LONGECITY

Newbie waving hello to everyone!

Long before I registered I've been in lurkdom checking LawrenceW's thread. Very helpful and informative indeed. Thanks to LawrenceW and everyone else for sharing his/her experiences. Couldn't wait to join you guys and I also started taking NMN a month ago. The effects? Long story....


Before taking NMN I've been on resveratrol on and off for 2 years. The effects have largely been positive. But despite the apparant increase in energy and endurance, my joints seemed to age faster than they ought to. I'm not sure if it should be attributed to resveratrol but as Sherlock Holmes said, when you eliminate the impossible, whatever remains, no matter how improbable...


Since my first day on NMN I cut out all other supplements cold turkey. I can't say NMN has no effect on me but the effects fall far below my expectation. Since I switched to NMN, I began to have difficulty getting up in the morning.(resveratrol kept me energetic all day long. No need for noon naps and woke up naturally in the morning without eye being foggy)


That said I still have faith in NMN. But I need advice on what other supplements should I take along with NMN? I vaguely remember Dr. Sinclair once said for those who work out regularly, activators are not needed. But any suggestions for sedentary(AND BUSY) people? To make it worse, my joint problem doesn't allow me to do physical exercises...


Can I have resveratrol together with NMN? I heard that resveratrol is sort of in conflict with NMN in human body. But to what extent? If the extent of the "confliction" is tolerable or, neglectable, I'd love to come back to resveratrol because, despite the joint problem it caused me, resveratrol by far did me more good than any other supplement.

You are in the wrong board. Personally I don’t believe in Resveratrol. NR is better than NMN because NMN needs to change to NR before entering cells. Many people cured their joint problems with NR. The commercial brand is Tru Niagen.

NR is better than NMN because NMN needs to change to NR before entering cells.

 

Hello Mike.

 

I know that you were missing from this board for quite awhile and would like to bring you up to speed with the latest research on your statement from above.

 

https://www.nature.c...2255-018-0009-4

 

Specifically. "We have previously shown that NMN is absorbed from the gut into blood circulation within 2–3 min and transported into tissues within 10–30 min (refs 5,15). NMN is then immediately utilized for NAD+ biosynthesis, significantly increasing NAD+ content in tissues over 60 min. This fast pharmacokinetics has recently been confirmed by using doubly labelled isotopic NMN (C13-D-NMN), showing its rapid absorption and conversion to NAD+ in peripheral tissues15. It has also been proposed that NMN is converted extracellularly to NR, which is transported into cells and reconverted to NMN21. Recent studies, however, have shown that the analyses of in vivo kinetics of these NAD+ intermediates are affected by differences in sample collection and extraction methodologies22,23 (also see Methods). Therefore, it is critical to understand the mechanism by which NMN or NR is transported into cells or tissues. The fast pharmacokinetics of NMN led us to the hypothesis that there is an effective transporter that facilitates the direct uptake of NMN into the gut and other organs. Thus, we set out to identify this presumed NMN transporter in mammals."

 

Also, "We further show that Slc12a8 specifically transports NMN, but not nicotinamide riboside"

Edited by LawrenceW, 24 September 2019 - 09:19 PM.

This paper has been discussed many times. Even if the paper is correct, the amount of NMN that is transported is very small and only in the intestine. But Brenner has published a paper disputing the claims. The data was made up from noise. There is no NMN transporter.

https://www.nature.c...2255-019-0085-0

But Brenner has published a paper disputing the claims. The data was made up from noise. There is no NMN transporter.

https://www.nature.c...2255-019-0085-0

 

And a very speedy response:

 

"We appreciate the authors’ insightful comments and the opportunity to clarify the important issues related to our recent publication2. However, their claim of ‘absence of evidence’ has no concrete foundation and the data in our article strongly support our conclusion that Slc12a8 is an NMN transporter, although there are still many interesting questions regarding the structure and function of Slc12a8 as an NMN transporter."

 

https://www.nature.c...DUOdTkcoS9pdnYo

The new Fig. 2 in the response by Grozio et al. makes matters worse because they did not analyse what an NMN standard looks like in the hepatocyte extract and decided to quantify a peak that has inexplicably drifted from a 22-min retention time to a 19-min retention time.

Brenner is doing a big study on all NAD+ precursors with double label. It will be more accurate than liu’s work.
In the meantime, look at liu’s data and decide which precursor is better.

Oral NR and NMN increased NR in circulation. NR increases more than twice as NMN.
Both NR and NMN failed to increase NMN in circulation.

NMN transporter does not even come into play here because there is no NMN in circulation.

Only very small amount of double labeled NAD+ was formed in the liver from NR. Even smaller from NMN.

Brenner is doing a big study on all NAD+ precursors with double label. It will be more accurate than liu’s work.
In the meantime, look at liu’s data and decide which precursor is better.

 

 

Mike.

 

You can throw out Liu's NMN data because "Dr Imai points out this most recent study measured NAD+ metabolites in blood immediately, as they say freezing and thawing blood (which is what was done in the Liu study) destroys some NAD+ metabolites"

Oral NR and NMN increased NR in circulation. NR increases more than twice as NMN.
Both NR and NMN failed to increase NMN in circulation.

