75 replies to this topic

[porthose]

I understand that taking NMN sublingually makes it more bioavailable, so you don't need as much as when swallowing. To my knowledge, there is currently only one supplier of NMN for sublingual administration, which is AliveByNature.

(Just FYI, I'm not involved with the company.)

Or, maybe you can crush your current pills and take them under the tongue.

 

Cheers, Rays. Thank you.

 

Peter

[Fredrik]

I understand that taking NMN sublingually makes it more bioavailable, so you don't need as much as when swallowing. To my knowledge, there is currently only one supplier of NMN for sublingual administration, which is AliveByNature.

(Just FYI, I'm not involved with the company.)

Or, maybe you can crush your current pills and take them under the tongue.

 

But where are the studies showing that NMN is better absorbed sublingually through the mucosa than orally? Any proof at all or just a market that is responding to a consumer "demand"?

 

Why are none of the two human clinical trials of the safety of NMN using sublingual treatment but a pill? If there was a problem with bioavailability they would have designed the formulation for maximal uptake.

 

Does someone really think that a small supplement company outsmarts the very researchers doing the research these companies are citing?

Edited by Fredrik, 06 February 2019 - 09:32 AM.

[Rays]

But where are the studies showing that NMN is better absorbed sublingually through the mucosa than orally? Any proof at all or just a market that is responding to a consumer "demand"?

 

Why are none of the two human clinical trials of the safety of NMN using sublingual treatment but a pill? If there was a problem with bioavailability they would have designed the formulation for maximal uptake.

 

Does someone really think that a small supplement company outsmarts the very researchers doing the research these companies are citing?

 

Maybe it's harder to do a placebo controlled trial using sublingual administration because the patient will taste the compound.

Does a safety trial use a placebo control group?

 

There exists other medication that you have to take sublingually. The small supplement company did not invent that. I don't think they outsmart the big companies and researchers, but they may understand NMN is still too expensive for normal people to swallow a gram a day, as Sinclair does. The researchers doing the research don't have to concern themselves with price.

 

For me, it seems plausible that sublingual administration has a higher bioavailability because it bypasses the liver.

But I don't know of any studies.

[Fredrik]

So there are no human trials comparing oral vs sublingual NR/NMN and therefore zero evidence that sublingual NMN/NR is more bioavailable than the oral administration used in every human trial of NR/NMN to date.

 

"Plausible" and "feelings" of efficacy does not cut it when it comes to science. Useful when formulating a hypothesis but useless when you want to establish the truth.

 

The discussions of sublingual formulations in this forum give readers the false impression that it is proven to be more bioavailable.

Edited by Fredrik, 06 February 2019 - 11:36 AM.

[Iporuru]

So there are no human trials comparing oral vs sublingual NR/NMN and therefore zero evidence that sublingual NMN/NR is more bioavailable than the oral administration used in every human trial of NR/NMN to date.

 

"Plausible" and "feelings" of efficacy does not cut it when it comes to science. Useful when formulating a hypothesis but useless when you want to establish the truth.

 

The discussions of sublingual formulations in this forum give readers the false impression that it is proven to be more bioavailable.

 

It's not exactly true. There was a study posted on these boards at least twice, showing superior availability of sublingual administration of medications over oral. I don't have time to look for it, but it's in one or two of the NAD+ threads.
 

[LawrenceW]

It's not exactly true. There was a study posted on these boards at least twice, showing superior availability of sublingual administration of medications over oral. I don't have time to look for it, but it's in one or two of the NAD+ threads.
 

 

 

Is this the sublingual study that you are thinking of?

 

https://innovareacad...Suppl2/1092.pdf

[Fredrik]

It's not exactly true. There was a study posted on these boards at least twice, showing superior availability of sublingual administration of medications over oral. I don't have time to look for it, but it's in one or two of the NAD+ threads.
 

 

It IS entirely true that no study has shown sublingual NMN/NR to be superior to oral administration. I don´t understand why some people seem to have just accepted this unproven hypothesis based on marketing fluff.

 

You are generalizing about "medications" and that paper (not a study) says nothing about NMN/NR. There are lots of drugs that would not be suitable for sublingual administration. You need to test the drug before drawing any conclusions.

