529 replies to this topic

[midas]

I think various dosages from various people is best. Someone taking 7 grams a day may find that it works and someone on 125mg a day may not have any effect no matter how many years they take it. The reverse could also be true. It is quite possible that only over a certain level that the effects are felt, the mice got a lot. I'd rather piss some away than miss the effect that could keep me alive. We are all dying, there is no time for patience )

 

 

We have also got to be careful with taking really large doses as we may not be able to metabolize a great deal of NR all at once, and may possibly lose a lot of it passing through the body...This is all new stuff here and I think smaller doses (max 2 grams) per day over a prolonged period would be the best way to go until we know something different through trial results. Better smaller doses getting metabolised than large doses getting half of it pissed away.
Like I said in that post....Patience is a virtue.

Just my opinion. 

 

 

You are correct, we are all dying, but we also don't want to hasten the process.

 

As of yet NR is an unknown quantity and has not been tested in humans in large doses. So there is an element of risk involved, especially in large doses.

An example of that is Niacinamide, to large a dose has been known to affect the liver in some people in a negative way at over 3 grams per day. NR being from the same Vitamin B family may have similar issues in high dosage.

 

I suppose what I am saying is we are responsible for our own clinical trials with NR, and I would hate that someone on this forum took too much of a leap of faith here and hurt themselves.

I think it was yesterday someone on the Niagen results thread was saying that he had painful lymph glands after using it subliminally and you yourself had an issue with a very sore jaw two days in a row doing the same thing...Lymph glands are protective and get rid of poisons so that makes me think it might not be such a good thing to rush into large doses straight away.

I certainly think that two or three grams would be safe but I personally wouldn't be going any higher than that without hearing more from the researchers.

Those mice that were used in the NMN experiments were sacrificed shortly after, so we don't know what the long term use and effects would have been...

And this was not NR it was NMN.

 

I was reading a day or two ago they have announced they have found a cure for Hep C, the dosage is spread over three months, the article I was reading also said this was liver toxic if taken in large doses to quickly...So in essence, a cure for a liver disease if taken to quickly, can do the exact opposite and possibly damage the liver even more..

 

Like I say, patience is a virtue

 

[PWAIN]

As I say, depends of individual and circumstances. At healthy 18, I probably wouldn't even take Nr. At 86 with age associated problems, I'd be more likely to try gram quantities. As time passes and safety of Nr becomes more apparent, dosages can be varied. Each person should assess their own age and health and what level of risk they are willing to take before determining dosage. Of course it is good to remind people that there is very real risk associated with taking a largely untested chemical like Nr, especially in larger doses that are unlikely to be encountered in diet.

[Aditya Kumar]

Do you guys think the approach to increase NAD+ can at least STOP muscle aging?

 

Also, wht do you guys think about blackberries as source for C3G - a CD38 inhibitor? they seem better than chokeberries?

[mikeinnaples]

Given that one day of a mouse life is approx equal to one month of a human life, I don't see how daily dosing and the circadian clock can be compared in any way.

 

I agree that using a mouse circadian rhythm to model human dosing directly is a bad idea. However, we should be using human circadian rhythm to do so in this case. The mouse to human lifespan you mentioned is irrelevant in my opinion when it comes to determining daily dosing schedule.

 

In the case of NAD+ levels and circadian rhythm, would we want to increase the spike at the peaks, reduce the lows of the valleys, or try to flatten the curves to keep NAD+ levels high as much as possible? Then there is the whole timing issue based on that.... when do supplement NA/NR to increase the NAD+ potential? When do we, or even should we, tinker with CD38/AMPK/NAMPT etc.

 

I wish I had a broader understanding of this

 

This is an interesting read on AMPK -> PARP1 expression.

