2255 replies to this topic

[albedo]

Metabolic control of muscle and muscle stem cell function

http://memento.epfl....le-stem-cell-2/

[Bryan_S]

Reductive carboxylation is a major metabolic pathway in the retinal pigment epithelium

http://www.pnas.org/...572113.abstract

 

'NAD+ declines with age (47, 51), and supplementation with NAD precursors can delay aging, liver disease, and vascular dysfunction (52–54). NAD+ precursors, such as nicotinamide riboside, can be used safely in humans (55, 56). In the absence of animal models for AMD, our findings highlight the need for clinical trials that evaluate NAD+ precursors for their ability to prevent and treat AMD."

 

Significance

In the vertebrate eye, a monolayer of cells, called the retinal pigment epithelium (RPE), is between the choroidal blood supply and the retina. The RPE provides metabolic support for the retina, including delivery of glucose and other nutrients. Here, we show that reductive carboxylation of α-ketoglutarate, a type of metabolism that supports growth and survival of cancer cells, is a prominent feature of RPE cells. We show that extreme oxidative stress can overwhelm the reductive carboxylation pathway. However, we also found that the RPE can be protected from extreme oxidative stress by supplementation with an NAD+ precursor or α-ketoglutarate.

 

Abstract

The retinal pigment epithelium (RPE) is a monolayer of pigmented cells that requires an active metabolism to maintain outer retinal homeostasis and compensate for oxidative stress. Using 13C metabolic flux analysis in human RPE cells, we found that RPE has an exceptionally high capacity for reductive carboxylation, a metabolic pathway that has recently garnered significant interest because of its role in cancer cell survival. The capacity for reductive carboxylation in RPE exceeds that of all other cells tested, including retina, neural tissue, glial cells, and a cancer cell line. Loss of reductive carboxylation disrupts redox balance and increases RPE sensitivity to oxidative damage, suggesting that deficiencies of reductive carboxylation may contribute to RPE cell death. Supporting reductive carboxylation by supplementation with an NAD+ precursor or its substrate α-ketoglutarate or treatment with a poly(ADP ribose) polymerase inhibitor protects reductive carboxylation and RPE viability from excessive oxidative stress. The ability of these treatments to rescue RPE could be the basis for an effective strategy to treat blinding diseases caused by RPE dysfunction.

 

[midas]

I pointed this out a week or two ago......Keep in mind that the majority of cancers in later life and NAD declines with age. So, if NAD was such a big deal when it comes to cancer wouldn't that mean we were more susceptible to cancers when our NAD pool was full rather than when its running low.

[Daniel Cooper]

So at this point the summary seems to be that higher NAD+ levels are unlikely to cause you to develop cancer and in fact my offer some protection against the formation of cancerous cells, but once you actually get cancer higher NAD+ levels may cause come cancers to become more aggressive (e.g. glioblastoma) but may have the opposite effect on others (e.g. breast cancer).

 

If so, it this makes determining what to do with regards to NR supplementation very murky indeed.  None of us has a crystal ball to see what types of cancer we will ultimately develop.  I have suspended my NR supplementation for other reasons but have intended to restart it in a few months.  Now I'm not so sure.  This would seem to merit more study and some caution.  I can certainly say that if I had relatives that developed glioblastoma I would be very reluctant to supplement with NR at this time, but even that position has it's difficulty as glioblastoma is not currently thought to be strongly tied to heredity.

 

 

[Daniel Cooper]

So let's take the assumption I made above, i.e. that increased levels of NAD+ don't generally cause cancer, but they can fuel some cancers once they develop, glioblastoma in particular.

 

That assumption would probably lead you predict that children (which have higher NAD+ levels) which develop glioblastoma would have a worse prognosis than those that develop glioblastoma at middle age or later.

 

However, that doesn't seem to be the case.  

