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Sublingual NR and NMN

sublingual

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#61 warner

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Posted 14 July 2018 - 06:59 PM

About a week ago we replaced 250 mg/d NR with 375 mg/d NMN as ABN sublingual tablets (a little more expensive than the powder), 125 mg morning, aft, and evening.  Unlike NR, the NMN is not affecting my (or wife's) sleep.  Too early to report results, but nothing negative so far.  Would like to see something positive though before upping dose.  Bryan Nettles, owner of ABN, reported good results with 3-4 sublingual tablets per day, and increased that to 6-8, and then 10-12...

 

https://alivebynatur...nger-healthier/


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#62 Qrazy

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Posted 14 July 2018 - 07:14 PM

 

 

It is a hassle to carry the jar around and take a scoop every hour or so. Really want to try the transdermal patch.

 

Better than keeping it in a baggie in your pocket.... Might be tough to explain should someone ask what the powder is. :) :)

 

Thanks for the answer.



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#63 Michael

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Posted 14 July 2018 - 11:42 PM

Got my 'New Sublingual' NMN tabs last week, and have taken some concerns

1) each tablet is approximately the size of a dime, and three times as thick. It weighs almost a gram. This shape and size is not easily kept under the tongue as they suggest to do. It's not comfortable. It would be better formed into a capsule shape that would fit under the tongue. And/or make the cap half size by simply cutting out half the non-NMN ingredients. Or cut the dose in half per tab.


A capsule shape would give you less exposed surface area, which might be disadvantageous.
 

2) It takes more than a while to dissolve. I've kept in there for up to 20 minutes waiting. And they say don't swallow, so you end up with a mouth full of saliva (and the remains of the tablet) for the whole time. Not particularly pleasant.

 
Unless it has really good sublingual absorption, slow dissolution is probably preferable, exactly so that you don't just wind up swallowing it all as it dissolves. One reason to potentially favor buccal administration is that while it's not important to absorb the stuff quickly (unlike a lot of SL drugs, like nitroglycerin), it's counterproductive to just dissolve it all in the saliva and swallow it, which you're more prone to do under the tongue.
 
Harjkin's solution might help, provided that there isn't some kind of layering in the tablet.


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#64 Heisok

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Posted 15 July 2018 - 12:19 AM

Thanks Able, that helps. I might try a little bit when I wake at night. Will be interesting. Warner, I thought that I remembered at some point you had some NR sleep issues, but they kind of resolved. Mine sublingual NR sleep issues only resolved by skipping afternoon NR doses. Helpful to know about the NMN.

 

 



#65 warner

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Posted 15 July 2018 - 01:25 AM

Yes, with NR I had to resort to taking it in the morning and mid-afternoon, avoiding evening doses, but have had no problem taking ABN sublingual NMN in the evening.

 

There's lots of stuff we're watching, and I'll post more later in more appropriate threads, although I can preliminarily report no immediate changes in params like morning blood pressure, heart rate, body temperature, etc., nor any immediate changes to visual field counts.  With respect to the latter, I was intrigued by Lawrence's report of improved visual acuity, which might have translated into improved visual field response (i.e., being able to better distinguish weak signals from background noise), but did not find that to be the case in the first few days after starting supplementation.

 

This all assumes, of course, that ABN's NMN is the real stuff, and that we are not the subjects of an elaborate con. :)  As best as I can tell, Bryan's getting the NMN from a Chinese company (possibly Bontac Bioengineering), and is having it properly tested.  (See the Q&A for the sublingual product on Amazon for more such info.)


Edited by warner, 15 July 2018 - 01:31 AM.


#66 LawrenceW

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Posted 15 July 2018 - 01:47 PM

There's lots of stuff we're watching, and I'll post more later in more appropriate threads, although I can preliminarily report no immediate changes in params like morning blood pressure, heart rate, body temperature, etc., nor any immediate changes to visual field counts.  With respect to the latter, I was intrigued by Lawrence's report of improved visual acuity, which might have translated into improved visual field response (i.e., being able to better distinguish weak signals from background noise), but did not find that to be the case in the first few days after starting supplementation.

