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Sublingual NR and NMN

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#1 Harkijn

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Posted 20 February 2018 - 05:06 PM


 

Give peace a chance, someone  said. Debating NMN vs NR will not lead to any useful conclusion. Let us wait for the outcome of human trials. And, I keep reminding, several top researchers in the field think that all Nad precursors have different values for different tissues.

Meanwhile, this company

https://store.revgenetics.com/

offers NMN as bulk powder for a less outrageous price than for capsules. Can anyone tell me: is NMN stable enough to survive after opening the pot?

 

 

I've been taking that NMN powder for 4 months.  

 

I had the same question as you about stability, so I intentionally left a little in the bottom of the first jar I tried.    4 months later, I see no noticeable difference from the powder in a new jar.

 

I see other suppliers with better pricing, but like this without fillers and more convenient for using sublingual.  I feel like I'm getting more benefit that way.

 

Anyone else trying NMN sublingual?

 

Thanks Able, glad to hear the voice of sanity in the din here.

Sublingual is  a very good idea, I had not thought of that.

Can the benefit you perceive be put into words? Like, more energy in general, or more fitness performance?

I will try this. In addition to my NR dosage of about  375mg daily. 

Any other sublingualists around here?



#2 able

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Posted 20 February 2018 - 05:18 PM

 

 

Give peace a chance, someone  said. Debating NMN vs NR will not lead to any useful conclusion. Let us wait for the outcome of human trials. And, I keep reminding, several top researchers in the field think that all Nad precursors have different values for different tissues.

Meanwhile, this company

https://store.revgenetics.com/

offers NMN as bulk powder for a less outrageous price than for capsules. Can anyone tell me: is NMN stable enough to survive after opening the pot?

 

 

I've been taking that NMN powder for 4 months.  

 

I had the same question as you about stability, so I intentionally left a little in the bottom of the first jar I tried.    4 months later, I see no noticeable difference from the powder in a new jar.

 

I see other suppliers with better pricing, but like this without fillers and more convenient for using sublingual.  I feel like I'm getting more benefit that way.

 

Anyone else trying NMN sublingual?

 

Thanks Able, glad to hear the voice of sanity in the din here.

Sublingual is  a very good idea, I had not thought of that.

Can the benefit you perceive be put into words? Like, more energy in general, or more fitness performance?

I will try this. In addition to my NR dosage of about  375mg daily. 

Any other sublingualists around here?

 

 

I have been taking NR for 2 1/2 years and experienced many benefits others mention such as more energy, better sleep, better skin, hair, nails.

 

I didn't really notice much difference  in the 1-2 months  I used NMN capsules vs NR, but was a short time and many confounding factors such as diet and exercise changes.

 

With sub-lingual NMN, I don't notice more energy, but do seem to have more endurance - no sleepy or tired feelings throughout the day.  Of course, that is very subjective and near meaningless as an anecdote.  

 

The one difference I find so far that is not subjective is, my swimming and running times at the track (220 to 1 mile) have improved quite a bit - back to where I was 10 years ago.  I can't be sure the cause, but  am sure it is not my imagination or placebo.

 

 

https://medium.com/@...fe-8ef1854a8a7e

 

This guy wrote an interesting bit about NMN sublingual, and convinced me to add some xylitol.  I don't know if it is more easily absorbed like he says, but it makes it a lot more palatable.


Edited by able, 20 February 2018 - 05:34 PM.

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#3 stefan_001

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Posted 20 February 2018 - 09:11 PM

 

 

 

 

 

I have been taking NR for 2 1/2 years and experienced many benefits others mention such as more energy, better sleep, better skin, hair, nails.

 

I didn't really notice much difference  in the 1-2 months  I used NMN capsules vs NR, but was a short time and many confounding factors such as diet and exercise changes.

 

With sub-lingual NMN, I don't notice more energy, but do seem to have more endurance - no sleepy or tired feelings throughout the day.  Of course, that is very subjective and near meaningless as an anecdote.  

