurodegenerative diseases and cancer, as well as for some rare diseases such as mitochondrial diseases and lipodystrophies. In this Review, we examine the role of reversible acetylation in metabolic control and how changes in levels of metabolites or cofactors, including nicotinamide adenine dinucleotide, nicotinamide, coenzyme A, acetyl coenzyme A, zinc and butyrate and/or β-hydroxybutyrate, directly alter KAT or KDAC activity to link energy status to adaptive cellular and organismal homeostasis.

Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects

Emerging Role of Sirtuin 2 in the Regulation of Mammalian Metabolism

Pharmacological activation of AMPK prevents Drp1-mediated mitochondrial fission and alleviates endoplasmic reticulum stress-associated endothelial dysfunction.

http://www.ncbi.nlm....pubmed/26196303

 

   

Why has the Nicotinamide Riboside Current News And Updates thread been closed??? .....It is getting very difficult for some of us to follow whats actually going on with NR here these days..

 

 

ChromaDex Enters Into an Exclusive Joint Development Agreement with The Procter & Gamble Company - See more at: http://www.globenews...h.rIPeyKcH.dpuf

 

I was going to write the same thing from Day 1. This makes no sense. I look forward to Byan_S' posts but moderated by him? huh? Weird and not helpful.

Yea it was a surprise to me but I recently became a paying member and Admin felt I should be able to moderate the thread and evidently they couldn't make the first thread work. Here we are same updated content and way less views. 

The Procter & Gamble announcement I think is important to the long term survival of the company and the CVS announcement as well. I think greater sales volume might help bring the price down but as we can see from there financials they have a long way to go to get into the black.

 

 

The Procter & Gamble announcement I think is important to the long term survival of the company and the CVS announcement as well. I think greater sales volume might help bring the price down but as we can see from there financials they have a long way to go to get into the black.

I used to work for P&G and you can trust me on this........That company do not touch anything less than the best products when they buy a new brand or company worldwide......

"On August 1, 2014, P&G announced it was streamlining the company, dropping around 100 brands and concentrating on the remaining 80 brands, which produced 95 percent of the company's profits."..........They made $83 billion's worth of sales last year

........After trimming down the company the way they recently have, they wouldn't be getting into bed with Chromadex like this unless they were 100% sure that NR is the real deal.....

Yea it was a surprise to me but I recently became a paying member and Admin felt I should be able to moderate the thread and evidently they couldn't make the first thread work. Here we are same updated content and way less views. 

 

The Procter & Gamble announcement I think is important to the long term survival of the company and the CVS announcement as well. I think greater sales volume might help bring the price down but as we can see from there financials they have a long way to go to get into the black.

 

There was no reason to let the other thread die so just end this one and resume the original thread. 

Everyone this post was important.

Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects

If you can blunt NLRP3 with Nicotinamide Riboside you have a handle on the inflammatory cycle. The inflammasome is responsible for activation of inflammatory processes, need I say more.

Yea it was a surprise to me but I recently became a paying member and Admin felt I should be able to moderate the thread and evidently they couldn't make the first thread work. Here we are same updated content and way less views. 

 

The Procter & Gamble announcement I think is important to the long term survival of the company and the CVS announcement as well. I think greater sales volume might help bring the price down but as we can see from there financials they have a long way to go to get into the black.

the thread name "nicotinamide riboside" and the few people who complain every time we enlarge the topic (off topic) is the reason of the problem for me..

I see bluebrainboost are selling NR @ $1 per gram.  Seems like a good deal?  They offer independent lab testing on their products.  

Buyer beware, I've inquired about this company and as of this moment they do not appear to be reselling a verified Nicotinamide Riboside from ChromaDex. For this reason I've not mentioned them on our forums because they can not be confirmed. Last year, as a group we investigated a large number of Chinese sources, in fact today when I search for Nicotinamide Riboside News and Updates I'm overwhelmed with these Chinese advertisements. All these sources claim to have certificates of analysis (COA), paperwork. So if a Bethesda Maryland post office box at "The UPS Store" and a San Francisco California phone number gives you any sense of security be my guest. But if your going to roll the dice you are likely buying from one of these unverified Chinese sources. To date we have not identified a genuine source of NR from China. My recommendation would be to secure a sample and find a lab yourself for verification. 

