693 replies to this topic

[Nattzor]

 

 

You would daily dose 40 grams (40,000 MG) of NR for a 220 pound human using the study dose of 400 MG per KG. 40 grams of NR is very expensive, but humans may not need the same dose as mice but they would still need a big dose..

 

 

The other dude used HED dosage I assume, which takes into consideration the difference in metabolism and size.

[DrW]

 

 

 

You would daily dose 40 grams (40,000 MG) of NR for a 220 pound human using the study dose of 400 MG per KG. 40 grams of NR is very expensive, but humans may not need the same dose as mice but they would still need a big dose..

 

 

The other dude used HED dosage I assume, which takes into consideration the difference in metabolism and size.

 

So is 40 grams per 220 pounds of mice is the HED dose of 2.3 grams/day for a human (what weight human)?

 

What is the HED dose for humans if the dose for mice is 40 grams per 220 pounds of mice ? 

[Nattzor]

 

 

 

 

You would daily dose 40 grams (40,000 MG) of NR for a 220 pound human using the study dose of 400 MG per KG. 40 grams of NR is very expensive, but humans may not need the same dose as mice but they would still need a big dose..

 

 

The other dude used HED dosage I assume, which takes into consideration the difference in metabolism and size.

 

So is 40 grams per 220 pounds of mice is the HED dose of 2.3 grams/day for a human (what weight human)?

 

What is the HED dose for humans if the dose for mice is 40 grams per 220 pounds of mice ? 

 

 

400*(3/37)=32.4324324324 mg / kg for humans.

 

So that would mean around 32*100=3.2 g for a 100 kg male.
 

[Geoffrey1]

 

 

 

Although it was not a longevity study, the oral dosage they used looks workable:

 

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

 

I think that translates to around 2.3 grams/day for a human.

 

Howard

 

 

I'm sure someone with more knowledge on this can clarify, but from what I have read about sub-lingual dosing you need around a third of the dosage.

So, if a daily dose of 250mg was taken sub-lingually then that should get you 750mg per day from a 250mg oral dose.

 

 

Not at all disagreeing---would love for that to be true. But where did you get that idea from---is there research saying one third of dose?  Niagen of course is mostly not NR at least half of the capsule is excipients. Not everything is effectively absorbed sublingually.  Would have to pass the BBB and not really sure NR in this form (perhaps micronized; I really do not know)  would pass the BBB by just taking sublingually---although I have seen some here suggest it would. 

 

So I'm with you would very much like to hear from folks who may have thots on this based on research especially. I know not all powder (supplements etc.) are absorbed effectively sublingually so do we know NR is?  And again that one third amount ---where did you see that Midas?  

Thanks

[slotrite]

http://suppversity.blogspot.de/2011/06/ask-dr-andro-what-are-human-equivalen.html

[DrW]

 

 

 

 

 

You would daily dose 40 grams (40,000 MG) of NR for a 220 pound human using the study dose of 400 MG per KG. 40 grams of NR is very expensive, but humans may not need the same dose as mice but they would still need a big dose..

 

 

The other dude used HED dosage I assume, which takes into consideration the difference in metabolism and size.

 

So is 40 grams per 220 pounds of mice is the HED dose of 2.3 grams/day for a human (what weight human)?

 

What is the HED dose for humans if the dose for mice is 40 grams per 220 pounds of mice ? 

 

 

400*(3/37)=32.4324324324 mg / kg for humans.

 

So that would mean around 32*100=3.2 g for a 100 kg male.
 

 

 

 

Thanks. 40 grams for mice is equivalent to 3.2 grams for humans, for 220 pounds (100 KG). Still a large dose, and an expensive one. But NR is usable as an oral dose, baked into chow and kept cold in storage (they used -20 C).

[midas]

 

 

 

 

Although it was not a longevity study, the oral dosage they used looks workable:

 

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

 

I think that translates to around 2.3 grams/day for a human.

 

Howard

 

 

I'm sure someone with more knowledge on this can clarify, but from what I have read about sub-lingual dosing you need around a third of the dosage.

So, if a daily dose of 250mg was taken sub-lingually then that should get you 750mg per day from a 250mg oral dose.

 

 

Not at all disagreeing---would love for that to be true. But where did you get that idea from---is there research saying one third of dose?  Niagen of course is mostly not NR at least half of the capsule is excipients. Not everything is effectively absorbed sublingually.  Would have to pass the BBB and not really sure NR in this form (perhaps micronized; I really do not know)  would pass the BBB by just taking sublingually---although I have seen some here suggest it would. 