 

The one difference I find so far that is not subjective is, my swimming and running times at the track (220 to 1 mile) have improved quite a bit - back to where I was 10 years ago.  I can't be sure the cause, but  am sure it is not my imagination or placebo.

 

 

https://medium.com/@...fe-8ef1854a8a7e

 

This guy wrote an interesting bit about NMN sublingual, and convinced me to add some xylitol.  I don't know if it is more easily absorbed like he says, but it makes it a lot more palatable.

 

 

I have now been using NR sublingual in the early morning at 250mg for some time. In the evening I use normal oral dose at 250mg. My perception is that the sublingual does something. Hard to describe but I would say clearing of mind, a sense of "strong" body.

 



#4 able

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Posted 25 February 2018 - 09:33 PM

I’ve been reluctant to post my experience here as I know it will be attacked incessantly by certain NR fanatics, but there are some thoughts I wanted to share and get feedback from others on.  Hopefully that can happen.

 

I started NR 2 1/2 years ago and had good results in increased energy, improved hair, skin, nails, and sleep.

 

In the beginning, I was so energized I had to stop all caffeinated coffee.  I gradually found I could tolerate caffeine in the morning and still sleep, and later, maybe a little after lunch, but not always.

 

In 2017, I began to be curious about NMN, and started taking it at about 1/2 my usual  750-1000 mg of NR - mostly due to cost.

 

I frankly couldn’t tell much difference from the NR.  

 

As prices came down a bit, I moved to 500-750 Mg a day, split in 2 dosages (unlike my daily NR)

 

No change in energy, but I did start making some progress in my endurance/stamina at the track and swimming.  But nothing that I would normally mention as being outside normal variation.

 

Sometime in December, I started using the same quantity of Revgenetics powder sublingual, twice a day.

 

For me, that made a big difference.  More energy - back to how it was when I first started NR, and better workouts.

 

What really kicked it up for me tho, was increasing the dosage.  Reading more about Lawrences results, I began to think that NMN might not have the same “upper limit” of effectiveness around 1000 mg.    

 

I always like the slow, time-release action of NR, since I’m lazy and don’t like taking supplements more than once a day.  But if motivated I can.   

 

So I kicked it up to 500 mg, 3 times a day.   Been doing that for 2 weeks and it’s been fabulous so far.  Energy like a 20 year old, clear headed, and just ran a sub-7 minute mile and 89 second 1/4 mile yesterday - back to my time of 10 years ago.  I had to stop all caffeine again for now, but decaf taste almost the same to me.

 

Of course, homeostasis may kick in and these benefits fade.  Will have to see.

 

My questions  are: 

 

Does it make sense that sublingual could be moving more of the NMN direct to blood and then muscle?  

 

Is it likely NMN has a higher maximum effective dosage than NR for some people, since it is faster acting?  

 

I don't know if the higher dosages, or splitting to 3 a day is yielding the increased benefit - will have to test.

 


Edited by able, 25 February 2018 - 09:38 PM.

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#5 stefan_001

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Posted 18 March 2018 - 09:57 PM

"Sublingual (abbreviated SL), from the Latin for "under the tongue", refers to the pharmacological route of administration by which substances diffuse into the blood through tissues under the tongue. Many drugs are designed for sublingual administration, including cardiovascular drugs, steroids, barbiturates, benzodiazepines,[1] opioid analgesics, enzymes and, increasingly, vitamins and minerals"

 

"When a chemical comes in contact with the mucous membrane beneath the tongue, it is absorbed. Because the connective tissue beneath the epithelium contains a profusion of capillaries, the substance then diffuses into them and enters the venous circulation. In contrast, substances absorbed in the intestines are subject to "first-pass metabolism" in the liver before entering the general circulation"

 

"a number of factors, such as pH, molecular weight, and lipid solubility, may determine whether the route is practical. Based on these properties, a suitably soluble drug may diffuse too slowly through the mucosa to be effective."

 

To remove the uncertainty of what happens to NR via the oral route as is regular discussed on the forum I am now taking 250mg in morning sublingual (and 250mg oral in the evening). As far as i understand the molecular weight is low enough. Views of others?



