471 replies to this topic

[Bryan_S]

Design and synthesis of stable Nicotinamide Riboside analogues with potential therapeutic application

 

http://www.findaphd....D=55285&LID=127

 

PhD studentships - University of Birmingham

http://www.birmingha...hips/index.aspx

 

So if your looking for a postgraduate study program in the UK we've found you one. And for those of you live in the UK here is another developing focal point for NAD research.

[Bryan_S]

Increasing NAD+ availability in skeletal muscle to augment energy metabolism

 

http://www.endocrine...ea0037ep389.htm

 

http://www.endocrine...389_eposter.pdf

Edited by Bryan_S, 25 May 2015 - 01:33 AM.

[Bryan_S]

Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model

 

http://paperity.org/...-deficits-in-an

 

 

http://www.ncbi.nlm....les/PMC4358858/

[Bryan_S]

Neuronal death induced by misfolded prion protein is due to NAD+ depletion and can be relieved in vitro and in vivo by NAD+ replenishment

 

http://www.ncbi.nlm....pubmed/25678560

 

http://brain.oxfordj...10/brain.awv002

 

 

[ceridwen]

How much would a human need to take? Would it have to be intra nasal? and how would it have to be administered if I was to take it properly?

[Bryan_S]

ChromaDex's (CDXC) CEO Frank Jaksch on Q1 2015 Results

http://seekingalpha....call-transcript

 

For those wanting some insight on where ChromaDex is taking its NAD precursor in the world marketplace. 

 

I used comments from this transcript to look for some new "Key Word" searches.

 

As it turns out NAD depletion was a term used often in the ChromaDex investor meeting and it's a broad term frequently used by researchers to depict this newly discovered disease condition.

 

Here are 2 recent publications related to this condition.

 

Predicted Role of NAD Utilization in the Control of Circadian Rhythms during DNA Damage Response

http://www.ncbi.nlm....pubmed/26020938

 

http://journals.plos...al.pcbi.1004144

 

Mitochondrial Depletion Could Underlie the Energy Problems in Chronic Fatigue Syndrome

http://www.cortjohns...tigue-syndrome/

 

These search results were just the "recent" tip of the iceberg and generated pages of results. For those of you keeping up with the latest findings on "NAD augmentation" or "NAD supplementation" then you will find much/much more to round out this topic by searching for "NAD depletion" because this now becoming a recognized disease condition.

Edited by Bryan_S, 29 May 2015 - 04:08 PM.

[Asor]

my google alerts blew up today from this new research on mitochondrial damage related to aging, seems interesting, especially this part:

 

"The research, published this month in the prestigious journal Nature’s
‘Scientific Reports’, looked at the function of the mitochondria in human fibroblast cell lines
derived from young people (ranging in age from a fetus to a 12 year old) and elderly people
(ranging in age from 80-97 years old). The researchers compared the mitochondrial
respiration and the amount of DNA damage in the mitochondria of the two groups,
expecting respiration to be reduced and DNA damage to be increased in the cells from the
elderly group. While the elderly group had reduced respiration, in accordance with the
current theory, there was, however, no difference in the amount of DNA damage between
the elderly and young groups of cells. This led the researchers to propose that another form
of genetic regulation, epigenetic regulation, may be responsible for the age-associated
effects seen in the mitochondria."

...

 

"The researchers then looked for genes that might be controlled epigenetically resulting in
these age-associated mitochondrial defects. Two genes that regulate glycine production in
mitochondria, CGAT and SHMT2, were found. The researchers showed that by changing the
regulation of these genes, they could induce defects or restore mitochondrial function in the
fibroblast cell lines. In a compelling finding, the addition of glycine for 10 days to the culture
medium of the 97 year old fibroblast cell line restored its respiratory function. This suggests
that glycine treatment can reverse the age-associated respiration defects in the elderly
human fibroblasts."

 

http://www.alphagali...&CultureCode=en

 

 

 

 

[mikeinnaples]

I think this is still on topic, mostly.