 

 

Edited by Fredrik, 06 February 2019 - 04:37 PM.

[Fredrik]

Is this the sublingual study that you are thinking of?

 

https://innovareacad...Suppl2/1092.pdf

 

Thank you LawrenceW. That paper though (not a study) says absolutely nothing about NMN/NR with no references to any trials comparing those molecules via sublingual vs oral route.

 

We can´t just be so gullible to accept marketing fluff as facts. The companies selling sublingual formulations need to pay for "hands-off" studies in humans before we even can think about believing anything they claim.

Edited by Fredrik, 06 February 2019 - 04:30 PM.

[Iporuru]

Is this the sublingual study that you are thinking of?

 

https://innovareacad...Suppl2/1092.pdf

I think it was a different one. Perhaps I'll try to find it later

[LawrenceW]

Thank you LawrenceW. That paper though (not a study) says absolutely nothing about NMN/NR with no references to any trials comparing those molecules via sublingual vs oral route.

 

 

 

 

Exactly.

 

As with every other aspect of NMN supplementation, we are early and have choices to make.  Dr. Sinclair first made his announcement on NMN in Dec. 2013. We could either wait for the studies to get published  or do self experimentation.  We decided that we were too old already and did not have the years to wait for the studies to get published (we would still be waiting 5 years later). As you may or may not be aware, we began self experimentation under medical supervision late in 2014. After 6 months of 1 individual supplementing with NMN, our medical supervisor was comfortable in that he could find no side effects and cleared the next 6 (of which I was one) individuals to begin supplementing.  Since that time we have proven to our selves and confirmed with blood tests that the vast majority of benefits that have been written about in the mouse and rat studies translate to humans.  Over the years we have proven to our selves as to what we believe the optimum oral dose to be.  It was very comforting to us that almost a year after we settled on  the 1,000 mg daily oral dose that Dr. Sinclair stated that he was now taking 1,000 mg per day. 

 

In April 2018 we (now 70 individuals) began experimenting with sublingual administration of NMN.  After testing both dosing amount and frequency and comparing them against our blood work results for the 1,000 mg oral, we proved to our selves that:

 

A. We believe that a 30 mg per dose is the largest amount of NMN that is transported sublingually per dose. We believe that the membrane is saturated at that amount and any extra NMN is simply swallowed.

B. We found that 8-10 doses of 30 mg of sublingual per day a minimum of 1 hour apart gave us the same blood work results as 1,000 mg taken orally.

C. We believe that as with oral supplementation, homeostasis kicks in at around 4 weeks.

D. We believe that by keeping multiple anti-aging pathways in balance that the triggering of the homeostatic negative feedback loop can be avoided.

 

These are our personal findings and beliefs and we look forward to some day in the future, when some one else publishes their studies, as to the accuracy of our findings.

 

So the question remains.  Do you want to wait until some or all the studies have been published or do you want to self experiment and find the answers for your self?

Edited by LawrenceW, 06 February 2019 - 05:52 PM.

[Iporuru]

Thank you LawrenceW. That paper though (not a study) says absolutely nothing about NMN/NR with no references to any trials comparing those molecules via sublingual vs oral route.

 

We can´t just be so gullible to accept marketing fluff as facts. The companies selling sublingual formulations need to pay for "hands-off" studies in humans before we even can think about believing anything they claim.

 

It probably wasn't this paper. And it's true that the one I mean didn't compare NMN/NR, but proved that generally sublingual absorption is better than oral absorption so there's some INDIRECT evidence. Based on that information many people have decided to follow this route. We are all (most of us) experimenters and it doesn't always make sense to wait for double-blind randomized placebo-controlled trials because sometimes youl'll never get one

[Iporuru]

I think it was a different one. Perhaps I'll try to find it later

 

As far as I can remember, this is the paper I meant: http://www.journalof...cle/view/118766

 

"Conclusion: Sublingual tablets or any sublingual dosage form can be used to achieve a rapid onset of action, better
patient compliance and increased bioavailability. The sublingual route of administration can be used for drugs which
undergo extensive first pass metabolism or degradation in the GIT. Drugs administered sublingually tend to have
better bioavailability which correlates to dose reduction when compared to conventional oral tablets."
 