 

And here on PARP1 -> NAD+

 

 

The biosynthesis of NAD⁺ occurs through both salvage and de novo pathways (Fig. 4; Rongvaux et al. 2003). The salvage pathways begin with either nicotinamide or nicotinic acid, collectively referred to as niacin or vitamin B3. The de novo pathway leads from tryptophan to quinolinate, which connects to the nicotinic acid salvage pathway through nicotinic acid mononucleotide (NaMN). In most mammalian tissues, nicotinamide, a product of NAD⁺ hydrolysis by PARP-1 and SIRT1, is likely the most relevant NAD⁺ precursor for the regulation of PARP-1 functions (Rongvaux et al. 2003). Nicotinamide is first converted to NMN by nicotinamide phosphoribosyltransferase (NAMPT). The production of NAD⁺ from NMN and ATP is then catalyzed by a family of NMN adenylyltransferases (NMNATs) (Magni et al. 2004). The enzymes possessing NMNAT activity also have NaMN adenylyltransferase (NaMNAT) activity and are, therefore, required for all NAD⁺ biosynthetic pathways. Interestingly, the nicotinamide salvage pathway is not well conserved. In lower eukaryotes—including Saccharomyces cerevisiae, Drosophila melanogaster, and Caenorhabditis elegans—no NAMPT activity has been found (Rongvaux et al. 2003). In these species, nicotinamide is converted to nicotinic acid, which then enters the parallel nicotinic acid (“Preiss-Handler”) salvage pathway found in all eukaryotic species. Recently, nicotinamide riboside was also shown to be a precursor for NAD⁺ synthesis, connecting to the nicotinamide salvage pathway through NMN (Fig. 4; Bieganowski and Brenner 2004).

 

 

More conclusive evidence for the regulation of NAD⁺-dependent nuclear enzymes by NAD⁺ biosynthetic pathways comes from studies on the activity of yeast Sir2/mammalian SIRT1, an NAD⁺-dependent nuclear protein deacetylase whose activity is modulated by PNC1, NMNATs, and NAMPT (Anderson et al. 2002, 2003; Araki et al. 2004; Revollo et al. 2004). These same studies suggest that removal of nicotinamide, an inhibitor of both Sir2/SIRT1 and PARP-1 (Hageman and Stierum 2001; Bitterman et al. 2002), by enzymes in the salvage pathways (e.g., PNC1, NAMPT) may be as important for the activation of Sir2/SIRT1 (and perhaps PARP-1) as the production of NAD⁺. An interesting possibility that has not yet been explored is the potential recruitment of NAD⁺ biosynthetic enzymes to sites of PARP-1 action, providing tightly controlled local NAD⁺ production as a means to regulate PARP-1 functions. Finally, PARPs and other NAD⁺-dependent nuclear enzymes, such as SIRT1, may compete for a common pool of NAD⁺ that could become limiting under conditions of severe DNA damage (Zhang 2003). Therefore, NAD⁺ metabolism in the nucleus may play a key role in coordinating multiple aspects of nuclear functions through the regulation of NAD⁺-dependent nuclear enzymes.

 

Edited by mikeinnaples, 16 April 2014 - 01:48 PM.

[midas]

Do you guys think the approach to increase NAD+ can at least STOP muscle aging?

 

Also, wht do you guys think about blackberries as source for C3G - a CD38 inhibitor? they seem better than chokeberries?

 

Up to now the only true laboratory evidence that NR does anything at all, is on mouse muscle tissue, so I figure that is the most likely area for human benefit. But hopefully it will work in other places too. 

 

I do know blackberries are excellent but I cant answer your question as I don't know anything about C3G - a CD38

[APBT]

to age or not to age:

As a group, Longecity members and registered users are way ahead of the general public on the topic of life/health span extension. Additionally, you have a large group of folks who are already self-experimenting and salivating for more information - realizing that much of this is dynamic conjecture; i.e. no definitive, one-size-fits-all answers.

I have a proposal, if you find it amicable.  In your role as a documentarian film-maker, we could provide a list of possible questions for you to ask the researchers in future interview sessions or discussions.  Acting as a conduit between the lab and real-world lab rats.  I know their insight would be greatly appreciated here.

I'd invite others to add their questions to this list.  Without further ado, I'm curious about:

Is the circadian clock a crucial consideration in the timing of supplemental NAD+ precursor consumption?  If so, how?

What would be a reasonable (and safe) dosage range of NR, to (potentially) achieve results similar to those of the Sinclair et al. study, for a human being, based on body weight?  Would it be a scaled dose of 1/12 the amount used in the study?