 

Glycine metabolism involves NAD+ and I am kind of curious what impact supplementing it would have on those of use striving to increase NAD+ via NR and other methods.

 

 

[Kevnzworld]

I try to check this thread often, but I have been traveling recently.
Correct me if I'm wrong. Chromadex completed a pharmakinetics study on NR sometime in the fall of 2014. The study was subsequently submitted for peer review and publication. Chromadex alluded to it in December claiming NR supplementation efficacy in raising NAD levels.
It's now June 2015 and we've heard nothing. We still have no evidence that oral administration of NR raises NAD levels, and if so how much, and for how long.
Am I the only one that thinks that this is odd? Why wouldn't Chromadex use the results of this study to advise what the appropriate administration of NR is? How much, and how often?

[Bryan_S]

Study: Vitamin B3 May Help Prevent Certain Skin Cancers

http://abcnews.go.co...ancers-31024391

 

Guess this will be no surprise to this thread. It is at least encouraging that the DNA repair aspects of boosting NAD are being documented. 

 

http://www.nbcnews.c...er-risk-n358446

 

Obviously this benefit isn't confined to only the skin. 

 

As you were all aware this article was released prior to the American Society of Clinical Oncology 2015 meeting and now that the meeting has concluded we can tease out the details. See Link https://am.asco.org/...ancer-formation

http://meetinglibrar...tent/149209-156

 

If someone could post the full study text this would be appreciated.

 

I don't think the importance of these results should be understated. If these findings are true and I'm not suggesting otherwise, the health savings alone in the treatment of Non-Melanoma Skin Cancers is going to be enormous.

 

Related Reading:

http://www.ncbi.nlm....les/PMC4065271/

http://www.onclive.c...se-at-High-Risk

http://onlinelibrary...99da692ae1ee471

 

As we comb thru the research it becomes obvious the connection to DNA repair has been previously recognized.  In previous studies, nicotinamide has been shown to enhance DNA repair after UV exposure and reduce UV immunosuppression.

See http://carcin.oxford.../34/5/1144.long

http://www.ncbi.nlm....les/PMC4319842/

http://www.hindawi.c...na/2010/157591/

 

I think this study represents the low hanging fruit however. Here we have a clear connection to an agent that promotes DNA repair. We have a study group predisposed to easily recognizable and reoccurring skin cancers. The cost of treatment per patient for this study was relatively low at under $10 per month. I have to tip my hat to the researchers for setting this study up but it now needs to be correlated to other cancer maladies. I'm sure this point hasn't been lost but it stands to reason this treatment represents an entire system response, not just repairing and protecting the cells of the skin. I think if this study group included a much larger number of people you would notice some statistically significant reductions in other less frequent cancers as well.  

 

What I find amusing is "the supplementation of (Nam) does not seem so effective in elevating cellular NAD contents beyond the basal level" study Revollo, J. R., Grimm, A. A., and Imai, S. (2004) J. Biol. Chem. 279, 50754–50763 What (Nam) it has going for it is its cheap and has been well studied since the 1940's and has been proven to be safe. Another amusing tidbit "Nicotinamide protects against ethanol-induced apoptotic neurodegeneration in the developing mouse brain." So if you ignore all the other reasons to take (Nam) maybe combating the deleterious effects of ethanol can persuade you, if you indulge in such activities. This alone is reason enough to start this regiment. 

 

So if Nicotinamide AKA Niacinamide does not seem effective at elevating cellular NAD but it's still generating measurable statistical results, what could we expect by utilizing a more potent bioactive NAD precursor such as Nicotinamide Riboside? And incidentally (NR) eventually produces Nam after becoming NMN and NAD in the NAD salvage cycle, so we get a doubled utilization from a single compound.

