392 replies to this topic

[John250]

In General NR is better at generating NAD+ In all cell types, But NMN generates more NAD+ in kidney from mice studies up to 135min after taking NR or NMN. How NMN compares with NR after that we don’t have data. We also don’t have clinical trials data on NMN yet.

That’s too bad since NMH was studied,what, well over a decade+ ago. Is this still the only current human trial?
https://www.nature.c...es/npjamd201621

[MikeDC]

That’s too bad since NMH was studied,what, well over a decade+ ago. Is this still the only current human trial?
https://www.nature.c...es/npjamd201621

There is another one registered at clinicaltrials.gov. Sinclair is also supposed to be doing another NMN trial.

[able]

That’s too bad since NMH was studied,what, well over a decade+ ago. Is this still the only current human trial?
https://www.nature.c...es/npjamd201621

 

Sinclair has completed Phase 1 and is planning to start Phase 2 this fall.  

 

He didn't register at clinical trials.org, for whatever reason.  

 

My belief is he wants to control the flow of information, and isn't interested in publishing his Phase 1 results until one or more of the many companies he owns is ready to capitalize.  

 

There are NMN products available now, yet he always says we are a few years away.  He's very slick/sly/smooth.

 

Edited by able, 09 April 2018 - 06:51 PM.

[MikeDC]

Sinclair has completed Phase 1 and is planning to start Phase 2 this fall.

He didn't register at clinical trials.org, for whatever reason.

My belief is he wants to control the flow of information, and isn't interested in publishing his Phase 1 results until one or more of the many companies he owns is ready to capitalize.

There are NMN products available now, yet he always says we are a few years away. He's very slick/sly/smooth.

Sinclair is definitely helping to sell NMN and NR with his marketing. I think he is trying to raise capital.

[LawrenceW]

MikeDC.

 

"Sinclair is definitely helping to sell NMN and NR with his marketing."

 

When is the last time that Dr. Sinclair talked about NR? 

[LawrenceW]

A major difference between NR and NMN just surfaced as a result of the release of the Impairment of an Endothelial NAD⁺-H₂S Signaling Network Is a Reversible Cause of Vascular Aging study.

 

From the Elysium study we know that the maximum percentage increase of NAD in the liver is 55% after 60 days of supplementation.

 

From the above NMN  study 

 

we learned that NMN increased the liver NAD percentage by approximately 500% after 60 days of supplementation.

Edited by LawrenceW, 21 April 2018 - 02:35 PM.

[MikeDC]

A major difference between NR and NMN just surfaced as a result of the release of the Impairment of an Endothelial NAD⁺-H₂S Signaling Network Is a Reversible Cause of Vascular Aging study.

From the Elysium study we know that the maximum percentage increase of NAD in the liver is 55% after 60 days of supplementation.

From the above NMN study


we learned that NMN increased the liver NAD percentage by approximately 500% after 60 days of supplementation.

The Elysium study was on humans. The paper you quoted was on mice. Can you post the full paper so we can read it in context?

[LawrenceW]

Hello Mike.

 

I have the full text in PDF, but I can't seem to upload it to this thread.  Could you please guide me through the process?

 

Thanks

[LawrenceW]

Hello Mike.

 

I found a link to the entire study:

 

http://sci-hub.tw/10...ell.2018.02.008

 

Enjoy

[MikeDC]

I think the baseline NAD+ in the liver is under reported in the diagram. That makes the percentage increase larger. I don’t believe GA has 300% higher NAD+ than Liver.

In the 2016 NMN paper, 300mg/kg NMN didn’t increase steady state NAD+ levels when mice were fed NMN water for long term.
This study used 500mg/kg NMN in drinking water for 4 weeks and detected significant increase in NAD+. Is this increase due to the extra 200mg/kg NMN or shorter time frame? Not much details were given in the paper.

Remember Brenner increased his blood NAD+ over 200% with a single dose of 1g NR.
We need to wait for NMN clinical trials results to compare with NR.

Edited by MikeDC, 21 April 2018 - 11:40 PM.

[LawrenceW]

MikeDC.

 

You attributed the wrong dosing and time frame to the liver NAD results.  

 

From page 10.  "To restore NAD+ levels, we administered NMN to 18-month-old mice via drinking water for 2 months at 400 mg/kg/day (Figures S6A–S6C)."

