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Paper: Therapeutic Evidence of NAD boosting molecules:In Vivo Evidence by Sinclair et al.

nad in vivo

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#1 malbecman

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Posted 12 March 2018 - 06:39 PM


 
Looks to be a pretty thorough review paper, lots of good figures and details.
 
 
Cell Metab. 2018 Mar 6;27(3):529-547. doi: 10.1016/j.cmet.2018.02.011.
Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence.
Abstract

Nicotinamide adenine dinucleotide (NAD), the cell's hydrogen carrier for redox enzymes, is well known for its role in redox reactions. More recently, it has emerged as a signaling molecule. By modulating NAD+-sensing enzymes, NAD+ controls hundreds of key processes from energy metabolism to cell survival, rising and falling depending on food intake, exercise, and the time of day. NAD+ levels steadily decline with age, resulting in altered metabolism and increased disease susceptibility. Restoration of NAD+ levels in old or diseased animals can promote health and extend lifespan, prompting a search for safe and efficacious NAD-boosting molecules that hold the promise of increasing the body's resilience, not just to one disease, but to many, thereby extending healthy human lifespan.

PMID: 29514064  

 

 

https://www.scienced...550413118301220


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#2 Harkijn

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Posted 12 March 2018 - 08:17 PM

Thanks for alerting us, Malbecman!

After a preliminary scan, I thought it important that many posters can read the full text, but the file is bigger than 2 MB. I hope someone else will be able to upload.

Some people will be surprised how balanced and fair Sinclair (and others) discuss NADprecursors.... :)


Edited by Harkijn, 12 March 2018 - 08:21 PM.

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#3 malbecman

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Posted 12 March 2018 - 08:42 PM

Yes, its 2.5MB. Darn.    Is linking to Google drive allowed here?



#4 LawrenceW

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Posted 12 March 2018 - 09:24 PM

Yes, its 2.5MB. Darn.    Is linking to Google drive allowed here?

 

Can you break it into 2 files?  



#5 able

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Posted 12 March 2018 - 09:52 PM

You can access it on http://sci-hub.tw

 

Search for the PMID # (29514064) not the title.


Edited by able, 12 March 2018 - 10:12 PM.


#6 LawrenceW

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Posted 12 March 2018 - 11:00 PM

"Whether or not NMN is taken up by a transporter is currently the subject of debate (Mills et al., 2016; Ratajczak et al., 2016). Brenner, Canto´ and colleagues argue that NMN is not taken up quickly enough to invoke the presence of a transporter and that both NAD+ and NMN undergo extracellular degradation to generate permeable precursors that can be taken up by cells (Ratajczak et al., 2016). On the other hand, Imai argues that this is likely a cell-type-specific phenomenon and that some cell types can rapidly take up NMN (Mills et al., 2016). If so, the identification of the putative transporter will help resolve the debate and help identify which cell types and tissues are able to transport NMN across the plasma membrane. Additional studies with isotopically labeled NAD+ precursors to trace the uptake and metabolism of these molecules should help answer these questions."


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#7 ledgf

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Posted 13 March 2018 - 02:53 PM

Thanks for finding this! Of course there is already a Phase 2 human study on NR... but some @#$! journal is sitting on it. The Chromadex management keeps saying that it is going to be published "imminently". 

Academic publishing is still slowing down biology by an average of ten months...


Thanks for the sci-hub link, too... I had an old one but apparently the US figured out how to block it. 



#8 hav

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Posted 15 March 2018 - 12:36 AM

Part of the paper I found most interesting was the "Human Trials" section that includes research in progress:

 

NAD+ boosters have shown efficacy in a variety of mouse models of human disease (Figure 4), prompting numerous clinical trials of NAD+ boosters in humans (Table 1). The most studied of the NAD+ precursors in humans is NA (niacin). In large doses, greater than a gram, NA is an effective way to treat hypercholesterolemia, as it lowers LDL and is one of the few drugs that significantly raises HDL (Altschul et al., 1955; Garg et al., 2017; Rivin, 1962). It is commercially available either as compressed NA (Niacor) or extended-release to prevent the flushing caused by prostaglandin release (Niaspan, Advicor, Simcor). Niaspan was first approved for several indications by the FDA in 1997 and later used in combination with statins for the treatment of primary hyperlipidemia and mixed dyslipidemia. NA and NAM have been or are currently being evaluated for other health benefits, including treatments for acne, kidney diseases, lupus, AD, schizophrenia, diabetes mellitus, non-small-cell lung carcinoma, obesity, HIV-induced dyslipidemia, NAFLD, sickle cell disease, and others. Though NA has been shown to raise NAD+ levels in rodents (Canto´ et al., 2012; Santidrian et al., 2013), the possibility that NA improves cholesterol profiles in humans, at least in part by raising NAD+ levels (Gariani et al., 2016), is generally not discussed in the literature.