 

[Bryan_S]

I try to check this thread often, but I have been traveling recently.
Correct me if I'm wrong. Chromadex completed a pharmakinetics study on NR sometime in the fall of 2014. The study was subsequently submitted for peer review and publication. Chromadex alluded to it in December claiming NR supplementation efficacy in raising NAD levels.
It's now June 2015 and we've heard nothing. We still have no evidence that oral administration of NR raises NAD levels, and if so how much, and for how long.
Am I the only one that thinks that this is odd? Why wouldn't Chromadex use the results of this study to advise what the appropriate administration of NR is? How much, and how often?

 

This is not unusual and there have been in fact 2 not just one clinical studies completed. See https://clinicaltria...e&Search=Search

 

I expect as the summer approaches those involved in the undergraduate and graduate studies will be getting these studies ready for publication.

[Bryan_S]

Status Public on Jun 04, 2015

 

Title Defective Mitophagy in XPA via PARP1 activation and NAD+/SIRT1-depletion: Implications for neurodegeneration (mouse)

 

http://www.ncbi.nlm....gi?acc=GSE55485

[Bryan_S]

Nicotinamide Riboside Kinase Structures Reveal New Pathways to NAD+

 

http://journals.plos...al.pbio.0050263

 

http://www.plosbiolo...resentation=PDF

 

 

[Bryan_S]

Regenerative Neurogenesis After Ischemic Stroke Promoted by Nicotinamide Phosphoribosyltransferase–Nicotinamide Adenine Dinucleotide Cascade

http://stroke.ahajou...216.short?rss=1

 

Here we find a study pointing to the activation of neural stem cells by the "post injury" administration of a NAD precursor. Obviously there is a time period after the initial injury where neuron's could be rescued but after that time period your best hope is a regenerative strategy, which is to promote neural stem cells to help restore neural functionality.

 

. Yan Zhao, MD, PhD*, Yun-Feng Guan, BSc*, Xiao-Ming Zhou, MD*, Guo-Qiang Li, MD, Zhi-Yong Li, MD, PhD, Can-Can Zhou, BSc, Pei Wang, MD, PhD andChao-Yu Miao, MD, PhD

+

Author Affiliations

. From the Department of Pharmacology, Second Military Medical University, Shanghai, China (Y.Z., Y.-F.G., G.-Q.L., Z.-Y.L., C.-C.Z., P.W., C.-Y.M.); Department of Science and Education, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China (X.-M.Z); and Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China (C.-Y.M.).

. Correspondence to Chao-Yu Miao, MD, PhD or Pei Wang, MD, PhD, Department of Pharmacology, Second Military Medical University, Shanghai, China. E-mailcymiao@smmu.edu.cn or pwang@smmu.edu.cn

. ↵* Y. Zhao, Y.-F. Guan, and X.-M. Zhou contributed equally.

 

Abstract

Background and Purpose—Nicotinamide adenine dinucleotide (NAD) is a ubiquitous fundamental metabolite. Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme for mammalian NAD salvage synthesis and has been shown to protect against acute ischemic stroke. In this study, we investigated the role of Nampt–NAD cascade in brain regeneration after ischemic stroke.

Methods—Nampt transgenic (Nampt-Tg) mice and H247A mutant enzymatic-dead Nampt transgenic (ΔNampt-Tg) mice were subjected with experimental cerebral ischemia by middle cerebral artery occlusion. Activation of neural stem cells, neurogenesis, and neurological function recovery were measured. Besides, nicotinamide mononucleotide and NAD, two chemical enzymatic product of Nampt, were administrated in vivo and in vitro.

Results—Compared with wild-type mice, Nampt-Tg mice showed enhanced number of neural stem cells, improved neural functional recovery, increased survival rate, and accelerated body weight gain after middle cerebral artery occlusion, which were not observed in ΔNampt-Tg mice. A delayed nicotinamide mononucleotide administration for 7 days with the first dose at 12 hours post middle cerebral artery occlusion did not protect acute brain infarction and neuronal deficit; however, it still improved postischemic regenerative neurogenesis. Nicotinamide mononucleotide and NAD+ promoted proliferation and differentiation of neural stem cells in vitro. Knockdown of NAD-dependent deacetylase sirtuin 1 (SIRT1) and SIRT2 inhibited the progrowth action of Nampt–NAD axis, whereas knockdown of SIRT1, SIRT2, and SIRT6 compromised the prodifferentiation effect of Nampt–NAD axis.