Should NR be cycled?  If so, how?

Is nicotinic acid (NA) a reasonable replacement for NR?  Do they work similarly mg for mg?  Can they be used simultaneously for a synergistic effect?

[niner]

Do you guys think the approach to increase NAD+ can at least STOP muscle aging?

 

No. Nothing that we have today will absolutely stop any form of aging. We have some things that might slow aging, e.g. c60-oo. NR has been shown in rodents to shift some aspects of metabolism to a more youthful state.  If you're already youthful, I don't expect it will do much. 

[Aditya Kumar]

 

Do you guys think the approach to increase NAD+ can at least STOP muscle aging?

 

Also, wht do you guys think about blackberries as source for C3G - a CD38 inhibitor? they seem better than chokeberries?

 

Up to now the only true laboratory evidence that NR does anything at all, is on mouse muscle tissue, so I figure that is the most likely area for human benefit. But hopefully it will work in other places too. 

 

I do know blackberries are excellent but I cant answer your question as I don't know anything about C3G - a CD38

 

 

C3G is a compound, present in blackberries, which is a effective CD38 inhibitor. It was discussed in this thread. But as i have seen from another thread of mine, some say the most effective one is luteolin or apigenin. and i hope NR does something for muscle tissue.
 

 

Do you guys think the approach to increase NAD+ can at least STOP muscle aging?

 

No. Nothing that we have today will absolutely stop any form of aging. We have some things that might slow aging, e.g. c60-oo. NR has been shown in rodents to shift some aspects of metabolism to a more youthful state.  If you're already youthful, I don't expect it will do much. 

 

 

Ok,, but in the NAD+ study, i thought they found that the muscles were reverted back to a young stage. that is why i asked. and i thought that since cell communiction was no longer impaired in NAD+ study, it might prevent one aspect of aging. but thanks for the info.
 

[niner]

Do you guys think the approach to increase NAD+ can at least STOP muscle aging?

 
No. Nothing that we have today will absolutely stop any form of aging. We have some things that might slow aging, e.g. c60-oo. NR has been shown in rodents to shift some aspects of metabolism to a more youthful state.  If you're already youthful, I don't expect it will do much.

 
Ok,, but in the NAD+ study, i thought they found that the muscles were reverted back to a young stage. that is why i asked. and i thought that since cell communiction was no longer impaired in NAD+ study, it might prevent one aspect of aging. but thanks for the info.

Aging is an ongoing process. NR can take some aspects of that and dial them back, but the other causes of aging are still going to be there. Because of the improved metabolic status of the cell that NR brings about, some aspects of aging will be slowed, so it makes small animals live longer, and we hope that it will have effects in humans that are similar in nature, if not in magnitude. I don't want to sound like an NR naysayer- I think it's a very promising compound. I just don't want to create false hopes regarding outcomes.

[midas]

 

Ok,, but in the NAD+ study, i thought they found that the muscles were reverted back to a young stage.
 

 

 

Just so you are clear on this, the study that showed muscle tissue that was regressed to a younger age was on NMN (Nicotinamide Mononucleotide) which is a little diferent to Nicotinamide Riboside though both are supposed to be very good precursors of NAD+

Hopefully Nicotinamide Riboside will have a similar effect over time.

 

This was released last week and it was Nicotinamide Riboside that was used.

http://www.scienceda...40407090403.htm

 

I think I read earlier in one of your posts that you are in your early 20's, if this is so then you may not see much of a difference with NR as I presume your biological condition will be in pretty good shape at that age.....

To be honest I am not expecting many of us to see much change at all for months....

 

It was also stated in the original study on NMN that the muscle tissue did not gain any strength after this regeneration, but, that may come with time and use.

For example, if you got identical twins and they were both young and one worked out and the other did not, then you would see the one that worked out gaining strength and the other would stay the same. This may be how the NMN worked in that mouse, the muscle was regenerated but needed working to gain strength...Just a thought.
 

[APBT]

Some information about more research very interesting research with Nicotinamide Riboside....

