16 replies to this topic

[bluemoon]

Charles Brenner: "NMN is not a uniquely different molecule than NR; it's just wasteful... NMN doesn't really make any sense."

 

If he is correct, why do some say they get much better results with NMN than NR?

 

starts around 14:40

https://www.podcasto...-eva-marie-show

[ledgf]

Brenner is financially connected to Chromadex, therefore backs NR. Sinclair is hoping to get money out of NMN. 
 

Right now, there hasn't been much testing of NMN, which is plenty good reason to avoid it. There are 33 human studies listed in the US clinicaltrials dot gov site for NR, only one for NMN.... and the user base for NR supplements is even more outsize for NR... and with more years of experience as well. 

That doesn't mean research on NMN should stop, but you need to consider the risks for yourself. "A pioneer is a guy with an arrow in his back"

Hopefully in a couple of years we'll actually know where the heck all the NR and NMN go and all the pathways. Maybe they'll be used in combination. 

[bluemoon]

　

Hopefully in a couple of years we'll actually know where the heck all the NR and NMN go and all the pathways. Maybe they'll be used in combination. 

 

David Sinclair has said he at expects to know the results of his larger NMN trial by the end of this year. Wouldn't that be listed as a clinical trial?

[Heisok]

"If he is correct, why do some say they get much better results with NMN than N.R. ? "

 

My impression is that most NMN is taken sublingually, and N.R. orally by capsule. Stephan's experience seems positive for sublingual N.R. I do not mind the salt taste of N.R., but the excipients bother me. If there was available pure N.R., with COA, I would take it sublingually. Currently, I am finally able to take 250 mg of N.R. orally. I take around 250 mg +-  maybe 25 mg of NMN sublingually spread into about 4 doses.

[able]

Dr Brenner makes statements that seem quite a stretch to me, such as continuing to repeat his refrain that NMN must lose the phosphate to enter any cells, when the research in January clearly proved that the Slc12a8 transporter moves NMN intact, without breakdown, directly into cells in small intestine. In fact, it only moves NMN  (not NR) 

 

He also says quite emphatically that  NAD+ cannot cross the cell membrane.  But there have been several studies showing NAD+ crosses the cell membrane to hypothalamus, among other organs

 

The study he is most excited about in that podcast seems  to say that NAD+ has no problem moving between cells.

 

He says NR increases NAD+ in the blood, which then increases NAD in mammary by 10x, and increases NAD+ in the mothers milk to benefit her pups.

 

That sounds to me like NAD+ is not "stuck" in the blood and has no problem making it to other tissues such as mammary.

 

I don't understand the science and maybe there is some loophole that allows him to make such statements that don't really seem true. The guys at ABN just posted a review of that podcast that points these things out much better than I can.

 

 

But I would agree with Heisok, that the reports of people getting better results with NMN are due to sublingual use.  Sublingual NR might be even better, once they get it out.  I couldn't handle the saltiness when opening capsules.

Edited by able, 28 March 2019 - 10:48 PM.

[Phoebus]

NAD+ crosses the BBB, no idea why this man suggests otherwise. Hard to take some of the crap he says seriously. 

 

 

 

Conclusions: Exogenous NAD is effectively transported to the hypothalamus via a connexin 43-dependent mechanism and increases hypothalamic NAD content. Therefore, NAD supplementation is a potential therapeutic method for metabolic disorders characterized by hypothalamic NAD depletion.

https://www.ncbi.nlm...ic-connexin-43/

[able]

NAD+ crosses the BBB, no idea why this man suggests otherwise. Hard to take some of the crap he says seriously. 

 

https://www.ncbi.nlm...ic-connexin-43/

 

True, but sometimes I feel a bit sorry for him.  Dr Sinclair is very eloquent when he  goes on with Peter Attia, Joe Rogan, and such.  Besides the obvious advantage Sinclair has in appearance, it just doesn't come natural for Dr Brenner.  

 

For instance,   NR was a known molecule for at least a decade before 2004, when he  discovered that NR can take an alternate pathway using NRK1 to NAD+.  

 

He sometimes says something like he "discovered NR as a vitamin precursor to NAD+".   Sometimes he will shorten it to say he simply discovered NR, which isn't true at all, but sounds a lot better.

 

I think he takes the same shortcut when describing some of the science, to try and simplify it.