 

Conclusions—Our data demonstrate that the Nampt–NAD cascade may act as a centralizing switch in postischemic regeneration through controlling different sirtuins and therefore represent a promising therapeutic target for long-term recovery of ischemic stroke.

 

• Received April 20, 2015.
• Revision received May 9, 2015.
• Accepted May 14, 2015.

 

[Bryan_S]

Here is a question that's been on my mind without a clear path of how to find an answer; "How do we know what tissues of the body can process Nicotinamide Riboside?" and "How do we know its being utilized at all?"

 

I read something a year ago suggesting which cells of the body benefited the most. It went something like this, "Nicotinamide riboside (NR) is phosphorylated by the products of nicotinamide riboside kinase genes (NRK1 and NRK2) to form NMN, which is converted to NAD+ by NMNAT1-3" . . . "The use of NR as a precursor in mammalian cell types was first demonstrated in DRG neurons, which induce the NRK2 transcript when damaged by axotomy (71). The ubiquitous expression of Nrk1 in mammalian tissues (80) suggests utilization of NR and/or NaR (83) in a diverse array of cell types. However, Nrk2 is present in heart, brain, and skeletal muscle, and is notably absent in kidney, liver, lung, pancreas, and placenta (48, 71). The fact that DRG neurons cannot be protected from damage induced neuropathy by Na or Nam without concurrent gene expression of Na or Nam salvage genes suggests that NR is a uniquely useful precursor to the nervous system (71) when de novo synthesis of NAD+ from Trp is not sufficient."

 

OK that's all well and great, it seems some cells are more equipped than others to take advantage of certain NAD precursors than others. However where do these statements come from. Sure its nice to "hear" that my brain and skeletal muscle can take advantage of (NR) as a NAD precursor and that my neurons can't readily process (Na) or (Nam) but many studies have fallen short of explaining how researchers can make these assertions. Then I came across the topic of Transcriptomics.

 

For those who haven't read up on Transcriptomics it's the study of the transcriptome—the complete set of RNA transcripts that are produced by the genome, under specific circumstances or in a specific cell—using high-throughput methods, such as microarray analysis. In essence we can now look at a cell type and by measuring the RNAs that are expressed we can tell what genes are turned on or off on a cell by cell basis. See link: RNA activity mapped across cells Now researchers can tell exactly what tasks each cell tissue is capable of performing.

 

OK, that got deep fast.

 

So what does that mean to our Nicotinamide Riboside audience. How do we know we aren't just being mislead by the marketing, where do I go to find the proof to back up these assertions suggesting one NAD precursor is better than another?

 

Its called the "Expression Atlas." I found several sources of information depicting which tissues of the human anatomy were equipped to utilize Nicotinamide Riboside (NR) and each database shared similar research links backing up their data. What differences I did find is how the information was graphically presented. Here is the best tissue utilization map I can find for Nicotinamide Riboside thru NRK1 and NRK2 RNA expression.

 

Link NMRK1 Homo sapiens nicotinamide riboside kinase 1

 

Link NMRK2 Homo sapiens nicotinamide riboside kinase 2

 

So here is a tool we can use to lookup specific gene expressions and tell if one study statement or the other is backed up by RNA expression research. 

[ymc]

Here is a question that's been on my mind without a clear path of how to find an answer; "How do we know what tissues of the body can process Nicotinamide Riboside?" and "How do we know its being utilized at all?"

Thank you for your input.

I don't think people here seriously think NR can bring dramatic improvement. We all know NMN is the real thing. NR is a stopgap until NMN becomes cheap enough.

[BigLabRat]

 

 

Thank you for your input.

I don't think people here seriously think NR can bring dramatic improvement. We all know NMN is the real thing. NR is a stopgap until NMN becomes cheap enough.

