142 replies to this topic

[Vastmandana]

veritus, are you saying Sinclair, Duarte and other highly thought of longevity researchers are that ignorant or duplicit in some scam?  I can't imagine them bypassing the straight niacin/niacinimide plus sprinkle in some ribose compounds to make money... nor jigger lab results... which seem pretty cool... BTW, Brian, thanks for reposting those vids.... 

 

they have/are developing data... you/we are all speculating...at least that's how it seems to me.  I'm looking for the data. As Duarte notes, these systems are extremely complex, interactions are not fully understood, and there is a lot to learn still...While I love piecing together puzzles, this isn't an easy one to pull bits and pieces from this and that, and do anything but formulate a possibility which would need to be tested.

 

Of course, I'm fairly dumb in chemistry but the above seems to be what falls out of listening/reading a lot of stuff...

 

Mind you, I am taking a gram of niacin a day... in divided doses.... And I just ordered a couple Jiaogulan (Gymnostemma pentaphyllum) plants as an inexpensive and tasty growable tea to "AMPK" myself up once I grow them sufficiently to harvest...LEF already sells this as an AMPK activator...It's one of the most intriguing and promising things I've seen in following all these discussions...that I'm not already doing and is not pure conjecture... plus it appears to taste wonderful and I grow plants!

 

So I'm fully interested in less costly modulators... but your statement,

 

 

"Anyway, again it appears NR itself can be effectively (and far more economically) mimicked by SR-niacinamide, or simply taking niacinamide throughout the day, perhaps best with some ribose, which certainly could not hurt, is cheap and available enough - a 'better safe than sorry' means to ensure an adequate supply."

 

is mearly conjecture, in my humble opinion...

 

 

 

Edited by Vastmandana, 17 November 2014 - 03:19 AM.

[Bryan_S]

Increasing nicotinamide phosphoribosyltransferase (nampt) alone did not raise NAD levels. This was a strategy favored by many to promote NAD synthesis. Another unseen factor must be at work.

 

Increasing NAD Synthesis in Muscle via Nicotinamide Phosphoribosyltransferase is not Sufficient to Promote Oxidative Metabolism

[Vastmandana]

The hunt for red October continues....hmmmmm

[Darryl]

More correctly, muscle-specific Nampt overexpression increased NAD by 50%, but didn't increase NAD/NADH redox ratio, mitochondrial biogenesis or mitochondrial function.

 

This suggests that repeatedly observed NR effects on mitochondrial myopathy are indirect, via systemic signalling, rather than autonomous in each cell, and that the Sinclair's lab's proposed mechanism for NMN via directly increasing nuclear NAD+ may be mistaken.

Edited by Darryl, 25 November 2014 - 10:23 PM.

[Bryan_S]

I started a thread we can use for breaking news items and announcements related to Nicotinamide Riboside because they don't always fit into our other board conversations. So now if any of us come across any new NR topics and updates we have a place to centrally list them.

  Nicotinamide Riboside Current News and Updates

 

So check the web often and add any new news items in there.

 

Keep in mind we can still start individual topics like this thread on the effectiveness of other NAD precursors but now we can list the latest "developments" and "news" conveniently under one roof.

 

I'd like us to use this thread to list, announce and promote other worthwhile NR reading from outside threads and blogs as well. So what I'm saying is if you want long in-depth conversations on specific NR or related NAD topics lets create individual threads to support those conversations but use and support the central thread to advertise the new topic discussion for other NR readers in our community to find.

 

You'll find I've put some new news topics on NR in there all ready like the one above just to kick off the thread.

[mikey]

 

 

mikeinnaples, on 16 Oct 2014 - 2:41 PM, said:

Trance, if I recall correctly, the hepatoxicity issues were primarily with the sustained release nicotinic acid and not the immediate release. I would think that taking immediate release NA at levels typically used for cholesterol treatment would be safe for most healthy people provided you can handle the flush or build up tolerance.

mikey, on 16 Oct 2014 - 4:11 PM, said:

 

In communicating with William Parsons, MD, the Mayo Clinic researcher who showed in the '60's niacin's cholesterol-lowering effects, he told me that the McKenney study that showed hepatotoxicity with sustained-release (SR) niacin was a "hatchet job" paid for by Merck, to kill the competition when they brought our their first statin. He dismissed the study. 

 

Abram Hoffer, MD.,PhD. further told me that SR niacin's purported hepatotoxicity was "highly exaggerated." He said that if he had a patient with a compromised liver he would monitor them when giving high-dose SR niacin, but that he frequently did and found little as to liver problems.

 

Perhaps someone has solid published data that are contrary to what these two niacin "champions" said.

 

 

So what is implied here Merck tainted the Niacin data? I think for many of us it's the risk of toxicity that holds many of us back from taking multi gram doses of Niacin or Nicotinamide. I don't think any of us are qualified to question decades of research but highly exaggerated claims have to be addressed. Where I try and divide the true from the false is eliminate the manufactures noise from the researchers and weigh the consensus. In fact we had a perfect example of that here pumping NADH in spite of a 2006 study saying it was broken down in the digestive track. With many of these once you eliminate the opinions supporting a marketing push one way or the other your left with unbiased research.

 

So we have:

Niacin

Nicotinamide

Nicotinamide Riboside

and NADH as contenders.