 

Long-term outcomes in children with glioblastoma     https://www.ncbi.nlm...pubmed/20672935

 

Of course, we're trying to look a single variable here in isolation, which we can't do.  Perhaps a child's immune system is a bit more successful at fighting glioblastoma than someone in middle age.  Or it could be one of any numbers of other differences in a child versus an adult that overcome to some extent the tendency for higher levels of NAD+ to fuel glioblastoma.

 

 

 

 

[Harkijn]

Valid points Midas and Daniel, though I am not totally reassured yet. Meanwhile I am happy that this press release just reached me.

 

 https://www.elysiumh...l-press-release

[Daniel Cooper]

Valid points Midas and Daniel, though I am not totally reassured yet. Meanwhile I am happy that this press release just reached me.

 

 https://www.elysiumh...l-press-release

 

 

Oh believe me, I am by no means reassured.  In fact I have to be careful in my evaluation of this given how badly I don't want this to be a problem with NR.  At this point all I see is murkiness, and the study on glioblastoma in children vs adults is by no means any sort of definitive answer.  It's really only an indication of how inadequate our knowledge is on NR vs. cancer promotion.

 

 

What we really need is a mouse model for glioblastoma (does one exist?) and then feed a control and study group NR and see what happens.

 

 

Edited by Daniel Cooper, 07 December 2016 - 04:35 PM.

[Thell]

Valid points Midas and Daniel, though I am not totally reassured yet. Meanwhile I am happy that this press release just reached me.

 

 https://www.elysiumh...l-press-release

 

We've been waiting to hear some results information (let alone the study publication) so this is indeed a happy occasion.

 

A quote to those involved in the 'max' NAD+ level discussion a few pages back...

 

 

The study, which was placebo-controlled, randomized, and double-blinded, evaluated the safety and efficacy of BASIS™ [nicotinamide riboside (NR) and pterostilbene] in 120 healthy participants ages 60-80 over an eight-week period. Participants received either the recommended dose (250 mg NR and 50 mg pterostilbene), double the recommended dose or a placebo daily for the eight-week trial.

The study found that participants experienced no serious adverse events and confirmed that BASIS™ is safe for daily use as determined by standard safety measures. The study also showed that in participants taking the recommended dose of BASIS, ™ NAD+ levels increased from baseline in whole blood by an average of 40% at four weeks and maintained that increase for the duration of the trial. Participants taking double the recommended daily dose saw their NAD+ levels increase approximately 90% at four weeks, and a significantly higher level of NAD+ (compared to the recommended dose of BASIS™) was maintained for the duration of the trial. This first-in-humans study demonstrates clearly that BASIS™ can increase NAD+ levels in the blood safely and sustainably. Confirming that BASIS™ is an effective NAD+ precursor in humans is a vital first step to elucidating how BASIS™ supports human health.

 

Can't wait to read the study!

Edited by Thell, 07 December 2016 - 04:43 PM.

[bluemoon]

 

Can't wait to read the study!

 

 

But how long for the wait? Late next year, right?

[Anthony_Loera]

 

Valid points Midas and Daniel, though I am not totally reassured yet. Meanwhile I am happy that this press release just reached me.

 

 https://www.elysiumh...l-press-release

 

We've been waiting to hear some results information (let alone the study publication) so this is indeed a happy occasion.

 

A quote to those involved in the 'max' NAD+ level discussion a few pages back...

 

 

The study, which was placebo-controlled, randomized, and double-blinded, evaluated the safety and efficacy of BASIS™ [nicotinamide riboside (NR) and pterostilbene] in 120 healthy participants ages 60-80 over an eight-week period. Participants received either the recommended dose (250 mg NR and 50 mg pterostilbene), double the recommended dose or a placebo daily for the eight-week trial.

