NAD+ PreserversRoadmap to boosting cellular NAD+ with natural supplements: apigenin, quercetin, leucine etc (NAMPT, PARP1))

p75213
Posts: 75
Joined: Wed Sep 11, 2019 12:04 am

Re: Roadmap to boosting cellular NAD+ with natural supplements: apigenin, quercetin, leucine etc (NAMPT, PARP1))

Post by p75213 »

AlbertY wrote: Sat Oct 12, 2019 3:40 pm
p75213 wrote: Fri Oct 11, 2019 3:19 pm Any experimenters out there? Shouldn't be too difficult to make up some powder using Nuchido's ingredients.

One serving:

10 mg ascorbic acid
250 mg nicotinamide
300 mg alpha lipoic acid
5 mg zinc

1.1 g Propietary Blend
green tea leaf extract (~500)
parsley leaf powder (~400)
rutin extract (~150)
black pepper fruit extract (~50)
On their website, they claimed "Trial results show that on average, this increase is 4 times more than precursor-based supplements such as NR and NMN." But I didn't find any trial result, anyone knows where did they publish it?
As far as I know nothing has been published. Dr Conlon talked about it on one of her videos but I think that's about it.
Last edited by p75213 on Sun Oct 13, 2019 7:03 am, edited 1 time in total.


p75213
Posts: 75
Joined: Wed Sep 11, 2019 12:04 am

Re: Roadmap to boosting cellular NAD+ with natural supplements: apigenin, quercetin, leucine etc (NAMPT, PARP1))

Post by p75213 »

AlbertY wrote: Sat Oct 12, 2019 3:40 pm
p75213 wrote: Fri Oct 11, 2019 3:19 pm Any experimenters out there? Shouldn't be too difficult to make up some powder using Nuchido's ingredients.

One serving:

10 mg ascorbic acid
250 mg nicotinamide
300 mg alpha lipoic acid
5 mg zinc

1.1 g Propietary Blend
green tea leaf extract (~500)
parsley leaf powder (~400)
rutin extract (~150)
black pepper fruit extract (~50)
On their website, they claimed "Trial results show that on average, this increase is 4 times more than precursor-based supplements such as NR and NMN." But I didn't find any trial result, anyone knows where did they publish it?
Scroll to the bottom of the page.
https://nuchido.com/pages/science
p75213
Posts: 75
Joined: Wed Sep 11, 2019 12:04 am

Re: Roadmap to boosting cellular NAD+ with natural supplements: apigenin, quercetin, leucine etc (NAMPT, PARP1))

Post by p75213 »

The herbal proprietary blend estimate from longecity was wrong (in particular too much green tea leaf extract). This is his revised estimate:
1.1 g Propietary Blend
green tea leaf extract (~330)
parsley leaf powder (~316)
rutin extract (~300)
black pepper fruit extract (~150)
Fred

Re: Roadmap to boosting cellular NAD+ with natural supplements: apigenin, quercetin, leucine etc (NAMPT, PARP1))

Post by Fred »

p75213 wrote: Sun Oct 13, 2019 6:04 pm The herbal proprietary blend estimate from longecity was wrong (in particular too much green tea leaf extract). This is his revised estimate:
1.1 g Propietary Blend
green tea leaf extract (~330)
parsley leaf powder (~316)
rutin extract (~300)
black pepper fruit extract (~150)
So the DAILY dose (two servings = 6 capsules) would be double that and I included the lipoic-acid since it is one of the active ingredients although not part of the "proprietary botanical blend". Known amounts are in bold:

-alpha-lipoic acid 600 mg
-EGCG 300 mg (from about 600+ mg of green tea leaf extract)
-parsley leaf powder (~632)
-rutin extract (~600)
-black pepper fruit extract (~300)

+ nicotinamide 500 mg or other NAD precursors like NR/NMN.
The additional zinc (10 mg) and vitamin C (20 mg) you get from food or supplements.

I wonder why there´s no resveratrol in the cocktail though to indirectly replenish NAD+ levels via enzymatic activation of NMNAT-1:

"Resveratrol is a polyphenol with major health benefits that is thought to operate through direct activation of the “antiaging” enzyme SIRT1. However, recent reports have challenged this “direct activation” hypothesis, suggesting that the mechanism by which resveratrol increases SIRT1 function is still unknown (39, 86).