#6 able

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Posted 19 March 2018 - 03:37 AM

Makes sense to me.  Might be more available to blood, and doubt it could be worse.

 

I've been trying the Revgenetics (not niagen) powder for a few days now - 500mg sublingual in morning and another 500 at night.  Seems to provide more "kick" energy wise, but of course is hard to know if that is placebo, especially after a few days.

 

I don't really find it less convenient than capsules, so will continue with sublingual NR for a while and likely switch to sublingual NR/NMN mix later.   



#7 Harkijn

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Posted 19 March 2018 - 07:11 AM

After earlier posts by able I ordered sublingual NR to give it a try, but my order is very slow to come.

The idea seems to make sense, though the difficult part is 'patient compliance': it would be optimal to take several small amounts in the course of,say, an hour and then not eat or drink anything for at least another hour.

Many years ago I daily took sublingual vitamin B12 and had bloodwork done very regularly. It turned out that B12 blood level was higher when I cut the sublingual tablet in two or three and paused 15 minutes or so in between.



#8 stefan_001

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Posted 19 March 2018 - 12:24 PM

After earlier posts by able I ordered sublingual NR to give it a try, but my order is very slow to come.

The idea seems to make sense, though the difficult part is 'patient compliance': it would be optimal to take several small amounts in the course of,say, an hour and then not eat or drink anything for at least another hour.

Many years ago I daily took sublingual vitamin B12 and had bloodwork done very regularly. It turned out that B12 blood level was higher when I cut the sublingual tablet in two or three and paused 15 minutes or so in between.

 

As @able write I have the same impression on the energy side.

Thats interesting info, if B12 passes through then NR probably does as well. Powder form may then actually be quite good. The capsules I open contain the filler which I am thinking doesn't help. Anobody knows how much filler there is per capsule?



#9 Harkijn

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Posted 19 March 2018 - 01:22 PM

I believe the companies have some basic formula for that. But more important is which fillers and excipients are used. I  would not mind using HPN sublingually, because last  time I checked they only added microcellulose, but other brands also include silicium dioxide and other substances which are only guaranteed to be safe if the capsule opens in the stomach acid, so are not meant to have contact with the mouth etcetera, let alone to be accidently breathed in on a regular basis. I think Bryan S placed some important posts about this in the old Curated thread.



#10 able

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Posted 19 March 2018 - 05:15 PM

After earlier posts by able I ordered sublingual NR to give it a try, but my order is very slow to come.

The idea seems to make sense, though the difficult part is 'patient compliance': it would be optimal to take several small amounts in the course of,say, an hour and then not eat or drink anything for at least another hour.

Many years ago I daily took sublingual vitamin B12 and had bloodwork done very regularly. It turned out that B12 blood level was higher when I cut the sublingual tablet in two or three and paused 15 minutes or so in between.

 

Interesting.   Did they test if the sublingual delivery resulted in higher b12 blood levels vs supplements, and if so, any recall on how much?



#11 Harkijn

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Posted 19 March 2018 - 06:09 PM

 

After earlier posts by able I ordered sublingual NR to give it a try, but my order is very slow to come.

The idea seems to make sense, though the difficult part is 'patient compliance': it would be optimal to take several small amounts in the course of,say, an hour and then not eat or drink anything for at least another hour.

Many years ago I daily took sublingual vitamin B12 and had bloodwork done very regularly. It turned out that B12 blood level was higher when I cut the sublingual tablet in two or three and paused 15 minutes or so in between.

 

Interesting.   Did they test if the sublingual delivery resulted in higher b12 blood levels vs supplements, and if so, any recall on how much?

 

Well, it started with me developing the medical condition called 'pernicious anemia' (somewhat outdated term). That means that I had never in my life been able to absorb B12 from food and  now had depleted my prenatal stash of vitamin B12 in the liver. This is potentially lethal and initially I got B12 injections every week to make up for the deficit. Once the injections stopped blood levels fell back to 300 pmol/l and symptoms returned.