 

Figure S6A shows the 500% increase.

[LawrenceW]

Everyone in our group of NMN supplementers has experienced reversal of muscle wasting.  It was nice to read about the mechanisms behind how NMN reverses muscle wasting which also showed that we weren't imagining that benefit. 

 

From page 10: 

 

"NMN restored the number of capillaries and capillary density of the old mice to those typically seen in young mice (Figures 6B and S6D). Resting muscle perfusion  (Figures 6C and S6E) and soluble oxygen (sO2) levels were significantly higher in NMN-treated mice compared to controls (Figure 6D). Mitochondrial protein and activity levels and other muscle properties remained unaltered (Figures S6F–S6L). NMN supplementation dramatically increased home-cage oxygen consumption (Figure S6M), but the most striking effect was a 56%–80% improvement in endurance, with lower post-exercise blood lactate (Figures 6E and 6F; Movie S5)."

 

 

[able]

I think the baseline NAD+ in the liver is under reported in the diagram. That makes the percentage increase larger. I don’t believe GA has 300% higher NAD+ than Liver.

In the 2016 NMN paper, 300mg/kg NMN didn’t increase steady state NAD+ levels when mice were fed NMN water for long term.
This study used 500mg/kg NMN in drinking water for 4 weeks and detected significant increase in NAD+. Is this increase due to the extra 200mg/kg NMN or shorter time frame? Not much details were given in the paper.

Remember Brenner increased his blood NAD+ over 200% with a single dose of 1g NR.
We need to wait for NMN clinical trials results to compare with NR.

 

 

The 500% is waaaayyy higher than other studies, which is why I pointed it out in the other thread, looking for some explanation.

 

The 2016 Mills study was for 12 months on mice, so it seems that homeostasis does eventually kick in. 

 

These mice were 20 months at completion of the study.  A bit older than Mills or Elysium study, which may contribute somewhat to the huge NAD+ increase.

 

But there must be more reason.  Maybe the number for NAD+ baseline in liver is faulty - that would make some sense of this 500% result.  

Edited by able, 22 April 2018 - 02:38 AM.

[LawrenceW]

Let's get back to the basics of what we are trying to accomplish.  From the time that we were born until puberty, our internal biology is all about keeping us as healthy as possible to get us to the point in our lives where we can procreate.  To accomplish that, it seems that our internal biology keeps our NAD at level X.  Once we hit puberty our internal biology shifts gears to get busy with procreating.  In males, it dials up the testosterone and is not so concerned about keeping us healthy, so it allows our NAD levels to diminish and by the time we are middle aged we only have about half the NAD that we had as prepubescents (X/2).  Our goal is to at least double (100% increase) our current middle aged NAD levels back to the levels we enjoyed when we were young.  NR gets us 40 to 55% there.  It appears that NMN gets us at least to a 100% increase. 

Edited by LawrenceW, 22 April 2018 - 02:54 PM.

[MikeDC]

Let's get back to the basics of what we are trying to accomplish. From the time that we were born until puberty, our internal biology is all about keeping us as healthy as possible to get us to the point in our lives where we can procreate. To accomplish that, it seems that our internal biology keeps our NAD at levels it deems to be optimal. Once we hit puberty our internal biology shifts gears to get busy with procreating. In males, it dials up the testosterone and is not so concerned about keeping us healthy, so it allows our NAD levels to diminish and by the time we are middle aged we only have about half the NAD that we had as prepubescents. Our goal is to double (100% increase) our current middle aged NAD levels back to the levels we enjoyed when we were young. NR gets us 40 to 55% there. It appears that NMN gets us at least to our goal of 100% increase.

You are making claims based on a single faulty mice data. We don’t even know NMN can increase NAD+ on humans. We at least know NR increases NAD+ in humans from all published clinical trials. NR also increased NAD+ up to 100% from University of Washington clinical trial and 200% from Brenner paper all on just 1g of NR. The NMN study used 500mg/kg which is 37g for a human weighs 75kg. Until you can prove that NMN can get into cells without converting to NR first, NMN is an inferior NAD+ precursor unless you target the kidney.

Edited by MikeDC, 22 April 2018 - 02:57 PM.