[LawrenceW]

As far as I can remember, this is the paper I meant: http://www.journalof...cle/view/118766

 

"Conclusion: Sublingual tablets or any sublingual dosage form can be used to achieve a rapid onset of action, better
patient compliance and increased bioavailability. The sublingual route of administration can be used for drugs which
undergo extensive first pass metabolism or degradation in the GIT. Drugs administered sublingually tend to have
better bioavailability which correlates to dose reduction when compared to conventional oral tablets."
 

 

Thanks Iporuru.  I had not seen that one.  Here is a link to the full text: 

 

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

[Fredrik]

So the question remains.  Do you want to wait until some or all the studies have been published or do you want to self experiment and find the answers for your self?

 

Thank you for that short presentation of what your company is doing and what you are selling but that was not the question here at all.

 

We were not discussing your customers self-experimentation but the validity in claims of superior bioavailability of sublingual vs oral supplementation.

Edited by Fredrik, 06 February 2019 - 06:35 PM.

[Fredrik]

As far as I can remember, this is the paper I meant: http://www.journalof...cle/view/118766

 

"Conclusion: Sublingual tablets or any sublingual dosage form can be used to achieve a rapid onset of action, better
patient compliance and increased bioavailability. The sublingual route of administration can be used for drugs which
undergo extensive first pass metabolism or degradation in the GIT. Drugs administered sublingually tend to have
better bioavailability which correlates to dose reduction when compared to conventional oral tablets."
 

 

The paper is not referring to NMN or NR at all.

 

Conclusion: no proof provided that sublingual NMN or NR has superior bioavailability compared to the oral route chosen by the researchers in human NR and NMN trials.

Edited by Fredrik, 06 February 2019 - 06:10 PM.

[Fredrik]

It probably wasn't this paper. And it's true that the one I mean didn't compare NMN/NR, but proved that generally sublingual absorption is better than oral absorption so there's some INDIRECT evidence. Based on that information many people have decided to follow this route. We are all (most of us) experimenters and it doesn't always make sense to wait for double-blind randomized placebo-controlled trials because sometimes youl'll never get one

 

But the thing is, we HAVE placebo-controlled trials of NR and none of them used sublingual formulations.

 

We HAVE ongoing safety trials of NMN and none of them are using sublingual formulations.

 

So based on the information at hand, that oral supplementation is used in ALL human trials you chose to disregard that based on what? A commercial company's glossy marketing pages online?

Edited by Fredrik, 06 February 2019 - 06:18 PM.

[able]

But the thing is, we HAVE placebo-controlled trials of NR and none of them used sublingual formulations.

 

We HAVE ongoing safety trials of NMN and none of them are using sublingual formulations.

 

So based on the information at hand, that oral supplementation is used in ALL human trials you chose to disregard that based on what? A commercial company's glossy marketing pages online?

 

Researchers used NR and NMN in the chow, or drinking water, or oral garage on mice. They have no way of testing sublingual dosage with mice afaik.  

 

Putting the supplements in capsules is of course the obvious first step with humans.  Everyone wants a simply one a day pill to swallow, so that is what sells.

 

 

It wasn't until last year that we saw the proof that oral delivery (in water) for mice was far less bioavailable than anyone realized, so it doesn't seem strange to me that researchers have not tested sublingual delivery yet.

 

This is all new, and if sublingual administration is so much better, it will be tested some years down the road.

 

I doubt it will ever be tested in NR though, as it tastes horrible.

 

The papers Lawrence linked show the physical properties a drug needs to be effective with sublingual delivery - hydrophilic, low molecular weight, low PH.  

 

It seems NMN is a perfect candidate, so must have SOME bioavailability thru that method, but yes, we don't have any proof yet.

 

I don't need to wait for proof if it is better or not.     If NONE of the sublingual delivery gets to bloodstream, it would be exactly the same as a capsule.

 

But I personally know for 100% fact that some does get absorbed.  

