529 replies to this topic

[niner]

Is anyone saying that high doses of NR is safe, actually taking high doses of NR?

 

In the Sinclair study of NMN, the mice were fed a high doe for just one week and they were sacrificed very soon afterwards ....No one knows the long term effects.

 

Sinclair said in December 2013..."It would be a year to conclude if the NMN molecule trial on humans was safe and successful."

 

You may want to wait for an FDA approved product, but others here have different levels of risk tolerance.  Sinclair certainly isn't going to make a public statement telling people it's safe.  That would be rash and unnecessary.  If people like Guarente are taking it themselves, that tells us something.  The community is sharing experiences with it, and we are building up a knowledge base.  This isn't a placebo controlled Phase 3 trial, but it also doesn't cost a hundred million dollars and take ten years.
 

[midas]

 

Is anyone saying that high doses of NR is safe, actually taking high doses of NR?

 

In the Sinclair study of NMN, the mice were fed a high doe for just one week and they were sacrificed very soon afterwards ....No one knows the long term effects.

 

Sinclair said in December 2013..."It would be a year to conclude if the NMN molecule trial on humans was safe and successful."

 

You may want to wait for an FDA approved product, but others here have different levels of risk tolerance.  Sinclair certainly isn't going to make a public statement telling people it's safe.  That would be rash and unnecessary.  If people like Guarente are taking it themselves, that tells us something.  The community is sharing experiences with it, and we are building up a knowledge base.  This isn't a placebo controlled Phase 3 trial, but it also doesn't cost a hundred million dollars and take ten years.
 

 

 

I understand all that and I am prepared to use it myself, I already have Niagen...All I was saying is that it might not be a good idea to take 7 grams per day as has been suggested. As we have no idea if that dosage is safe in humans taken long term, I just urge caution, that's all.

 

Why would I be on the group buy thread if I was waiting for FDA approval (not that I have any faith in your FDA, far to many of the drugs they have signed off kill thousands of people every year)

And I must have missed something along the way because I have not seen or read anywhere that Guarente is taking NR?? Did he say how much he was taking?

 

In case you didn't notice I am part of the community you speak of, and I have just as much right to share my thoughts and speak my mind as anyone else.

Whether you actually agree with them or not is of no concern to me,(I also don't care about the little points award thing under my name ) all I want is for people to think before they jump with high dose NR.

 

I also find it strange that for people that want to live longer and healthier it is sort of going against the tide to chance taking to much of something that we know virtually nothing about in human terms.That sort of flies in the face of what its all about from my way of thinking..

 

Attempt to live longer and healthier by risking your health. ........Something wrong there!!

 

One of my friends when I was younger was a victim of thalidomide

 

 

Edited by midas, 25 April 2014 - 12:53 AM.

[niner]

In case you didn't notice I am part of the community you speak of, and I have just as much right to share my thoughts and speak my mind as anyone else.
Whether you actually agree with them or not is of no concern to me,(I also don't care about the little points award thing under my name )

Uh, yeah. I noticed. You are rather defensive for someone who doesn't care if anyone agrees with them or not. No one is denying you a chance to voice your opinions. When you put your opinions in a post, others get to reply with their opinions, which may or may not agree with yours. That's how the forum works.

[midas]

 

In case you didn't notice I am part of the community you speak of, and I have just as much right to share my thoughts and speak my mind as anyone else.
Whether you actually agree with them or not is of no concern to me,(I also don't care about the little points award thing under my name )

Uh, yeah. I noticed. You are rather defensive for someone who doesn't care if anyone agrees with them or not. No one is denying you a chance to voice your opinions. When you put your opinions in a post, others get to reply with their opinions, which may or may not agree with yours. That's how the forum works.

 

I don't know that replying to a post directed at me is defensive.

 

But we seem to be on the same page with the other part of your statement.

 

[aribadabar]

midas,

 

Despite your apparent belief that most of the people here cannot think for themselves as evidenced by your redundant warnings, they actually can. Believe it or not - we got it (the first time)!

If you have nothing different to share you only water down the discussion here stating the same thing all over again.