 

Unless you guys think there is ample data supporting NADH making it past the digestive barrier I'd like to take it off the list and move forward with discussion on the other 3.

 

A 96 week study is good info even if it is from a pharmaceutical company I did read that paper and it is encouraging. I would however like to see independent supporting data. 

 

I recently read this compendium on Niacin and Nicotinamide as it focused on the "Tolerable Upper Intake Levels of Nicotinic Acid and Nicotinamide (Niacin)" which is the direction we're interested in.

http://ec.europa.eu/...f/out80j_en.pdf

 

 

Nicotinamide plus ribose is considerably less costly than NR.

 

As far as toxicity, nicotinamide appears to be safe up to 3,000 mg a day, according to Safety of high-dose nicotinamide: a review." 

 

Further, a human study at UC Irvine is currently studying 3,000 mg/day of sustained-release nicotinamide for Alzheimer's after a mouse study showed significant beneficial effects for the mouse version of Alzheimer's, and so the IRB considered 3,000 mg/day to be safe enough to study with humans, allowing the UC Irvine study to happen.

 

And of course, nicotinamide (niacinamide) has been shown to exhibit considerably less potential toxicity than nicotinic acid (niacin), the vitamin B3 form that causes the warm, itchy skin flush.

 

And there is a cost-effective source of pharmaceutical-grade sustained-release nicotinamide available and I already buy big bags of ribose for cheap to use rather than sugar.

 

Then note that niacinamide only lasts about 90 minutes in the body, so taking a true sustained-release niacinamide is the way to go, rather than taking plain niacinamide every 90 minutes.

[Bryan_S]

Nicotinamide plus ribose is considerably less costly than NR.

 

As far as toxicity, nicotinamide appears to be safe up to 3,000 mg a day, according to Safety of high-dose nicotinamide: a review." 

 

Further, a human study at UC Irvine is currently studying 3,000 mg/day of sustained-release nicotinamide for Alzheimer's after a mouse study showed significant beneficial effects for the mouse version of Alzheimer's, and so the IRB considered 3,000 mg/day to be safe enough to study with humans, allowing the UC Irvine study to happen.

 

And of course, nicotinamide (niacinamide) has been shown to exhibit considerably less potential toxicity than nicotinic acid (niacin), the vitamin B3 form that causes the warm, itchy skin flush.

 

And there is a cost-effective source of pharmaceutical-grade sustained-release nicotinamide available and I already buy big bags of ribose for cheap to use rather than sugar.

 

Then note that niacinamide only lasts about 90 minutes in the body, so taking a true sustained-release niacinamide is the way to go, rather than taking plain niacinamide every 90 minutes.

 

 

 

I reviewed a number of websites and the following site had some of the most extensive overall information. I've added 2000 mg of (NAM) to my (NR) regiment along with 3000 mg of Ribose. If I could afford it I'd take only the (NR). I take 1000 mg of (NR) at the beginning of the day and end with the nicotinamide before bed. I'll follow this regiment for 2 months and see if it adds any noticeable benefits.

 

The study results you spoke of for human Alzheimer's is long overdue. It should have concluded this summer and the results are unknown at this point. This study has been referenced by many Alzheimer's articles and if the mouse data is correct it could point to a treatment. 

Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice

 

 

 

NICOTINAMIDE
CASRN: 98-92-0

 

 

http://toxnet.nlm.ni...rn @rel 98-92-0

Biological Half-Life:

The mean half life values were 2.7 hr, 5.9 hr, and 8.1 hr after taking 1, 3, or 6 g of Niacinamide, respectively.
[Cosmetic Ingredient Review (CIR) Expert Panel; Final Report of the Safety Assessment of Niacinamide and Niacin; Intl J of Toxicology 24 (Suppl 5): 1-31 (2005) p.6] **PEER REVIEWED**

[Ukko]

I am bit confused. Have you guys not read the studies showing how high niacinamide reduces NAD+. There's a feedback loop such that the cells use the NAD+ breakdown product niacinamide to sense ambient NAD+ levels. Artifially high niacinamide this shuts down NAD+ synthesis. Niacinamide is no solution, certainly not at higher levels. Free form niacin may be, but I am still not sold on it from the PGD2 and methylation angle.

[Ukko]

I am bit confused. Have you guys not read the studies showing how high niacinamide reduces NAD+. There's a feedback loop such that the cells use the NAD+ breakdown product niacinamide to sense ambient NAD+ levels. Artifially high niacinamide this shuts down NAD+ synthesis. Niacinamide is no solution, certainly not at higher levels. Free form niacin may be, but I am still not sold on it from the PGD2 and methylation angle.

Here's what I mean with the methylation angle. Niacinamide is a massive methylation agent mop. And niacin ends up being niacinamide. Now, long term niacin supplementation increased homocysteine by a whopping 55%. Massive. And pure niacinamide should raise it even more. To put it in context, such increase in homocysteine ups heart disease risk by 80%. Not to mention what it does to your dopamine system and mood. Sure hope that this too was a hatched job study by the Big Pharma. http://www.ahjonline...e/S0002-8703(99)70073-6/abstract

[Vastmandana]

link not working, Ukko

[VERITAS INCORRUPTUS]

Increased eNA/eNAM is absolutely, in the short term, enhancing NAD+ levels - as studies reveal.  Over time if feedback mechanisms will counter such I am unaware has been determined.  Such as a study measuring levels of the course of a month of continuous supplementation.  Maybe it exists, but I do not recall - working on a lot of other projects. 