 

 

Do you know of research showing that NMN is more effective than NR? Could you point me to it?

 

For some reason, I don't seem to be able to copy and paste. But the attached study, which I know most people here have already seen, shows that oral administration of Niacin (NA), NR, or NMN to rats across a week all raise NAD+ concentration in liver tissue--and that NA is by far the most effective, followed by NR, with NMN coming in a distant third.

 

In the same experiment, In muscle tissue, NA and NR both increase NAD+ significantly (and by about the same amount), but NMN doesn't.

 

This may seem to contradict what was found by Sinclair and the gang in mice, but they used injection of massive doses of NMN--and they didn't do side-by-side with NR or NA.

 

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

 

For me, the real question isn't which of NR or NA or NMN are more effective (though based on short-term studies, NA leaves the others in the dust*). The real question is whether any of this persists in the long term. Sinclair's stuff was for a week. The Cell Metabolism study attached was for a week. What Chromadex released on it's first human trial of NR was one dose.

 

What I'd like to know is if this all gets downregulated across time--and to what extent.

 

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

*In fact, the Cell Metabolism study below seems to tacitly admit that NA is excellent at producing NAD, and has a number of other benefits, and that their study was motivated by searching for something that worked like NA without inducing flushing!

Attached Files

•  Cell Metabolism--NR.pdf   898.96KB   15 downloads

[Bryan_S]

"Furthermore, NR protects against metabolic dysfunction at lower concentrations than those reported for NMN, and we proved that it is effective after oral administration when mixed with food, in contrast to NMN, which is injected intraperitoneally." Cell Metabolism--NR.pdf 

 

You guys might find something here:

Are Other Precursors as Effective in Increasing NAD+ as NR?

 

NMN Nicotinamide Mononucleotide I believe what we found is the molecule is hydrolyzed in the gut and injection was the most potent application method. I can't immediately put my finger on the thread. I think I remember a diabetes study where NMN was put in the water supply but that study isn't filtering to the top.

 

NMN Injection links

http://www.sciencedi...550413111003469

 

 

"Recent observations suggest that, at least for some cell types, NMN needs to be converted into NR through dephosphorylation performed by extracellular 5′-nucleotidases in order to penetrate into the cell (Nikiforov et al., 2011). Given that the presence of NMN in plasma is debated (Hara et al., 2011), the most likely scenario is that NR, rather than NMN, is the entity directly taken up by the cell, to then become metabolized in the cytosolic compartment to NMN. The lack of NRK1 and NRK2 in the mitochondrial compartment (Nikiforov et al., 2011) supports that NMN might act as the precursor entering the mitochondria or other compartments for further metabolism into NAD+ by the various NMNAT enzymes (see Fig.7 for a scheme)." http://www.ncbi.nlm....les/PMC3616313/

 

Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging

http://www.ncbi.nlm....les/PMC4076149/

 

 

Nicotinamide Mononucleotide, an Intermediate of NAD+ Synthesis, Protects the Heart from Ischemia and Reperfusion

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048236/

 

 

Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204926/

Edited by Bryan_S, 17 June 2015 - 09:43 PM.

[Bryan_S]

New Nicotinamide Riboside study

 

ChromaDex Announces a Collaborative Human Clinical Study on NIAGEN® With the University of Colorado Boulder

 

- The Integrative Physiology of Aging Laboratory, Headed by Dr. Douglas Seals, Will Investigate the Effects of NIAGEN® on Physical Function and Metabolism in Healthy Adults Aged 45-79 Years -

 

IRVINE, Calif., June 18, 2015 (GLOBE NEWSWIRE) -- ChromaDex Corp. (OTCQX:CDXC), an innovator of proprietary health, wellness and nutritional ingredients that creates science-based solutions for dietary supplement, food and beverage, skin care, sports nutrition, and pharmaceutical products announced today that a collaborative human clinical study on NIAGEN® (Nicotinamide Riboside—NR) is underway at the University of Colorado Boulder.

