142 replies to this topic

[trance]

 Researching the possibility that other niacin precursors along with tryptophan may increase NAD+  levels safely and be less costly than NR.  There may also be a synergistic effect via a combination of precursors within safe doses.

 

 Seems that NA (nicotinic acid) has some potential benefits towards raising NAD+ as long as dose is not at hepatic toxic levels, but some individuals do not enjoy the flush effect. 

 

 NAM (nicotinamide) has some lessor benefits as it's found to have inhibitory effects on sirtuins.

 

 Various papers (old and new) attached for your reading pleasures.

 

 Trance

 

 

 Nicotinic Acid-Nicotinamide-Nicotinamide Riboside.pdf   1.24MB   43 downloads

 

 Large Supplements of Nicotinic Acid Etc.pdf   1.39MB   34 downloads

 

 Nicotinamide Mononucleotide Diet Age Diabetes Mice.pdf   1.05MB   20 downloads

 

 NAD Biosynthesis in Human Cells.pdf   315.67KB   21 downloads

 

 NAD+ and Vitamin B3 From Metabolism to Therapies.pdf   209.16KB   23 downloads

 

 The Secret Life of NAD+ An Old Metabolite.pdf   435.71KB   17 downloads

 

 Comparative Genomics of NAD.pdf   412.87KB   18 downloads

 

 Exploring the therapeutic space around NAD+.pdf   1.2MB   23 downloads

 

 

.

[Bryan_S]

OK good start, most of us who are on this path have been pushing for alternatives and if there are none why. So of all the precursors which have been shown to raise NAD levels the most? I think what we should endeavor to do is build a matrix of benefits and qualify the pros and cons of each precursor. I'm at the office now but will start assembling some of this when I get home.

[Kevnzworld]

Until more is published I've decided to take both NR and NA.
100 mg of NA is all I can tolerate.
From everything I've read ( and watched via to age or not age ), I've also increased my daily resveratrol dosage to 200 mg.

[VERITAS INCORRUPTUS]

If not deemed inappropriate may I posit this as per bioavailability of NAD+ and NADH:

 

There is a study displaying that NAD itself is well absorbed orally and in a far superior fashion to NADH, which is shown in that study to be metabolically altered within the digestive tract to agents that were not identifiable within the scope of the study.  Within that study NADH displayed a lack of significant oral bioavailabilty, however, again, NAD did show solid oral ROA efficacy.

 

The above referenced study is cited within the below link so to get some further overview see this link perhaps that gives a brief overview:

http://teamtlr.com/a...ide-nad-99.html   

 

As well for reference:

Pharmacol Toxicol. 2002 Apr;90(4):220-5.

Bioavailability of reduced nicotinamide-adenine-dinucleotide (NADH) in the central nervous system of the anaesthetized rat measured by laser-induced fluorescence spectroscopy.

Rex A1, Hentschke MP, Fink H.

Author information

• 1Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Koserstr. 20, D-14195 Berlin, Germany. andrerex@zedat.fu-berlin.de

Abstract

Drugs intended to increase wellness or quality of life ("lifestyle drugs") have gained popularity and/or importance over recent years. Biogenic substances like nicotinamide adenine dinucleotide (NADH) are supposed to increase the physical and intellectual performance without side-effects. NADH is an energy-delivering co-substrate in the respiratory chain. Clinical studies showed positive effects of peripherally given NADH in Morbus Parkinson and major depression. NADH can be measured by its fluorescence. In this study a pulsed N2-laser combined with a fibre-optic probe and photomultipliers was used to induce and measure NADH fluorescence in the rat cortex. The aims of the study were to assess the suitability of the laser-induced spectroscopy for in vivo and on-line measurement of NADH in neuroscience and the assessment of the central availability of NADH after peripheral administration. NADH (50 mg/kg) but not the precursor nicotinamide caused a significant rise of the NADH fluorescence intensity indicating an increase of the NADH concentration in the rat cortex. In conclusion, the results suggest that NADH given orally or intraperitoneally increases the amounts of NADH in the brain. The results may thus help to explain the clinical effects reported.