 

Hello Warner.

 

I did not notice the improved visual acuity until about month 6 of taking NMN. Please realize that it took us many decades for our health to deteriorate to our current states.  To reverse that will take some time and expecting results in a few days is unrealistic.



#67 stefan_001

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Posted 15 July 2018 - 01:52 PM

I made NR eyedrops those give an immediate improvement. Ofcourse that fades. My vision is currently very good, so I put the long term usage on hold for now.

Edited by stefan_001, 15 July 2018 - 01:53 PM.

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#68 warner

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Posted 15 July 2018 - 02:49 PM

Hello Warner.

 

I did not notice the improved visual acuity until about month 6 of taking NMN. Please realize that it took us many decades for our health to deteriorate to our current states.  To reverse that will take some time and expecting results in a few days is unrealistic.

Hi Lawrence.  Sure, that's one reason I'm still taking it, but I think it's important to distinguish between immediate and longer-term effects.  In this case, does NMN have just a transient effect on vision, and/or does it change vision in some more fundamental and lasting way over a longer time-frame?  The answer to the first question, at least for the 375 mg/d sublingual intake, appears to be no short-term vision improvement.  But I'll keep testing periodically and we'll see what happens in the longer-term.  (btw, the visual field testing was done morning, aft, and evening, and I couldn't see any obvious effect of its proximity to NMN dosing, although I wasn't looking at that specifically, but rather whether my overall visual field response differed from the months prior to supplementation.)


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#69 Blueflash

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Posted 16 July 2018 - 05:33 PM

  "  I made NR eyedrops those give an immediate improvement. Of course that fades. My vision is currently very good, so I put the long term usage on hold for now. "

 

How did you make eyedrops?



#70 stefan_001

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Posted 07 August 2018 - 08:05 PM

Have not read it yet:

 

METHOD AND THE USE TO IMPROVE ORAL ABSORPTION OF NICOTINAMIDE AND NICOTINAMIDE RIBOSIDE

http://www.freepaten...18/0200275.html



#71 Oakman

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Posted 29 August 2018 - 03:04 PM

I got thinking about the best way to do sublingual dosing of NMN, since I’m doing a lot of it recently. I wanted to better understand the process in hopes of maximizing results. What I found surprised me. I realize this study below is for sublingual asenapine, but the process for sublingual delivery is the same and is explained well and with great detail.

 

https://www.ncbi.nlm...les/PMC3513449/

 

12249_2012_9839_Fig1_HTML.jpg

 

Some takeaways…

 

No direct route to blood/plasma taking sublingual molecules

Mucosa absorbs sublingual molecules for storage and delivers later to blood/plasma

Speed of plasma delivery varies by molecule

Water taken after absorption by mucosa has little effect

 

Here’s a graph of other molecules and time to Tmax. I wonder where NMN falls in this continuum? Supposedly it's relatively fast.

 

12249_2012_9839_Fig5_HTML.jpg

 

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#72 aaaaaaal

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Posted 17 October 2018 - 02:33 PM

Could anyone tell me if you can still take the sublingual NMN pills normally if desired? Or are they exclusively made for sublingual use only?


Edited by aaaaaaal, 17 October 2018 - 02:38 PM.


#73 able

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Posted 17 October 2018 - 02:54 PM

They are made to dissolve and absorb in the mouth.  There is no problem swallowing a sublingual pill, you just lose the effectiveness.  

 

I am too impatient to wait for them to dissolve myself, and often chew a bit.  

 

The research someone posted months back showed that different parts of the mouth and throat also absorb, just a bit lower % than under the tongue.  Something like 20-30%, vs 30-35% under the tongue.

 

If you chew and it mostly dissolves in the mouth and esophagus, that will still be a lot better than swallowing it whole.