 

So I'm with you would very much like to hear from folks who may have thots on this based on research especially. I know not all powder (supplements etc.) are absorbed effectively sublingually so do we know NR is?  And again that one third amount ---where did you see that Midas?  

Thanks

 

 

I found that here when I was looking into taking medication sub-lingually here.....

 

http://en.wikibooks....ines/Sublingual

 

"Approximately 1/3 of an oral dose has the same effects when taken sub-lingually"

 

I really don't know for sure that this is going to work with NR but I did say in my last post that mabe someone with more knowlege about this might chime in and put us straight.

I personally don't know if this is a good idea or not.
 

[Nattzor]

That greatly depends on which drug it is. If it has 100% oral bioavailability, sublingual wont outperform it that much (or at all (if peak plasma concentration doesn't matter)).

[DrW]

advantage of subligual is it bypasses the liver and digestive system

Edited by DrW, 24 May 2014 - 07:27 PM.

[pedr0vsky]

http://foodbeverageb...e/592265_1.html

Anyone tried this guys?

[midas]

http://foodbeverageb...e/592265_1.html

Anyone tried this guys?

 

That Cas Number (CAS No.: 98-92-0) is for Nicotinamide (Niacinamide) and not Nicotinamide Riboside.

Edited by midas, 25 May 2014 - 02:41 PM.

[DrW]

So why can't we take Niacinamide, at far less expense, and just pretend it is Nicotinamide Riboside?

 

 

lol

[DrW]

Niacinamide may be important in increasing NAD+
 
The follwing are excerpts from
 
 
http://www.life-enha...d-nad-nad-world
 
Changes in NAD+ metabolism have been associated with several pathologies, including neurodegenerative diseases, cancer, cardiovascular disease, and normal ageing.4 In fact, the authors of paper #4 suggest that, NAD+ synthesis through the kynurenine pathway [de novo synthesis of NAD+ from tryptophan] and/or salvage pathway [from nicotinamide] is an attractive target for therapeutic intervention in age-associated degenerative disorders.
 
PARP1 has been reported in the brains of Alzheimers disease patients, as well as in those with diabetes, MTPT-caused Parkinsons disease, shock, and other conditions. It has been suggested that PARPs may play a role in aging by promoting NAD+ depletion. One study5 reported that PARP-1 activity in mononuclear blood cells increases with aging in at least thirteen mammalian species. In another study,5A researchers reported that [o]ur results suggest that oxidative stress induced NAD+ depletion could play a significant role in the aging process, by compromising energy production, DNA repair and genomic surveillance. The latter study5A examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female Wistar rats, reporting that [o]ur results are the first to show a significant decline in intracellular NAD+ levels and NAD/NADH ratio in all organs by middle age (i.e., 12 months) compared to young (i.e., 3 month old) rats The strong positive correlation observed between DNA damage associated NAD+ depletion and Sirt1 activity suggests that adequate NAD+ concentrations may be an important longevity assurance factor.
 
The authors of one paper5B write that when cells are subjected to oxidative stress by exposure to H2O2 [hydrogen peroxide], PARP-1 is activated and SIRT1 activity is robustly reduced, as PARP-1 activation limits NAD+ bioavailability. Treatment with PARP inhibitors in these circumstances allows the cell to maintain NAD+ levels and SIRT1 activity. these observations indication that PARP-1 is a gatekeeper for SIRT1 activity by limiting NAD+ availability.
 
The authors of paper #4 report that [p]revious work from our group has shown for the first time that resveratrol induces a dose-dependent increase in activity of the NAD+ synthetic enzyme nicotinamide mononucleotide adenyl transferase (NMNAT1) but that this is unpublished data.
the activity of SirT1 relies on NAD+ as a necessary coenzyme. The paper6A goes on to describe how, in its study of exercise in mice, chronic contractile activity (exercise) has a robust effect on mitochondrial biogenesis and that resveratrol acted synergistically with exercise to increase mitochondrial content when SirT1 was activated. [T]he maximal effect of RSV [resveratrol] requires both SirT1 and a condition of energy demand in muscle that would be high in NAD+ and AMP, cofactors which activate SirT1 and AMPK, respectively
There are three main physiological precursors: tryptophan, niacin, and niacinamide. It is reported that, the administration of radiolabeled nicotinamide and nicotinic acid [niacin] has clearly shown that nicotinamide is a better precursor of NAD+ and that nicotinic acid is rapidly cleared by being converted to nicotinamide and excreted as nicotinuric acid.6B Resveratrol was reported in paper #4 (but only as unpublished data) to dose-dependently increase the activity of the NAD+ synthetic enzyme nicotinamide mononucleotide adenyl transferase. In another paper,7 quercetin was reported to oxidize NADH to NAD+ in rat liver, thus increasing the availability of NAD+. However, as the researchers also explain, direct measurements of NADH/NAD+ are very difficult to perform.7 This was as of the papers publication in 2005. The researchers inferred the NADH/NAD+ ratio from the ratio of beta-hydroxybutyrate to acetoacetate. Quercetin has also been reported to be a PARP-1 inhibitor.7B Niacinamide is known to be an inhibitor of PARP, thus may prevent the decrease in NAD+ that results from PARP activity. There is a salvage pathway of specific enzymes that converts niacinamide to NAD+.
 