 

[Bryan_S]

That great I would also like us to make a full list of all of the available NAD precursors and examine the bioavailability of each and the effects on sirtuins. My reading lately has drawn me towards looking at (NAM) nicotinamide. I am however hesitant to move towards therapeutic dosages because of the suggested toxicity. (NR) also hasn't been discussed in detail in this nicotinamide light either, after all (NR) is taken up into the salvage pathway and after (NAD) is produced and metabolized we are concentrating (NAM) nicotinamide levels as well.

 

VERITAS INCORRUPTUS,

 

Here is one of the more recent comparisons on your topic.

Comparison of Metabolic Fates of Nicotinamide, NAD+ and NADH Administered Orally and Intraperitoneally; Characterization of Oral NADH

https://www.jstage.j..._2_142/_article

 

We are all after the same thing I think what we all want is the best way to get there.

[VERITAS INCORRUPTUS]

Yes, that is the study I was referencing and that study and a few others are referenced in our overview page for NAD+ that is within the link included in my post.

 

Indeed, the outcome is to foster research and pursuit for overall best means to the goals so involved within this area of research. 

 

Thanks!

[Bryan_S]

Bioavailability is a fundamental part of this: I don't think most of us will inject ourselves but we can include that sort of data if applicable because I know some on our forums who will administer some of these substances that way. I think most of us would consider sublingual before the needle but sublingual isn't going to be a path explored at all in animal studies. There are also other means of administration we can address to avoid the digestive track however data will become scarce for many of these. One often overlooked area is from the cosmetics industry and I know Niacin and (NAM) nicotinamide have both been well explored from a topical application standpoint. Both are active ingredients in a number of products.

 

I look forward to how this discussion will develop.

Edited by Bryan_S, 16 October 2014 - 06:35 PM.

[VERITAS INCORRUPTUS]

We are supplying high purity pure powder for those who wish to conduct animal research (NAD+) within any ROA including oral, intranasal, injectable, transdermal, or, well, there are other routes as well, though not perhaps as applicably of interest.

 

As noted, we hope to supply NR in this pure powder form as well, and as of now NM seems too formidable as to cost for any practicality.

 

In the future we may be supplying compounded in other formats within this and other agents

[mikeinnaples]

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.

[mikeinnaples]

Until more is published I've decided to take both NR and NA.
100 mg of NA is all I can tolerate.
From everything I've read ( and watched via to age or not age ), I've also increased my daily resveratrol dosage to 200 mg.

 

Thing thing about the flush is that tolerance can be built up slowly over time by steadily ramping up dosage. I used to flush at 50mg of NA, and now I can take 2g at a time with no flush (* slight disclaimer I will get to in a bit). With that said, even if you have issues with flushing and tolerance, you could try taking an aspirin about 30 minutes prior to the niacin and see if that helps. Since many of us are taking at least a baby aspirin daily anyways and in light of some of the prior discussions on the boards around the synergies of aspirin regarding the NAD cycle, it seems like a no brainer to at least try.

 

Back to my disclaimer, I will flush if I drink hot liquid such as tea or coffee fairly soon after taking NA. I have also noticed that a methyl donor like TMG, which I have just started taking again, just prior to or with the NA increases flushing. Not sure why, though I have some theories.

[Bryan_S]

We are supplying high purity pure powder for those who wish to conduct animal research (NAD+) within any ROA including oral, intranasal, injectable, transdermal, or, well, there are other routes as well, though not perhaps as applicably of interest.

 

As noted, we hope to supply NR in this pure powder form as well, and as of now NM seems too formidable as to cost for any practicality.

 

In the future we may be supplying compounded in other formats within this and other agents

 

Nicotinamide Mononucleotide (NMN) is very exciting but from a digestive standpoint on another thread we determined this was only an injectable and as such very expensive.