NR appears, as per Logic noting it is broken down in the gut in a SR manner, to be solely just SR-Niacinamide and SR-Ribose as to actual practical outcomes; so if accurate such is a waste o' funds and eNA/eNAM combo taken through the day will do nicely to emulate any NR studies.

Ribose is likely not needed to be supplemented, but certainly could not hurt, neither as to health or the pocket.

As some of the original progressive work showed eNA enhanced mood and was beneficial to cardiovascular parameters.  If under-methylation is an issue have at some TMG.

 

So....where's the problem and the confusion?

 

Take some ALA and Biotin if concerned about hepatotoxicty - it's a good idea as well regardless.  Among other agents many here might take for general underlying health and wellness optimization

 

One issue is to note it is likely best to cycle these high doses, even as for efficacy itself, as indeed do not forget about feedback loops/homeostatic regulations.  1-2 week(s) on/1 week off may be best.  "Pounding" the body even with things that solely seem good actually is not generally a good thing - making things ever more complicated to work our physiology where we want it.

 

Off weeks perhaps best to cut dosages to 20% of full dose.  Perhaps during the off weeks it may be an idea to supplement straight eNAD+ (or increased levels of such over 'on' weeks) as that may be an optimal factor to include somewhere in the equation. eNAD+ best of course i.n. or subL, if one is so opposed to pinning it - which would be best  (mostly a joke, but would be most efficacious)

 

Surprised no one is aware eNAD+ does cross into the plasma membrane intact and can enter into the cell...because it HAS been shown to do so...but I can't give it all away, lol ...

 

Just some quick thoughts as to the issues addressed by Ukko.

[Vastmandana]

As this issue keeps being bandied around, I googled the question about d-ribose/nam vs NR and came across this very interesting human asking that question... and he proceeded to assemble a huge amount of background... people were looking at NR every since it was discovered in 2004!  Maybe the thread is old news to many of you or I'm just becoming more lucid/diligent of late... but I found it facinating... Also, as I read it, Chromadex only has a patent on a particular way of making/extracting NR (developed by cornel)...

 

Don't know if it's kosher, but here is the thread... it's pretty long... but, lying in bed rather than sleep I enjoyed the info... lots of studies with significant bits lifted.... for example:

 

Aragorn starts off like this:

 

Longevity and Nicotinamide riboside

« on: August 01, 2012, 10:21:25 PM »

 

The benefits of nicotinamide riboside/ribose (NR) was recently discussed on the 'Life without bread' thread, and there was THIS recent study that I think got us all (at least me) excited. I know that some of you have already experimented with supplementing with NR (combining niacin and D-ribose). I've been searching for confirmation on how this combination of niacin and D-ribose produces NR, and the only thing I've found is this:

_http://www.yeastgeno...m.pl?goid=70635

Quote

Definition: Catalysis of the reaction: nicotinamide riboside + H2O = nicotinamide + D-ribose.

Synonyms: N-ribosylnicotinamide hydrolase activity; nicotinamide ribonucleoside hydrolase activity

I have no expertice in chemistry, so I don't know if I'm looking for the right things. But reading the above makes me think if this catalysis formula is 'reversable'. Maybe some of you chemists can help out here? In the scientific papers I found the synthesis of NR looks very complicated, with all sorts of things besides Nam and D-ribose.

---

Anyway, I thought it would be cool to collect information about longevity, NR etc. in a new thread instead of posting this stuff to the LWB thread. I've been going through a bunch of scientific papers, and I'm going to start by posting excerpts from a quite "readable" article that gives a good overview of the processes involved.

Quote

Nicotinic Acid, Nicotinamide, and Nicotinamide Riboside:A Molecular Evaluation of NAD+ Precursor Vitamins in Human Nutrition.
Katrina L. Bogan and Charles Brenner
Annu. Rev. Nutr. 2008. 28:115–30
First published online as a Review in Advance on April 22, 2008
The Annual Review of Nutrition is online at nutr.annualreviews.org
This article’s doi: 10.1146/annurev.nutr.28.061807.155443

This is a facinating paper but you may have it already.... if not, it's worth looking at the thread... Next he  cites a 2007 study which indicates... [...]

Vitamins are small molecules that are required in diets to prevent malnourishment. Metabolites are compounds that are naturally produced in particular biosynthetic pathways. Data presented in this study and in a previous study (Bieganowski and Brenner, 2004) establish the vitamin functions of NR in yeast. New data establish the role of NR salvage enzymes in maintaining NAD+ homeostasis in nonsupplemented cells. NR appears to be unique among NAD+ precursors in stably elevating NAD+ levels in yeast and may have advantages in human systems in which activation of Sirtuins is desired. Indeed, providing supplements to boost NAD+ synthesis may be a therapeutically important treatment modality for neurodegenerative conditions stemming from chemotherapy (Araki et al., 2004), physical nerve damage (Wang et al., 2005), Alzheimer’s disease (Qin et al., 2006), and multiple sclerosis (Kaneko et al., 2006). 

In ex vivo experiments to protect dorsal-root-ganglion neurons from transection-induced axonopathy, the combination of Nam plus overexpression of Nam PRTase and the combination of nicotinic acid plus overexpression of nicotinic acid PRTase had neuro- protective activity. However, NR was the only nonphosphorylated, drug-like NAD precursor to protect DRG neurons from axonopathy without concurrent gene therapy (Sasaki et al., 2006). This appears to be because Nrk2 transcription is induced by nerve damage (Sasaki et al., 2006).