Previous work from our group has shown for the first time that resveratrol induces a dose-dependent increase in NMNAT-1 activity. As SIRT1 requires NAD+ as a substrate to perform its gene silencing function, higher NAD+ levels will enhance SIRT1 activity.

This finding suggests that resveratrol may promote SIRT1 function by enhancing NAD+ synthesis in whole cell systems without requiring direct activation. Our observation that resveratrol increases NAD+ levels in primary human brain cells by acting on NMNAT, together with the neuroprotective effects of green tea polyphenols against QUIN-mediated excitotoxicity (47), supports the view that polyphenols have considerable therapeutic potential, particularly for the treatment of neurodegenerative diseases.

As NMNAT can accelerate NAD+ synthesis from all six substrates, QUIN, NR, NMN, NA, NAR, and NAM, NMNAT activation by resveratrol may represent an ideal natural therapeutic to replenish NAD+ levels. Maintenance of higher cellular NAD+ will enhance SIRT1 activity and other NAD+-dependent pathways, impacting positively on cell viability and longevity."

https://www.ncbi.nlm.nih.gov/pmc/articl ... 7084/#s032
p75213
Posts: 75
Joined: Wed Sep 11, 2019 12:04 am

Re: Roadmap to boosting cellular NAD+ with natural supplements: apigenin, quercetin, leucine etc (NAMPT, PARP1))

Post by p75213 »

Fred wrote: Mon Oct 14, 2019 1:07 am
p75213 wrote: Sun Oct 13, 2019 6:04 pm The herbal proprietary blend estimate from longecity was wrong (in particular too much green tea leaf extract). This is his revised estimate:
1.1 g Propietary Blend
green tea leaf extract (~330)
parsley leaf powder (~316)
rutin extract (~300)
black pepper fruit extract (~150)
So the DAILY dose (two servings = 6 capsules) would be double that and I included the lipoic-acid since it is one of the active ingredients although not part of the "proprietary botanical blend". Known amounts are in bold:

-alpha-lipoic acid 600 mg
-EGCG 300 mg (from about 600+ mg of green tea leaf extract)
-parsley leaf powder (~632)
-rutin extract (~600)
-black pepper fruit extract (~300)

+ nicotinamide 500 mg or other NAD precursors like NR/NMN.
The additional zinc (10 mg) and vitamin C (20 mg) you get from food or supplements
That's it.
p75213
Posts: 75
Joined: Wed Sep 11, 2019 12:04 am

Re: Roadmap to boosting cellular NAD+ with natural supplements: apigenin, quercetin, leucine etc (NAMPT, PARP1))

Post by p75213 »

Fred wrote: Mon Oct 14, 2019 1:07 am
p75213 wrote: Sun Oct 13, 2019 6:04 pm I wonder why there´s no resveratrol in the cocktail though to indirectly replenish NAD+ levels via enzymatic activation of NMNAT-1:

"Resveratrol is a polyphenol with major health benefits that is thought to operate through direct activation of the “antiaging” enzyme SIRT1. However, recent reports have challenged this “direct activation” hypothesis, suggesting that the mechanism by which resveratrol increases SIRT1 function is still unknown (39, 86).

Previous work from our group has shown for the first time that resveratrol induces a dose-dependent increase in NMNAT-1 activity. As SIRT1 requires NAD+ as a substrate to perform its gene silencing function, higher NAD+ levels will enhance SIRT1 activity.

This finding suggests that resveratrol may promote SIRT1 function by enhancing NAD+ synthesis in whole cell systems without requiring direct activation. Our observation that resveratrol increases NAD+ levels in primary human brain cells by acting on NMNAT, together with the neuroprotective effects of green tea polyphenols against QUIN-mediated excitotoxicity (47), supports the view that polyphenols have considerable therapeutic potential, particularly for the treatment of neurodegenerative diseases.