 

I can see now that you have several horses in this derby. Didn't catch that you were a vender in your first post, I'll have to go back and explore that link in more detail. 

Edited by Bryan_S, 16 October 2014 - 07:35 PM.

[APBT]

 

We are supplying high purity pure powder for those who wish to conduct animal research (NAD+) within any ROA including oral, intranasal, injectable, transdermal, or, well, there are other routes as well, though not perhaps as applicably of interest.

 

As noted, we hope to supply NR in this pure powder form as well, and as of now NM seems too formidable as to cost for any practicality.

 

In the future we may be supplying compounded in other formats within this and other agents

 

Nicotinamide Mononucleotide (NMN) is very exciting but from a digestive standpoint on another thread we determined this was only an injectable and as such very expensive.

 

I can see now that you have several horses in this derby. Didn't catch that you were a vender in your first post, I'll have to go back and explore that link in more detail. 

 

 

 

Here’s their sponsored forum link: TrueLIFE Research

[mikey]

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.

 

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.

[trance]

If possible, would one of the moderators move the posts with links to a sales site by VERITAS INCORRUPTUS to one of the vendor threads?   Thanks!

Edited by trance, 17 October 2014 - 12:55 AM.

[trance]

OK good start, most of us who are on this path have been pushing for alternatives and if there are none why. So of all the precursors which have been shown to raise NAD levels the most? I think what we should endeavor to do is build a matrix of benefits and qualify the pros and cons of each precursor. I'm at the office now but will start assembling some of this when I get home.

 
From my reading, nicotinic acid seems to be most effective.  I don't mind the flush myself, and as someone else stated, you develop a tolerance for it over a period of time.  It's really one of the few supplements you can actually "feel" of course.
 
I've been taking a time released 500 mg formula for about a month now, along with NR.  Oddly enough, I don't experience the immediate flush at all as with a normal non-time released capsule.  However during the day I will feel my face and upper arms become engulfed with the typical niacin flush, but it only happens to last for 4-5 minutes at a time.  
 
If I take a 500 mg of non-timed release nicotinic acid, I get the flush in 5-6 minutes, and it lasts for about 30 minutes.
 
I'm thinking there may be a synergistic combination of NAD precursors with nicoticic acid, niacotinamide, and tryptophan that can be just as effective as the new high-priced product.
 
There was an older paper (one by Jackson et al) that indicated nicotinic acid was more effective than nicotinamide in increasing NAD levels in rats, and there was the potential to increase the levels.

"Jackson et al. (1995) also showed that nicotinic acid increases NAD concentrations in liver and blood, similar to nicotinamide. In addition, NAD biosynthesis was increased in heart (50%) and kidney (100%) as well. These results show that nicotinic acid generally has a broader effect than nicotinamide for NAD increases in the body. These results also indicate that the Preiss-Handler pathway is typically operating below saturation in most tissues."

Edited by Michael, 07 May 2017 - 03:05 AM.
Correcting "nictonic acid"

[trance]

 

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.

 

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.

 

 

 Here's the original full paper of the 1994 McKenney study:

 

 jama_271_9_033.pdf   1.94MB   9 downloads

 

 Here's a 1998 paper that asserts their brand (Niaspan) of SR niacin is safe up to 3000mg per day and is well tolerated over 96 weeks:

 

 1-s2.0-S0002914998007310-main.pdf   214.07KB   7 downloads

 

 Here's a chart of tolerance to flushing over those 96 weeks with daily doses of 1000-3000mg (M=2000mg) SR niacin (Niaspan) after initial 4 week ramp up period showing that there is a continual buildup to flushing tolerance:

 

Edited by trance, 17 October 2014 - 02:22 PM.

[Bryan_S]

 

trance, on 14 Oct 2014 - 1:30 PM, said:

 

"I was doing some research on the possibility that plain ole cheap nicotinamide, nicotinic acid, and tryptophan may offer as much precursor value as NR"

 

OK from the other thread I wanted to examine your list and as I mentioned plain ole cheap nicotinamide caught my attention.

 

 

 

 

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

 

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.

 

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

 

Edited by Bryan_S, 17 October 2014 - 05:57 PM.

[Logic]

The above chart is from a study summary done in 2006 called
Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?
http://mmbr.asm.org/...t/70/3/789.full
Its a good read but more recent studies may have improved on what was known then.
Assuming that the information is still good; the chart is great for seeing what is required to increase NAD+ while decreasing SIRT limiting Nam, but is not the whole picture:
Ribose sneaks into and out of the picture with hardly a mention!?
 
Below are my observations,  research leads and questions about these pathways:

1: The salvage of NR?
The only study looking at what happens to NR once ingested says NR is "...slowly cleaved by an enzyme associated with the mucosal cells to nicotinamide..." and that "...NR was not found in intestinal tissue or the perfusate fractions..."
http://jn.nutrition..../113/2/412.long
http://www.longecity...ndpost&p=690504

This study is old and a subsequent studies may have proved it wrong?
Does anybody have any more recent info?

Nicotinamide Riboside feeds into this NamPT salvage pathway between Nam and NAD+. As such it looks like NR will increase NAD+, but this increase will lead to less need for using up/decreasing Nam and hence less SIRT?

2: The salvage of Nam.
If you follow the path from NAD+ to Nam NAD+ is hydrolysed by PARP, MART, SIRT, etc. which releases the Nam from NAD and produces a whole lot of Ribose containing substances, right up to 5-phosphribosyl-1-pyrophosphate. (PRPP)

Starting with NAD+ and working back to Nam its easy to see that we want to improve the NAM salvage pathway by increasing nicotinamide phosphoribosyl transferase (NamPT) and nicotinamide mononucleotide adenylyl transferases (Na/NMNAT-1, -2, and -3), respectively.

3: The salvage of NA.
PRPP is also used up in the salvage of NA, so supplementing with it might decrease the amount available for the salvage of Nam?
 
4: ATP.
ATP is used up all over the place in these pathways, so is there sufficient ATP for these processes and is it in the right places?
 
5:  Phosphate and other minerals etc.
Phosphate in numerous forms is all over the place

6: Ribose.
What the chart doesn't show is where Ribose comes into and leaves the picture??

"ATP (3 phosphates) is converted to ADP (2 phosphates) with the release of energy for work. ADP passes into the mitochondria where ATP is remade by oxidative phosphorylation (ie a phosphate group is stuck on). ATP recycles approximately every 10 seconds in a normal person

If ATP levels drop as a result of leakage of AMP, the body then has to make brand new ATP. ATP can be made very quickly from a sugar D-ribose, but D-ribose is only slowly made from glucose via the pentose phosphate shunt... This takes anything from one to four days"
http://www.drmyhill....ondrial_Failure

It seems to be a common practice to emphasise one part of a molecule in a supplement and not mention the other, important part, for the sake of profit.
Magnesium L-Threonate comes to mind as a good example. It turns out that L-Threnate does way more than make the magnesium bioavailable:
MAGNESIUM L-THREONATE is NO more effective than SULFATE form
http://www.longecity...n-sulfate-form/
L-Threonate for neurogenesis, alzheimer's, hair loss, osteoarthritis
http://www.longecity...osteoarthritis/
The better Vitamin B complexes have many the B as a phosphate..?

Ribose is present in NAD and seems to leave the picture with PRPP.
Nicotinamide looks the worst choice for maximising NAD+ while minimising SIRT limiting Nicotinamide.
Nicotinic Acid Riboside seems like a better choice except for the fact that its Hygroscopic and needs to stored at -20˚C in an inert atmosphere.
http://www.trc-canad...inic Riboside�;

As I have said before:
http://www.longecity...ndpost&p=690504
I think it likely that NR is nothing more than a slow release Nicotinamide and Ribose combo?

