392 replies to this topic

[LawrenceW]

tunt01.

 

Yes there was an initial 90% increase of NAD+ measured at Day 30 of the 500mg per day dose, but that dropped to 55% when measured at Day 60 after it appeared that the higher dose had run into a homeostatic feedback loop. The 250mg lower dose increase of NAD+ also appeared to drop slightly at Day 60.  It would have been interesting and more definitive to see what the readings were at days 90 and 120. As per the study, it appears that the maximum long term increase of NAD+ from NR supplementation is somewhere in the 40 to 55% range.

[stefan_001]

tunt01.

 

Yes there was an initial 90% increase of NAD+ measured at Day 30 of the 500mg per day dose, but that dropped to 55% when measured at Day 60 after it appeared that the higher dose had run into a homeostatic feedback loop. The 250mg lower dose increase of NAD+ also appeared to drop slightly at Day 60.  It would have been interesting and more definitive to see what the readings were at days 90 and 120. As per the study, it appears that the maximum long term increase of NAD+ from NR supplementation is somewhere in the 40 to 55% range.

 

I think thats to broad of a conclusion. Certainly more study would be useful not just longer term but also 4 weeks on and one week off schemes.
 

Edited by stefan_001, 04 May 2018 - 01:40 PM.

[TMNMK]

And also we don't know the mechanism of homeostasis as far as I am aware, there seems to be an assumption that it is a negative feedback of some kind, similar to down-regulation of NAMPT via nicotinamide but would it also be fair to ask if this is perhaps a slower onset of consumer activity and if so which consumers?

[LawrenceW]

Here is a link to the Elysium study:

 

https://www.nature.c...1514-017-0016-9

 

Graph showing drop off of NAD+ increase.

 

 

 

[bluemoon]

Is there a reason to think that at week 12, 500 mg of NR won't continue to decrease to the 40% level for a healthy person, apart from the fact that Charles Brenner says he now takes 500 mg?

[stefan_001]

Is there a reason to think that at week 12, 500 mg of NR won't continue to decrease to the 40% level for a healthy person, apart from the fact that Charles Brenner says he now takes 500 mg?

 

That would be very intriguing if over time a 500mg and 250mg dose would lead to same NAD+ level level. Sounds very unlikely. Like TMNMK I am also wondering whether there are slow onset consumers that over time consume more NAD+. That could be processes that are usefull but faded over time. Or then who knows if feeding CD38 may actually be usefull for something etc.

[bluemoon]

Just look at the graph. Do you think the 500 mg line just stops suddenly at 55% after 4 weeks of sliding down?  It is clearly converging with 40% which is where 250 mg is, but we need 12  week results to know. So what is your reasoning that convergence at 40% is very unlikely? 

[John250]

How are these studies testing NAD+ levels? I thought there wasn’t a blood test available for it?

[MikeDC]

How are these studies testing NAD+ levels? I thought there wasn’t a blood test available for it?

There is no blood test of NAD+ for consumers. Scientists can test it.

[stefan_001]

Just look at the graph. Do you think the 500 mg line just stops suddenly at 55% after 4 weeks of sliding down?  It is clearly converging with 40% which is where 250 mg is, but we need 12  week results to know. So what is your reasoning that convergence at 40% is very unlikely? 

 

Its not a line, just 2 measurement points, it can have stabilized there, go up or still somewhat down. But its unlikely that both 250mg and 500mg dosing over time would lead to the same NAD+ boost. And if that happens that would be really interesting because it would point to a systematic change triggered by the higher dose but not by the 250mg. I am not a believer of a negative feedback loop. At younger age our NAD+ is much much higher, any negative feedback loop would have been triggered then already.
 

[John250]

There is no blood test of NAD+ for consumers. Scientists can test it.

Then how are studies getting the NAD% #’s?

[John250]

I’m sure there is a negative feed back loop to a degree. I think the only way to truely have 24/7 increased NAD+ levels would be if you are in ketosis while implementing intermittent fasting and mild excercise. That’s too hard for me. Just give me a pill or and injection instead Maybe thrown in some Oxaloacetate with NR 4 weeks on/1week off,repeat.

[OP2040]

Seems like cycling between NMN and NR might help a lot with feedback and tolerance issues?  I certainly don't want to lose what NMN supplementation seems to have provided me.

 

There was an article out yesterday containing an interview with the CEO of this new company

https://nuchido.com/

She basically said that they have solved the NAD+ feedback issue and succeeded in keeping levels sustained at extremely high, youthful levels for long periods of time with some cocktail.  Also, they are moving forward quite fast with it.  Sorry can't find the interview....

 

It's really crazy that there is a new company popping up seemingly every month related to some anti-aging target,  We live in exciting times, and in that respect, I'm not too worried about things like NAD+ feedback, because these days you give a problem 5 years at most and someone has solved it.  And I really believe that ICT revolution has run its course, the next wave will be biotech, and amazing things are going to happen so hang in there!

 

 

[MikeDC]

Then how are studies getting the NAD% #’s?

Scientists can test NAD+ in labs for clinical trial participants.

[MikeDC]

I’m sure there is a negative feed back loop to a degree. I think the only way to truely have 24/7 increased NAD+ levels would be if you are in ketosis while implementing intermittent fasting and mild excercise. That’s too hard for me. Just give me a pill or and injection instead Maybe thrown in some Oxaloacetate with NR 4 weeks on/1week off,repeat.

Might be some kind of feed back loop for high doses. But NR is still working for me after 2 years. I started to take 3 days off every month.