 

I have been taking the powder for almost a year now, and have mentioned many times here how too big of a dose (over 250 mg) is too stimulative and elevates my heart rate 10-15 bpm.

 

I can feel the effect of 125-250 mg every time I take it, in 1-2 minutes.  My wife and several friends ALL feel a response.

 

So yes, you can say there has been no studies published proving the availability of sublingual administration vs capsules, but I don't need any "glossy marketing pages" to know that there is some delivery direct to bloodstream.  

 

True, we don't know that getting some NMN direct to the blood is better - although the early research where they used IV or IP delivery required much smaller dosages and had far more noticeable effect, so I would certainly bet that direct to bloodstream is better than going thru the stomach and liver. 

Edited by able, 06 February 2019 - 06:44 PM.

[Fredrik]

So yes, you can say there has been no studies published proving the availability of sublingual administration vs capsules, but I don't need any "glossy marketing pages" to know that there is some benefit over capsules.  

 

Good for you. I do need more than advertisement and (mostly) anonymous anecdotes online though. Like facts.

[able]

Good for you. I do need more than advertisement and (mostly) anonymous anecdotes online though. Like facts.

 

 

Fair enough.  But you could try it yourself and know within minutes.  Or wait a few years.

[Fredrik]

Fair enough.  But you could try it yourself and know within minutes.  Or wait a few years.

 

I will use an NR/NMN product when there is proof of some sort of worthwhile efficacy in humans.

 

Until then I am sticking with the plain old SIRT-1 activator metformin and a low dose (a dose which in rats is not toxic to beta-cells and do not increase FBS) of the NAD-precursor nicotinic acid.

 

Yes, I am taking metformin with no conclusive proof of efficacy or long term safety in non-diabetics. YOLO

 

It would be potentially "dangerous" and definitely "irresponsible" to take this post as medical advice. 

Edited by Fredrik, 06 February 2019 - 07:20 PM.

[LawrenceW]

Until then I am sticking with the plain old SIRT-1 activator metformin and a low dose (a dose which in rats is not toxic to beta-cells and do not increase FBS) of the NAD-precursor nicotinic acid.

 

Yes, I am taking metformin with no conclusive proof of efficacy or long term safety in non-diabetics. YOLO

 

Fredrik.

 

It appears that you have chosen to self experiment with Metformin. 

 

We have chosen to self experiment with NMN.  

 

We are happy to share our self experimenting experience on this forum for the benefit of other like minded self experimenters.  They can either learn from our mistakes or confirm our findings for themselves.

 

We are also very interested in hearing about your experience with Metformin.

 

Lawrence

[Iporuru]

The paper is not referring to NMN or NR at all.

 

Conclusion: no proof provided that sublingual NMN or NR has superior bioavailability compared to the oral route chosen by the researchers in human NR and NMN trials.

 

Nowhere did I claim this paper compared NMN/NR. On the contrary - I wrote: "And it's true that the one I mean didn't compare NMN/NR, but proved that generally sublingual absorption is better than oral absorption so there's some INDIRECT evidence. Based on that information many people have decided to follow this route."
 

Please read the posts you're replying to.

[Fredrik]

Fredrik.

 

It appears that you have chosen to self experiment with Metformin. 

 

We have chosen to self experiment with NMN.  

 

We are happy to share our self experimenting experience on this forum for the benefit of other like minded self experimenters.  They can either learn from our mistakes or confirm our findings for themselves.

 

We are also very interested in hearing about your experience with Metformin.

 

Lawrence

 

I don´t understand why you keep on talking about your companys self-experimentation like someone attacked it. We were talking about the lack of proof of sublingual superiority of NR/NMN vs oral but it is like you are having a separate discussion of your self-experiments with someone else. Not with me though.

 

Who are "we"? Your NMN-company or the 70 customers?

 

The FDA approved TAME-trial (Targeting Aging with MEtformin) on 3000 non-diabetics will give us answers in 5 years time. I have no way of measuring those biomarkers and I prefer the statistical power of 3000 persons instead of just 1 person.