 

This is all old stuff which kind of blows me away! He then quotes extracts from a the original huge report  (500+ pgs) discovering NR back in 2004... then a 2009 study on

 "The Importance of NAD in Multiple Sclerosis"

W. Todd Penberthy and Ikuo Tsunoda

Link: _http://www.ncbi.nlm....nihms-96557.pdf

 

This was another facinating study... He cites a lot more than just this:

 

2.4. Glia as Suppliers of NAD to Neurons

[...]
p.68: Given the divisions of labor reserved for glia, it makes sense that glia are likely more efficient at NAD biosynthesis than neurons and consequently serve critical functions as providers of NAD to neurons. Collectively experimental data supports the notion that glial may be required for the essential delivery of NAD to neurons starting from tryptophan, nicotinic acid/niacin, or nicotinamide/niacinamide, but not nicotinamide riboside.

 

[...]
p.83: With the statins as the most commercially successful class of pharmaceuticals in the world, yet nicotinic acid still outperforms them in spite of unparalleled investments to develop something better, this is truly remarkable. Thus, nicotinic acid acid is the gold standard for correcting dyslipidemia on the whole. [...] Nicotinic acid appears to be preferred over nicotinamide as a NAD precursor primarily when it is applied at the high concentrations. Nicotinic acid is the more preferred substrate in evolution based on experimental radioactive labeling and comparative genomic studies examining to date (presentation by Mathias Ziegler at PARP 2008 meeting, Tucson, Arizona, U.S.A.). In glia, nicotinic acid provides greater levels of NAD biosynthesis per mole than nicotinamide or tryptophan by 200 and 500 fold respectively. This also appears to be true for glia. However, neurons are distinctively inefficient in their ability to convert dietary NAD precursors to NAD [27]. As described above this may be another biosynthetic job for glia like that of cholesterol biosynthesis. {Reading p.68, if I've understood correctly, Nicotinamide Riboside is an exception}

 

 

 [...]

p.86: Thus there is a long history of clinical use for high doses of nicotinic acid and nicotinamide. By contrast, nothing is known regarding the utility of nicotinamide riboside in the clinic. 

Of potentially great clinical therapeutic significance nicotinamide riboside is distinguished as the only NAD precursor capable of providing NAD directly to neuronsand delaying Wallerian degeneration assay.  [...] More clinical research is needed given the tremendous potential therapeutic benefit of nicotinamide riboside therapy for treating neurodegenerative diseases. [...] Perhaps, the effect is more immediately beneficial to the neuron since glia are not apparently required for synthesis of NAD from nicotinamide riboside. 

 

Lots of interesting reading, at least to me, although I'm in no sleep mode since before black friday trying to decide on mastering tools for my studio...However, what I got from this is... 

 

1. Rather doubt we can just chug a bunch of d-ribose and niacinamide/niacin and it magically becomes NR

2. NR is operating differently than either other, and even they operate differently. so... No, Veritis... ya can't just chug the others and get the same result...

3. This is way beyond our pay grade... they (super smart people) haven't figured it all out yet and we're talkin 10 years! 

 

Unless this is old news or already been posted, this is well worth taking the time to read, from another forum...

Edited by Vastmandana, 30 November 2014 - 04:45 PM.

[Ukko]

To be clear, hepatotoxicity does not worry me for immediate release niacin/niacinamide.

But the fact that niacinamide silences SIRT-1, likely causes diabetes and rapidly downregulates NAMPT and thereby NAD+ in high doses does worry me. I will look for more studies, but here is one: http://openscholarsh...tl.edu/etd/991/

Then there's the methylation angle. I will find the study showing a massive 55% increase in homocysteine. This too should be a result from high dose niacinamide, though niacin converts to niacinamide with a delay. Maybe TMG helps. I for one have been taking it simultaneously.

So, for me, NR is too pricey for the long haul. Have been taking 500mg together with 1000mg TMG, other activated Bs and GLA + quercetin + baby aspirin to mitigate the massive PGD2 release from the niacin. Oh, and resveratrol also to fight back against the downregulated NAMPT. Timing is key too. Given circadian rhytm with NAD+, supplementation should be done early in the day. For now, sticking with free form niacin at 500mg.

Edited by Ukko, 30 November 2014 - 05:27 PM.

[Ukko]

Here's the methylation study. Again, it is the methyl mop niacinamide resulting from niacin that does this. Sure hope it is a hatchet job.