#74 aaaaaaal

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Posted 17 October 2018 - 03:50 PM

They are made to dissolve and absorb in the mouth.  There is no problem swallowing a sublingual pill, you just lose the effectiveness.  

 

I am too impatient to wait for them to dissolve myself, and often chew a bit.  

 

The research someone posted months back showed that different parts of the mouth and throat also absorb, just a bit lower % than under the tongue.  Something like 20-30%, vs 30-35% under the tongue.

 

If you chew and it mostly dissolves in the mouth and esophagus, that will still be a lot better than swallowing it whole.

 

Thanks a lot, but how do the new sublingual pills compare to the old pills when taking orally? Thanks.

 

For example, if you take the new sublingual pills orally would it be the equivalent of taking the old pills normally?


Edited by aaaaaaal, 17 October 2018 - 03:56 PM.


#75 midas

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Posted 17 October 2018 - 05:13 PM


For example, if you take the new sublingual pills orally would it be the equivalent of taking the old pills normally?

 

As long as the amount of NMN in the pill is the same, yes. Only difference is that sublingually more of the NMN gets into the blood stream.

 

 

Has anyone done any testing to see how much NAD is raised with NMN? This was done quite early on with NR by Chromadex, Elysium Health and and independent lab in Colorado.

I find it strange that this has not been done with NMN.

 

I have recently bought some NMN and have been taking it for around one month. Whilst I was taking NR I noticed more or less straight away, as have others, my finger nails were growing a lot faster. Since I started taking NMN this has stopped?



#76 aaaaaaal

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Posted 17 October 2018 - 05:46 PM

As long as the amount of NMN in the pill is the same, yes. Only difference is that sublingually more of the NMN gets into the blood stream.

 

Are you sure about that? There is nothing in the sublingual pills that could make them not be absorbed orally?



#77 midas

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Posted 17 October 2018 - 08:34 PM

Are you sure about that? There is nothing in the sublingual pills that could make them not be absorbed orally?

No mate, if anything it would be the other way around. Pills meant to be taken orally would probably have ingredients that would make them unsuitable for sublingual use.

 


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#78 XRT doc

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Posted 17 October 2018 - 08:55 PM

As long as the amount of NMN in the pill is the same, yes. Only difference is that sublingually more of the NMN gets into the blood stream.

 

 

Has anyone done any testing to see how much NAD is raised with NMN? This was done quite early on with NR by Chromadex, Elysium Health and and independent lab in Colorado.

I find it strange that this has not been done with NMN.

 

I have recently bought some NMN and have been taking it for around one month. Whilst I was taking NR I noticed more or less straight away, as have others, my finger nails were growing a lot faster. Since I started taking NMN this has stopped?

 

Testing for NAD is very complex- what do you test? the blood where it appears for a few minutes, liver etc?  It is not like they are taking a simple blood measurement.

In the studies, it seems to me they are lysing white blood cells to measure how much is in the cell (not sure if this is individual cells or some sort of precipitate of pmls).  This is obviously not something many places can do. 

 

I have to believe that Brenner has tested NMN/NAD on himself and if the results were poor, he and chromadex would be touting it.


Edited by XRT doc, 17 October 2018 - 09:20 PM.

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#79 Fredrik

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Posted 24 October 2018 - 01:38 PM

Dr David Sinclair who is one of the most vocal researchers on NMN and NAD+ for human health said in his AMA Reddit yesterday that there are NO issues with oral bioavailability of NMN.

 

Attached File  Screenshot 2018-10-24 at 15.27.38.png   84.78KB   2 downloads

 

So, if Dr Sinclair sees no issues and no need for sublingual...why do you?

 

The NMN in clinical trial are oral tablets and NR is orally administered in all human trials.

 

Why are some snorting NMN and NR, using it sublingually, inhaling and looking for other cavities to explore when the human trials are using oral tablets?



#80 able

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Posted 24 October 2018 - 03:45 PM

Dr David Sinclair who is one of the most vocal researchers on NMN and NAD+ for human health said in his AMA Reddit yesterday that there are NO issues with oral bioavailability of NMN.