 

http://medicalxpress...in-b3.html#nwlt

 

 

 

Here's the full text of the study:  http://onlinelibrary....201403943/full

[malbecman]

 

 

Ok,, but in the NAD+ study, i thought they found that the muscles were reverted back to a young stage.
 

 

 

Just so you are clear on this, the study that showed muscle tissue that was regressed to a younger age was on NMN (Nicotinamide Mononucleotide) which is a little diferent to Nicotinamide Riboside though both are supposed to be very good precursors of NAD+

Hopefully Nicotinamide Riboside will have a similar effect over time.

 

This was released last week and it was Nicotinamide Riboside that was used.

http://www.scienceda...40407090403.htm

 

I think I read earlier in one of your posts that you are in your early 20's, if this is so then you may not see much of a difference with NR as I presume your biological condition will be in pretty good shape at that age.....

To be honest I am not expecting many of us to see much change at all for months....

 

It was also stated in the original study on NMN that the muscle tissue did not gain any strength after this regeneration, but, that may come with time and use.

For example, if you got identical twins and they were both young and one worked out and the other did not, then you would see the one that worked out gaining strength and the other would stay the same. This may be how the NMN worked in that mouse, the muscle was regenerated but needed working to gain strength...Just a thought.
 

 

 

 Here is the abstract & reference for that paper, FWIW....

 

 edit, I notice our old friend ,Auwerx, is on this one, a big Sirt and resveratrol researcher.

 

 

EMBO Mol Med. 2014 Apr 6. [Epub ahead of print]

Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3.

Khan NA¹, Auranen M, Paetau I, Pirinen E, Euro L, Forsström S, Pasila L, Velagapudi V, Carroll CJ, Auwerx J, Suomalainen A.

Author information

Abstract

Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD⁺/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD⁺ precursor, was previously shown to boost NAD⁺ levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD⁺ levels are a promising treatment strategy for mitochondrial myopathy.

PMID: 24711540

 

Edited by malbecman, 18 April 2014 - 10:16 PM.

[eighthman]

One part of the NR study bothers me - it says the Delector mice have a normal lifespan and physical performance. It is also said that they are significantly analogous to humans with mitochrondrial disease.

 

If so, what's the point of this and how is the disease a "disease"?  I don't follow. NR seems to have a number of technical benefits, observable by microscope and other tests, but what would the practical benefit be to the mice (and hence, humans)? Are we saying that they would have lived longer if not sacrificed?  Are we thinking that they would have enjoyed youthful vigor at advanced age ( and died 'healthy') ????????

[midas]

One part of the NR study bothers me - it says the Delector mice have a normal lifespan and physical performance. It is also said that they are significantly analogous to humans with mitochrondrial disease.

 

If so, what's the point of this and how is the disease a "disease"?  I don't follow. NR seems to have a number of technical benefits, observable by microscope and other tests, but what would the practical benefit be to the mice (and hence, humans)? Are we saying that they would have lived longer if not sacrificed?  Are we thinking that they would have enjoyed youthful vigor at advanced age ( and died 'healthy') ????????

 

Those questions are what we all want answers to, problem is, no one knows yet.

I'm sure that they are doing further research as we speak. They may even have answers that have not been published yet.

 

What brought me here, was the possible muscle rejuvenation/remodelling aspect of NR for a medical condition that I have. If that side of it works even to a small or medium degree then I will be happy, anything more than that will be a welcome bonus is the way I am looking at it.
 

[maxwatt]

FWIW:

 

I have been corresponding with a doctor ( M.D.) who has been taking NR for over four years at 7 grams a day.  No ill effects.  Absent controls, nothing positively positive, except his health by his evaluation is excellent given his age (sixties) and the fact he has been a type 2 diabetic for 30 years. 

 

I conclude from his example that such large doses of NR are unlikely to be dangerous for the general population.

[niner]

One part of the NR study bothers me - it says the Delector mice have a normal lifespan and physical performance. It is also said that they are significantly analogous to humans with mitochrondrial disease.
 