Niacinamide (NAM) As a PARP Inhibitor May Explain NAMs Antiviral Effects
Interestingly, PARP is reported to be critical for the integration of foreign DNA, as absence of the PARP enzyme interrupts the HIV life cycle.7C An early study published in 1996 on the effects of niacin reported that a daily niacin (combining niacin and niacinamide) intake in AIDS patients that equaled only 34 times the U.S. recommended daily allowance (at that time) of 20 mg/day experienced slower progression and improved survival.7D That was, of course, well before the current multidrug cocktails were developed that enable HIV infected individuals to survive 20 years or more, but still demonstrates the anti-viral effects of the vitamin.
 
Other natural PARP inhibitors include the flavonoids fisetin and tricetin8 and flavone
 
Full disclosure: my wife sells Quercetin and Fisetin, mentioned above as NAD+ precursors via inhibiting NAD+ robbing PARP1, on Ebay

Edited by maxwatt, 26 May 2014 - 03:44 AM.

[APBT]

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

 

[DrW]

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

 

 

Thanks. Useful info.

 

 

 

Edited by DrW, 26 May 2014 - 09:30 PM.

[Castiel]

 

Some polarized views on the marketed product 

 

Anyone tried this version?

 

 

Nicotinic acid have many health benefits and increase NAD in many tissues (brain (most important in glial cells), liver, hart, kidneys, intestine...) but NR have only on laboratory rat muscle? No human trial, no negative effects?   And many of us are willing to spend XXX amount of money on "magic pill" ?

 

 

supposedly NR resulted in increased sirtuin activity in yeast, and achieved about 80% replicative lifespan increase.   That[replicative lifespan increase] is what was initially used to single out resveratrol.

[DrW]

User reviews of recent experience with any supplement is suspect. Expectancies of benefits color such evaluations and skew them as positive when they are not.

 

Most supplements only have effects on a long range basis, and then may not be efects that can be experienced even though life extending. 

 

 

[tunt01]

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

 

 

Thx for this datapoint.  Still lines up with ~1950 mg NR per day for 60 kg male.  Does anyone know how they arrive at these figures?  What is the measurement being used to determine these dosage figures?

[Castiel]

The 400 MG per KG,study referenced an earlier study as a basis for dosage where it was said NR did not affect brain NAD, iirc.  But elsewhere I've read there are effects in the brain.  Is it by alternate means?

 

As for dosing with several grams wouldn't the CL element which dissociates cause digestion problems at that high a dose? or would it be a nonissue?

 

Given that the 400MG per KG is for maximal dose dependent NAD ratio modification, would lower doses be as effective if (complemented by) Moderate CR (was engaged)?

 

[maxwatt]

The amount of Cl in a gram of NR-Cl is about the same as in 200 mg of salt, without the sodium. Non-issue, I think.

Different studies often are contradictory. Eventually with enough studies, the truth will out.

If NR requires a threshold amount to have an effect, lower doses won't be effective combined with CR, but without specific studies, we don't know.

[midas]

The amount of Cl in a gram of NR-Cl is about the same as in 200 mg of salt, without the sodium. Non-issue, I think.

Different studies often are contradictory. Eventually with enough studies, the truth will out.

If NR requires a threshold amount to have an effect, lower doses won't be effective combined with CR, but without specific studies, we don't know.

 

Until we can get a decent amount of NR at a reasonable price. The way I am looking at it is, the small amount of Niagen I take just now, is vastly more than I took before.

 

If NR is a really good thing, then we were only getting trace amounts from nature (Milk and Beer) So we should be benefiting to some degree, as we wait for a decent supply until we can afford to up the dose.

[Castiel]

The amount of Cl in a gram of NR-Cl is about the same as in 200 mg of salt, without the sodium. Non-issue, I think.