I second you Bryan. There is for now no way to synthesis NR without falling under the patent owned by chromadex.

Yep.  Good point about not just blindly trusting them.  I'll see about testing to verify it is actually NR.

Either it's bunk NR (could be just niacinamide?) or someone has leaked/sold the NR-yeast biosynthesis production pipeline to another chinese lab for profit.

I came across the vendor after seeing them mentioned by lostfalco here on longecity for quality methylene blue.  

Moved from the 

if NA lowers cholesterol through NAD, why Nam doesn't have the same effect...which I've wondered, too.

We know that Sirt3 regulates lipid metabolism and we know that Nicotinamide is inhibitory towards Sirt3. 

Now I can only point to various studies that show the various feedback loops involved. 

Here is a clue to what's going on that I posted back on 18 August 2015. It has to do with the Nicotinamide SIRT3 binding pocket. Its one of those inhibitory feedback mechanisms that signals our nutritional status. So as we buildup more SIRT3 thru NAD Boosting eventually nicotinamide accumulates thru the NAD salvage cycle to modulate mitochondrial activity by binding to SIRT3. 

So if you are looking for why NA and NR work as a treatment for Hyperlipidemia and NAM doesn't this might be why. Still I haven't seen much research directed in this direction and I would like to read more before stating this as the way things are but the research suggests this might be the active mechanism in the background. 

Guys we've hijacked the personal experience thread long enough. For the Tech stuff lets post those responses on http://www.longecity...boside-curated/ because we're diluting the experience thread.

 

Yea it was a surprise to me but I recently became a paying member and Admin felt I should be able to moderate the thread and evidently they couldn't make the first thread work. Here we are same updated content and way less views. 

 

The Procter & Gamble announcement I think is important to the long term survival of the company and the CVS announcement as well. I think greater sales volume might help bring the price down but as we can see from there financials they have a long way to go to get into the black.

 

 

There was no reason to let the other thread die so just end this one and resume the original thread. 

 

Agreed. This has made following the topic far worse.

ChromaDex Lead Ingredient NIAGEN® Nicotinamide Riboside Receives New Dietary Ingredient (NDI) Status From the FDA

http://investors.chr...icle&ID=2112546

The Federal Food, Drug, and Cosmetic Act (the FD&C Act) requires that manufacturers and distributors who wish to market dietary supplements that contain "new dietary ingredients" notify the Food and Drug Administration about these ingredients. Generally, the notification must include information that is the basis on which the manufacturer or distributor has concluded that a dietary supplement containing a new dietary ingredient will reasonably be expected to be safe under the conditions of use recommended or suggested in the labeling. (See Section 413(d) of the FD&C Act, 21 U.S.C. 350b(d)).

Frank Jaksch Jr., founder and CEO of ChromaDex, commented, “Receiving NDI status from the FDA validates the safety dossier we have compiled for NIAGEN^®.  Achieving NDI status is a significant milestone given that the FDA objected approximately 88% of NDI notifications in FY 2014. NDI status opens the door for the mainstream commercialization of NIAGEN^® in dietary supplements.” 

Volume: 18 Issue 11: October 26, 2015 In the "Journal of Medicinal Food" a study we touched on last May was revisited. 

http://www.longecity...e-6#entry728015

Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes.

This reinforces the recent human study we just read:

Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects

http://www.longecity...ed/#entry750259

From these 2 studies its becoming apparent the translation of findings from animal to human subjects is proving consistent. 

In a parallel Niacin study The Effects of Niacin on Inflammation in Patients with Non-ST Elevated Acute Coronary Syndrome This study used a different inflammation marker called C-Reactive Protein (CRP). C-reactive protein -- or CRP -- appears to be correlated to heart disease risk. Inflammation (swelling) of the arteries has been linked to an increased risk of heart disease, heart attack, stroke, and peripheral arterial disease. While this study didn't alleviate this condition it did prove niacin therapy could lead to a significant decrease in hs-CRP levels. This finding provides evidence that niacin therapy may improve the vascular environment, and is compatible with previous studies evaluating the use of extended release niacin in patients with coronary disease. 

Since the B3's take different paths but suggest similar although different outcomes it would be interesting to see how Nicotinamide Riboside would fair in patients with coronary disease. Food for thought.