If so, what's the point of this and how is the disease a "disease"?  I don't follow. NR seems to have a number of technical benefits, observable by microscope and other tests, but what would the practical benefit be to the mice (and hence, humans)? Are we saying that they would have lived longer if not sacrificed?  Are we thinking that they would have enjoyed youthful vigor at advanced age ( and died 'healthy') ????????

In the paper, regarding Deletor mice they say:

These mice have a normal lifespan and physical performance despite typical morphological changes in MM, cytochrome c oxidase (COX)-negative fibers, and ultrastructural mitochondrial abnormalities, in their muscle. The histological and physiological findings in Deletors mimic closely those of patients with the same mutation (Suomalainen et al, 1992, 1997), making Deletor mice an optimal model for therapy trials.

Even though they appear to have normal physical performance, they are physiologically messed up in a way that mimics mitochondrial myopathy. While these mice may be capable of the same performance as wild type mice, they might not feel as good while doing it.

[midas]

FWIW:

 

I have been corresponding with a doctor ( M.D.) who has been taking NR for over four years at 7 grams a day.  No ill effects.  Absent controls, nothing positively positive, except his health by his evaluation is excellent given his age (sixties) and the fact he has been a type 2 diabetic for 30 years. 

 

I conclude from his example that such large doses of NR are unlikely to be dangerous for the general population.

 

Makes you wonder where he was getting large quantities of it back then (2009/10)?

How did he come up with a dose of 7 grams all that time ago when it was well before the Sinclair study on NMN was done?

 

And it would also say that the guys in Switzerland that have done all that hard work on NR are wrong??

 

"A Switzerland-based research team says nicotinamide riboside could help prevent weight gain and diabetes and improve muscular performance."

 

As this guy is still diabetic, and after taking such a large dose for such a long time feels no different.

 

Hmmm!....Personally I am a little suspicious of his claim, well see!

[midas]

I know a Doctor who has acquired several kilograms of Nicotinamide riboside and plans on taking 7 grams a day. We are awaiting test results, but if it is good, and if he finds measurable improvements in several markers, I will be joining him. The price you get from Chinese suppliers is all over the map, but 70 or 80 $ a kilogram in bulk is the low end.


 

 

 

FWIW:

 

I have been corresponding with a doctor ( M.D.) who has been taking NR for over four years at 7 grams a day.  No ill effects.  Absent controls, nothing positively positive, except his health by his evaluation is excellent given his age (sixties) and the fact he has been a type 2 diabetic for 30 years. 

 

I conclude from his example that such large doses of NR are unlikely to be dangerous for the general population.

 

 

 

I just remembered something you posted two or three weeks ago....see below.

This is very confusing, when you read your post from two weeks ago about this doctor, their you say he "has acquired several kilograms" he "plans" on taking 7 grams a day....and you were awaiting test results on the quality of what he had bought

 

"I know a Doctor who has acquired several kilograms of Nicotinamide riboside and plans on taking 7 grams a day. We are awaiting test results, but if it is good, and if he finds measurable improvements in several markers, I will be joining him."

 

Post 353 here on the group buy thread...http://www.longecity...oup-buy/page-12

 

And in your post above you say he "has" been taking 7 grams a day for over four years?

 

All very strange if you ask me!!...................I would strongly advise against anyone taking the "safe" part of seven grams a day as a given, chances are it is but there is nothing set in stone here with NR as yet. Caution is advised as far as I'm concerned.

Edited by midas, 20 April 2014 - 04:22 AM.

[maxwatt]

The doctor acquired several kilos of NR years ago from a Chinese pharmaceutical manufacturer, and had it tested.  The doctor had already been diabetic type 2.   The condition is well controlled, and has not progressed the way it usuallly does in diabetics.  I do not have specific measurements, but am inclined to take him at his word on that.  There were sufficient papers published at that time, and I he was corresponding with Guarantee et al.  to derive the dose, but still made some assumptions wrt. scaling.  

 

His supply is running low, as one would expect at that dose after several years, so he recently purchased more, different source at a price considerably lower than his original purchase.  I expect he'll have the test results shortly.  So he will be taking it at that dose. 