 

I am here to discuss the science and the thinking behind supplemental and dietary strategies, not the homemade experiments. There is an experience-thread on that where you can post and read about subjective experiences.

 

I can not draw any conclusions of mine or others uncontrolled self-experimentation. So I don´t. Sorry.

Edited by Fredrik, 06 February 2019 - 10:24 PM.

[bluemoon]

At the 36 minute mark of this video:   there is a slide of Dr. Sinclair's monthly biological age tracking.  According to that chart he began taking NMN in April 2016. So in this coming April it will be 3 years.

 

You missed that he said at 35:30 that in 2014 he took his health into his own hands and started to take NMN and metformin, so coming up on 5 years. I thought so since I thought I remembered that he said he took NMN when he gave a talk in Sydney in late 2014. 

[bluemoon]

I will use an NR/NMN product when there is proof of some sort of worthwhile efficacy in humans.

 

 

I'm curious why you dismiss Elysium's study that demonstrated 500 mg of NR + 100 mg pterostilbine showed healthy 50 to 79 year olds saw an 8% increase in speed in a 6 minute walking test and and 8% improvement in a chair/balancing test.

[Fredrik]

I'm curious why you dismiss Elysium's study that demonstrated 500 mg of NR + 100 mg pterostilbine showed healthy 50 to 79 year olds saw an 8% increase in speed in a 6 minute walking test and and 8% improvement in a chair/balancing test.

 

Hi Bluemoon,

 

1. I am not going to pay 60 dollars a month to walk 8% faster or improve my balance by 8% (not even 40 dollars a month through Elysiums auto-renew offer). I do not think it is a worthwhile effect.

 

2. I said this when that trial was published: this was not a trial of NR, it was a trial of NR + pterostilbene. I don´t know what molecule did what or if they did it together.

 

3. Pterostilbene increases LDL-cholesterol which, in concert with inflammation and foam cells, promotes atherosclerosis.

Edited by Fredrik, 07 February 2019 - 07:27 AM.

[QuestforLife]

C. We believe that as with oral supplementation, homeostasis kicks in at around 4 weeks.

D. We believe that by keeping multiple anti-aging pathways in balance that the triggering of the homeostatic negative feedback loop can be avoided.

 

 

Would you expand on these points, please?

[bluemoon]

Hi Bluemoon,

 

1. I am not going to pay 60 dollars a month to walk 8% faster or improve my balance by 8% (not even 40 dollars a month through Elysiums auto-renew offer). I do not think it is a worthwhile effect.

 

2. I said this when that trial was published: this was not a trial of NR, it was a trial of NR + pterostilbene. I don´t know what molecule did what or if they did it together.

 

3. Pterostilbene increases LDL-cholesterol which, in concert with inflammation and foam cells, promotes atherosclerosis.

OK, but there is a difference between a worthwhile efficacy and a worthwhile efficacy for you personally.

 

Based on what Sinclair has said, NR is almost certainly a factor in improving that performance even if the amount compared to pterostilbne isn't known.

[Fredrik]

OK, but there is a difference between a worthwhile efficacy and a worthwhile efficacy for you personally.

 

Based on what Sinclair has said, NR is almost certainly a factor in improving that performance even if the amount compared to pterostilbne isn't known.

 

At current prices, I don´t think it is worthwhile overall or for me personally.

 

NR did not improve performance in younger (20-year olds) but in older (70-year olds) and in Martens clinical trial NR did not improve V02max, motor-performance, grip-strength or any other measurable physical attributes.

 

So we need more studies before "almost certainly" turns into "certainly true".

 

Studies on older, younger, healthy and diseased and we need pharmacogenetics to show us who may or may not benefit from NR/NMN and under what circumstances and at what dosages.

 

Maybe NAD-precursor treatment is detrimental or at best useless before you reach a certain age.

 

Should it be used before or after sports? Does it hinder beneficial ROS-signaling in the young but decreases excessive ROS in the elderly?

[Engadin]

 

 

NR did not improve performance in younger (20-year olds)  ...

 

What? Are you serious? Sure it didn't improve performance in even younger (10-years-olds) ...

Edited by Engadin, 07 February 2019 - 12:40 PM.