[able]

Let's get back to the basics of what we are trying to accomplish.  From the time that we were born until puberty, our internal biology is all about keeping us as healthy as possible to get us to the point in our lives where we can procreate.  To accomplish that, it seems that our internal biology keeps our NAD at levels it deems to be optimal.  Once we hit puberty our internal biology shifts gears to get busy with procreating.  In males, it dials up the testosterone and is not so concerned about keeping us healthy, so it allows our NAD levels to diminish and by the time we are middle aged we only have about half the NAD that we had as prepubescents.  Our goal is to double (100% increase) our current middle aged NAD levels back to the levels we enjoyed when we were young.  NR gets us 40 to 55% there.  It appears that NMN gets us at least to our goal of 100% increase. 

 

Good point Lawrence.  The 500% likely has some error in it.  But perhaps 100% increase is achievable.

 

From this study, it seems NMN is not subject to the homeostasis effect lowering NAD+ levels nearly as quickly as with NR.  

 

But homeostasis does seem to take over by the end of the Mills study at 12 months.  I wonder if they have unpublished data of NAD+ levels throughout the 12 months?

[able]

You are making claims based on a single faulty mice data. We don’t even know NMN can increase NAD+ on humans. We at least know NR increases NAD+ in humans from all published clinical trials. NR also increased NAD+ up to 100% from University of Washington clinical trial and 200% from Brenner paper all on just 1g of NR. The NMN study used 500mg/kg which is 37g for a human weighs 75kg. Until you can prove that NMN can get into cells without converting to NR first, NMN is an inferior NAD+ precursor unless you target the kidney.

 

 

Yes, a single dose of NR greatly elevates NAD+.  The point Lawrence makes here, is that homeostasis kicks in and that increase drops dramatically to 50% or so.  

 

This one study suggests NMN is not as quickly affected by homeostasis bringing NAD+ levels back down.

Edited by able, 22 April 2018 - 03:18 PM.

[MikeDC]

Good point Lawrence. The 500% likely has some error in it. But perhaps 100% increase is achievable.

From this study, it seems NMN is not subject to the homeostasis effect lowering NAD+ levels nearly as quickly as with NR.

But homeostasis does seem to take over by the end of the Mills study at 12 months. I wonder if they have unpublished data of NAD+ levels throughout the 12 months?

This NAD+ level was measured at 4 weeks while the human study was measured at 8 weeks. The dose used on mice is also extremely high compared with human study. There is no evidence that NMN homeostasis takes longer than NR.

[LawrenceW]

MikeDC

 

"You are making claims based on a single faulty mice data." Let me see if I understand your premise. They perform a test to establish baseline NAD levels.  60 days later they perform the same test and come out with a percentage increase that threatens the Chromadex stock price and you deem that the mouse data is faulty?

 

"NR also increased NAD+ up to 100% from University of Washington clinical trial and 200% from Brenner paper all on just 1g of NR." If you accept that as truth, then why is it not plausible that 60 days of 400mg/kg of NMN raised NAD by 500%?

 

 

"The NMN study used 500mg/kg which is 37g for a human weighs 75kg."  One of these days you will get your math correct. According to the allometric calculator at http://clymer.alterv...allometry.html the 400mg/kg dose converts to 3,833 mg for a 75 KG human. You came close, but you had the decimal point in the wrong place.

 

"Until you can prove that NMN can get into cells without converting to NR first, NMN is an inferior NAD+ precursor unless you target the kidney." It is the end result that counts and therefore a 500% increase of NAD after 60 days of NMN beats a 40 to 55% increase of NAD after 60 days of NR in my book any day.

 

 

 

 

[LawrenceW]

This NAD+ level was measured at 4 weeks while the human study was measured at 8 weeks. The dose used on mice is also extremely high compared with human study. There is no evidence that NMN homeostasis takes longer than NR.

 

You need to brush up on your reading and comprehension skills!  Go and read page 10 again.

 

You once again attributed the wrong dosing and time frame to the liver NAD results.  

 

From page 10.  "To restore NAD+ levels, we administered NMN to 18-month-old mice via drinking water for 2 months at 400mg/kg/day (Figures S6A–S6C)."

 

Figure S6A shows the 500% increase.

[MikeDC]

You need to brush up on your reading and comprehension skills! Go and read page 10 again.

You once again attributed the wrong dosing and time frame to the liver NAD results.

From page 10. "To restore NAD+ levels, we administered NMN to 18-month-old mice via drinking water for 2 months at 400mg/kg/day (Figures S6A–S6C)."