 

I found out about his purchase and plans first, and some time later that he had already been using NR.  If one decides to follow his example, one will not be the first such pioneer.  It is not acutely toxit, at least.

[midas]

I'm sorry I just find it rather strange that you are communicating with a medical doctor about this subject that informs you that he has just bought several KG's of NR, and completely omits/forgets to tell you that he has been taking it in large quantities for over four years. I personally have no confidence in what your "MD"  friend says.

 

Anyways, I asked you around three weeks ago if he would share the name and address of his supplier and you said you would get back to us on that?

And I certainly don't think that there is any evidence that it is not "acutely toxic" in high doses just yet. After all, Niacinamide from the same B3 family has been shown to damage the liver in some cases in doses over 3 grams.

 

I seem to remember Prophets and someone else saying they were feeling an effect at 250mg so it is likely maybe some of us will have different tolerances of NR and to say that 7 grams is safe on the dubious claims of this doctor is jumping the gun in my view.

 

See Prophets post 354 on this page... http://www.longecity...oup-buy/page-12

 

Lets just say that NR in large doses ha the same effect on us that NMN had on the mouse that reverted back 30 years in muscle tissue age....we have no idea of how that would be coped with by the body and the rest of out organs. I urge caution with high doses over an extended period of time until we see more information as to how NR works, or for that matter doesn't work in humans.

Edited by midas, 20 April 2014 - 03:33 PM.

[tunt01]

 

I seem to remember Prophets and someone else saying they were feeling an effect at 250mg so it is likely maybe some of us will have different tolerances of NR and to say that 7 grams is safe on the dubious claims of this doctor is jumping the gun in my view.

 

See Prophets post 354 on this page... http://www.longecity...oup-buy/page-12

 

 

 

 

For the record, I see less of an effect and I am still experimenting.  

 

My glucose seems to be coming in high post-consumption of Niagen (per my note the other day), but I am not feeling a surge in energy anymore like I did in the first few days of consumption.  I took 500mg this AM and my glucose is running a bit high, but I think there is a confounding factor of coffee and I really need to get off caffeine to have a better idea of what is going on here.

 

However, based on Sinclair's work (500 mg/kg) a human equivalent dose should be ~2.4grams.  7 grams seems rather large and if this MD is communicating with Guarente or some other expert and justifying such a large dose, it would be rather useful to know how they arrived at that math (if through multiple dosing per day or what not).

Edited by prophets, 20 April 2014 - 06:07 PM.

[niner]

And it would also say that the guys in Switzerland that have done all that hard work on NR are wrong??
 
"A Switzerland-based research team says nicotinamide riboside could help prevent weight gain and diabetes and improve muscular performance."
 
As this guy is still diabetic, and after taking such a large dose for such a long time feels no different.
 
Hmmm!....Personally I am a little suspicious of his claim, well see!

Prevention is one thing, and a cure is something else entirely.

[midas]

 

And it would also say that the guys in Switzerland that have done all that hard work on NR are wrong??
 
"A Switzerland-based research team says nicotinamide riboside could help prevent weight gain and diabetes and improve muscular performance."
 
As this guy is still diabetic, and after taking such a large dose for such a long time feels no different.
 
Hmmm!....Personally I am a little suspicious of his claim, well see!

Prevention is one thing, and a cure is something else entirely.

 

 

I dont see any mention of the word cure there, but I do see "feels no different"

 

I think that quote has been taken a bit out of context there!

[blood]

I'm sorry I just find it rather strange... I personally have no confidence in what your "MD"  friend says.

All this aggression makes for unpleasant reading! A suggestion... use your inquisitorial mind to interrogate the scientific literature, not other posters!

(I do appreciate your suggestions of caution re: a 7 gram/day schedule for NR.)

Edited by blood, 21 April 2014 - 01:25 PM.

[midas]

 

I'm sorry I just find it rather strange... I personally have no confidence in what your "MD"  friend says.

All this aggression makes for unpleasant reading! A suggestion... use your inquisitorial mind to interrogate the scientific literature, not other posters!

(I do appreciate your suggestions of caution re: a 7 gram/day schedule for NR.)