 

Since you have obtained Niagen already, it would be far more valuable to share your experience taking NR at a dosage you consider safe for yourself.

 

 

Sorry for the off-topic, guys.

Edited by aribadabar, 25 April 2014 - 02:15 AM.

[midas]

midas,

 

Despite your apparent belief that most of the people here cannot think for themselves as evidenced by your redundant warnings, they actually can. Believe it or not - we got it (the first time)!

If you have nothing different to share you only water down the discussion here stating the same thing all over again.

 

 

Sorry for the off-topic, guys.

 

OK, so in your world everyone is clever and no one needs to go to an internet forum for advice....Yeah, good luck on that planet!

 

Dude, if you don't like what I post don't read it!

[PWAIN]

OK, so in your world everyone is clever and no one needs to go to an internet forum for advice....Yeah, good luck on that planet!
 
Dude, if you don't like what I post don't read it!

No need to be defensive. Everyone agrees with you to different levels. For some, more risk is ok with them and others would probably be even more cautious than you. You just come across as preaching because you have repeated your warnings so often.

I said this before, different people and circumstances require different response. If you were 103 years old, would you think a bit more risk is warranted? Now if you're 18 and super fit, would you take the risk at all? People will decide their own level of comfort with the risks they are taking. Someone sent me a pm asking about Niagen and indicated they are in their 20s. I suggested not to take Niagen at this time and focus on other things like good sleep, diet, sleep and low stress. If he had been in his 80s or in poor health, I would have responded differently.

We are all dying and if we don't find something and for many of us damn soon then we are going to die!!!!! We can sit around and try live as long as possible with our inaction or we can take certain risks that may backfire badly, but also may just be what we need to keep us alive. That is why I take these untested chemicals, it may, just maybe save my life. I weigh up the risks and try to err on the side of caution but I also have to consider how much life I might have left and realise that if nothing changes, I'm a gonna.

[midas]

 

. Everyone agrees with you to different levels. For some, more risk is ok with them and others would probably be even more cautious than you. You just come across as preaching because you have repeated your warnings so often.

I said this before, different people and circumstances require different response. If you were 103 years old, would you think a bit more risk is warranted? Now if you're 18 and super fit, would you take the risk at all? People will decide their own level of comfort with the risks they are taking. Someone sent me a pm asking about Niagen and indicated they are in their 20s. I suggested not to take Niagen at this time and focus on other things like good sleep, diet, sleep and low stress. If he had been in his 80s or in poor health, I would have responded differently.

We are all dying and if we don't find something and for many of us damn soon then we are going to die!!!!! We can sit around and try live as long as possible with our inaction or we can take certain risks that may backfire badly, but also may just be what we need to keep us alive. That is why I take these untested chemicals, it may, just maybe save my life. I weigh up the risks and try to err on the side of caution but I also have to consider how much life I might have left and realise that if nothing changes, I'm a gonna.

 

 

Nicely put, I hadn't quite thought of it like that before.

 

But having said that, I think some people that have heard about NR and came straight here without any experience of these things, may not have enough knowledge about NR and just instantly take 7 grams a day because of what someone else said, and from what I can see, it may not ever have happened.
 

[Hebbeh]

 

 

 take 7 grams a day because of what someone else said, and from what I can see, it may not ever have happened.
 

 

 

So now you are once again repeatedly calling out a long time member and valuable longecity contributor as a liar....Incredible.  Have you learned nothing from the tactful suggestions of the members attempting to help you see the light?  Or do you treat everybody with disrespect?

[midas]

 

 

 

 take 7 grams a day because of what someone else said, and from what I can see, it may not ever have happened.
 

 

 

So now you are once again repeatedly calling out a long time member and valuable longecity contributor as a liar....Incredible.  Have you learned nothing from the tactful suggestions of the members attempting to help you see the light?  Or do you treat everybody with disrespect?

 

 

I didn't call anybody a liar....It could have been the doctor that was talking through his hat.