 

http://investors.chr...icle&ID=2060413

 

http://finance.yahoo...-103000527.html

[Bryan_S]

NMN Nicotinamide Mononucleotide

 

You guys might find something here:

Are Other Precursors as Effective in Increasing NAD+ as NR?

 

 

Came across this recent article that mentions NMN Nicotinamide Mononucleotide. Its from Shin-ichiro Imai who we've all come to recognize from his papers on NAD boosting research.

 

 

Fat signals control energy levels in the brain

http://medicalxpress...ergy-brain.html

[Bryan_S]

Kidney International advance online publication 17 June 2015; doi: 10.1038/ki.2015.157

Sirtuin and metabolic kidney disease

http://www.nature.co...ki2015157a.html

 

"As mentioned, Sirt1 catalyzes deacetylation with the aid of the coenzyme NAD⁺, the cellular level of which is important for its enzymatic activity. NAD⁺ is also important for oxidizing and reducing reactions as a coenzyme. NAD⁺ is synthesized through two biological pathways, these being de novo synthesis using an essential amino-acid tryptophan supplied by dietary intake, and a salvage pathway in which NAD⁺ is resynthesized from nicotinamide (NAM). The rate-limiting factor in the salvage pathway is nicotinamide phosphoribosyltransferase (NAMPT), which catalyzes the synthesis of nicotinamide mononucleotide (NMN) from NAM and 5’-phosphoribosyl-1-pyrophosphate (Figure 2).¹³ Two NAMPT have been identified in mammals: intracellular NAMPT (iNAMPT) and extracellular NAMPT (eNAMPT), found in the circulation. iNAMPT is known to be involved in energy metabolism.¹⁴ For instance, overexpression of iNAMPT in the liver suppresses induction of hepatic steatosis.¹⁵ It is also reported that systemic administration of iNAMPT-expression vector alleviates abnormal glucose tolerance.¹⁶ Calorie restriction increases the expression level of iNAMPT in muscles and mitochondria.¹⁷ These effects are possibly due to the activation of Sirt1, which is caused by activation of iNAMPT, followed by an increase in NAD⁺ supply. Activation of Sirt1 leads to activation of the salvage pathway through an increase in NAM and following activation of iNAMPT. At the same time, activation of Sirt1 leads to suppression of the clock genes, thereby reducing iNAMPT expression. This prevents excess activation of Sirt1 and iNAMPT and an excess in the positive feedback loop.^18, 19 NAD, iNAMPT, and Sirt1 are currently recognized as important new factors in energy metabolism."

[Bryan_S]

 

Here is a question that's been on my mind without a clear path of how to find an answer; "How do we know what tissues of the body can process Nicotinamide Riboside?" and "How do we know its being utilized at all?"
 

Thank you for your input.

I don't think people here seriously think NR can bring dramatic improvement. We all know NMN is the real thing. NR is a stopgap until NMN becomes cheap enough.

 

 

Nicotinamide Mononucleotide (NMN)

 

One company (RevGenetics, their pre-order link now gone) was slated to manufacture it for supplementation and has since backed away. So I don't think its only a matter of cost. Here is the post by LongeCity member Phoenicis that spelled it out. http://www.longecity...nt/#entry678289

 

Pathways and subcellular compartmentation of NAD biosynthesis in human cells: from entry of extracellular precursors to mitochondrial NAD generation.

http://www.ncbi.nlm....pubmed/21504897

"Our results demonstrate that, besides nicotinamide and nicotinic acid, only the corresponding nucleosides readily enter the cells. Nucleotides (e.g. NAD and NMN) undergo extracellular degradation resulting in the formation of permeable precursors."

 

Here is another representation of how NMN is handled.

