The NMN anti-aging FAD

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The NMN anti-aging FAD

Postby BioWizard on January 5th, 2018, 1:33 pm 

So SciAmeriKen, what are your thoughts on this? I recently got sufficiently interested that I opened up my biochemistry book and am refreshing myself on nucleotide biochemistry :]

I saw that the clinical trial has started and some PK data was already published (which helped me figure out a good dosing schedule ;-] )
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Re: The NMN anti-aging FAD

Postby zetreque on January 5th, 2018, 1:56 pm 

We found that heat shock results in an increase in the cellular NAD+/NADH ratio and an increase in recruitment of SIRT1 to the hsp70 promoter.

http://scholarcommons.usf.edu/etd/4567/

Also came across this just now when looking up stuff. Maybe another reason to get Vit D the natural way.
Our data indicates that NIR light alters mitochondrial biogenesis signaling and may represent a mechanistic link to the clinical benefits.

https://www.ncbi.nlm.nih.gov/pubmed/24246911
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Re: The NMN anti-aging FAD

Postby BioWizard on January 5th, 2018, 2:13 pm 

Ugh, I'm so tired of people peddling vitD into every freakin biomedical story. It's useless and nobody cares about vitD deficiency because it's not a real thing! *snickers*
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Re: The NMN anti-aging FAD

Postby zetreque on January 5th, 2018, 2:14 pm 

not my fault it came up when I looked into ways to increase NAD.
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Re: The NMN anti-aging FAD

Postby BioWizard on January 5th, 2018, 2:15 pm 

zetreque » 05 Jan 2018 01:14 pm wrote:not my fault it came up when I looked into ways to increase NAD.


Just take NMN or NR, that has been clinically proven to increase NAD+ (both are upstream metabolites). VitD pshaaaaw.
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Re: The NMN anti-aging FAD

Postby zetreque on January 5th, 2018, 2:17 pm 

BioWizard » Fri Jan 05, 2018 10:15 am wrote:
zetreque » 05 Jan 2018 01:14 pm wrote:not my fault it came up when I looked into ways to increase NAD.


Just take NMN or NR, that has been clinically proven to increase NAD+ (both are upstream metabolites). VitD pshaaaaw.


Sure,
I also like to look at natural ways to increase it so I'm getting other possible benefits in balance and seeing a bigger picture.
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Re: The NMN anti-aging FAD

Postby BioWizard on January 5th, 2018, 2:19 pm 

zetreque » 05 Jan 2018 01:17 pm wrote:
BioWizard » Fri Jan 05, 2018 10:15 am wrote:
zetreque » 05 Jan 2018 01:14 pm wrote:not my fault it came up when I looked into ways to increase NAD.


Just take NMN or NR, that has been clinically proven to increase NAD+ (both are upstream metabolites). VitD pshaaaaw.


Sure,
I also like to look at natural ways to increase it so I'm getting other possible benefits in balance.


Your obsession with something arbitrarily defined is somewhat irrational. If your goal is to increase NAD+, then take some NMN or NR and be done with it.
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Re: The NMN anti-aging FAD

Postby BioWizard on January 5th, 2018, 2:22 pm 

Just make sure it's not from a shady overseas source that cannot guarantee quality and safety. Other than that, it's just a metabolite that "naturally" exists in your body. If you are weary of ingesting anything non-whole, just open the pill and mix the powder with a meal or into a drink. Easy peasy, don't stress too much about arbitrary definitions :]
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Re: The NMN anti-aging FAD

Postby Braininvat on January 5th, 2018, 5:14 pm 

NAD, NR, resveratrol, pterostilbene....lots of potential mixes there to research. SciAm had something a couple years ago on sirtuin boosters and the whole youth-in-mitochondria thing. See if I can find it....

Here: https://blogs.scientificamerican.com/gu ... g-nad-fad/
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Re: The NMN anti-aging FAD

Postby zetreque on January 5th, 2018, 8:50 pm 

Devils advocate.

low levels of NAD+ might help fight cancer.
http://www.cell.com/cell-metabolism/fulltext/S1550-4131(15)00266-1

Increased NAD+ possible decreased exercise performance.
https://www.ncbi.nlm.nih.gov/pubmed/27489522
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Re: The NMN anti-aging FAD

Postby zetreque on January 5th, 2018, 9:57 pm 

Looks like in about 8 weeks a phase II human study will be done.

http://rctportal.niph.go.jp/en/detail?t ... N000030609

Phase I
https://upload.umin.ac.jp/cgi-open-bin/ ... R000024575

At Keio, Hiroshi Itoh, Professor of Endocrinology, Metabolism, and Nephrology and his team are leading the study. Shin-ichiro Imai, Professor of Developmental Biology, is involved in the study at the US side.
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Re: The NMN anti-aging FAD

Postby BioWizard on January 5th, 2018, 11:15 pm 

zetreque » 05 Jan 2018 07:50 pm wrote:
Increased NAD+ possible decreased exercise performance.
https://www.ncbi.nlm.nih.gov/pubmed/27489522


The amount they gave the rat seems insanely high to me. Probably screwed up their metabolism.
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Re: The NMN anti-aging FAD

Postby SciameriKen on January 6th, 2018, 10:37 pm 

Of all the interventions we've tried in the lab (Resveratrol and vitamin D) I'd say I am most optimistic about NR.