 

He said three weeks ago the doctor was thinking of taking 7 grams per day and three weeks later he says that he has been taking it for four years, and that the batch of NR even tests to be something else...I just don't know what to believe, but I am guessing I'm right that he hasn't been taking 7 grams for over four years......I was merely pointing out the inconsistencies in the posts

Some of you people read what you want into stuff, that's your prerogative.

 

I question everything until I have the evidence I need to make a decision, that's how science works, oddly enough!

 

 

All I know is I am on a forum with a hell of a lot of invisible people with made up names and until I know a damn site more about them they could be anybody. I trust no one 100% on the internet, and if you do more fool you. I've seen many people wrongly advised, resulting in damage that cost lots and lots of money. and ripped off on the net.

 

I have also spent a fair amount of time on motorcycle forums and people that have been long standing members dont always work out to know as much as you think they do. I learned a long time ago, not to blindly believe everything I read on the internet....I wonder how many people on here have actually met?

 

If this guy has so much experience and is such an upstanding member of the community why is he advising it is safe to take 7 grams of something that he doesn't take that amount of? That is nothing more than irresponsible

I cant imagine advising someone to do something I hadn't done myself and was 100% sure was safe to do so.

 

Like I said earlier, if you don't like what I post then don't read it. And climbing all over my back on stuff wont do you much good either. The world is full of different people and we are all allowed to have a say......That's democracy for you!............Or is this one of those forums where the forum Gestapo come running out telling me I've been a naughty boy, and you cant speak your mind.

[follies]

Vince has a new blog entry
http://www.anti-agin...o-faces-of-p53/

Very technical. My very simple minded take from it was that P53 is critical to aging and that increasing P53 can slow down or reverse aging ( gross generalization) up to a point. Too much P53 can be harmful with regards to aging. There is much more info in the article.

[midas]

Vince has a new blog entry
http://www.anti-agin...o-faces-of-p53/

Very technical. My very simple minded take from it was that P53 is critical to aging and that increasing P53 can slow down or reverse aging ( gross generalization) up to a point. Too much P53 can be harmful with regards to aging. There is much more info in the article.

 

Also of interest..... http://medicalxpress...blood.html#nwlt

[tunt01]

Vince has a new blog entry
http://www.anti-agin...o-faces-of-p53/

Very technical. My very simple minded take from it was that P53 is critical to aging and that increasing P53 can slow down or reverse aging ( gross generalization) up to a point. Too much P53 can be harmful with regards to aging. There is much more info in the article.

 

James Watson is very bright.  There is a lot going on upstairs with that guy.  I wonder how he is a plastic surgeon in Beverly Hills given the depth of his knowledge in metabolism.  I wish he wrote with more concise, concrete takeaways at the end of each paragraph/section he covers.  Every time I read one of his articles about XYZ protein / ABC enzymatic pathway / whatever, there are only maybe 1 or 2 actionable takeaways which is probably to be expected, but small given the density of the reading he provides.

Edited by prophets, 28 April 2014 - 07:34 PM.

[to age or not to age]

Is it my imagination, or has the thread about NR user experience disappeared?

[APBT]

Is it my imagination, or has the thread about NR user experience disappeared?

It's right here  http://www.longecity...erience-thread/

[albedo]

I registered to participate yesterday to this seminar of L. Guarente on " SIRTUINS, NAD and AGING" which unfortunately was canceled:

http://memento.epfl....-nad-and-aging/

At the end of the link there is an interesting review by LG on "Calorie Restriction and Sirtuins Revisited"

Attached Files

•  Calorie restriction and sirtuins revisited.pdf   773.52KB   27 downloads

[APBT]

FULL TEXT:  http://embomolmed.em...404179.abstract

 

• Download figure
•  
• Open in new tab
•  
• Download powerpoint

Figure 1. The salvage/recycling pathway for NAD+ biosynthesis from nicotinamide riboside (NR) in man

NR, taken in to the body, can be converted to nicotinamide mononucleotide (NMN) by one of two highly conserved NR kinases in the cytoplasm (pathway 1a). NAM (nicotinamide) can also be converted by NMN synthetase to NMN (pathway 1b). NMN is further converted to NAD+ by the action of one of three adenylyltransferases (NMNAT1‐3) that also acts on NaMN (nicotinic acid mononucleotide) to produce NaAD+ (nicotinic acid adenine dinucleotide). The latter is subsequently converted by NAD synthase to NAD+. Nicotinic acid (Na) feeds into the pathway through conversion to NaMN by Na phosphoribosyltransferase (pathway 1c). Tryptophan is the de novo precursor of NAD+ that also feeds into NaMN synthesis via a multistep pathway (2) described in Bogan and Brenner (2008).