 

A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration

http://www.nature.co...dd2014164a.html

"The likely mechanism of NMN uptake is extracellular conversion to nicotinamide riboside (NR).^33, 34, 35 Although direct uptake of phosphorylated nucleotides may occur,³¹ the ectoenzymes nucleotide pyrophosphatase and 5′ nucleotidase are proposed to catalyse two- or one-step conversion of NAD and NMN to NR³³(Supplementary Figure S4A). Intracellular NR kinases (NRKs) use NR to resynthesize NMN,³⁶ which in turn is used to synthesize NAD, but only if NMNAT is present. Consistently, exogenous NR (Figure 2c) and NAD (Figure 2d;Supplementary Figure S4C) also abolished FK866-induced neurite protection"

 

So for the moment let's put aside the difference of taking (NMN) orally or by injection as the first hurdle because the cell seems to prefer converting it to Nicotinamide Riboside (NR) first anyway and then it re-synthesizes (NMN) before building NAD. I believe nature works it this way to cross the cell membrane barrier and I remember a similar article depicting 2 (NMN) pathways thru the cell membrane.

 

Assimilation of Nicotinamide Mononucleotide Requires Periplasmic AphA Phosphatase in Salmonella enterica

See http://www.ncbi.nlm....les/PMC1151756/

"In route 1, nicotinamide is removed from NMN in the periplasm and enters the cell as the free base. In route 2, described here, phosphate is removed from NMN in the periplasm by acid phosphatase (AphA), and the produced nicotinamide ribonucleoside (NmR) enters the cell via the PnuC transporter. Internal NmR is then converted back to NMN by the NmR kinase activity of NadR." 

 

As Phoenicis pointed out "If this is cheaper than NR, then it may be worth a go, but otherwise whats the point?" And as many of the previous studies seem to have illustrated the preferred administration was Injection over Oral and some of us don't like needles. Either way it doesn't seem like the most effective path. . . JMHO

Edited by Bryan_S, 22 June 2015 - 12:36 AM.

[BigLabRat]

Great stuff, Bryan. And it matches with what we see in other literature: strong effects for Na and NR, and not much for NMN.

 

NMN was important as a signpost pointing to the possible benefits of supplements for raising NAD+, but it doesn't seem to be a very good supplement!

[Asor]

I went to my neurologist for a checkup and hear about news regarding the NR trial on patients with mitochondrial diseases and got some bad news, they are still waiting for tests that are being done by Chromadex on "larger animal models", she told me the dosage they're testing for toxicity is 2 grams per day (2 grams is the dosage they need to use on humans with mitochondrial diseases, i guess they use a proportional size on animals), in other tests they realized small dosages arent effective in tested animals with mitochondrial diseases.

 

If everything goes smooth they should start the trial early 2016... but it's still not financed so it's all up in the air.

 

And this cuts short any of my ideas of taking NR by myself because

1) i cant afford 2 grams a day

2) they need to test the toxicity for such big amount.

3) they're going to run a bunch of tests pre and post trial on human patients (if/when it starts) to asses toxicity AND efficacy.

 

I asked if their study is somewhat related to David Sinclair and Guarente's work, she said there is a connection but it's two very different things, for healthy humans even small dosages of NR can be effective, for people with mitochondrial disease it's another story.

 

I wanted to ask more questions but i have been basically threw out of the office, they were in a hurry... im kinda pissed... 3+3 hours of driving and got basically nothing/bad news, and on top on that she wants me to stop taking idebenone (which is 100% subsidized and i dont pay if prescribed) because my cholesterol raised a little, while:
1) i dont think idebenone is the culprit.

2) i dont really care about high cholesterol levels, and they arent even that high: 243mg/dL total, 157 mg/dl LDL, 75 mg/dL HDL which is great.

 

So this new doctor revealed itself like one of those scared to give you something that can improve your condition and rather take away something that can help just because it presents a little side risk, GREAT.

 

Im going to follow up this visit with an email that she gave me to ask for eventual clarifications, let me know if you have any questions, but i bet she wont even answer me, im one of those pain in the ass patients that ask too many questions.

 

 

 

 

 

 

 

 

 

 

 

 

 

[midas]

Asor, be very careful with these people, the only thing they are interested in is study results. You as a person do not count, they will tell you not to take other supplements that they know are doing you good because they may affect the study results....THE STUDY IS PARAMOUNT to them.....