 

 

No aggression involved my friend.    I am questioning what has been said because it is inconsistent. And I would rather believe the scientific literature than inconsistent hearsay.

It is difficult to question the scientific literature without a lab and the knowledge to do so.

[Ukko]

Folks,

 

I think we should expand our reserach beyond the precursors, beyond the circadian rhythm issues and beyond CD38 blocking. I have been trying to look into these two things lately, but finding it harder than usually.

 

1. Supplementing L-Glutamine or Beta-Alanyl-Glutamine (aka Sustamine) to boost the creation of NAD+ from plain niacin through the glutamine dependent form of NAD synthetase.

 

http://www.jbc.org/c.../13/10914.short

 

2. Supplementing 5-HTP, likely ideally at night, to saturate the other path using L-tryptophan in the body so that more L-tryptophan gets diverted to de novo synthesis of NAD+. This in particular seems to be a challenging direction to study. This is like the closest thing I have found, but it really is more about analytical chemistry.

 

http://www.ncbi.nlm....pubmed/15828802

[hav]

FWIW:

 

I have been corresponding with a doctor ( M.D.) who has been taking NR for over four years at 7 grams a day.  No ill effects.  Absent controls, nothing positively positive, except his health by his evaluation is excellent given his age (sixties) and the fact he has been a type 2 diabetic for 30 years. 

 

I conclude from his example that such large doses of NR are unlikely to be dangerous for the general population.

 

Based on this UK study of the usual worsening progression of the disease over time, even when treated with medication,  that doctor's anecdotal experience is noteworthy.  He's obviously been doing allot of right things to stem the tide for so many years.  The fact that he's taken NR for 4 years at 7 grams/day is at least good evidence of its lack of negative effects.

 

Not so sure that a 7 gram/day dose of NR is all that high in light of the Sinclair study which used NMN, which is an order of magnitude higher (50 mg/ml) in solubility than its precursor, NR (5.34 mg/ml), and then administered it by ip injection at a rate of 500 mg/kg of body weight.  Even assuming 1/12 scaling and loss-less oral intake, it might take an adult human around 30 grams/day of NR to equal the NMN dosage Sinclair gave to his mice.

 

Howard

Edited by hav, 21 April 2014 - 05:16 PM.

[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."

[to age or not to age]

A little background. In August 2012, I filmed David SInclair speaking at the podium in a private dinner honoring

Lenny Guarente, at which time he declared what is in the December 2013 paper.  I wasn't allowed to share this info

until the paper was published.  We should appreciate the time lags in emerging  breakthroughs.  In my most recent

interviews with Guarente (Feb 2014) he was as upbeat and positive as Lenny can be; as opposed to David, who

utters the dramatic take-away, if Lenny had discovered the cure for all human disease, he would say something like

"it's looking quite favorable that we're making striking progress."  That's Lenny.

He did say and intimate that these "natural molecules" are very likely safe, and that this year is really

an emerging thing.  In light of my opening sentence in this paragraph, one might surmise that these

scientists know more that they are willing to go on camera with.  I myself cannot confirm anything at this  time

with regard to human efficacy. 

 

I will publish another part of these interviews soon.  On a practical note, MIND mentioned that I might want to 

do a video editor guest spot on longecity.  I think this is a good idea because it would be easier to

locate these video bits at a place on the site. Also, there is an underlying thread that would emerge.

I sometimes stay with Vince Guiliano when I'm in Boston, and he has asked me to collaborate (we have in the past)

where in my video and our chat would be integrated around the filmed pieces.

 

 

[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."

 

Got an interesting answer in my email today from one of the lead researchers of the study i mentioned about Nicotinamide Riboside.

As i said i  have mitochondrial myopathy and this study showed some effectiveness of nicotinamide riboside for this disease on mice.

 

"Thank you for your interest in our research. I do understand why you are interested. However, your doctors are wise to say that the compounds need to be tested first in humans - because humans are not mice. We are initiating a patient trial after the summer. It is very important, because sometimes unexpected side effects occur in mitochondrial disease patients with these seemingly little-harming but actually metabolically very active compounds. New compounds need to be tested in tight follow-up of a physician, with lab test follow up as well."