The study found that participants experienced no serious adverse events and confirmed that BASIS™ is safe for daily use as determined by standard safety measures. The study also showed that in participants taking the recommended dose of BASIS, ™ NAD+ levels increased from baseline in whole blood by an average of 40% at four weeks and maintained that increase for the duration of the trial. Participants taking double the recommended daily dose saw their NAD+ levels increase approximately 90% at four weeks, and a significantly higher level of NAD+ (compared to the recommended dose of BASIS™) was maintained for the duration of the trial. This first-in-humans study demonstrates clearly that BASIS™ can increase NAD+ levels in the blood safely and sustainably. Confirming that BASIS™ is an effective NAD+ precursor in humans is a vital first step to elucidating how BASIS™ supports human health.

 

Can't wait to read the study!

 

 

Well this is some good news Thell,

 

Thanks for sharing.

A

[bluemoon]

Ten years ago David Sinclair said that he thought there would be a pharmaceutical drug that would cost about $3 a day that would boost surtuins and lower the risk of some major diseases. If one takes the double dosage of Elysium Basis at 500 mg of NR and 100 mg of pterostiline for the 90% boost of NAD+, that is about what it costs with a subscription: $3.33 a day. 

Edited by bluemoon, 07 December 2016 - 05:43 PM.

[Thell]

Pathway linked to slower aging also fuels brain cancer

http://medicalxpress...ging-fuels.html

 

We don't know what this study will reveal since it doesn't seem to be listed anywhere on pnas.org even though the 'press statement' states it was published Dec. 5 in Proceedings of the National Academy of Sciences. The primary author's lab publications list indicates it will be named 'NAMPT controls tumor growth and therapy responsiveness in glioblastoma'.

 

Also, keep in mind that NAMPT is not needed for conversion of NR to NAD+. To me, the interesting aspect of the various studies done regarding NAMPT and cancer/tumors is we know that the vast majority of cancer is recorded in the elderly and NAMPT is shown to decrease with age and yet the correlation seems to indicate the presence of over expression of NAMPT. I'd like to know what leads to an over expression of NAMPT where it should be reduced rather than seeing multiple studies saying that things (PARP, SIRT, COX, CD38, etc...) that prolong cell life also support cancer growth. There's a non-repaired mutation in there somewhere!

 

Given that last statement I find it encouraging to see that Paul Modrich joined the Elysium Health scientific advisory board, as noted in that earlier press release today. He won a 2015 Nobel Prize in Chemistry for work showing how cells monitor and signal for repairing incorrect replications of DNA. Perhaps he is in it for the money but I think not. I think it may be believed that a properly functioning NAD cycle will help keep mutations down.

[Bryan_S]

Valid points Midas and Daniel, though I am not totally reassured yet. Meanwhile I am happy that this press release just reached me.

 

 https://www.elysiumh...l-press-release

 

I just pass this stuff on. I think its better to have NAD levels at more youthful levels for the prevention of cancers but should one develop consult your oncologist.

 

========================================================

 

ELYSIUM HEALTH™ RAISES $20 MILLION IN SERIES B FINANCING LED BY GENERAL CATALYST, ANNOUNCES TOPLINE CLINICAL TRIAL RESULTS FOR ITS FIRST PRODUCT BASIS™, AND WELCOMES LEADING SCIENTISTS AND PHYSICIANS TO ITS SCIENTIFIC ADVISORY BOARD

 

The human clinical trial, evaluating safety and efficacy of BASIS™,met its primary and secondary endpoints

 

NEW YORK (December 6, 2016) – Elysium Health, Inc. ™, a provider of scientifically-sound dietary supplements, today announced it has raised $20 million in Series B financing led by General Catalyst and joined by Breyer Capital, Morningside Ventures and Sound Ventures. Existing investors include Jim Manzi, chairman, Thermo Fisher Scientific Inc. and former chairman, president and CEO of Lotus Development Corp.; biotech venture capitalist Robert Nelsen; and entrepreneur Matthew Mullenweg.