Abstract

Background Studies have reported high levels of plasma homocyst(e)ine as an independent risk factor for arterial occlusive disease. The Cholesterol Lowering Atherosclerosis Study reported an increase in plasma homocyst(e)ine levels in patients receiving both colestipol and niacin compared with placebo. Thus the objective of this study was to examine the effect of niacin treatment on plasma homocyst(e)ine levels. Methods The Arterial Disease Multiple Intervention Trial, a multicenter randomized, placebo-controlled trial, examined the effect of niacin compared with placebo on homocyst(e)ine in a subset of 52 participants with peripheral arterial disease. Results During the screening phase, titration of niacin dose from 100 mg to 1000 mg daily resulted in a 17% increase in mean plasma homocyst(e)ine level from 13.1 ± 4.4 μmol/L to 15.3 ± 5.6 μmol/L (P < .0001). At 18 weeks after randomization, there was an absolute 55% increase from baseline in mean plasma homocyst(e)ine levels in the niacin group and a 7% decrease in the placebo group (P = .0001). This difference remained statistically significant at the end of follow-up at 48 weeks. Conclusions Niacin substantially increased plasma homocyst(e)ine levels, which could potentially reduce the expected benefits of niacin associated with lipoprotein modification. However, plasma homocyst(e)ine levels can be decreased by folic acid supplementation. Thus further studies are needed to determine whether B vitamin supplementation to patients undergoing long-term niacin treatment would be beneficial. (Am Heart J 1999;138:1082-7.)

[mikey]

 

I am bit confused. Have you guys not read the studies showing how high niacinamide reduces NAD+. There's a feedback loop such that the cells use the NAD+ breakdown product niacinamide to sense ambient NAD+ levels. Artifially high niacinamide this shuts down NAD+ synthesis. Niacinamide is no solution, certainly not at higher levels. Free form niacin may be, but I am still not sold on it from the PGD2 and methylation angle.

Here's what I mean with the methylation angle. Niacinamide is a massive methylation agent mop. And niacin ends up being niacinamide. Now, long term niacin supplementation increased homocysteine by a whopping 55%. Massive. And pure niacinamide should raise it even more. To put it in context, such increase in homocysteine ups heart disease risk by 80%. Not to mention what it does to your dopamine system and mood. Sure hope that this too was a hatched job study by the Big Pharma. http://www.ahjonline...e/S0002-8703(99)70073-6/abstract

 

Great posts! Certainly creates a need for more information.

 

Now I've been taking grams of niacin for 47 years and my homocysteine measures mid-normal consistently.

 

Is that possibly because I also take 200 B6, 1,000 - 2,000 mg of methylfolate/folic acid, and 5,000 methyl-B12 sublingual a day, which reduces homocysteine?

 

I have wondered why my homocysteine doesn't measure high when I take so much niacin, so I have assumed, but have not done some blood tests with niacin but without B6, B12 and folate, so that's something I'll do with my anti-aging doctor to check. Sounds like worthwhile experimentation, because I love my niacin flushes, when I get them and the way it helps me wake up in the morning - for years now.

 

It would make sense that if one takes a single B-vitamin without any of its "partners" that something out-of-norm would happen, although B-vitamins have wide safety indexes and they typically have high LOAEL's.

 

There are certainly other methyl-donors that I take, like DMAE, that might help make up for losing some via taking high dose niacin.

Edited by mikey, 30 November 2014 - 05:59 PM.

[Vastmandana]

Thank you, Ukko... BTW, for those with the time, the entire dissertation linked to in Ukko's first post, two above this. ( above ), is some 160 pages long  and is downloadable as a pdf...

 

And you've reminded me to switch all my NR to the morning.  What about Resveratrol?  right now I'm doing 1-2g/day in divided doses....

[Ukko]

Mikey you are living proof that long term niacin supplementation is viable, IF you do it right. Seems like methyl donors are key. As to resveratrol,does it not have a bell shaped curve with benefits? I am only taking 250mg a day, but the form I take is 99% pure.

[Vastmandana]

I assume you're using trans-resveratrol, micronized like this? As a fellow multiverser, you should!  

[Ukko]

I assume you're using trans-resveratrol, micronized like this? As a fellow multiverser, you should!

I think so. For a while, I was on pterostilbene instead.

[M-K]

I am bit confused. Have you guys not read the studies showing how high niacinamide reduces NAD+. There's a feedback loop such that the cells use the NAD+ breakdown product niacinamide to sense ambient NAD+ levels. Artifially high niacinamide this shuts down NAD+ synthesis. Niacinamide is no solution, certainly not at higher levels. Free form niacin may be, but I am still not sold on it from the PGD2 and methylation angle.

Here's what I mean with the methylation angle. Niacinamide is a massive methylation agent mop. And niacin ends up being niacinamide. Now, long term niacin supplementation increased homocysteine by a whopping 55%. Massive. And pure niacinamide should raise it even more. To put it in context, such increase in homocysteine ups heart disease risk by 80%. Not to mention what it does to your dopamine system and mood. Sure hope that this too was a hatched job study by the Big Pharma. http://www.ahjonline...e/S0002-8703(99)70073-6/abstract

Great posts! Certainly creates a need for more information.

Now I've been taking grams of niacin for 47 years and my homocysteine measures mid-normal consistently.

Is that possibly because I also take 200 B6, 1,000 - 2,000 mg of methylfolate/folic acid, and 5,000 methyl-B12 sublingual a day, which reduces homocysteine?

Do you mean micrograms of B12 and FA?

Edited by M-K, 30 November 2014 - 10:41 PM.

[VERITAS INCORRUPTUS]

1. Rather doubt we can just chug a bunch of d-ribose and niacinamide/niacin and it magically becomes NR

2. NR is operating differently than either other, and even they operate differently. so... No, Veritis... ya can't just chug the others and get the same result...

3. This is way beyond our pay grade... they (super smart people) haven't figured it all out yet and we're talkin 10 years! 