Figure S6A shows the 500% increase.

So it is 8 weeks and 400mg. The dose is still very high compared to the NR human study. Previous mice studies used 300mg/kg. What was the reason to use 400mg/kg or 500mg?

I believe the placebo data is not right. An independent study will prove it.

Edited by MikeDC, 22 April 2018 - 03:45 PM.

[MikeDC]

Newbies might want to read this link

https://blog.truniag...cB&gclsrc=aw.ds

[John250]

Is the problem with absorption due to oral consumption? Why not get some lyophilized NM,NMN, NR with bacteriostatic water and administer it via intramuscular injection? Not sure on degradation timing or preferred solution but most supplements that don’t work well via oral consumption work via injection.

Also with what’s currently available now otc what would be recommended to take to increase NAD? Brand, dose,etc.?

Edited by John250, 22 April 2018 - 03:53 PM.

[able]

So it is 8 weeks and 400mg. The dose is still very high compared to the NR human study. Previous mice studies used 300mg/kg. What was the reason to use 400mg/kg or 500mg?

I believe the placebo data is not right. An independent study will prove it.

 

There is research evidence that NR has an effective upper limit of 500-1000 mg.  The anecdotal evidence agrees with that.  I recall many users (myself included) that tried 1-2 grams a day NR and didn't notice anything so dropped back down.

 

They do tend to use much higher dosages in studies with NMN.  Likely because they find it more effective than lower dosages.

 

Perhaps it does not bump into homeostasis as quickly as NR, so they can use higher dosages and achieve better results.

 

We need confirmation with studies in humans.  Dr Sinclair completed Phase 1 testing last year, and surely knows the answer.  I hope he shares that soon - hopefully before they start Phase 2 study this fall.

[MikeDC]

Is the problem with absorption due to oral consumption? Why not get some lyophilized NM,NMN, NR with bacteriostatic water and administer it via intramuscular injection? Not sure on degradation timing or preferred solution but most supplements that don’t work well via oral consumption work via injection.

Also with what’s currently available now otc what would be recommended to take to increase NAD? Brand, dose,etc.?

Not many people are willing to take a shot everyday to slow down aging. Maybe diabetes might benefit by mixing NR or NMN in the same shot.

[MikeDC]

There is research evidence that NR has an effective upper limit of 500-1000 mg. The anecdotal evidence agrees with that. I recall many users (myself included) that tried 1-2 grams a day NR and didn't notice anything so dropped back down.

They do tend to use much higher dosages in studies with NMN. Likely because they find it more effective than lower dosages.

Perhaps it does not bump into homeostasis as quickly as NR, so they can use higher dosages and achieve better results.

We need confirmation with studies in humans. Dr Sinclair completed Phase 1 testing last year, and surely knows the answer. I hope he shares that soon - hopefully before they start Phase 2 study this fall.

University of Washington Study showed 1g NR creates a steady state level of NAD+ that doesn’t change after one additional supplementation. So 1g should be the upper limit on supplementation. This is actually a very good news because current suggested 250mg is affordable and effective. You don’t need to spend a fortune to slow down aging.

[John250]

University of Washington Study showed 1g NR creates a steady state level of NAD+ that doesn’t change after one additional supplementation. So 1g should be the upper limit on supplementation. This is actually a very good news because current suggested 250mg is affordable and effective. You don’t need to spend a fortune to slow down aging.

Has to be on empty stomach correct?

[MikeDC]

Has to be on empty stomach correct?

Not really. I have been taking it with breakfast.

[John250]

Interesting. I wonder why Niagen recommends it that way. They should at least give a reason why. Like it makes sense L-tryptophan needs to be taken on an empty stomach because it competes with other amino acids but I find it annoying when other products say to take on an empty stomach and don’t list the reason why like Citrus Bergmont, nattokinase, rhodiola,etc.

[MikeDC]

Interesting. I wonder why Niagen recommends it that way. They should at least give a reason why. Like it makes sense L-tryptophan needs to be taken on an empty stomach because it competes with other amino acids but I find it annoying when other products say to take on an empty stomach and don’t list the reason why like Citrus Bergmont, nattokinase, rhodiola,etc.

My guess is they will recommend on empty stomach if the substance is not super stable so it can pass the stomach quicker.