 

When I'm feeling charitable, I think he is trying to speak in better soundbites to compete with Sinclair, but isn't really accurate when he does so.  Other times, I feel he is just so emotionally invested in NR, that his bias is overwhelming and he loses the objectivity a scientist should have.

[ledgf]

David Sinclair has said he at expects to know the results of his larger NMN trial by the end of this year. Wouldn't that be listed as a clinical trial?
 

I know what Sinclair said. But look for yourself. only one NMN trial listed (the second one is an NR trial):
 

https://clinicaltria...te=&city=&dist=
 

...and then when you search on NR, there are 33. (Maybe one of these is really an NMN trial? clinicaltrials dot gov IS dot gov, after all...)
 

https://clinicaltria...te=&city=&dist=

[bluemoon]

I know what Sinclair said. But look for yourself. only one NMN trial listed (the second one is an NR trial):
 

https://clinicaltria...te=&city=&dist=
 

 

But Sinclair seems to have tested the safety of NMN on some patients at a hospital in Boston in early 2017 and that isn't listed at clincaltrials.gov that I can see. Now he says he hopes to have other results by the end of this year.

[bluemoon]

 

Hopefully in a couple of years we'll actually know where the heck all the NR and NMN go and all the pathways. Maybe they'll be used in combination. 

 

In early 2014, Lenny Guarente said in an interview that you would take either NR or NMN. Since both raise NAD+ levels, I don't see why one would be "better" although one may be more efficient. Brenner is saying NR is more efficient, but I'm not sure. The price is also obviously a factor. 

[ledgf]

We may end up taking a mixture of both eventually. Right now, NR has been MUCH more thoroughly tested, so I won't be a NMN guinea pig until there's more data on NMN (and more hardy pioneers with multi-year survival records). 

Guarante: actual scientific fraud, PhotoShopping gels (badly... not even bothering to make the lanes look right side up). 

Sinclair: massive failure and confirmation bias in resveratrol. $720 million biotech dollars down the drain, and many careers. 

Brenner: biased toward NR, probably doesn't have all the pathways right yet (no one does). NR is a smaller molecule, so might be more "efficient" per weight, but who cares.

It's still biplane days in the NAD+ field, but at least we actually have some trials going. 

>Sinclair seems to have tested the safety of NMN on some patients at a hospital in Boston in early 2017 and that isn't listed at clincaltrials.gov that I can see.

Wish more people would use PLOS so we could actually see some data before it was obsolete. And I wish that more people would learn the Klingon proverb about "not fighting in a burning house"... let's get life extension technology first so we have time to think about everything else
 

The FDA/patent system is designed for cartelization of status-fighting upper-class twits, not for helping us. The whole system is a "Bad Project" (kudos to Zheng Lab):
https://www.youtube....h?v=Fl4L4M8m4d0
 

[bluemoon]

Guarante: actual scientific fraud, PhotoShopping gels (badly... not even bothering to make the lanes look right side up).  

 

 

 

It was an error but not considered scientific fraud. And no, many careers were not destroyed because of Sinclair and Sirtuis. 

[able]

Metrobiotech is the Sinclair company testing their NMN combination product, MIB-626.  

 

They have successfully completed MULTIPLE IRB approved Phase 1 trials.  

 

Dr Sinclair has a lot of respect and clout so  they are able to get funding without publishing the Phase 1 results, so may be operating more in stealth mode.    They don't have to put them on clinical trials.gov

 

from their website:

 

 

Metro International Biotech has conducted multiple IRB-approved human safety and bioavailability trials at a prominent Boston hospital, which demonstrated MIB-626 is well tolerated in healthy human volunteer subjects and raises blood levels of NAD+ and related metabolites.

 

 

 

 Clearly, they had positive results.  Dr Brenner knows that, so he is not being honest when he says there have been no Human studies with NMN.

 

They are planning Phase 2 trials this year, and  also plan to file for IND for 2 different diseases, which would jump them ahead of Chromadex, who cancelled their IND plans.

 

 

Dr Sinclair has said it is likely both will have things they are good at and we might very well take a combination.  

 

I believe he is the most "plugged in" to all the science going on.  Also  probably more objective than Guarante and Brenner, as he doesn't have all his eggs in one basket.  Of course he favors NMN, but is financially secure already and is involved in dozens of wide ranging anti-aging venture.