 

[APBT]

Leonard Guarente, author

 

http://www.cell.com/...34?showall=true

 

I can't access the full text version without paying.  Anyone have access?

 

 

 

 

Highlights

 

• •NAD+ plays a key role in regulating metabolism and circadian rhythm through sirtuins.
• •NAD+ becomes limiting during aging, affecting sirtuins’ activities.
• •NAD+ decline is likely to be due to a NAD+ biosynthesis defect and increased depletion.
• •Supplementing key NAD+ intermediates can restore NAD+ levels and ameliorate age-associated pathophysiologies.

 

Nicotinamide adenine dinucleotide (NAD+) is a classical coenzyme mediating many redox reactions. NAD+ also plays an important role in the regulation of NAD+-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD+ biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD+ levels decline during the aging process and may be an Achilles’ heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD+ by supplementing NAD+ intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD+ intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide.

 

 

[APBT]

I cross-posted this in the nicotinamide riboside group buy thread:  http://www.longecity...-21#entry664971

I contacted the authors' of the Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3

This was the study that was published subsequent (7 April 2014) to the Sinclair study. It lasted four months, using an oral mouse dose of 400 mg/kg/day of NR.  I asked what form of NR was used, below is their reply:

 

 

We used NR as a triflate salt but it can be synthesized also as a bromide salt.

Best wishes,
Eija Pirinen

 

[LexLux]

Shin-ichiro Imai, Leonard Guarente, NAD+ and sirtuins in aging and disease,

Trends in Cell Biology, 29 April 2014, ISSN 0962-8924, http://www.sciencedi...962892414000634

 

Some points -

• NR can be converted to NMN  (NR-> NR Kinase -> NMN)
• NR boosts NAD+ " in worms and mice and can counter effects of aging 18 and 40. NR supplementation also increases mitochondrial NAD⁺ levels and stimulates SIRT3-mediated deacetylation of mitochondrial proteins [40]."
• Circadian Machinery declines with aging, results in less NAMPT and NAD+, meaning "...NMN and NR, rather than earlier NAD⁺ precursors like nicotinamide would be critical in enhancing NAD⁺ biosynthesis efficiently in aged individuals."
• Chronic inflammation could be to blame - TNF-? significantly reduces NAMPT and NAD+ and "...suppresses CLOCK/BMAL-mediated clock gene transcription in the liver and SCN of TNF-?-treated mice [43]. [...] If this is found to be true, strategies to suppress chronic inflammation and sustain NAD⁺ biosynthesis and circadian function with aging might be effective in maintaining sirtuin activity and possibly robust health [9]."
• "PARP, CD38, and the nuclear sirtuins all compete for the same pool of NAD⁺ and inhibition of PARP or CD38 has the potential to activate sirtuins. [...] A possible explanation for these findings is that aging is associated with an increase in chronic nuclear DNA damage, which leads to NAD⁺depletion by PARP (Figure 4, left). The fact that loss of SIRT1 or SIRT6 activity exacerbates DNA damage[12] may create an autocatalytic downward spiral in the nucleus, with NAD⁺ depletion as the nexus."

 

 

Leonard Guarente, author

 

http://www.cell.com/...34?showall=true

 

I can't access the full text version without paying.  Anyone have access?