NMN transporter does not even come into play here because there is no NMN in circulation.

 

Dr Brenner published this study in august 2019 that found 1,000 mg NR per day in humans for 3 weeks had NO IMPACT on NR levels in the blood. 

 

https://www.ncbi.nlm...les/PMC6702140/

 

So, according to Dr Brenner, in humans, taking NR does not increase NR outside the liver.

 

It does increase NAD+ in the blood, which is found at 100-300x the levels of NR.

 

It also increases NMN, which is 10x more prevalent than NR.

 

Look at the units of measurement.  We've long known that NR is found at minuscule levels in blood. Now we know you can't increase that by taking supplements.

 

 

NMN and NAD+ are found at significant amounts in the blood, and can be increased.  But not NR.  It seems to be useful for increasing NMN and NAD+ in the blood.

 

 

 

 

 

Edited by able, 25 September 2019 - 01:57 AM.

Brenner’s name was on it. But it was done in other labs. The results are questionable. In the university of Washington study, NR was elevated for a few hours after supplementation.

If liu’s technique was bad, why was she able to measure NR and not NMN? NMN is more stable in liquid.

In addition NAD+ and NMN are secreted by liver as precursor to NR. NR and NAR are found to be intercellular NAD+ precursors from cells that can recycle NAM and cells that can’t. NRK1 has been found to be crucial for liver health even when NR is not supplemented. When NRK1 is removed, mice liver is damaged by high fat diet and NAM supplementation could not prevent it.

Looks like another form of it will be getting released at some point: https://www.reddit.c..._nad_precursor/

Looks like another form of it will be getting released at some point: https://www.reddit.c..._nad_precursor/

I created a new thread on NRH. It is reduced form of NR. It is more stable than NR both in water and blood. Oral supplementation raises 25% more NAD+ in the liver. It stays stable in circulation and is bioavailable. The little NR that gets into blood degrades to NAM quickly. NRH will be much superior to NR and NMN. Of course further study will be needed concerning toxicity and Sirt1 activation. It will cost about the same as NR to manufacture.

A friend who helps people in China buying US products told me that a 30 plus autism person getting better after taking Niagen. Before taking Niagen, the person started to have violent tendencies. After taking Niagen, he has become calm and even learning to do simple things.

NR Update.  I'm back on Elysium Basis after the shoulder/neck pain dissipated and all seems to be going well again. I'm not sure how accurate the blood markers at aging.AI are but I decided to put in my last blood test pre-Basis and my current blood test after almost 3 years on Basis.

 

2016 - Actual age 38 - aging.ai predicted age was 31 (Pre-Basis)

2019 - Actual age 41 - aging.ai predicted age was 30

 

No changes in physical activity or diet. I'm definitely looking older, mind you... and it sure isn't helping with my hairline!

NR Update.  I'm back on Elysium Basis after the shoulder/neck pain dissipated and all seems to be going well again. I'm not sure how accurate the blood markers at aging.AI are but I decided to put in my last blood test pre-Basis and my current blood test after almost 3 years on Basis.

 

2016 - Actual age 38 - aging.ai predicted age was 31 (Pre-Basis)

2019 - Actual age 41 - aging.ai predicted age was 30

 

No changes in physical activity or diet. I'm definitely looking older, mind you... and it sure isn't helping with my hairline!

 

I just plugged in last year's blood work into aging.ai (thanks for that link -- never knew about it before!) and I tested at 46, which is pretty cool since I'm 56. I've been taking NR for almost five years. There were a few nonessential markers I didn't have, though, but hopefully this is at least a good indication my longevity plan is working?

NAD+ precursor is something you really have to use after 40 or even 30. Niagen is really just the start. Bioavailability can be significantly improved down the road using delivery systems like softgel and liposome. In addition, NAR and NRH are probably significantly better that NR.

I just plugged in last year's blood work into aging.ai (thanks for that link -- never knew about it before!) and I tested at 46, which is pretty cool since I'm 56. I've been taking NR for almost five years. There were a few nonessential markers I didn't have, though, but hopefully this is at least a good indication my longevity plan is working?

 

I would say no since you didn't test before you started taking NR. 

Just in case you missed it I point here to dr.Patrick's NR overview. It seems to me fair and thorough. I place the link here in the PE thread because the article contains a very practical reminder that   NR Chloride is not heat stable. Even just one day in transport or storage above 25 degrees C is enough for serious degradation.

https://www.foundmyf...namide-riboside

Edited by Harkijn, 05 November 2019 - 10:15 AM.

Just in case you missed it I point here to dr.Patrick's NR overview. It seems to me fair and thorough. I place the link here in the PE thread because the article contains a very practical reminder that   NR Chloride is not heat stable. Even just one day in transport or storage above 25 degrees C is enough for serious degradation.

https://www.foundmyf...namide-riboside

 

 

I can't believe those degradation numbers are accurate.  