[MikeDC]

Taurine might be the solution to defeat the NAD+ feed back loop. This paper shows increasing H2S up regulated NAMPT. NAD+ precursors most likely down regulate NAMPT. H2S can counter that and stop the negative feed back loop.

https://twin.sci-hub...c59/sun2018.pdf

[John250]

Any chemistry gurus know another compound with a similar structure to NR? Maybe by researching the bioavailability of similar compounds could give us a better idea how to administer NR?

[MikeDC]

Any chemistry gurus know another compound with a similar structure to NR? Maybe by researching the bioavailability of similar compounds could give us a better idea how to administer NR?

The tracer studies only followed NAD+ up to 135 min. We know NR generates a peak at hour 6. Could more intact NR reaches liver and blood circulation between 135 min and 6 hours? We need more studies to find out.

[tunt01]

Taurine might be the solution to defeat the NAD+ feed back loop. This paper shows increasing H2S up regulated NAMPT. NAD+ precursors most likely down regulate NAMPT. H2S can counter that and stop the negative feed back loop.

https://twin.sci-hub...c59/sun2018.pdf

 

Thx for this paper Mike.  It's an interesting thought.

 

Methylene Blue has also been used to reverse this condition (diabetic cardiomyopathy).  It upregulates SIRT3, deacetylates lysine residues, but I don't think it upregulates NAMPT, per se.  Something to keep in mind, perhaps.

 

 

Berthiaume, J., Hsiung, C., Austin, A., McBrayer, S., Depuydt, M., & Chandler, M. et al. (2017). Methylene blue decreases mitochondrial lysine acetylation in the diabetic heart. Molecular And Cellular Biochemistry, 432(1-2), 7-24. doi:10.1007/s11010-017-2993-1

[APBT]

 

There was an article out yesterday containing an interview with the CEO of this new company

https://nuchido.com/

She basically said that they have solved the NAD+ feedback issue and succeeded in keeping levels sustained at extremely high, youthful levels for long periods of time with some cocktail.  Also, they are moving forward quite fast with it.  Sorry can't find the interview....

 

https://www.leafscie...nichola-conlon/

[OP2040]

https://www.leafscie...nichola-conlon/

 

Yep, that's the one, thanks,

[Kentavr]

Newbies might want to read this link

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

 

Newbies might want to read THIS link:

 

http://alivebynature...nad-booster-3/ 

 

Who is right?

Edited by Kentavr, 11 May 2018 - 08:00 PM.

[bluemoon]

Newbies might want to read THIS link:

 

http://alivebynature...nad-booster-3/ 

 

Who is right?

 

Alive By Nature's propganda seriously compares Sinclair's NMN mouse study with Elysium's NR human trial?

[Supierce]

Maybe the NMN vs. NR debate really comes down to which one survives the GI tract better.

Edited by Supierce, 12 May 2018 - 02:06 PM.

[MikeDC]

Maybe the NMN vs. NR debate really comes down to which one survives the GI tract better.

The Ling LIU paper showed NMN and NR are similar in terms of surviving the GI tract for the first 135 minutes anyway. Small amounts get into liver intact and even smaller amount get into blood circulation.

Current state of science doesn’t explain why NR and NMN are so much better at anti aging than NAM when most of them turned into NAM before reaching liver. Clinical results rules over science.

Edited by MikeDC, 12 May 2018 - 04:25 PM.

[Steve H]

wow, it almost looks like some people in this thread work for Chromadex I suggest we wait for Sinclair to publish clinical trial results and then we will see what the data says.

Also on September 18th, we launch an NMN project on Lifespan.io too which may be of interest to some of you here. This will be a Sinclair Lab project and we are hosting it on our platform to see if we can help fuel some new discoveries about NAD+ biology and the effects of NMN on lifespan. 

Edited by Steve H, 06 September 2018 - 11:23 PM.

[Samuel80]

Will this product do the job? I want to get my elderly parents onto this. 

 

https://au.iherb.com...-Capsules/57082

[Phoebus]

Will this product do the job? I want to get my elderly parents onto this. 

 

https://au.iherb.com...-Capsules/57082

 yes

wow, it almost looks like some people in this thread work for Chromadex I suggest we wait for Sinclair to publish clinical trial results and then we will see what the data says.

Also on September 18th, we launch an NMN project on Lifespan.io too which may be of interest to some of you here. This will be a Sinclair Lab project and we are hosting it on our platform to see if we can help fuel some new discoveries about NAD+ biology and the effects of NMN on lifespan. 

 

Sinclair is actually working on a modified, novel, NMN compound. Something that could be patented. 

 

So its possible his research may not apply to regular old NMN/NR 

[bluemoon]

 

Sinclair is actually working on a modified, novel, NMN compound. Something that could be patented. 

 

So its possible his research may not apply to regular old NMN/NR 

 

Sinclair's timeline seems to be 3 to 4 years until market and by then I expect others to enter the fray. By then, NR and NMN may be old news. Right now, I'm more curious about what Elysium might sell next year.   

[Phoebus]

Sinclair's timeline seems to be 3 to 4 years until market and by then I expect others to enter the fray. By then, NR and NMN may be old news. Right now, I'm more curious about what Elysium might sell next year.   

 

Elysium? ha!

 

Elysium will be lucky to be alive next year. they are about to slammed by the courts for their fraudulent nonsense and likely receive a huge fine to be paid to chromadex. Do they have the funds to pay the fines and keep trucking? We will see.