Then they started me on sublingual B12 in the form of Methylcobalamin 1000 mcg. After one month blood levels were up to 600 pmol which is in theory pretty good but clearly not helping enough. Some months(and monthly testing) later I started to cut the tablets and suck on them as described above. Blood levels went up to above 1000pmol. Higher than they care to measure but in my case apparently beneficial. Lots more to tell but this is it in brief. (I am a bit rusty on pmol vs nmol....)


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#12 stefan_001

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Posted 20 March 2018 - 12:45 PM

Now here is a reason to truly consider sublingual use:

 

"Intravenous, but not oral
administration of nicotinamide riboside or
mononucleotide delivered intact molecules to multiple
tissues, with skeletal muscle displaying a preference for NR. Thus, fluxes provide a novel
window into NAD biology"

 

another interesting quote:

"We showed that mitochondria directly import NAD and generate NAD from nicotinamide containing nucleotides, but not from NAM"

 

https://search.proqu...bl=18750&diss=y

 

Unfortunately I dont have access to the entire thesis to read more about these findings.

 


Edited by stefan_001, 20 March 2018 - 12:47 PM.


#13 Nate-2004

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Posted 20 March 2018 - 02:18 PM

I think some of the concern over sublingual NR wasn't just the filler, but the salt stabilized form of NR in that this form isn't readily absorbed in this manner.  I'm not sure exactly how one would go about improving the sublingual absorption though.

 

Intranasal ingestion might be another way, but again, there's a problem with its stabilization in liquids and I assume it would just break down into NAM+R.


Edited by Nate-2004, 20 March 2018 - 02:20 PM.


#14 TMNMK

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Posted 20 March 2018 - 03:00 PM

 

https://search.proqu...bl=18750&diss=y

 

Unfortunately I dont have access to the entire thesis to read more about these findings.

 

Nice find @stefan_001!

 

Here should be full text: https://dataspace.pr...0181D_12390.pdf



#15 TMNMK

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Posted 20 March 2018 - 03:29 PM

So based on the findings of this paper, it would seem that if you don't want to whip out your needles just yet (I joke, please whoever reads this, do not IV straight out of a capsule that contains excipients, obviously), you might aim for sublingual administration, I don't have any reason to doubt that sublingual administration would work for NR in order to bypass first-pass metabolism.

 

Also this:

 

"Interestingly, NR but not NMN was efficiently assimilated intact into NAD in muscle. To our knowledge, this is the first clear example of a differential metabolic effect between these two compounds in vivo. Thus, tissue-specific utilization of these compounds should be considered in the design of future NAD-boosting drugs. "

 

" Without formally ruling out such a possibility, we observed that IV administration of either compound results in its detection within the circulation (albeit to a much greater extent for NR) and a robust M+2 peak in the kidney, proving that the route of delivery has a profound effect on the ability of these precursors to reach target tissues. "

 

"Surprisingly, IV NR was much more effective than NMN for labeling the NAD pool in skeletal muscle. This is consistent with the proposal that at least some tissues are incapable of taking up NMN directly"


Edited by TMNMK, 20 March 2018 - 04:17 PM.

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#16 Harkijn

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Posted 20 March 2018 - 04:22 PM

Yes, very interesting study, and perhaps sublingual will be the only practical way forward.

I would however like to see his theory of concentration vs. flux as well as his exact way of measuring  confirmed by other experts.

Also: he admits that the administered amount of NR was low and that higher amounts could have yielded other results.

 

He quotes the Trammel study but  I think in his discussion does not mention possible reasons for the diametrically opposed findings.


Edited by Harkijn, 20 March 2018 - 04:23 PM.

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#17 stefan_001

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Posted 20 March 2018 - 09:26 PM

I am wondering the validity of measuring circulating NR and NMN after oral gavage. From the graph 2.7d it would seem that he simply measured that 5 minutes after oral administration. In my view you would need to measure every 30 seconds or so as you do not know at what speed the NR or NMN travels through the digestive system. Also it would seem logical to me that NR/NMN would enter more gradually as compared to rapid IV administration and is converted to NAM continuously. That is also substantiated by graph 2.7C that shows a gradual rise in NAM as result from the oral administration versus spiky IV behavior. So my take is that any NR or NMN that makes it to circulation is converted fast (see also his comments about rapid fall of NR/NMN concentration in blood t1/2=3min) and that only because of the rapid injection of NR/IV in the bloodstream you can actually measure it. This is exactly the same discussion we had couple months ago.