 

 

 

 

Highlights

 

• •NAD+ plays a key role in regulating metabolism and circadian rhythm through sirtuins.
• •NAD+ becomes limiting during aging, affecting sirtuins’ activities.
• •NAD+ decline is likely to be due to a NAD+ biosynthesis defect and increased depletion.
• •Supplementing key NAD+ intermediates can restore NAD+ levels and ameliorate age-associated pathophysiologies.

 

Nicotinamide adenine dinucleotide (NAD+) is a classical coenzyme mediating many redox reactions. NAD+ also plays an important role in the regulation of NAD+-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD+ biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD+ levels decline during the aging process and may be an Achilles’ heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD+ by supplementing NAD+ intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD+ intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide.

 

 

 

 

 

 

Edited by LexLux, 27 May 2014 - 01:56 AM.

[to age or not to age]

A side point.  I have known Dr. Leonard Guarente since 2007.  75 world class scientists (many former post docs) showed up to honor him in August 2012 at MIT.

They came from everywhere. Lenny is simply a generous person.  He has helped me continuously in my filming and research,

introducing me to other scientists.  We even did a press junket together.  I once had him wired at an event, and later heard the

recorded audio as he argued to colleagues about his belief about the truth always coming out in the end. He is quite

conservative in terms of what he will say, as opposed to David Sinclair, who ventures to "say it."  Though in my reading,

SInclair is a strong philosophical supporter of this website's cause.  I think it's an even money bet that these guys are in on the

nobel prize within a couple of years.

[albedo]

From readings and the small I know I stand with to-age-or-not-to-age. I liked his prudent but forward looking discussion in the link I posted above (red is mine):

 

"...The interaction of diet and nutrient-sensing pathways plays an important role in regulating mammalian physiology and health. This review focused on the sirtuins and CR to revisit the original hypothesis that nutrient-sensing regulators mediate the effects of this diet on aging and diseases (Guarente 2000). The original proposal was based on the findings that sirtuins were NAD+-dependent protein deacetylases and known to counter aging in yeast. Now, years later, a large volume of data, particularly from mammals, begins to illustrate an elaborate set of physiological adaptations to caloric intake mediated by sirtuins. Studies that connect sirtuin activation with prevention of aging and diseases of aging in mouse models are many. It is also clear that other nutrient sensors, such as AMPK (Kahn et al. 2005), mTOR (Johnson et al.2013), and FOXO (Kenyon, 2010), are very important in linking diet, metabolism, and aging. Indeed, numerous connections among all of these pathways are evident in the literature.

 

As far as medical intervention points, SIRT1 and mTORC1 appear to be candidate targets because small molecules have been described that can alter their activities (STACs and rapamycin, respectively). The idea that SIRT1 could be activated by small molecules was initially resisted but now seems very likely based on an allosteric site in the protein (Hubbard et al. 2013). The challenge will be to tailor drugs to specific tissues; for example, creating brain-permeable compounds to treat Alzheimer’s disease. In addition, it will be critical to learn whether activating compounds affect all SIRT1 substrates or only a subset, as suggested by recent biochemical studies. One might posit that small molecules that bind to the SIRT1 allosteric site mimic natural endogenous compounds that regulate the enzyme under certain physiological conditions; e.g.,CR. If so, then the spectrum of effects elicited by the drugs might mimic the effects triggered by these physiological conditions and elicit a coordinated, protective response. Finally, supplementation with the NAD precursors NMN or nicotinamide riboside has been shown to counteract aging (Ramsey et al. 2008; Mouchiroud et al.2013) and may offer another strategy of keying sirtuin surveillance to forestall aging and diseases...."

 

 

[APBT]

LexLux

It seems the highlights and link you provided in post #440 are the same I posted in #438 - the abstract of the study.  Was your link supposed to go the full study version?

[APBT]

I cross-posted this in the nicotinamide riboside group buy thread:  http://www.longecity...-21#entry664971

I contacted the authors' of the Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3

This was the study that was published subsequent (7 April 2014) to the Sinclair study. It lasted four months, using an oral mouse dose of 400 mg/kg/day of NR.  I asked what form of NR was used, below is their reply:

 

 

We used NR as a triflate salt but it can be synthesized also as a bromide salt.