 

Edited by able, 29 March 2019 - 02:33 PM.

[bluemoon]

Metrobiotech is the Sinclair company testing their NMN combination product, MIB-626.  

 

They have successfully completed MULTIPLE IRB approved Phase 1 trials.  

 

Dr Sinclair has a lot of respect and clout so  they are able to get funding without publishing the Phase 1 results, so may be operating more in stealth mode.    They don't have to put them on clinical trials.gov

 

Dr Sinclair has said it is likely both will have things they are good at and we might very well take a combination.  

 

I believe he is the most "plugged in" to all the science going on.  Also  probably more objective than Guarante and Brenner, as he doesn't have all his eggs in one basket.  Of course he favors NMN, but is financially secure already and is involved in dozens of wide ranging anti-aging venture.

 

Many biologists dislike Sinclair and there has not been "a lot" of respect for him. I didn't realize that funding was tied to being on the clinicaltrials.gov site.

 

I don't understand how NR and NMN can have separate good effects when both raise NAD+. I wish Sinclair would at least attempt to explain why.

 

This is a minor point, but lately Sinclair has been touting NMN as potentially helpful for people who go through scanners at airports. First, scanners that emit ionized radiation are rare but even those that exist emit at such a low level that they are completely harmless. Either Sinclair knows this and thinks he knows more than thousands of health physicists around the world who would disagree with him, or he won't bother to look up the science.

[LawrenceW]

This is a minor point, but lately Sinclair has been touting NMN as potentially helpful for people who go through scanners at airports. First, scanners that emit ionized radiation are rare but even those that exist emit at such a low level that they are completely harmless. Either Sinclair knows this and thinks he knows more than thousands of health physicists around the world who would disagree with him, or he won't bother to look up the science.

 

Probably has something to do with:

 

https://www.worldhea...dna-damage-nmn/

[Phoebus]

Being skeptical about Sinclair is a perfectly reasonable position to take given the following 

 

 

Studies from Sinclair's lab and others have linked SIRT1 activation to prolonging life spans and protecting organisms in lab experiments against diseases of aging. Based on his early research, he co-founded Cambridge, MA-based Sirtris Pharmaceuticals, which GlaxoSmithKline ($GSK) bought in 2008 for $720 million. And anyone who has followed the Sirtris saga since then knows that Sinclair's early resveratrol findings have been called into question in studies from outside labs that couldn't replicate his tantalizing results.

For instance, Pfizer ($PFE) scientists rained on the Sirtris party, concluding that resveratrol and other compounds from the biotech did not directly activate SIRT1, according to a 2010 paper in the Journal of Biological Chemistry. They also contended that SRT1720, a Sirtris compound, didn't perform as advertised in mice on a high-fat diet. 

https://www.fiercebi...eratrol-critics

 and then 

 

 

[Updated 2:25 pm ET, 3/13/13] GlaxoSmithKline is closing down Cambridge, MA-based Sirtris Pharmaceuticals, almost five years after it paid $720 millionto acquire the hot biotech with a plan to fight diseases of aging.

London-based Glaxo (NYSE: GSK) is shutting the Cambridge, MA Sirtris facility, and plans to offer transfers to the Philadelphia area for some of the 60 remaining Sirtris employees, according to news first reported today by FierceBiotech. Glaxo plans to review staff in coming weeks and decide who will get the opportunity to transfer, GlaxoSmithKline spokeswoman Melinda Stubbee says. Aside from the Sirtris operation, GSK still has staff in Waltham, MA and a few others in Cambridge, Stubbee tells Xconomy.

Glaxo paid $720 million to acquire Sirtris in April 2008, to get ahold of technology that generated lots of breathless media coverage as a modern-day fountain of youth. The company sought to make drugs that act on sirtuins, a class of proteins that scientists believe play a role in aging, programmed cell death, and other key cell processes.

 

 

so yeah, nothing wrong with skepticism in this instance with his track record 

 

also does not sound like anyone's career was 'destroyed' 

[bluemoon]

Probably has something to do with:

 

https://www.worldhea...dna-damage-nmn/

 

The radiation an astronaut receives is *way*larger than what a person gets walking through a scanner. People living in Denver get 5 times as much radiation and there is no cancer risk. If Sinclair keeps talking about NMN protecting against scanners, physicists will eventually call him on it.