1. Actually it is not magic, it is simply what the body does - but obviously there exists rate limiting factors (hence direct NAD+ may be of greatest benefit, or NR within only IF it is taken i.n./subL/inj.)

2. See 1 and see that NR is not absorbed intact, meaning it is all about 1 (within NR taken orally, as per intended by the supplement most are consuming)

3. See 1 and 2 (as example) - and no one can ever figure it ALL out as the body is not a simple math equation with known set dynamics and variables

***3a.  There is a lot more to it and a lot they obviously did not go about properly defining (intentionally?)...and still no one else can find the research paper demonstrating that NAD+ can enter the cell intact?  Within that maybe some people DO have more of a clue than the 'experts'.

[mikey]

 

 

 

I am bit confused. Have you guys not read the studies showing how high niacinamide reduces NAD+. There's a feedback loop such that the cells use the NAD+ breakdown product niacinamide to sense ambient NAD+ levels. Artifially high niacinamide this shuts down NAD+ synthesis. Niacinamide is no solution, certainly not at higher levels. Free form niacin may be, but I am still not sold on it from the PGD2 and methylation angle.

Here's what I mean with the methylation angle. Niacinamide is a massive methylation agent mop. And niacin ends up being niacinamide. Now, long term niacin supplementation increased homocysteine by a whopping 55%. Massive. And pure niacinamide should raise it even more. To put it in context, such increase in homocysteine ups heart disease risk by 80%. Not to mention what it does to your dopamine system and mood. Sure hope that this too was a hatched job study by the Big Pharma. http://www.ahjonline...e/S0002-8703(99)70073-6/abstract

Great posts! Certainly creates a need for more information.

Now I've been taking grams of niacin for 47 years and my homocysteine measures mid-normal consistently.

Is that possibly because I also take 200 B6, 1,000 - 2,000 mg of methylfolate/folic acid, and 5,000 methyl-B12 sublingual a day, which reduces homocysteine?

 

Do you mean micrograms of B12 and FA?

 

 

Good catch!

[Bryan_S]

Guys remember this thread is about alternative NAD+ precursors. As we determined from research earlier NAD+ can not be taken orally as it breaks down into (NAM) in the acidic environment of the digestive system.

 

Also somewhere along the line the (NAR) correlation was lost.  The #1 being bantered about is about nicotinic acid riboside (NAR) not (NR). Not sure how this got misinterpreted into a way to make nicotinamide riboside (NR), nothing could be further from the truth.

 

Charles Brenner investigated this pathway.  "Intracellular NAD+ metabolism in humans. Tryptophan (Trp), nicotinic acid (Na), nicotinamide (Nam), nicotinamide riboside (NR), and possibly nicotinic acid riboside (NaR) are utilized through distinct metabolic pathways to form NAD+." I doubt we will see any further investigation into this path because the lead researcher has another dog in this race and a vested interest in its success.  

http://www.medicine..../Content/73.pdf

 

(NAR) Synonyms:  D-Ribosylnicotinate, Nicotinate riboside, Nicotinic acid ribose, Nicotinic acid riboside, Ribosylnicotinate

 

http://www.ncbi.nlm....les/PMC2610512/

 

No one is planning on "chugging" down a bunch of d-ribose and niacinamide to make Nicotinamide riboside it's not that simple. As mentioned in an earlier post Sigma-Aldrich Co. LLC. has discontinued making nicotinic acid riboside (NAR) See link http://www.sigmaaldr...ng=en&region=US

There is another supplier that turned up since that search but the price would put must of us off: http://www.carbosynt...02579CF0061779A

 

What we found however is the stuff may readily combine chemically in the presents of water.

 

We reviewed the chemical reaction of nicotinic acid riboside in the following post.

http://www.longecity...e-3#entry698206

 

Seems like a simple reaction, its titled as: nicotinate D-ribonucleoside ribohydrolase REACTION: R10046

 

Nicotinate D-ribonucleoside + H2O <=> Nicotinate + D-Ribose

 

Equation C05841 + C00001 <=> C00253 + C00121

 

So (NAR) not (NR) "may" be as easy as "chugging" those components together. So far none of our biochemists have chimed in. The <=> means the reaction is assumed to be reversible when the equation includes this symbol so the following should be true.

 

Nicotinate + D-Ribose <=> Nicotinate D-ribonucleoside + H2O

 

"The chemical reaction in the form of an equation. The reaction is assumed to be reversible and reactants (substrates and products) are separated by '<=>'. Each compound in the left or the right side is separated by ' + '. There may be a coefficient before the compound name."

 

Logic felt we were rehashing an old topic on this precursor from a thread he found from 2009 but I can see now that the nicotinic acid riboside (NAR) message was lost.  

http://www.longecity...-3#entry698224 

 

Here is a chart including this pathway, see the bottom left corner. As the chart suggests NAR is not a straight shot to NAD but it does not follow the path of NAM, it instead follows a similar path to Niacin (Na) which is along the Preiss-Handler pathway.

 

[VERITAS INCORRUPTUS]

Honestly, what are you not getting...all these conjugates most likely are breaking down in the gut, certainly including NR, and certainly likely include NAR if such were available/evaluated (same for NAM).

Actually, the one with potential to be shown to perhaps survive the gut is NAD+ as it is most stable in acidic media as I am aware.  

That one study as being so 'referenced' above is not definitive, conducted suboptimally, and not wholly clear to note.

