LONGECITY

Highlights

• •Highly potent and specific CD38 inhibitor, 78c, prevents age-related NAD⁺ decline
• •Treatment of old mice with 78c improved physiological and metabolic parameters
• •Inhibition of CD38 promotes an increase in NAD⁺ and its precursors in tissue
• •78c is a novel NAD⁺-boosting therapy to prevent age-related NAD⁺ decline

 

https://www.cell.com...4131(18)30194-3

Apigenin does the same thing but then again it isn't patentable. I'd be wary about a "potent" CD38 inhibitor though the mouse results were certainly promising, if you care about aging mice. CD38 is important so what I'm basically saying is you wouldn't want to inhibit it below the levels of a 25 year old.

..."in mice"

 

Also...what Nate said.

Apigenin does the same thing but then again it isn't patentable.

 

Apigenin was shown to partially normalize the excessive CD38 in young (20-week-old), high-fat-fed obese, likely diabetic mice (PMID 23172919), and the dose  was 100 mg/kg by intraperitoneal injection, which is not the ideal test for an orally-administered compound, particularly if it's a phenolic compound and particularly if it's a phenolic compound being administered to a mouse (since rodents metabolize many phenolics very heavily). We have no peer-reviewed data showing it lowers CD38 in otherwise normal aging mammals (unless maybe it was used as a positive control in the new paper, which I haven't read) — let alone that it does so after oral administration and to metabolic benefit.

Apigenin was shown to partially normalize the excessive CD38 in young (20-week-old), high-fat-fed obese, likely diabetic mice (PMID 23172919), and the dose  was 100 mg/kg by intraperitoneal injection, which is not the ideal test for an orally-administered compound, particularly if it's a phenolic compound and particularly if it's a phenolic compound being administered to a mouse (since rodents metabolize many phenolics very heavily). We have no peer-reviewed data showing it lowers CD38 in otherwise normal aging mammals (unless maybe it was used as a positive control in the new paper, which I haven't read) — let alone that it does so after oral administration and to metabolic benefit.

 

Well this is a bit of a wet blanket. 

 

What is the significance of it being phenolic?

 

Also I read that resveratrol can enhance the bioavailability of apigenin. Then again, I think these mice were also injected, I read through the full text and can't be sure.

 

I give up, unless there's a human study, I'm not even bothering with anything. Mice are such a waste of time except where toxicity studies are concerned, then again even that may not translate well.

Edited by Nate-2004, 04 May 2018 - 01:22 PM.

What is the significance of it being phenolic?

Most phenolics are extensively metabolized iinto unabsorbable and/or biologically inactive metabolites in the intestines and liver. Depending on how much they are subject to enterohepatic circulation, i.p. injection can artificially inflate bioactivity  by bypassing such metabolism (more enterohepatic ciculation implies a more realistic reflection of oral dosing). We only discovered relatively late that curcumin is probably not subject to much enterohepatic circulation, contrary to exectations based on its lipophilicity, which helps explain its miserably low oral bioavailabilty (particularly for the free/parent compound). And rodents (mice and possibly even more so rats) metabolize phenolics less than humans, even after accounting for biometric scaling.
 

I give up, unless there's a human study, I'm not even bothering with anything. Mice are such a waste of time except where toxicity studies are concerned, then again even that may not translate well.

I think that's taking it too far in the other direction — but certainly, you want a study that reflects the actual use case (for most of us, basically healthy except for aging) and that isn't specifically known to have a translation problem (phenolics) unless there's some specific reason to expect translation anyway.

 

Does anyone have a copy of this new paper (especially the extended version) they could PM me (or if it's too big, send me via email, which I'll communicate via PM)?

Most phenolics are extensively metabolized iinto unabsorbable and/or biologically inactive metabolites in the intestines and liver. Depending on how much they are subject to enterohepatic circulation, i.p. injection can artificially inflate bioactivity  by bypassing such metabolism (more enterohepatic ciculation implies a more realistic reflection of oral dosing). We only discovered relatively late that curcumin is probably not subject to much enterohepatic circulation, contrary to exectations based on its lipophilicity, which helps explain its miserably low oral bioavailabilty (particularly for the free/parent compound). And rodents (mice and possibly even more so rats) metabolize phenolics less than humans, even after accounting for biometric scaling.

 

Hi Michael, its off-topic so sorry about that but I am recommending curcumin to a person in my close circle for arthritis relief. In the study you linked it talks about:

"Firstly, we orally administered highly bioavailable curcumin to rats to elucidate its kinetics, and observed not only the free-form of curcumin, but also, curcumin in a conjugated form, within the portal vein"

 

Would you know what highly bioavailable curcumin they refer to or have a recommendation? Your view would be greatly appreciated.
 