 

The funding will enable Elysium to expand its operations to support the rapid growth of its customer base, as well as initiate additional human clinical trials to evaluate the safety and efficacy of new products it plans to add to its offerings. In addition, the funds will support Elysium’s mission to be a leader in the study of NAD+ and sirtuins within the context of human aging.

 

“Since launching Elysium two years ago, we have worked tirelessly to create entirely new ways to make scientific breakthroughs accessible and actionable for people who want to take a proactive role in supporting their health,” said Eric Marcotulli, CEO and co-founder of Elysium. “Our first product BASIS™ is designed to optimize cellular health and is based on expansive research. We look forward to working with our financial partners and scientific advisory board to further develop our product pipeline to continue to bring meaningful health products to market.”

 

“Elysium is an innovative company, with an amazing executive team and scientific advisory board, committed to reframing the way we think about our health,” said David Fialkow, managing director, General Catalyst. “We are thrilled to invest in Eric and his team to help expand and enhance the scientifically-sound products they intend to bring to the market in the future.”

 

Elysium Announces Topline Clinical Trial Results

Elysium also announced today that its first human clinical trial designed to evaluate the safety and efficacy of its first product, BASIS™, met its primary and secondary endpoints. The study, which was placebo-controlled, randomized, and double-blinded, evaluated the safety and efficacy of BASIS™ [nicotinamide riboside (NR) and pterostilbene] in 120 healthy participants ages 60-80 over an eight-week period. Participants received either the recommended dose (250 mg NR and 50 mg pterostilbene), double the recommended dose or a placebo daily for the eight-week trial.

 

The study found that participants experienced no serious adverse events and confirmed that BASIS™ is safe for daily use as determined by standard safety measures. The study also showed that in participants taking the recommended dose of BASIS, ™ NAD+ levels increased from baseline in whole blood by an average of 40% at four weeks and maintained that increase for the duration of the trial. Participants taking double the recommended daily dose saw their NAD+ levels increase approximately 90% at four weeks, and a significantly higher level of NAD+ (compared to the recommended dose of BASIS™) was maintained for the duration of the trial. This first-in-humans study demonstrates clearly that BASIS™ can increase NAD+ levels in the blood safely and sustainably. Confirming that BASIS™ is an effective NAD+ precursor in humans is a vital first step to elucidating how BASIS™ supports human health.

 

“As we age, NAD+ levels in our cells decline. The trial results, which are the first of their kind, indicate that BASIS™ increases NAD+ levels in a sustained way. And since NAD+ is involved in hundreds of critical cellular processes, it is a vitally important component to optimizing our cellular health as we get older,” said Dr. Lenny Guarente, chief scientific officer and co-founder of Elysium who also serves as the director of the Glenn Laboratory for the Science of Aging at Massachusetts Institute of Technology. “We plan to submit the full results of the trial to a peer-reviewed scientific journal.”

 

Elysium Adds Three World-Renowned Scientists and Physicians to Its Scientific Advisory Board

To support Elysium’s mission of researching, validating and distributing scientifically-sound health products, it established an unprecedented Scientific Advisory Board composed of more than two dozen of the world’s leading scientists and clinicians. This scientific board works with the Elysium team to accelerate the exchange of ideas and research findings, evaluate data and help ensure a high level of scientific rigor and transparency in the development of Elysium’s products.

 

Elysium is honored to welcome to its Scientific Advisory Board:

 

George M. Church, the Robert Winthrop Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and MIT.

Richard Granstein, M.D., Chairman of Dermatology Weill Cornell Medical College.

Paul L. Modrich, James B. Duke Professor of Biochemistry at Duke University and recipient of the Nobel Prize in Chemistry in 2015.

About BASIS™

BASIS™ is a daily product that supports metabolic health. The proprietary formulation of nicotinamide riboside and pterostilbene is designed to increase levels of the coenzyme NAD+ and to support a class of proteins called sirtuins. NAD+ and sirtuins work together in vital cellular processes including energy production. BASIS™ is available to consumers exclusively through the Elysium Health™ website (www.elysiumhealth.com). The cost for BASIS™ is $60 for a 30-day supply or $50 per month on a subscription plan.