 

If I were you I would just take the NR at a level you can afford to take and see if you feel any benefit from it, these people will mess you around to suit their own agenda! .....You as a person are of no real interest to them, the study is the only thing that counts.....Even if you take the same 250mg dose per day that I take it may just stop your condition from progressing which is a very good thing, just don't tell them, their will be other people on the study that are jumping to their tune......Use them to suit you, if you don't they will use you to suit them!!

I have been through this around 12 years ago with a clinical study. They tricked me into taking a larger dose of a ACE inhibitor, not because I needed the larger dose but because everyone on the study had to be on the same level of medication to do the study on the drug they were using. I found this out at a later date when my cardiologist slipped up.

I have Chronic fatigue Syndrome and Dilated Cardiomyopathy and I have certainly noticed a difference since I started taking NR..

 

 

[relativityboy]

"these people will mess you around to suit their own agenda!"

WTF dude? You make them sound like villains. They're doing a study to gather scientific data so they can potentially help MILLIONS. Change your attitude midas. I don't think that finger of yours is turning anything to gold.

 

Astor, I'd suggest looking into the keto diet and pqq as a supplement. I don't know if they'll help, but some of what you say has me thinking it'll interest.

[midas]

"these people will mess you around to suit their own agenda!"

WTF dude? You make them sound like villains. They're doing a study to gather scientific data so they can potentially help MILLIONS. Change your attitude midas. I don't think that finger of yours is turning anything to gold.

 

Astor, I'd suggest looking into the keto diet and pqq as a supplement. I don't know if they'll help, but some of what you say has me thinking it'll interest.

 

Having been part of a study and experienced the way they manipulate people, as I stated in my last post I am speaking from experience.

 

You just try and get any results from these research study's that you took part in, it doesn't happen.

Try and communicate with the person that is conducting the study, it doesn't happen. Ask straight questions and try to get a straight answer to them, it doesn't happen.

 

Asor is already finding this out and the study is a long way off. he is after maybe the best part of 12 months of asking questions no closer to any answers, but they are willing to just leave him in limbo until it suits them. And even when it comes together, he will, as I have stated above struggle to get any answers to his questions.

 

And yes, as you say, they are looking to help maybe millions of people in the long run, but that doesn't do you any favors if you have a progressive debilitating illness and they are dragging their feet getting the study off the ground.

Also keep in mind the long term plan is for them to market a new drug and make money, you are a fool if you think this is all for the benefit of sick people without an ulterior financial motive.

 

Like I said, I am speaking from experience, like it or not.

 

I was also told 13 years ago my life expectancy was around 3-5 years, 13 years later I am still here and in reasonable health. That is most likely because I started doing my own research into my illness and helping myself rather than just sitting around waiting for medical advances....Of which I might ad their have been none in the treatment of Dilated Cardiomyopathy since I was diagnosed 13 years ago.

 

I am merely giving my opinion based on my PERSONAL clinical trial experience, you do not have to agree with it. And in case you missed it my post was intended for Asor, and I'm sure he can make his own mind up from his recent experience with the people that are conducting the trial whether my post is relevant or not!

 

 

Edited by midas, 23 June 2015 - 06:01 PM.

[Bryan_S]

Nicotinamde Riboside Delivery Generates NAD+ Reserves to Protect Vascular Cells Against Oxidative Damage

University of Western Ontario Krista M. Hawrylyshyn June 20, 2015

 

http://ir.lib.uwo.ca...491&context=etd

 

Nice paper, a hat tip to our Master of Science graduate!

Edited by Bryan_S, 23 June 2015 - 07:57 PM.

[Supierce]

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

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

[Bryan_S]

Protective effects of sirtuins in cardiovascular diseases: from bench to bedside

 

http://eurheartj.oxf...urheartj.ehv290

 

http://eurheartj.oxf...g/content/36/24