 

attachicon.gif Screenshot 2018-10-24 at 15.27.38.png

 

So, if Dr Sinclair sees no issues and no need for sublingual...why do you?

 

The NMN in clinical trial are oral tablets and NR is orally administered in all human trials.

 

Why are some snorting NMN and NR, using it sublingually, inhaling and looking for other cavities to explore when the human trials are using oral tablets?

 

What he said was:

 

"I unaware of issue with bioavailability via oral admin. I haven't studied those other routes of administration."

 

He did not say that other methods don't work - only that he is not studying them.  He is focused on some different combinations.  

 

He also said he takes resveratrol instead of pterostilbene, because he knows resveratrol better.  That is not the same as saying he thinks resveratrol IS better.

 

Why am I  trying to improve the effectiveness of NR/NMN?   I guess I am an impatient Bio-hacker who just  doesn't want to wait for human trials to publish.


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#81 Oakman

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Posted 24 October 2018 - 04:15 PM

What he said was:

 

"I unaware of issue with bioavailability via oral admin. I haven't studied those other routes of administration."

 

He did not say that other methods don't work - only that he is not studying them.  He is focused on some different combinations.  

 

He also said he takes resveratrol instead of pterostilbene, because he knows resveratrol better.  That is not the same as saying he thinks resveratrol IS better.

 

Why am I  trying to improve the effectiveness of NR/NMN?   I guess I am an impatient Bio-hacker who just  doesn't want to wait for human trials to publish.

 

I read his comments on Reddit as well, and frankly, was taken aback. I mean really - he's an anti-aging scientist and he was "unaware of issues with bioavailability"?

 

Moreover, he takes resveratrol because he knows it better??? How scientific is that. If he is (one of) our vanguards in this avenue of research, these types of comments are VERY unsatisfying to hear. I mean WTH? We tend to regard his words as based on facts and research, not ignorance because he simply hasn't bothered to look into something.

 

Many of us here at least TRY to get clear on core issues like compound bioavailability and which compounds are most effective based on available research. Mr Sinclair apparently is satisfied with just winging it in certain areas.


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#82 Nate-2004

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Posted 24 October 2018 - 04:45 PM

Yeah I can't imagine not being concerned with bioavailability. The whole reason we're looking at sublingual and other routes of administration is because of how NR appears to break down in the liver and gut before even arriving at cells. I don't want to take it orally only to have the gut turn it into plain old NAM. The point is to bypass the salvage cycle. 

 

And on that point, boosting NAMPT should really be the focus in the end anyway. Which is why, unless I'm fasting, I don't take it every day, only when I exercise or use the sauna.


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#83 Phoebus

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Posted 24 October 2018 - 05:51 PM

 

 

And on that point, boosting NAMPT should really be the focus in the end anyway. Which is why, unless I'm fasting, I don't take it every day, only when I exercise or use the sauna.

 

 

Is there some synergism between taking NMN and using the sauna? 



#84 Fredrik

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Posted 25 October 2018 - 12:26 AM

I read his comments on Reddit as well, and frankly, was taken aback. I mean really - he's an anti-aging scientist and he was "unaware of issues with bioavailability"?

 

Many of us here at least TRY to get clear on core issues like compound bioavailability and which compounds are most effective based on available researchMr Sinclair apparently is satisfied with just winging it in certain areas.

 

With all due respect Mr Oakman, you can be taken aback as much as you want but I am confident that professor Sinclair knows more about the bioavailability of niacin and niacin related metabolites than both you and I. He and Dr Valter Longo has been chosen by TIME magazine as two of the 50 most influential persons in medicine 2018.

 

You are not TRYING anything. You are not a prominent researcher, you do not run a lab, you do not have dozens of patents and you are not in charge of several biotech companies like Dr David Sinclair. You just google shit, like the rest of us.