Hi Michael, its off-topic so sorry about that but I am recommending curcumin to a person in my close circle for arthritis relief. In the study you linked it talks about:

"Firstly, we orally administered highly bioavailable curcumin to rats to elucidate its kinetics, and observed not only the free-form of curcumin, but also, curcumin in a conjugated form, within the portal vein"

 

Would you know what highly bioavailable curcumin they refer to or have a recommendation? Your view would be greatly appreciated.
 

 

Also to Michael:

 

Doesn't BioPerine not take care of the bioavailability problem with Curcumin?

We just completed an Apigenin pilot study on 19 elderly subjects. Nine of the patients had already undergone various NAD+ therapies over the past year and had been taking NR for more than half a year. The other ten hadn't taken any NAD+ or precursors before now. All subjects took placebo pills for one week prior to beginning the Apigenin at 300 mg/day (product obtained from Swanson). The blood samples we obtained will be analyzed in about a month. This was an arm of an IRB-approved NAD+ study. Over the past 16 months we've tested IV infusions, iontophoresis patches, I.M. and Subq injections, NR, and now Apigenin. Most of this work has been written up and submitted to journals for publication. I'm happy to report back, when the Apigenin results come in.

James

www.betterhumans.org/projects.html

CD38 is crucial for health.

https://www.ncbi.nlm...pubmed/29603313

I've learned by now you have to try the latest purportedly beneficial regimen, while it still works.

 

resveratrol? check.

Dasatinib plus quercetin?  check.

Methylene blue? check.

C60 olive oil? check.

rapamycin? check.

 

Nolo bene, this is not an exhaustive list. 

Nolo bene

Panis et Circenses!

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Human Biology!

I give up, unless there's a human study, I'm not even bothering with anything. Mice are such a waste of time except where toxicity studies are concerned, then again even that may not translate well.

For me it's an ongoing, long educational drama of wrapping my head around reasons for non-human animal studies in relation to LE; but I'm chipping away. See if this helps chip at it: https://www.ncbi.nlm...les/PMC4875775/

"...Despite all of the documented differences between mice and humans, and despite the history of “errors in translation” in the application of research on mice to humans, reports of research on mice are frequently accompanied by unwarranted and misleading claims, such as “Furthering our understanding of mouse X should provide novel insights into human Y.” Such claims raise false hopes and are ultimately self-defeating, in that they waste resources and increase public skepticism concerning the value of biomedical research. Indeed, the problems of translating research on mice and other model organisms to humans have led a number of scientists to question the value of this research..."

CD38 is crucial for health.

https://www.ncbi.nlm...pubmed/29603313

 

Well, true enough.

 

Nate made exactly that point in the second post of this thread.
 

Sedative effects of chamomile tea attributed to apigenin (it binds to benzodiazepine receptors in the brain) and as we experience it from a tea it should be pretty bioavailable orally.

Escande`s study also measured its effects on CD38 not only in vivo but also in human cell culture. 

To me its quite a compelling argument to count apigenin as CD38 inhibitor at least until new research come up.

 

 

Sedative effects of chamomile tea attributed to apigenin (it binds to benzodiazepine receptors in the brain) and as we experience it from a tea it should be pretty bioavailable orally.
Escande`s study also measured its effects on CD38 not only in vivo but also in human cell culture.
To me its quite a compelling argument to count apigenin as CD38 inhibitor at least until new research come up.

You can consider all anti inflammatory compounds as CD38 inhibitor since inflammation drives CD38 expression. So reducing inflammation is the correct target rather than brute force inhibition of all CD38.

We just completed an Apigenin pilot study on 19 elderly subjects. Nine of the patients had already undergone various NAD+ therapies over the past year and had been taking NR for more than half a year. The other ten hadn't taken any NAD+ or precursors before now. All subjects took placebo pills for one week prior to beginning the Apigenin at 300 mg/day (product obtained from Swanson). The blood samples we obtained will be analyzed in about a month. This was an arm of an IRB-approved NAD+ study. Over the past 16 months we've tested IV infusions, iontophoresis patches, I.M. and Subq injections, NR, and now Apigenin. Most of this work has been written up and submitted to journals for publication. I'm happy to report back, when the Apigenin results come in.

James

www.betterhumans.org/projects.html

 

 

I still don't see anything on this on the website and it's been more than a year.  Would love to know since NAD+ precursor cost almost makes dying a palatable option.

Although they didn't measure NAD+, apigenin increases muscle mass in both young and old mice: