13 replies to this topic

[able]

Strange that the first significant clinical study with NMN is published and no-one posts about it.

 

Looks like 250 Mg a day for 10 weeks resulted in significant increase in muscle insulin sensitivity.  

 

https://science.scie...ce.abe9985.full

 

 

These results demonstrate NMN increases muscle insulin sensitivity, insulin signaling and remodeling in women with prediabetes who are overweight or obese

 

 

I guess NR fans don’t bring this up because NR was unsuccessful in addressing Insulin resistance even when given at 2 grams a day for 12 weeks in the Dollarup study, as well as in 2 others.

 

https://pubmed.ncbi....h.gov/29992272/

 

 

12 wk of NR supplementation in doses of 2000 mg/d appears safe, but does not improve insulin sensitivity and whole-body glucose metabolism

 

https://pubmed.ncbi....h.gov/31412242/

 

 

NR supplementation of 1000 mg/d for 6 wk in healthy overweight or obese men and women increased skeletal muscle NAD+ metabolites, affected skeletal muscle acetylcarnitine metabolism, and induced minor changes in body composition and sleeping metabolic rate. However, no other metabolic health effects were observed.  

 

However, no effects of NR were found on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism.

 

 

 

https://pubmed.ncbi....h.gov/32320006/

 

 

However, no effects of NR were found on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism.

 

 

To be fair, Dr. Brenner points out his objection to this study on twitter:

 

https://twitter.com/...434248753029121

 

 

the placebo group's fatty liver started with > 2.3 x the fatty liver as the NMN group. this was significant with a P value of 0.003, which was greater than any NMN-dependent effect in the paper…I would LOVE for NMN and NR to do what these authors say it does in prediabetic women but the baseline characteristics of study participants don't permit one to make such conclusions. you can't compare women w/o fatty liver to those w fatty liver and call it a fair trial

Edited by able, 24 April 2021 - 07:05 PM.

[Phoebus]

why create a study with two groups, one with Fatty liver and and one without and then compare the two as if they are equal? 

 

Its bizarre 

Edited by Phoebus, 24 April 2021 - 07:35 PM.

[CharlieG]

Doesn't make sense to me how NMN would show positive results, yet NR failed for same thing in three different studies.  I thought NMN must convert to NR to enter cells, so why would in not be as good as NMN here?

[granth998]

Yes, that is strange.  Maybe due to NMN being partially converted to other metabolites by bacteria in the stomach.

 

Or, maybe NR is not stable enough in blood to reach the muscles in sufficient quantity

 

Or, maybe the 250 mg of NMN they used is a better dose, and giving 2 gram of NR just results in a lot of NAM that is counterproductive?

[able]

why create a study with two groups, one with Fatty liver and and one without and then compare the two as if they are equal? 

 

Its bizarre 

 

 

I am curious how they failed to randomize for that and hope we can hear more.  But research often has poor design or flaws in setup, and I don't see why that means we should ignore the study as Dr. Brenner wants.

 

It passed peer review, so it seems reviewers feel it's not a fatal flaw that renders the results meaningless.

 

Saw someone point out on reddit, that if you don't feel it is a fair comparison, just ignore the placebo arm.

 

The NMN group shows improvement in insulin sensitivity, with no other intervention.  I'm not sure how you can fake that, since it is not subjective, and was blinded.

Edited by able, 24 April 2021 - 08:57 PM.

[Phoebus]

 

Mike

 

@Hongma123

·

Apr 22

 

 

As I have showed many times before, low dose NR and NMN are more effective than high dose. The optimum dose for human is less than 3mg/kg. Previous NR trials used doses way to high that inhibit Sirtuins because of high concentration of NAM.

 

That guy tweets a lot about NR/NMN 

 

I am almost certain Sinclair says he takes over a gram a day of NMN. Meanwhile a 3mg/kg dose would be about right in that 250 mg range for most adults which is what the OP study used.

[Harkijn]

The scientific community sofar has shown curiously little interest in testing NMN in clinical trials. Perhaps they find it not all that promising. But let's be glad that at least one research group tries to find out more.

[Mind]

The for posting about this study AND bringing up counterpoints. More people should do this. Good discussion.

 

When I talk to people behind the scenes in the "Longevity Industry", they have often told me that the toughest part about advancing new therapeutics is sorting through all the "junk studies". One person told me that about 90% of the studies are junk because of poor design or other flaws. This forces the companies to spend a lot of time finding the quality work and then trying to replicate those quality findings before moving onto product development and their own studies.

 

In a sense, it is good that there is a somewhat unregulated anti-aging and biohacker marketplace. With more people doing more biomarker testing there is a greater opportunity to weed out the stuff that does not work.

[able]

Quote

 

Mike

 

@Hongma123

·

Apr 22

 

 

As I have showed many times before, low dose NR and NMN are more effective than high dose. The optimum dose for human is less than 3mg/kg. Previous NR trials used doses way to high that inhibit Sirtuins because of high concentration of NAM.

 

 

 

That guy tweets a lot about NR/NMN 

 

I am almost certain Sinclair says he takes over a gram a day of NMN. Meanwhile a 3mg/kg dose would be about right in that 250 mg range for most adults which is what the OP study used.

 

 

THAT guy is our own MikeDC, the worlds biggest NR fan.  He has become disillusioned with Chromadex for not coming out with a more bioavailable form of Niagen, and shares my concern that taking large dosages of NR or NMN result in massive NAM increase that may be problemmatic.

 

I recall Dr Sinclair often saying he takes 1 gram of NMN a day.  Did he change that?

 

I recall regular poster Lawrence was taking several grams a day, but said their group found it unhelpful and has decreased.

 

I don't recall anyone saying they found better results with taking 2-3 grams a day, and believe everyone has dropped down to 1 gram a day or less.

Edited by able, 25 April 2021 - 02:26 PM.

[Phoebus]

oh that is Mike? lol, had no idea 

 

Yeah I am glad there is more and more discussion around the proper dose. Larger does not equal better it seems. 

[Harkijn]

This guy once again seems to have a balanced view on precursors:

[Phoebus]

I highly recommend Dr Brad's YT channel, tons of great vids on there, very well researched 

[Harkijn]

See also this summary of this study report:

https://www.fightagi...upplementation/

[able]

See also this summary of this study report:

https://www.fightagi...upplementation/

 

Ah, hadn't seen that.

 

Also, found this review helpful

 

https://www.nmn.com/...-time-in-humans