Research/info on the Ribose metabolism/production would be great if anyone has any?

Research Leads:

Resveratrol
This study shows that Resveratrol increases NAMPT and SIRT1 in healthy liver cells while decreasing the same in cancerous cells leading to apoptosis!
I have not looked into whether the dosage used is attainable in vivo, but there is similar info on the forum.
http://www.plosone.o...al.pone.0091045
http://www.longecity...atrol-thus-far/

Circadian Control of the NAD+ Salvage Pathway by CLOCK-SIRT1
http://www.schulenbe.../05.08.09.1.pdf
This study was done on mice which are nocturnal? and is not an easy read.
It would be nice if a consensus could be reached on the best timing for the use of different NAD+ increasers.
I'm guessing we will to increase NAD+ at night as Resveratrol is a pro-oxidant during the day-time and an antioxidant at night/
http://www.ncbi.nlm....pubmed/19695122

Inositol hexanicotinate
This looks interesting if it is found that a slow release of NA is desired. (if there's no 'amide' in the word its NA)
I have not yet found any source of slow release Ribose beside NR.
https://www.scribd.c...-Health-Effects

Oops; I hit post in stead of preview.
More coming.

Edited by Logic, 17 October 2014 - 07:36 PM.

[Razor444]

I posted a few studies on NA/NAM via-à-vis Sirt 1 & NAD+, previously.

 

Halting NR ~week ago, and resuming NA, I've positive results with energy levels and focus.

 

 

Here's four quotes, with links to papers, which you may find convincing.

 

"More research is required to determine which clinical situations, what timing, and at what doses nicotinamide would augment or inhibit sirloins in way that best help to accomplish desired therapeutic outcomes. Since nicotinic acid can be used to generate NAD and does not have the inhibitory effects of nicotinamide, it might be a better choice when the goal is to augment sirtuin enzyme activity."  Source

 

"...induced by high-dose niacin (i.e., nicotinic acid given in the range of 2-6 grams) and resveratrol, since both increase sirtuin activity, causing post-translational protein modifications that alter expression of apolipoproteins, transporters, receptors and enzymes involved in lipid metabolism.27 However, nicotinamide riboside might be an even better partner for resveratrol since it increases the availability of NAD+ (and therefore sirtuin activity) without causing flushing." Source

 

"Why is nicotinic acid, but not niacinamide effective in improving dyslipidemia? Nicotinic acid activates Sirt1 in the liver. Sirt 1 deacetylates liver X receptor (LXR), a positive regulator of cholesterol and lipid homeostasis. Niacinamide, at the high doses required to impact dyslipidemia, inhibits sirtuin enzymes (via the mechanism shown above in The Sirtuin Deacetylation Reaction flowchart)." Source

 

"It is important to mention that, although only nicotinamide inhibits sirtuins, both nicotinic acid and nicotinamide lead to increased cellular NAD+ production." Source

 

Edited by Razor444, 17 October 2014 - 10:12 PM.

[Razor444]

 

I'm thinking there may be a synergistic combination of NAD precursors with nicoticic acid, niacotinamide, and tryptophan that can be just as effective as the new high-priced product.

 

 

 

Not sure how credible Ray Peat is? He's got a scolding account of tryptophan, in one of his articles: Tryptophan, serotonin, and aging. He goes as far as labelling it a carcinogen.

 

Edited by Razor444, 17 October 2014 - 10:13 PM.

[Vastmandana]

I'm so puzzled by the amount of posting of humans who don't reveal their age in longevity forums/discussions...

Seems particularly relevant to any discussion of impacts and experiences... I routinely check out the poster's profile and shake my head...

[Razor444]

I'm so puzzled by the amount of posting of humans who don't reveal their age in longevity forums/discussions...

Seems particularly relevant to any discussion of impacts and experiences... I routinely check out the poster's profile and shake my head...