 

Being a Dr Google, Oakman, is not the same thing as being an actual doctor of anything and malpractice online is rampant, as you have shown here with your ignorance.

 

Pay the man and his work some respect. Just because his research does not align with your preconceived notions does not mean he is "winging it" as you put it.


Edited by Fredrik, 25 October 2018 - 12:33 AM.

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#85 Oakman

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Posted 25 October 2018 - 03:10 AM

^ You may be indignant at my observation Fredrik, but after all, they were his words, not mine, and IMHO his responses were lacking. I didn't jnfere lack of respect for the man, just that his honest answers showed a surprising lack of knowledge on his part, considering his résumé.


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#86 Nate-2004

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Posted 25 October 2018 - 06:33 PM

Is there some synergism between taking NMN and using the sauna? 

There is some evidence based on liver temp in vitro I think. I would suspect that it does raise NAMPT the same way exercise does. Nobody's researched this yet.



#87 Phoebus

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Posted 25 October 2018 - 06:45 PM

There is some evidence based on liver temp in vitro I think. I would suspect that it does raise NAMPT the same way exercise does. Nobody's researched this yet.

 

very intereseting 

 

FYI - HSF1 = heat shock factor 1 

 

 

Qiao et al. (2017) started by determining how HSF1-deficient mice display a marked drop in cellular ATP and NAD+ levels. Because cellular ATP production is coupled to cellular NAD+ levels, the authors speculated that NAD+ deficits could be at the root of the ATP loss. In line with that, they observed that the livers from HSF1-deficient mice showed lower levels of nicotinamide phosphoribosyltransferase (Nampt), a key enzyme in the maintenance of intracellular NAD+ levels, by salvaging NAD+ from nicotinamide (Cantó et al., 2015). Qiao et al. (2017) explain this phenomenon by showing via chromatin immunoprecipitation quantitative PCR assays that HSF1 directly binds to the Nampt promoter.
 
 Interestingly, this binding to the Nampt promoter was higher when glucose availability was limited in cultured hepatocytes, as well as in fasted livers, as compared with the refed state. In contrast, they found that the binding of HSF1 to the Hsp70 promoter was higher in the refed condition, showing an opposite regulation to that of the Nampt promoter and suggesting that nutrient availability signals disentangle the metabolic transcriptional actions of HSF1 from its canonical ones related to the heat shock response.
 
 

 

https://www.ncbi.nlm...les/PMC5350526/

 

so doing sauna in the fasted state seems optimal 


Edited by Phoebus, 25 October 2018 - 06:46 PM.


#88 Nate-2004

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Posted 25 October 2018 - 07:46 PM

Yep I've been doing it 3 times this week, 95 hours into my fast right now. I should have high NAMPT at the moment. Taking my last sublingual NMN today right now.


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#89 able

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Posted 03 November 2018 - 04:37 AM

Looks like Chromadex is finally catching up with plans for a sublingual Niagen.  From this press release/interview:

 

https://www.nutraing...tics-ChromaDex#

 

 

"Additionally, Boileau spoke about the potential applications of NR beyond the current capsule format TRU NIAGEN uses, including a soluble powder form  particularly useful for older people who are likely to have 'pill fatigue'  and topical applications, which are likely to increase NR's skin health effects by allowing it to be absorbed directly into the skin"

 

 

Creative spin on the reason - for older people with pill fatigue.  
 
That  allows them to introduce it  for a reason other than better bioavailability - so they don't have  to admit the product  they've been pumping for 3 years and their entire company is based on is inferior.
 
 
 
 

 


Edited by able, 03 November 2018 - 04:40 AM.

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#90 Fredrik

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Posted 03 November 2018 - 07:40 AM

Thank you for posting. I watched the video and Amy Boileau Vice president of R & D at Chromadex said nothing about sublingual delivery of NR in that video. Transcribing freely:

”The oral bioavailability of NR is high, very high and the crystalline form in the capsules can be formulated as a powder and we are also interested in topical forms”.





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