Just some background -- This fad revolves around nicotinamide dinucleotide (NAD), and some good background about why this is important for aging can be found here: http://www.anti-agingfirewalls.com/2014/11/11/nad-an-emerging-framework-for-life-extension-part-1-the-nad-world-2/

NAD is a critically important molecule as it is used both in glycolytic and oxidative respiration (where it shuttles between NAD+ and NADH forms). However, its role in aging mainly comes from its role as a substrate for key longevity enzymes including the sirtuin gene family - which signals for mitochondrial health and lifespan, PARP family - which is important in DNA repair, CD-38 which plays a role in immunity, as well as many others. When these enzymes use NAD+ it becomes converted into Nicotinamide (NAM). Cells do their best to recover NAD+ pools, the salvage pathway recovers NAM, via an enzyme called NAMPT that converts NAM to nicotinamide mononucleotide (NMN), this is then converted into NAD+. However, as we age NAMPT expression/activity declines resulting in loss of NAD+.

It is therefore hypothesized that increasing our NAD+ pools may have beneficial health impacts. Supplementation is being looked at as a way to do this - specifically vitamin B3, aka Niacin is what is being looked at. Niacin actually includes three closely related molecules, NAM, nicotinic acid (NA), and nicotinamide riboside (NR). There are concerns that NAM and NA at standard doses may cause flushing in some people, however, NR at high doses does not seem to cause this. NR is a naturally occurring molecule that converts into NMN to enter the salvage pathway. To date, at least to my knowledge, only dosing trials have been performed in humans, but the animal studies have been very promising. The rat study you mentioned previously has been a small thorn in our sides as we've had reviewers mention that study. But its annoying because they are overselling their data by boldly claiming NR was bad for physical performance when the P-value for that was 0.07 and they had only treated for 21 days.

In our lab we treated for nearly 30 days in mice and found treadmill performance had improved. I've taken it myself and for the most part didn't feel any different other than while doing my 5K runs feeling like I had more endurance (could just be the power of placebo though :). We are hoping to secure a grant to do a true study with this, but we have a few ongoing studies as I type.

Its tough to get overly enthusiastic about this though. The main champions are Leonard Guarente who is working with Basis, a company that looks to combine NR with pterostibene, a molecule similar to resveratrol, that theoretically will give the one-two punch of NAD+ increase and Sirtuin activity. However, Guarente had previously championed resveratrol and Sirtuins in general and so far this has not panned out so well. All that being said I am carefully optimistic.
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Re: The NMN anti-aging FAD

Postby BioWizard on January 7th, 2018, 8:24 am 

Nice round up SciKen. I am on day 5, so too soon to tell. Bht my workouts have def not deteriorated and if anything have been more intense and longer lasting.
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Re: The NMN anti-aging FAD

Postby BioWizard on January 7th, 2018, 9:39 am 

BioWizard » 05 Jan 2018 10:15 pm wrote:
zetreque » 05 Jan 2018 07:50 pm wrote:Increased NAD+ possible decreased exercise performance.
https://www.ncbi.nlm.nih.gov/pubmed/27489522


The amount they gave the rat seems insanely high to me. Probably screwed up their metabolism.


What I was referring to there was therapeutic window. That is determined by both efficacy and safety studies - not just safety. Making any argument based on one very high dose is silly.

Another silly point about the study is that they used 4 months old rats. That’s “teenage” for rats. How much sense does it make to test a compound for age-related decline in teenage organisms?

Guys, never settle for what the abstracts say. Always dig into the methods and study design. Biomedical scientists can be quite the **** :)

SciKen, how can that study be a thorn in anybody’s side, other than the authors’ ability to design a meaningful study and properly interpret data? And you say reviewers have used that against you? May I please write your next rebuttal? I want to tell these **** how I really feel.
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Re: The NMN anti-aging FAD

Postby zetreque on January 8th, 2018, 12:40 am 

Question:

Any idea if carnivores or herbivores recover NAD+ pools differently?

Just thought of this since Niacin seems like it might be higher in fish or game meat diets of a carnivore.
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Re: The NMN anti-aging FAD

Postby SciameriKen on January 8th, 2018, 3:37 pm 

BioWizard » Sun Jan 07, 2018 1:39 pm wrote:SciKen, how can that study be a thorn in anybody’s side, other than the authors’ ability to design a meaningful study and properly interpret data? And you say reviewers have used that against you? May I please write your next rebuttal? I want to tell these **** how I really feel.


Lol well, reviewers like to read just abstracts too I guess :). If I get another reviewer coming after us for that paper I'm signing you up for sure! But now we got a not discussed on our most recent grant - this time the reviewer did not think a 20% improvement in treadmill performance with just 1 month of NR treatment was robust enough - sheesh!
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Re: The NMN anti-aging FAD

Postby BioWizard on January 8th, 2018, 3:38 pm 

seriously? what’s the p value?
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Re: The NMN anti-aging FAD

Postby SciameriKen on January 8th, 2018, 3:40 pm 

zetreque » Mon Jan 08, 2018 4:40 am wrote:Question:

Any idea if carnivores or herbivores recover NAD+ pools differently?

Just thought of this since Niacin seems like it might be higher in fish or game meat diets of a carnivore.



I am not sure though it wouldn't surprise me. You may also want to note that there is also de novo synthesis of NAD+ from Tryptophan, although the salvage pathway is more important for humans. Additionally I am not sure if the De novo pathway is enough as vitamin B3 deficiency causes a condition called Pellegra https://en.wikipedia.org/wiki/Pellagra
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Re: The NMN anti-aging FAD

Postby SciameriKen on January 8th, 2018, 3:42 pm 

BioWizard » Mon Jan 08, 2018 7:38 pm wrote:seriously? what’s the p value?


NR300: p=0.0055, NR600: p=0.0288 -- the 600 only had about a 10% improvement - so maybe there is an upper limit?
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Re: The NMN anti-aging FAD

Postby BioWizard on January 8th, 2018, 4:23 pm 

I’ve seen a bunch of studies with similar results, where the very high dose starts to dip.
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