 

 

I think people on the forum are fairly heterogeneous. For example, I've got an autoimmune condition; even if I added my DoB, that's a variable that throws off reasonable extrapolations based on my age.

[Vastmandana]

Razor, I disagree totally... in fact if you indeed have an autoimmune condition, this is an important disclosure as is your age. What IS your autoimmune condition? How old are you?

While any forum is going to be filled with "garbage", we should be striving for full disclosure so the relative merits and applicability of reported observations can be reflected on. Without such disclosures the ability to formulate insights and hopefully greater understanding in a crowd sourced environment is severely limited.

Corporate propaganda and marketing/money driven drivel are bad enough but we are hopefully striving for much more...

Lazy, self absorbed, ignorant, fantasy based stories...or even corporate shills...all come to mind when full disclosure is poo pooed. On the other hand, posters may well be striving to share real insights/experiences... it's hard to tell...

Denying the relevant of age in a potentially amazing longevity compound or the importance of your (still undisclosed) particular condition, which might negate any possible impact NR would have otherwise... places your post in the "garbage" pile to me....as does your objections to the relevance of full disclosure by your mentioning another thing you haven't shared...

Personally I feel every member should spend a bit more effort on their profiles in these areas if we are to get the most out of our shared experiences.

Edited by Vastmandana, 18 October 2014 - 01:06 AM.

[Razor444]

Razor, I disagree totally... in fact if you indeed have an autoimmune condition, this is an important disclosure as is your age. What IS your autoimmune condition? How old are you?

While any forum is going to be filled with "garbage", we should be striving for full disclosure so the relative merits and applicability of reported observations can be reflected on. Without such disclosures the ability to formulate insights and hopefully greater understanding in a crowd sourced environment is severely limited.

Corporate propaganda and marketing/money driven drivel are bad enough but we are hopefully striving for much more...

Lazy, self absorbed, ignorant, fantasy based stories...or even corporate shills...all come to mind when full disclosure is poo pooed. On the other hand, posters may well be striving to share real insights/experiences... it's hard to tell...

Denying the relevant of age in a potentially amazing longevity compound or the importance of your (still undisclosed) particular condition, which might negate any possible impact NR would have otherwise... places your post in the "garbage" pile to me....as does your objections to the relevance of full disclosure by your mentioning another thing you haven't shared...

Personally I feel every member should spend a bit more effort on their profiles in these areas if we are to get the most out of our shared experiences.

 

With all due respect, we've gotten off topic. As such, I'm not following this line of enquiry any longer.

I'm happy to talk about anything I know -- or could research -- relating to precursors of NAD+.
 

[Vastmandana]

Razor I do apologize for posting my perspective in this particular thread as it it's more relevant to the personal experiences thread.... And I do appreciate your links... it will take me the weekend to digest the voluminous information recently posted in this very interesting thread.

What particularly caught my interest was your stated discontinuation of NR for what you say is a superior result from niacin... it's those kind of observations/statements that would benefit from more personal info when crowd sourcing data.

Edited by Vastmandana, 18 October 2014 - 02:35 AM.

[mikey]

Inositol hexanicotinate
This looks interesting if it is found that a slow release of NA is desired. (if there's no 'amide' in the word its NA)
I have not yet found any source of slow release Ribose beside NR.
https://www.scribd.c...-Health-Effects
 

William Parsons, MD, the Mayo Clinic researcher who did the work confirming niacin's effects on blood lipids told me that Riker Labs, "a good pharmaceutical company" paid to have him study inositol hexanicotinate, because they were considering marketing it in the USA.

 

But he found that it didn't work and so Riker didn't move forward with it.

 

 

Edited by mikey, 18 October 2014 - 09:24 AM.

[Logic]

Inositol hexanicotinate
This looks interesting if it is found that a slow release of NA is desired. (if there's no 'amide' in the word its NA)
I have not yet found any source of slow release Ribose beside NR.
https://www.scribd.c...-Health-Effects
 
William Parsons, MD, the Mayo Clinic researcher who did the work confirming niacin's effects on blood lipids told me that Riker Labs, "a good pharmaceutical company" paid to have him study inositol hexanicotinate, because they were considering marketing it in the USA.
 