 

In rodents, NAD+ boosters such as NR and NMN appear to raise NAD+ to greater levels than NA and NAM, though no head-to-head study has yet been performed. NR is currently sold by companies such as Elysium Health and HPN as a supplement, either alone or in combination with methylated resveratrol, that typically contains ‘‘Niagen’’. Research into the effects of NR and NMN in humans is gaining considerable traction, with a number of registered clinical trials being recently completed or currently underway (see Clinicaltrials. gov). For example, a randomized, double-blind, three-arm crossover pharmacokinetic study in 12 human subjects showed that NR raises NAD+ by as much as 2.7-fold in human blood with a single oral dose of 1,000 mg, with NAAD emerging as a sensitive biomarker (Trammell et al., 2016a). Researchers at the University of Washington completed a clinical trial with 140 participants showing that orally administered NR gives a dose-dependent increase in NAD+ from 250 to 1,000 mg/day, plateauing at a 2-fold increase in NAD+ at day 9 (Airhart et al., 2017). Another study reported positive effects of NR on vascular endothelial function in healthy middle-aged and older adults, with further investigations of motor and cognitive changes to come (Heilbronn, 2017). At least seven other studies are now underway assessing the effects of NR on such parameters as muscle mitochondrial function, cognition, immune function, kidney function, TBI, brown fat activity, lipid accumulation, energy metabolism, cardiovascular risk, body composition, and acetylcarnitine levels.

 

An international collaborative team between Keio University in Tokyo and Washington University School of Medicine in St. Louis is running a phase I human clinical study of NMN in Japan (Tsubota, 2016). Clinical trials examining the safety and efficacy of NMN are also currently being run at Washington University, investigating the effect on insulin senstivity, endothelial function, lipids, body and liver fat, and markers of cardiovascular and metabolic health. MetroBiotech, a Boston-based company, has generated a pipeline of novel NAD+ precursors, the first of which, MIB-626, is being tested in clinical trials in Boston. Calico has a program to develop NAMPT activators, but the program is on hold. Luteolin, a CD38 inhibitor, had positive neuroprotective effects on children with autism, but whether NAD+ is responsible for the benefit was not investigated (Tsilioni et al., 2015). SARM1, a promising therapeutic target for axonopathies (Essuman et al., 2017) is in preclinical development at Disarm Therapeutics.

 

PARP1/2 inhibitors improve the health of mice on a HFD (Cerutti et al., 2014). Although their toxicity may preclude them from use in chronic diseases, there are others with fewer side effects in development (Malyuchenko et al., 2015).

 

Howard


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#9 Michael

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Posted 21 March 2018 - 08:08 PM

Thanks for alerting us, Malbecman!
After a preliminary scan, I thought it important that many posters can read the full text, but the file is bigger than 2 MB. I hope someone else will be able to upload.
Some people will be surprised how balanced and fair Sinclair (and others) discuss NADprecursors.... :)

 

Harkijn, as a Member, you can upload this paper to the Resource Sharing section for other Members; this particular Member would appreciate it if you did so ;) .

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#10 Harkijn

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Posted 21 March 2018 - 10:04 PM

 

Thanks for alerting us, Malbecman!
After a preliminary scan, I thought it important that many posters can read the full text, but the file is bigger than 2 MB. I hope someone else will be able to upload.
Some people will be surprised how balanced and fair Sinclair (and others) discuss NADprecursors.... :)

 

Harkijn, as a Member, you can upload this paper to the Resource Sharing section for other Members; this particular Member would appreciate it if you did so ;) .

 

Tried my best Michael, but all options there , too,  refuse anything bigger than 2MB :sad:







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