 

What is clear however is that NR that does enter the bloodstream is contributing to tissue NAD (and doing it better than NMN). So taking NR, at least part of it sublingual makes sense. Lots of data to digest in this work...Views from others welcome.


Edited by stefan_001, 20 March 2018 - 09:30 PM.

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#18 MikeDC

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Posted 20 March 2018 - 11:47 PM

I am wondering the validity of measuring circulating NR and NMN after oral gavage. From the graph 2.7d it would seem that he simply measured that 5 minutes after oral administration. In my view you would need to measure every 30 seconds or so as you do not know at what speed the NR or NMN travels through the digestive system. Also it would seem logical to me that NR/NMN would enter more gradually as compared to rapid IV administration and is converted to NAM continuously. That is also substantiated by graph 2.7C that shows a gradual rise in NAM as result from the oral administration versus spiky IV behavior. So my take is that any NR or NMN that makes it to circulation is converted fast (see also his comments about rapid fall of NR/NMN concentration in blood t1/2=3min) and that only because of the rapid injection of NR/IV in the bloodstream you can actually measure it. This is exactly the same discussion we had couple months ago.

 

What is clear however is that NR that does enter the bloodstream is contributing to tissue NAD (and doing it better than NMN). So taking NR, at least part of it sublingual makes sense. Lots of data to digest in this work...Views from others welcome.

 

I agree with you that substantial amount of NR enters blood stream and utilized immediately by other tissues. Since the speed of draining by other tissues is almost instant, the circulating NR level stays low.  The defective experimental design caused many to think NR and NAM are the same. From clinical trials results and user experiences we know NR and NAM are substantially different. It is a matter of trusting human clinical data or experimental research data. Clinical data always overrides the experimental data.


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#19 Michael

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Posted 22 March 2018 - 03:53 AM

So my take is that any NR or NMN that makes it to circulation is converted fast (see also his comments about rapid fall of NR/NMN concentration in blood t1/2=3min) and that only because of the rapid injection of NR/IV in the bloodstream you can actually measure it. This is exactly the same discussion we had couple months ago.

 
You are forgetting or somehow missed the UWash human pharmacodynamics trial, which for the first time painstakingly extracted NR from whole blood using methods similar to the Liu thesis: they clearly show a ≈3h Cmax, with significant interindividual variation in magnitude seemingly related to baseline levels. The Forum software won't let me insert the money shot inline, but it's here. Rodents might well have a more truncated cycle, but surely not as short as you speculate here.
 


 


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#20 stefan_001

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Posted 22 March 2018 - 08:06 AM

 

So my take is that any NR or NMN that makes it to circulation is converted fast (see also his comments about rapid fall of NR/NMN concentration in blood t1/2=3min) and that only because of the rapid injection of NR/IV in the bloodstream you can actually measure it. This is exactly the same discussion we had couple months ago.

 
You are forgetting or somehow missed the UWash human pharmacodynamics trial, which for the first time painstakingly extracted NR from whole blood using methods similar to the Liu thesis: they clearly show a ≈3h Cmax, with significant interindividual variation in magnitude seemingly related to baseline levels. The Forum software won't let me insert the money shot inline, but it's here. Rodents might well have a more truncated cycle, but surely not as short as you speculate here.
 


 

 

That's true. Clear difference with what is seen in Liu. It would have been very usefull if double labelled NR was used in the UWash study, This Cmax at 3h might be a secondary effect.


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#21 Michael

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Posted 22 March 2018 - 02:38 PM

There isn't as much of a difference here as you might think. Liu only looked for 2 hours after a one-time gavage. UWash used a higher dose (remember to account for allometric scaling), and the curve baseline t=0 is on day 9, after having ramped up to 2 g NR/d on the previous two days and having had 1 g twelve hours before, such that their NR level att=0 on day 9 is already residually elevated from the unsupplemented baseline levels.