New oral bioavailability research of all these agents should be the top priority - however, these scientists now so involved are all BIASED in their research - as I stated as well - pure COI!!!

 

For now it may be best to assume all are not surviving the gut intact.  NR again is simply working as so demonstrated via acting as a SR-conjugate, within that a rather costly one.

(Most are of course taken orally, so again this is a primary concern for optimal benefit - especially what is optimal to your wallet!)

 

So again, NR taken orally is JUST SR-NAM and SR-Ribose - and as such ingestion of NR can be mimicked FAR mosr economically via using the single agents and not the 'conjugated SR-delivery system' that NR appears to be.

 

So it's NA and NAM as simple cost effective agents to use, along with Ribose which cannot hurt.  

Ukko pointed out to use morning preferably, which mikey does as well, as to take advantage of the window for superior efficacy as to the body's natural rhythm of production.

I noted as well direct NAD+ and NR taken in a manner other than oral is certainly of potential benefit - within that perhaps go for the NAD+ primarily.

DO NOTE: NAD+ can directly enter the cell.

 

Otherwise we have ascertained it is a wise idea to consider making sure to evaluate matters that pertain to methylation and liver stress status.

Within that, if such appears to cause undermethylation TMG, MB12, MF, and related are good adjuncts.

Further hepatoprotectants may best be increased, such as ALA and biotin, et al.

 

The low dose aspirin factor and resveratrol are as well indicated as to display benefit as so stated.

 

Further that, note if any means to promote increase in maintained continuously there may be a downregulation, so that should be accommodated or at least considered in some manner.

(So 'chug' a bit, but do not just chug away, lol - or better 'chug wisely')

 

Further that, what I am missing?  I am just trying to define the most practical methods and understanding.

 

Above that I would add do NOT overthink it too much as the body may just not be complying to what you may be thinking to tweak any and every little angle as all are not understood and the complexity is enormous.

Again, looking at a most practical protocol basis from the understanding as now stands, and within not to think we can manipulate the body in some overly precise manner - good luck with that.

 

If I missed anything this was banged out while juggling some stuff - so apologies if a bit rough - but I would hope someone sees the point - as practical protocols of practical(realizable) benefit I would think are the goal. Look at the core, not trying to tweak every and any pathway, as the body likely will not be 'accommodating' as you might so think.

Edited by VERITAS INCORRUPTUS, 01 December 2014 - 03:19 PM.

[mikeinnaples]

Great posts! Certainly creates a need for more information.

 

Now I've been taking grams of niacin for 47 years and my homocysteine measures mid-normal consistently.

 

Is that possibly because I also take 200 B6, 1,000 - 2,000 mg of methylfolate/folic acid, and 5,000 methyl-B12 sublingual a day, which reduces homocysteine?

 

I have wondered why my homocysteine doesn't measure high when I take so much niacin, so I have assumed, but have not done some blood tests with niacin but without B6, B12 and folate, so that's something I'll do with my anti-aging doctor to check. Sounds like worthwhile experimentation, because I love my niacin flushes, when I get them and the way it helps me wake up in the morning - for years now.

 

It would make sense that if one takes a single B-vitamin without any of its "partners" that something out-of-norm would happen, although B-vitamins have wide safety indexes and they typically have high LOAEL's.

 

There are certainly other methyl-donors that I take, like DMAE, that might help make up for losing some via taking high dose niacin.

 

 

2 grams nicotinic acid / day here and my homocysteine hasn't been high either

 

Possible factors:

 

TMG - 1g/day

P5P -  50mg/day

Methyl B12 sublingual - 1000mcg 3x/week

Methyl Folate - 400mcg 3x/week

NAC - 600mg 3x/week

C60?

[VERITAS INCORRUPTUS]

^

Such would seem well indicated as so noted for an optimized total protocol - which maybe can be worked up from within all this.

Notably though, it would be great to know the outcomes were not the agents so included in these high dose, chronic administration protocols, as per mikey may evaluate as so noted.

Too bad no one will do actual studies here, as some of the published science seems perhaps 'tainted'

 

[Ukko]

http://www.ncbi.nlm....pubmed/19913571

 

Or we all ... could ... just ... like ... work out ... a lot more

 

 

[VERITAS INCORRUPTUS]

http://www.ncbi.nlm....pubmed/19913571

 

Or we all ... could ... just ... like ... work out ... a lot more

 

Sound exercise makes most everything work better - to put it simply, and as stated prior (but re-emphasis and a good study is never a bad thing IMB)

- the ultimate 'precursor', lol 

 

Take your NA/NAM/Ribose (et al) 30-45 minutes prior to your workouts, preferentially conducted prior to noon - and likely get the most out of your body's natural mechanisms.

Probably best method overall would be to take twice per day, upon waking and late in the morning, close to noon.  Than allow the body to restore for the next day.

NR too if one likes, but as so noted, unless taken subL it is likely just expensive NAM in the end per oral route.

 

Take direct NAD+ as subL in the later hours seems a good bet here as well.

[Bryan_S]

Honestly, what are you not getting...all these conjugates most likely are breaking down in the gut, certainly including NR, and certainly likely include NAR if such were available/evaluated (same for NAM).

Actually, the one with potential to be shown to perhaps survive the gut is NAD+ as it is most stable in acidic media as I am aware.  

That one study as being so 'referenced' above is not definitive, conducted suboptimally, and not wholly clear to note.