Best wishes,
Eija Pirinen

 

DISCLAIMER: I am not a chemist.

Perhaps niner (or another qualified person) could confirm or clarify and correct my analysis below.

The difference between nicotinamide riboside (NR) bromide and chloride relates to the cation used to stabilize the NR molecule. The bromide salt contains a bromine atom, while the chloride salt contains a chlorine ion. Given that bromine has no known metabolic role in the human body in normal circumstances, the chloride salt is likely a preferable form.

[blood]

Short interview with David Sinclair from last night's 7:30 Report (news/ politics show):
Anti-ageing pill imminent...

The interview is a bit vague/ short on specifics (they're talking about resveratrol, more so than NAD+ precursors), but this bit on self-experimentation was interesting:
 

SARAH FERGUSON: ... you come from a long line of scientists who self-experiment. You did this work on yourself too, didn't you?

DAVID SINCLAIR: ... Yes, we found this molecule in red wine that seemed to slow down ageing in animals and I thought, "What have I got to lose?" So I started, now 10 years ago, experimenting on myself to see how it would go and I'm still alive.

SARAH FERGUSON: If you're taking the molecule yourself, how do you actually check whether it's having an effect as opposed to the natural ageing process?

DAVID SINCLAIR: Right, right. So we need thousands of people like me and - being carefully monitored, so ...

"I'm still alive" is not much of an endorsement.

Is he still on resveratrol, I wonder, or is he experimenting with some of the synthetic sirtuin activators? I wonder what his dose of resveratrol is/was.

Edited by blood, 28 May 2014 - 11:57 PM.

[Darryl]

Curiously, the intraperitoneal NMN the Sinclair paper used may only enter cells as NR.

 

Nikiforov, A., Doelle, C., Niere, M., & Ziegler, M. (2011). Pathways and subcellular compartmentation of NAD biosynthesis in human cells: From entry of extracellular precursors to mitochondrial NAD generation. Journal of Biological Chemistry, jbc-M110.

Besides nicotinamide and nicotinic acid, only the corresponding nucleosides (NR and NAR) readily enter the cells. Nucleotides (e.g. NAD and NMN) undergo extracellular degradation resulting in the formation of permeable precursors.

 

Addition of CMP, which competes with NMN as substrate for dephosphorylation by the external 5-nucleotidase, notably reduced cell viability of 293mitoPARP cells and HeLa S3 cells. This correlated with a reduced mitochondrial NAD content and was dose-dependent. NMN lost its capacity as extracellular NAD precursor also in the presence of dipyridamole and NBTI, inhibitors of plasma membrane nucleoside transporters. 

...

Together, these results established that, besides NA and Nam, only the riboside precursors NR and NAR serve as extracellular precursors of intracellular NAD, whereas mono-(NMN and NAMN) and dinucleotides (NAD and NAAD) need to be processed to the corresponding nucleosides.

 

 

Perhaps the NMN form is preferred for extracellular stability or experimental pharmakokinetics. NR would certainly be a good deal less expensive for future experiments. 

[Kevnzworld]

[quote name="Darryl" post="665929" timestamp="1401513073"]

[size=4][font=arial]Curiously, the intraperitoneal NMN the Sinclair paper used may only enter cells as NR.
 
[size=4][font=arial]Perhaps the NMN form is preferred for extracellular stability or experimental pharmakokinetics. NR would certainly be a good deal less expensive for future experiments. 

Darryl , are you currently taking NR or any other form of niacin?

[Darryl]

Presently, 2 x 500 mg nicotinic acid, as I don't mind the (now) mild flush and I like pluripotent supplements: The GPR109A activation which causes the flushing also has almost paradoxical anti-inflammatory benefits.

 

However in the cited paper in my last post NA had no effect on NAD+ levels in HepG2 cells, due to that cell line's lack of the NAPRT enzyme. If it turns out normal human liver cells don't express NAPRT (which would be strange), I may consider NR in addition to NA.