 

There could also be some difference in actually capturing the NR, which all agree is challenging.

 

To be a secondary effect, you'd have to have more NR derived from retroconversion from NMN than from NR itself: I put it to you that that's an implausible scenario.

 



#22 Michael

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Posted 22 March 2018 - 04:15 PM

What seems reasonably clear to meis that at these doses (50 mg/kg in a likely 25 g mouse ≈ 284 mg in a 70 kg human per FDA HED, or 481 mg per direct allometric scaling), where the great majority of the tissue shift in NAD+ flux comes from NAM derived from earlier metabolism of supplement (M+1 — Fig 2.7e), and only a very small fraction coming directly from intact circulating NR from supplement (M+2), NR levels in circulation are low because they've been soaked up by the liver and converted to NAM, which is then used to increase tissue NAD+. At higher doses, you get higher levels of intact NR escaping into the circulation.

 

I must say that people are jumping a bit prematurely to the conclusion that sublingual NR would be absorbed intact into the circulation rather than either hydrolyzed in the mouth or metabolized in the mucosal membranes.


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#23 able

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Posted 22 March 2018 - 04:34 PM

What seems reasonably clear to meis that at these doses (50 mg/kg in a likely 25 g mouse ≈ 284 mg in a 70 kg human per FDA HED, or 481 mg per direct allometric scaling), where the great majority of the tissue shift in NAD+ flux comes from NAM derived from earlier metabolism of supplement (M+1 — Fig 2.7e), and only a very small fraction coming directly from intact circulating NR from supplement (M+2), NR levels in circulation are low because they've been soaked up by the liver and converted to NAM, which is then used to increase tissue NAD+. At higher doses, you get higher levels of intact NR escaping into the circulation.

 

I must say that people are jumping a bit prematurely to the conclusion that sublingual NR would be absorbed intact into the circulation rather than either hydrolyzed in the mouth or metabolized in the mucosal membranes.

 

 

Are you saying that  with a single small dose such as Liu study, very little NR escapes into circulation. But higher, repeated dosages that have elevated NAD+/NAM levels allow more NR to escape to circulation and reach other tissues?

 

So would that suggest taking the less expensive NAM supplements would elevate NAM/NAD+ levels, combined with NR that would then be more likely to escape to circulation?

 

As for sublingual - isn't it possible that some NR is absorbed into circulation?  I personally don't mind taking sublingual, so if there is a chance it is more effective, fine with me.


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#24 stefan_001

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Posted 22 March 2018 - 04:38 PM

What seems reasonably clear to meis that at these doses (50 mg/kg in a likely 25 g mouse ≈ 284 mg in a 70 kg human per FDA HED, or 481 mg per direct allometric scaling), where the great majority of the tissue shift in NAD+ flux comes from NAM derived from earlier metabolism of supplement (M+1 — Fig 2.7e), and only a very small fraction coming directly from intact circulating NR from supplement (M+2), NR levels in circulation are low because they've been soaked up by the liver and converted to NAM, which is then used to increase tissue NAD+. At higher doses, you get higher levels of intact NR escaping into the circulation.

 

I must say that people are jumping a bit prematurely to the conclusion that sublingual NR would be absorbed intact into the circulation rather than either hydrolyzed in the mouth or metabolized in the mucosal membranes.

 

I also think that is a reasonable hypothesis.

 

This is an interesting topic:

"rather than either hydrolyzed in the mouth or metabolized in the mucosal membranes"

 

and would be great to know whether that may be occuring.
 


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#25 Michael

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Posted 22 March 2018 - 05:45 PM

 

What seems reasonably clear to me is that at these doses (50 mg/kg in a likely 25 g mouse ≈ 284 mg in a 70 kg human per FDA HED, or 481 mg per direct allometric scaling), where the great majority of the tissue shift in NAD+ flux comes from NAM derived from earlier metabolism of supplement (M+1 — Fig 2.7e), and only a very small fraction coming directly from intact circulating NR from supplement (M+2), NR levels in circulation are low because they've been soaked up by the liver and converted to NAM, which is then used to increase tissue NAD+. At higher doses, you get higher levels of intact NR escaping into the circulation.