 

Research quoted in the GRAS application showed much better stability.

 

If the numbers used in Dr Patricks review are accurate, NR wouldn't be a viable commercial product as it could not be shipped without major  deterioration.

Edited by able, 05 November 2019 - 01:36 PM.

According to the gras, 92% NRCL remains after 11 months at 40 degrees.

It happens that reference 15 link in the article does not work. Maybe the data is for NR without CL.

When I posted in the PE tread I did not expect any discussion about this. Just a reminder that NR should at least be refrigerated after purchase.

Perhaps I should have chosen  to open yet another thread  . Michael, if you choose to move these posts please go ahead.

 

For discussion about GRAS I upload the GRAS notice. I am sure a lot can be said for and against  the stability statement. Note that it is not particularly about NR but about Niagen.

Dr. Patrick has now posted a new very interesting podcast with dr. Sinclair.

The subject of stability comes up again and I think he says that NMN as well as NR should be kept cool as well as dry. What do you think?

 

https://www.foundmyf.../david-sinclair

Dr. Patrick has now posted a new very interesting podcast with dr. Sinclair.
The subject of stability comes up again and I think he says that NMN as well as NR should be kept cool as well as dry. What do you think?

https://www.foundmyf.../david-sinclair

Read the GRAS. Niagen is very stable at 40 degree and moderate humidity.

Read the GRAS. 

About the GRAS see above.

I've been using pterostilbene and tru niagen NR since April.  I'm a 45 year old male.  I started pterostilbene a few days earlier than NR and it didn't take long to help my concentration and temperament to a small but still noticeable degree.  When I added NR, I felt a little light headed and even mildly disassociated.  My sleep has been a bit better but that might be explained by the light headedness.  I can't say I've seen anything else besides those minor changes.  Having said that,  should I still give this more time? 

So I tried NMN in Sept of 2019 and felt it almost immediately in terms of energy.  Having felt such notable increases of energy for weeks after using it, I assumed it was just the NMN which I started at 250 mg and then in a few weeks upped it to 500mg.  I also decided to stop NR because of the total expense.  After a few weeks, I noticed some sleep disturbance. 

 

In October, I  ditched  pterostilbene and added resveratrol as I noticed some mental acuity decrease and that's also what David Sinclair takes with NMN which I continued with at 500mg. Sleep wasn't as good as it was before but it wasn't as bad as pre NR

 

In November, my sleep went to shit.  I struggled with it until December and  I then went back to using NR (2 caps for a total of 250mg).  In about 5 days, there was a notable increase in sleep length and quality.  In 2 weeks,  my sleep got back to almost the same quality as before I dropped it.  I continued with NMN + NR + resveratrol until 2020.  At that point, I stopped taking resveratrol for budget reasons and started 300 mg @ 1 capsule of tru niagen but still kept taking 500mg NMN. 

 

In February, I stopped taking NMN and didn't notice too much change in me. 

 

In March, I added back 100mg of pterostilbene. In a few weeks, I felt my sleep approved. 

 

In April, I re-added 250mg of NMN (prohealth brand which I had for several months) and felt the high energy increase that I initially had when I first tried it.  Since it was sitting in the freezer for a while, it was good to see that it still had an effect considering all the talk of how quickly it loses potency.  After a few months, it did lose that high energy feel but it was replaced by a steadier stamina that was not there with NR + pterostilbene.  Sleep quality has remained steady.  I had the right formula all along in Sept 2019 but it's good to see that I tried just about every combination of pterostilbene, resveratrol, NMN and NR and now have a stack I won't be changing anytime soon.  In the future, I might increase the dosage of NMN  but it's pretty expensive as is so it will stay the way it is for now. 

 

I recently added back in magnesium threonate before bed which didn't have much affect when I first tried it and it's added an increase in sleep quality and reduction in headaches and migraines so I plan on taking that for the next while as well. 

 

My current stack:

 

100mg pterostilbene - double wood

250mg NMN - prohealth bulk powder but would use double wood caps or bulk powder as I didn't notice much difference between the 2.  Prohealth is a bit cheaper so that's why I will probably use that one instead generally

300 mg - tru niagen.  It used to be  2 caps for 250mg but they changed the format to 1 cap for 300mg

Edited by parsons, 04 July 2020 - 02:46 PM.

hi everyone, as posted before by some other users ,i just realized after so many trial& error what was jeopardizing my deep sleep, NR

 

 

NR, regardless of the amount and when i take it , sublingual or non sublingual . my CRP blood test reading are amazing but my homocysteine skyrockets despite of supplementing with B12 colabamin , 5 -mfth and TMG, and betaine HCL. I've kept the same meals, even the timings , the same amount of light exposure in the morning followed by blue blocking lights and the same temperature  and roughly the same bed timings.

 

and not only i wake up in the middle of the night for 30-50 min but my deep sleep suck when i take NR, thoughts? any mitigations ? ive tried apigenin with no success 

 

thanks

 

ive attached my oura rings readings which are 95% accurate