Different studies often are contradictory. Eventually with enough studies, the truth will out.

If NR requires a threshold amount to have an effect, lower doses won't be effective combined with CR, but without specific studies, we don't know.

 

iirc, the study on which the 400mg per kg dosage was based said there was a dose dependent effect with maximal effect at 400 iirc.

[M-K]

 

The amount of Cl in a gram of NR-Cl is about the same as in 200 mg of salt, without the sodium. Non-issue, I think.

Different studies often are contradictory. Eventually with enough studies, the truth will out.

If NR requires a threshold amount to have an effect, lower doses won't be effective combined with CR, but without specific studies, we don't know.

 

Until we can get a decent amount of NR at a reasonable price. The way I am looking at it is, the small amount of Niagen I take just now, is vastly more than I took before.

 

If NR is a really good thing, then we were only getting trace amounts from nature (Milk and Beer) So we should be benefiting to some degree, as we wait for a decent supply until we can afford to up the dose.

 

I concur.  Nearing five months, my wife and I have seen enough results from 250 mg per day to have no doubts about its effectiveness.  The mental effects alone have been strong enough to make me cautious of higher doses.  I also wonder if other cofactors, such as B complex, aren't warranted.  Anyone know what other nutrients are required for NR, NMN, and NAD to function properly?

[midas]

 

  Anyone know what other nutrients are required for NR, NMN, and NAD to function properly?

 

 

More NR?

[pedr0vsky]

Anyone know what other nutrients are required for NR, NMN, and NAD to function properly?

 

Resveratrol and PQQ are known sirtuins agonists. They are good to add to NR. I am currently on 500 NR a day + 10mg PQQ + Resveratrol.

[Bryan_S]

Some polarized views on the marketed product 

 

Anyone tried this version?

 

 

 

 

 

That is the same thing I'm taking and have for the last 3 months.

 

I take it sublingual, experienced burping when I took the capsule, the taste under the tongue isn't so bad. Haven't seen any real adverse reactions but maybe soft stool since I started. I did however experience several days between deliveries where I ran out and felt like I'd crashed which I attributed to not having the NR. These things can easily be imagined as well. Overall I haven't noticed a huge energy gain but I'm just not as tiered. Maybe I need to take in a higher dose, I'm taking the recommended dose on the bottle which is 2 Caps.

 

Now I cant attribute this to the NR alone but I own a VersaClimber and have felt compelled to use it since I started taking the NR. Maybe its just my mental state of wanting to get back in shape but either way I have no trouble lying to myself and saying its the NR if that gets me through my next workout. 

 

Like everyone else I need to find a cheaper source, today I spent $47.99 which is down slightly from its previous $52.98.

 

Been lurking this thread for a while, seems one of us should be able to find a better source. Before I found you guys I went through 6 Alibaba sellers trying to do the same thing. The best one I found was "Nicotinamide Riboside   Medical grade Price:USD1540/KG" from Zhengzhou Friend Biolongical Eenineering Co.,Ltd but I couldn't afford the 1KG all at once. I haven't vetted them and I haven't seen them mentioned on this thread yet.

[APBT]

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.

[Volcanic]

I'm also not a chemist, but I can say this: The NR is the cation (positive charge), and the chloride is the anion (negative charge). I suspect than when dissolved, they dissociate (just as other salts do), resulting in a bunch of NR and chloride ions bouncing around in the water. Your stomach is full of chloride ions anyway, owing to the stomach acid (hydrochloric acid), and/or the salt you've eaten (sodium chloride), so the chloride probably won't hurt anything. Bromide, on the other hand, is controversial, and some people advocate using high-dose iodide to drive bromide out of the body. I've no idea whether there's any merit to that position, but if you're unsure, chloride seems to be the safer choice.

[maxwatt]

Bromides were used in the 19th century as sedatives.

[APBT]

I'm also not a chemist, but I can say this: The NR is the cation (positive charge), and the chloride is the anion (negative charge). I suspect than when dissolved, they dissociate (just as other salts do), resulting in a bunch of NR and chloride ions bouncing around in the water. Your stomach is full of chloride ions anyway, owing to the stomach acid (hydrochloric acid), and/or the salt you've eaten (sodium chloride), so the chloride probably won't hurt anything. Bromide, on the other hand, is controversial, and some people advocate using high-dose iodide to drive bromide out of the body. I've no idea whether there's any merit to that position, but if you're unsure, chloride seems to be the safer choice.

 

Thank you for your contribution.  If this is accurate, it seems that NR chloride (Niagen) is an efficacious option as an NAD+ precursor.