[LexLux]

Essentially the author suggests that low NAD levels may be a major pathological factor in schizophrenia, which is why it can be treated with niacin. Seems that some chronic sufferers did not recover, I wonder what role declining NAMPT played in the results. According to the author, the niacin flush should also be serving as a sort of biomarker for NAD+ levels. Time for a test? What do you guys think about a niacin, NR, glutamine combo? 

 

The Niacin Flush Pathway in Recovery from Schizophrenia and how Arginine and Glutamine may Provide Added Benefit

W. Todd Penberthy, PhD, JOM Volume 27, Number 1, 2012

 

"Explanations for the Simultaneous Recovery from Acute Schizophrenia and the Niacin-Flush Response

 

Hoffer observed that treatment with high doses of the non-flush NAD precursor, nicotinamide, also frequently resulted in recovery from acute schizophrenia similar to recovery from pellagra dementia. While restoration of the nicotinic acid-mediated flush response does correlate with niacin-mediated recovery from schizophrenia, it does not necessarily mean that this effect was primarily the result of the flush response.It seems much more likely that the restoration of NAD levels is central to recovery, where NAD as NAD+, NADP+, NADH, and/or NADPH, may be restoring prostaglandin- flush pathways by one or a combination of the >450 reactions that require NAD for ac- tivity. There are several possible explanations for the observed reduced flush response. In this section we give consideration to each explanation and ultimately come to the conclusion that the reduced flush response is firstly an NAD deficiency, where PUFA reductions are likely to be secondary to this effect. This analysis concludes that schizo- phrenia is most likely not an essential fatty acid deficiency disease, but more of a NAD deficiency disease.

 

Firstly, the reduced niacin flush response observed in schizophrenia likely involves nia- cin receptor ligand mediated desensitization. A metabolic study of schizophrenia indicates a general increase in PUFA catabolism.31 Beta-hydroxybutryate levels were found to be elevated 2.6 fold. Beta-hydroxybutyrate is proposed to be the naturally occurring endogenous ligand for the high affinity nicotinic acid G-protein coupled receptor.32 Decreased levels of the GPR109a protein are observed in the brains of schizophrenics, as are increased GPR109a transcripts.33 Such ligand dependent receptor down-regulation (a.k.a., receptor desensitization) is a common theme with the G-protein coupled receptor protein superfamily. Thus, NAD may be simply restoring PUFA metabolism such that the levels of the beta-hydroxybutyrate ligand for the high affinity nicotinic acid G- protein coupled receptor are returned to normal levels. The GPR109a protein may then be expressed at correct levels, thus restoring the niacin-flush response to normal as well. This general alteration is surely a major contributor to the reduced flush response seen in schizophrenics."

[...]

"Glutamine is required for the last step in the conversion of niacin to NAD when starting from either tryptophan or nicotinic acid/niacin. [...] Glutamine is the most abundant amino acid in the body. To date glutamine studies have mostly focused on treating severely burned patients, those experiencing cancer cachexia, or undergoing chemotherapy.63 Therapeutic benefits were observed for all of these situa- tions. The most effective doses were seen after administration of 10-15 g three times each day with the biggest responses seen closer to the 45 g per day dosage.[...] In sum- mary, 3-10 g of arginine three times each day, and 10-15 g of glutamine three times each day may additionally provide therapeutic benefit to the schizophrenic."

 

 

 

LexLux

It seems the highlights and link you provided in post #440 are the same I posted in #438 - the abstract of the study.  Was your link supposed to go the full study version?

 

 

I added in some additional details, the abstract tends to be a close reflection of the content. Was there something specific you wanted to find? It was a pain getting access to the fulll text, it wouldn't let me download a pdf unfortunately. 

Edited by LexLux, 01 June 2014 - 01:05 AM.

[smithx]

I asked this in the NR experiences thread, but I think this thread is the correct place for it:

 

Is there any possibility that supplementing with NR could down regulate some metabolic processes which would cause dependency on NR supplementation?

 

In other words, is is possible that after supplementing with NR for a few weeks, months or years, if it were to be discontinued, the individual would suffer some worse deficiency in NAD+ than they would have had if they had never supplemented with NR at all?