But he found that it didn't work and so Riker didn't move forward with it.

Thx Mikey

I assume they were looking at getting the cholesterol improving effect of increasing HDL and lowering LDL?
If so this may still be of interest as a slow release low level niacin source.

[Logic]

Resveratrol and Nampt - What is Resveratrol's true target?
http://www.longecity...arget/?hl=nampt


Targeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+?
"...SIRT1 uses NAD+ as a substrate to remove acetyl groups from a target protein...

...nicotinamide (NAM), which exerts a potent end-product inhibition on SIRT1 activity in a noncompetitive fashion with NAD+ (Bitterman et al., 2002; Anderson et al., 2003). Kinetic studies demonstrate that NAM acts at a Km between 30 and 200 μM (Bitterman et al., 2002). The reference values for the intracellular concentration and subcellular compartmentalization of NAM are still far from determined, an issue that is further complicated by the diffusive nature of NAM (van Roermund et al., 1995). Indirect evidence of the large influence of NAM on SIRT1 activity is derived from experiments that manipulate NAM metabolism through changing the activity of nicotinamide phosphorybosyltransferase (Nampt). In the cell, NAM is used as a substrate for NAD+ resynthesis through the action of Nampt (Revollo et al., 2004). Inhibition or down-regulation of Nampt leads to NAM accumulation and NAD+ depletion, ultimately decreasing SIRT1 activity (Revollo et al., 2004). This highlights how NAM can influence SIRT1 activity through different means: first, as a noncompetitive SIRT1 inhibitor, and, second, as an NAD+ precursor. Low levels of NAM might therefore be beneficial for SIRT1 activity, because NAM can act as an NAD+ precursor, but, more importantly, accumulation of NAM could be deleterious through the inhibition of SIRT1 (Yang and Sauve, 2006)..."
http://intl.pharmrev...t/64/1/166.full

[mikey]

 

Inositol hexanicotinate
This looks interesting if it is found that a slow release of NA is desired. (if there's no 'amide' in the word its NA)
I have not yet found any source of slow release Ribose beside NR.
https://www.scribd.c...-Health-Effects
 
William Parsons, MD, the Mayo Clinic researcher who did the work confirming niacin's effects on blood lipids told me that Riker Labs, "a good pharmaceutical company" paid to have him study inositol hexanicotinate, because they were considering marketing it in the USA.
 
But he found that it didn't work and so Riker didn't move forward with it.

Thx Mikey

I assume they were looking at getting the cholesterol improving effect of increasing HDL and lowering LDL?
If so this may still be of interest as a slow release low level niacin source.

 

 

You're quite welcome!

However, Dr. Parsons said that IH didn't work for blood lipids, thus I would not include it.

 

Further, just for the record because someone had doubts about taking niacin long term and liver toxicity, I've been taking it at doses between 300 and 3,000 mg a day for 46 years, since I was about 15 and first read about what it did for schizophrenics, having been in the mental hospital for depression and refusing drugs and shock therapy.

 

I was released from the mental hospital and stumbled on an article about Hoffer's use of quick-release plain niacin for schizophrenics at 3,000 mg a day and took that dose for about six months and it changed my life completely, as far as depression. I've been taking some level of high dose ever since.

 

I do multiple comprehensive blood tests every year - since my 30's and my transaminases and GGT always measure OK, even when drinking a lot of alcohol in my 20's and 30's.

 

I take several liver-protecting dietary supplements, so that may be why they always measure well.

[Logic]

Forget the science; just tell me what to take!?
Oh all right:
http://www.longecity...ndpost&p=656403

AMPK Activators from Natural Products:
http://img.kisti.re....riginalView.jsp

Edited by Logic, 18 October 2014 - 10:28 PM.