NMN ⇒ New study: less metabolic benefit from exercise with nmn

[rhett]

https://www.biorxiv.org/content/10.1101 ... 2.164459v1

EXERCISE-INDUCED BENEFITS ON GLUCOSE HANDLING IN A MODEL OF DIET-INDUCED OBESITY ARE REDUCED BY CONCURRENT NICOTINAMIDE MONONUCLEOTIDE

Unexpectedly, NMN administration impaired several aspects of exercise-induced benefits in HFD mice, including glucose tolerance, glucose stimulated insulin secretion from islets and reduced hepatic triglyceride accumulation. Mechanistically, HNEx mice displayed increased antioxidant and reduced prooxidant gene expression in both islets and muscle, suggesting that altered redox status is associated with the loss of exercise-induced health benefits with NMN co-treatment.

[RobSmith]

There was also this comment, "We suggest NMN administration may not be beneficial when NAD+ levels are replete."

So I don't think the headline is as bad as it looks - if you are short of NAD+ then taking the NMN is beneficial; once you have enough NAD+ then it's pointless or detrimental in trying to increase it even further.
I guess for those older members who will naturally have lower NAD+ levels then its why we have only tended to see beneficial effects of taking the NMN.
All we need now is a cheap accurate way of measuring our NAD+ levels!!

[rhett]

Excellent point. This matches similarly to the reproductive study where increasing nad improved fertility up to a point but dosing above that level decreased it again. I seem to remember the best dose scaled to humans was something like 400-1200mg (I think?)

[ALIVEBYNATURE]

There was also this comment, "We suggest NMN administration may not be beneficial when NAD+ levels are replete."

So I don't think the headline is as bad as it looks - if you are short of NAD+ then taking the NMN is beneficial; once you have enough NAD+ then it's pointless or detrimental in trying to increase it even further.
I guess for those older members who will naturally have lower NAD+ levels then its why we have only tended to see beneficial effects of taking the NMN.
All we need now is a cheap accurate way of measuring our NAD+ levels!!

Right. The title of this study is quite misleading.

These were VERY YOUNG mice (5 WEEK old) with normal NAD+ levels, given a large dose of NMN. Raising NAD+ when not needed dampened some benefit from exercise.

Dr Sinclairs 2018 study with 20 month old mice for 2 months had increased muscular blood flow, enhanced physical performance and endurance and the old mice became as fit and strong as young mice.

Results were better with exercise + NMN that with either intervention alone.

So, if you are very young and healthy, NMN supplementation might dampen some benefit from exercise. If not young, or have some health issue that drains NAD+ levels, it is likely you will see the benefits found in Dr Sinclairs study.

[Newage]

I agree ABN.
At my “senior” age I find that my energy levels and training standards are elevated significantly with NMN & NAD+ supplementation.
I, along with pickle ball (from what I read in his posts) seem to be turning back the clock with a new found ability to train and compete. Being in our senior years we both should be slowing down and not competing with our new found vigour..
It seems that you are right in saying that the older you are, the more significant the positive changes. With my personal mindset I dreaded the detrimental effect that old age brings but as of starting on NMN & NAD+ I no longer give it a second thought..

[zmm]

The dose they gave in the study was 400mg/kg.
What would the equivalent be in a human?

I found this study from a few years ago, that had this snippet.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668137/

"For example, whereas the effects of NMN on body weight gain, insulin sensitivity, tear production, and bone mineral density were dose-dependent, 100 mg/kg/day of NMN improved oxygen consumption, energy expenditure, and physical activity better than 300 mg/kg/day"

"Given that 100 mg/kg/day of NMN was able to mitigate most age-associated physiological declines in mice, an equivalent surface area dose for humans would be ~8 mg/kg/day (Freireich et al., 1966), providing hope to translate our findings to humans."

So it would seem that 100mg/kg would be in a human 8mg/kg
so for a 175lb human the 100mg equivalent would be 640mg a day.

this study was done with 4x that amount.
So it would seem to just show that more of a good thing is not better

[drkris69]

Thanks for the study zmm. An oldie but goodie.

[Newage]

I agree that moderation is the key to most things in life.
Food, exercise, sunlight, stress and many other aspects of our existence show that more is not always better.
As we are all different we individually need to find our “sweet spots”

[Drdavid]

https://www.biorxiv.org/content/10.1101 ... 2.164459v1

EXERCISE-INDUCED BENEFITS ON GLUCOSE HANDLING IN A MODEL OF DIET-INDUCED OBESITY ARE REDUCED BY CONCURRENT NICOTINAMIDE MONONUCLEOTIDE

Unexpectedly, NMN administration impaired several aspects of exercise-induced benefits in HFD mice, including glucose tolerance, glucose stimulated insulin secretion from islets and reduced hepatic triglyceride accumulation. Mechanistically, HNEx mice displayed increased antioxidant and reduced prooxidant gene expression in both islets and muscle, suggesting that altered redox status is associated with the loss of exercise-induced health benefits with NMN co-treatment.

I think the title is a little misleading. We use NMN in several of our elite level athletes and have seen exciting positive changes in multiple catagories. Additionally, this study was on mice not on humans and the outcomes are typically different.