As NMNAT can accelerate NAD+ synthesis from all six substrates, QUIN, NR, NMN, NA, NAR, and NAM, NMNAT activation by resveratrol may represent an ideal natural therapeutic to replenish NAD+ levels. Maintenance of higher cellular NAD+ will enhance SIRT1 activity and other NAD+-dependent pathways, impacting positively on cell viability and longevity."

https://www.ncbi.nlm.nih.gov/pmc/articl ... 7084/#s032
Interesting read about resveratrol. Got some on order so I'll be taking that anyhow.
p75213
Posts: 75
Joined: Wed Sep 11, 2019 12:04 am

Re: Roadmap to boosting cellular NAD+ with natural supplements: apigenin, quercetin, leucine etc (NAMPT, PARP1))

Post by p75213 »

Here you go. Someone over at longecity found one of their patents. It's not the final product but they did have resveratrol in this version - NCD201. See page 26.
https://register.epo.org/documentView?n ... 0050327470
Fred

Re: Roadmap to boosting cellular NAD+ with natural supplements: apigenin, quercetin, leucine etc (NAMPT, PARP1))

Post by Fred »

The only thing concerning me by artificially boosting the net amount of NAD by blocking or enhancing enzymes is that the body may have a reason to keep NAD at a certain level and that is why it increases NAD anabolism or methylate and convert the excess into NAM-related metabolites.

By just taking in a surplus of raw materials in the form of NAD precursors we let the body decide on its own how much it wants to convert to NAD or excrete.

I DO believe in the beneficial hormetic effects of low doses of plant fungicides and pesticides and stress-signaling molecules like resveratrol, caffeine, curcumin, salicylates, jasmonic acid, EGCG, fisetin, apigenin and quercetin etc.

But nature has had hundreds of millions of years of product development. Perhaps we should take that into account before we blindly try to change its biochemistry overnight.
p75213
Posts: 75
Joined: Wed Sep 11, 2019 12:04 am

Re: Roadmap to boosting cellular NAD+ with natural supplements: apigenin, quercetin, leucine etc (NAMPT, PARP1))

Post by p75213 »

A further revision of proprietary blend:
1.1 g Propietary Blend
green tea leaf extract (~306 - based on 49% EGCG)
parsley leaf powder (~536)
rutin extract (~250)
black pepper fruit extract (~8)

The recommended max dosage of piperine is between 15 and 20 mg per day. Also Curcumin only has about 5 mg per 1 gram of Curcumin.

The rutin dose is 500 mg taken once or twice daily.

Apparently parsley leaf powder can be safely taken up to 6 grams daily.

I thought the green tea extract was for the quercetin. But after reading this I realised it is for the EGCG.

"Activation of NAD+ synthesis

An alternative approach to boost NAD+ levels is to directly activate NAD+ biosynthetic enzymes, in particular those that catalyze the rate-limiting steps of de novo synthesis and salvage pathways. Several enzymes are currently under investigation. The NAM salvage pathway is the predominant route in mammalian NAD+ biosynthesis (Magni et al., 1999) and NAMPT is the rate-limiting enzyme in the conversion of NAM to NAD+ (Revollo et al., 2007a). Under normal conditions NAMPT activity is sustained to maintain NAD+ homeostasis. NAMPT activity, however, declines with age and is exacerbated by acute lung injury, atherosclerosis, cancer, diabetes, rheumatoid arthritis and sepsis. Increasing systemic NAD+ biosynthesis with small chemical NAMPT activators is considered an attractive therapeutic approach. Several NAMPT activating compounds were apparently identified using a fluorometric NAMPT activity assay, but in that study only the inhibitors were characterized (Zhang et al., 2011). A neuroprotective agent, P7C3, may be a relatively weak NAMPT activator in vitro (Wang et al., 2014) although this result has not yet been replicated. NMNATs are also attractive targets for raising NAD+ in cells because they have dual substrate specificity for NMN and NaMN and contribute to both de novo and salvage pathways (Zhou et al., 2002). The green tea compound epigallocatechin gallate (EGCG) has been reported to activate NMNAT2 by more than 100% and NMNAT3 by 42% at 50 μM, although this needs to be confirmed, as no data was presented in the paper (Berger et al., 2005)."
Fred

Re: Roadmap to boosting cellular NAD+ with natural supplements: apigenin, quercetin, leucine etc (NAMPT, PARP1))

Post by Fred »

The daily dose of the proprietary blend is 2.2 grams (6 capsules), not one serving of 1.1 gram (3 capsules). Of that 2.2 g, no more than 300 mg can be EGCG since Nuchido warns that is the upper daily intake from the supplement.
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