 
Are you saying that  with a single small dose such as Liu study, very little NR escapes into circulation. But higher, repeated dosages that have elevated NAD+/NAM levels allow more NR to escape to circulation and reach other tissues?

Elevated NAD+, not elevated NAM: NAM is too far downstream to seem like a reasonable candidate mechanism. But yes: I'm hypothesizing that there may be more 'spillover' NR once NAD+ levels are built up, saturating the enzymes and allowing free NR to escape. Note also the spike in liver NMN after NR administration in Figure 5a in Trammel & Brenner, NMN being the direct product of NR and its intermediate in producing NAD+. Some gradual buildup of NR itself may play a role too.
 

able wrote: So would that suggest taking the less expensive NAM supplements would elevate NAM/NAD+ levels, combined with NR that would then be more likely to escape to circulation?

That's a provocative corollary! However, I don't think people should adopt a regimen just on mechanistic speculation, and I'd be especially reluctant to do it with NAM, because my hunch is that it'd be even more likely to be subject to feedback mechanisms (cf. the profound downregulation of NAMPT observed in the underappreciated NAM lifespan study), and because NAM raises 1N-methylnicotinamide more, at least in the short term (ibid, 5e — as you'd expect).
 

 

I must say that people are jumping a bit prematurely to the conclusion that sublingual NR would be absorbed intact into the circulation rather than either hydrolyzed in the mouth or metabolized in the mucosal membranes.


As for sublingual - isn't it possible that some NR is absorbed into circulation?  I personally don't mind taking sublingual, so if there is a chance it is more effective, fine with me.

Sure it is. I'm certainly not saying that it is not absorbed intact into the circulation: I'm merely saying that "people are jumping a bit prematurely to the conclusion" that it is. As I said above, I don't think people should adopt a regimen just on mechanistic speculation, and in this case we have zero data on the subject.


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#26 TMNMK

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Posted 22 March 2018 - 06:50 PM

Some google searching leads me to believe that there are permeation enhancers:

 

"The enhancing effect of menthol on buccal permeation of a hydrophilic nucleoside analog, dideoxycytidine, has been reported. It is thought to increase the partition coefficient of a drug by facilitating the transcellular pathway in a concentration independent manner"

 

http://www.ingentaco...01?crawler=true

 

 


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#27 livingguy

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Posted 07 April 2018 - 05:50 AM

Which NR products are suitable for sublingual use. Can someone please provide a few links ideally from iherb, I will be grateful.
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#28 able

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Posted 07 April 2018 - 03:16 PM

Which NR products are suitable for sublingual use. Can someone please provide a few links ideally from iherb, I will be grateful.

 

Good question.  I've been using the Revgenetics NR powder, but don't see it on their site anymore.  It was not Niagen tho, so maybe they were forced to stop selling it.

 

Only other NR powder I know is HPN, but theirs has 2 grams Fructooligosaccharides for 125 mg NR.   Not crazy about taking all that sweetener. 



#29 Harkijn

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Posted 07 April 2018 - 04:42 PM

My Revgenetics order was despatched to Holland via USPS and designated 'delivered' by them. But I never got it and probably someone else is sticking this up some orifice right now.  :mellow:  :) .

So AFAIK  at present there is no other way than opening capsules and sublingually absorbing not just NR but also the other stuff in it.

This situation will perhaps change so I would like to point here to ALCAR as a possible enhancer of sublingual absorption of a vast array of substances:

https://pharmacyrevi...ailability.html


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#30 able

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Posted 07 April 2018 - 05:03 PM

It is unfortunate no-one supplies pure NR powder now.  Hopefully someone steps up on that.

 

I've been using both NR and NMN sublingual for a few months now and am totally convinced it is more effective than capsules.

 

This has some good info on effectiveness  of sublingual delivery.  I was surprised to see in some drugs, it is more effective than IP injection.

 

http://www.journalof...le/118766/81984

 

 


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