New oral bioavailability research of all these agents should be the top priority - however, these scientists now so involved are all BIASED in their research - as I stated as well - pure COI!!!

 

For now it may be best to assume all are not surviving the gut intact.  NR again is simply working as so demonstrated via acting as a SR-conjugate, within that a rather costly one.

(Most are of course taken orally, so again this is a primary concern for optimal benefit - especially what is optimal to your wallet!)

 

So again, NR taken orally is JUST SR-NAM and SR-Ribose - and as such ingestion of NR can be mimicked FAR mosr economically via using the single agents and not the 'conjugated SR-delivery system' that NR appears to be.

 

So it's NA and NAM as simple cost effective agents to use, along with Ribose which cannot hurt.  

Ukko pointed out to use morning preferably, which mikey does as well, as to take advantage of the window for superior efficacy as to the body's natural rhythm of production.

I noted as well direct NAD+ and NR taken in a manner other than oral is certainly of potential benefit - within that perhaps go for the NAD+ primarily.

DO NOTE: NAD+ can directly enter the cell.

 

Otherwise we have ascertained it is a wise idea to consider making sure to evaluate matters that pertain to methylation and liver stress status.

Within that, if such appears to cause undermethylation TMG, MB12, MF, and related are good adjuncts.

Further hepatoprotectants may best be increased, such as ALA and biotin, et al.

 

The low dose aspirin factor and resveratrol are as well indicated as to display benefit as so stated.

 

Further that, note if any means to promote increase in maintained continuously there may be a downregulation, so that should be accommodated or at least considered in some manner.

(So 'chug' a bit, but do not just chug away, lol - or better 'chug wisely')

 

Further that, what I am missing?  I am just trying to define the most practical methods and understanding.

 

Above that I would add do NOT overthink it too much as the body may just not be complying to what you may be thinking to tweak any and every little angle as all are not understood and the complexity is enormous.

Again, looking at a most practical protocol basis from the understanding as now stands, and within not to think we can manipulate the body in some overly precise manner - good luck with that.

 

If I missed anything this was banged out while juggling some stuff - so apologies if a bit rough - but I would hope someone sees the point - as practical protocols of practical(realizable) benefit I would think are the goal. Look at the core, not trying to tweak every and any pathway, as the body likely will not be 'accommodating' as you might so think.

 

Are you here to just bash NR? trance and I started this thread to look for cost effective NAD precursors. My posts here have concentrated on the NAD precursors such as Tryptophan (Trp), nicotinic acid (Na), nicotinamide (Nam), nicotinamide riboside (NR), and nicotinic acid riboside (NaR). In fact when I brought up Charles Brenner and the whole NaR topic you said it was biased and tied his research to a conflict of interest. Really NaR, how does identifying nicotinic acid riboside (NaR) as a precursor in his paper demonstrate a conflict of interest? Charles Brenner may be tied to nicotinamide riboside (NR) because it's his baby but he has no vested interest in nicotinic acid riboside (NaR). You're not even subtle about bashing nicotinamide riboside and you mentioned it 6 times in a response to a post about (NaR).  

 

Obviously you must think I'm so pro (NR) that you need to battle me, think about why am I posting here and looking for alternative precursors?

 

We have not concentrated on NAD+ because no research has demonstrated it can be absorbed intact. That is why we are examining all the research into the NAD precursors which is the topic of this thread. In fact go out there and examine all the current research and find a recent orally administrated application for NAD+? Once you've completed that task examine all the intravenous or in vivo applications of NAD+ then like everyone else who has looked into this topic you'll release why this approach hasn't worked and why other solutions to increase NAD levels have been researched. If it was just as easy as taking NAD+ or NADH we'd all be taking it. "Honestly, what are you not getting."

 

So my point is the topic of this thread is "Are Other Precursors as Effective in Increasing NAD+ as NR?"

 

Also remember I'm not a vendor like you and don't work for a company like TrueLIFE Research selling NAD+, I don't make a dime off any of this banter. If you have another pet topic like "TrueLIFE Research demonstrates their NAD+ is more effective than ChromaDex's nicotinamide riboside" then please start a thread on that. If your companies NAD+ can make it passed the gut intact, and then make it past the second barrier of the cell membrane, produce the URL linked research to support that and you'll find a huge audience on Longecity but I haven't read any evidence to suggest that's even remotely true.

Edited by Bryan_S, 03 December 2014 - 01:09 AM.

[VERITAS INCORRUPTUS]

Are you here to just bash NR? trance and I started this thread to look for cost effective NAD precursors. My posts here have concentrated on the NAD precursors such as Tryptophan (Trp), nicotinic acid (Na), nicotinamide (Nam), nicotinamide riboside (NR), and nicotinic acid riboside (NaR). [...] We have not concentrated on NAD+ because no research has demonstrated it can be absorbed intact. [...]

 

I'm not a vendor like you and don't work for a company like TrueLIFE Research selling NAD+, I don't make a dime off any of this banter. If you have another pet topic like "TrueLIFE Research demonstrates their NAD+ is more effective than ChromaDex's nicotinamide riboside" then please start a thread on that. [...] I haven't read any evidence to suggest that's even remotely true.

 

 

 

http://molpharm.aspe...073916.full.pdf

 

Have a Nice Day 

Edited by Michael, 11 February 2015 - 06:51 PM.