About Elysium Health™

Elysium Health’s™ mission is to solve the biggest challenges in health with science, to help people live healthier, longer lives. Working directly with the world’s leading scientists and clinicians, Elysium Health™ translates advances in science and technology into effective, scientifically-sound products that help people manage their health in an actionable way.

 

###

 

Media Contacts:

Victoria E. Davis

Cell: 410-279-3049

Victoria@elysiumhealth.com

 

Pia Chatterjee

Cell: 510-384-0845

Pia@elysiumhealth.com

[Bryan_S]

Replicatively senescent human fibroblasts reveal a distinct intracellular metabolic profile with alterations in NAD+ and nicotinamide metabolism

 

http://www.nature.co...es/srep38489#f4

 

Conclusions

Although the metabolic profile of established PEsen cells is superficially complex there are two conclusions that are consistent with a large amount of the data. Firstly, PEsen cells appear to activate the same mechanisms that delay the initiation of senescence; a shift from oxidative phosphorylation towards glycolysis and the pentose phosphate pathway to reduce the production of ROS23 and an upregulation of pathways involved in redox homeostasis to ameliorate the effects of hydrogen peroxide. Secondly, other alterations such as the maintenance of NAD+ and nicotinamide levels, nucleotide catabolism, membrane breakdown and alterations in creatine metabolism could be interpreted as a strategy the senescent cells adopt to promote cell survival and generate energy and the building blocks for cell growth in the absence of functional mitochondria and oxidative phosphorylation. Our results also suggest caution in the use of supplements such as nicotinamide and antioxidants, as whilst there is evidence that these compounds may delay cellular senescence and age-related diseases, they are unlikely to eliminate existing PEsen cells and may actually aid their survival. Lastly, senescent cells are known to be generally resistant to apoptosis1 and recently targeting apoptotic pathways has achieved some success in selectively eliminating senescent cells and producing ‘senolytic drugs’14,53. Therefore, some of the senescence-specific pro-survival alterations in the metabolic pathways described here may also serve as targets for the future development of such drugs.

[albedo]

Nicotinamide riboside has also an entry in the Geroprotectors.org curated data base and probably additional inputs will be done in future, to keep an eye on. Geroprotectors.org is "...a manually curated online database that provides instant access to all of the above. An up-to-date, rapidly explorable system that catalogues and summarizes over 200 geroprotective compounds and links them to over 250 studies that support (or refute) their effects in model organisms, Geroprotectors is for the entrant or expert in the field alike..." (1).  Type "nicotinamide riboside" in the search engine.

 

(1) Moskalev A, Chernyagina E, De magalhães JP, et al. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease. Aging (Albany NY). 2015;7(9):616-28.

 

[bluemoon]

I just checked and saw Chromadex's stock price is still at a three-year low of $2.34 after the Elysium press release. Interesting. Maybe the Elysium press release wasn't surprising and not that important compared to the next efficacy results coming.

 

Jun  7  $5.49

July 7  $3.81

Aug 7  $4.04 

Sep 7  $2.94

Oct 7   $2.45

Dec 7  $2.34

[Oakman]

I just checked and saw Chromadex's stock price is still at a three-year low of $2.34 after the Elysium press release. Interesting. Maybe the Elysium press release wasn't surprising and not that important compared to the next efficacy results coming.

 

Jun  7  $5.49

July 7  $3.81

Aug 7  $4.04 

Sep 7  $2.94

Oct 7   $2.45

Dec 7  $2.34

 

The market is suspicious of pharma companies' success rate, and rightly so. I would venture 1 out of 1000 investors would have heard of Chromadex. Plus, for those that do, their sales went down last quarter¹. Not much to go on for the average investor, and way too small for most institutions to have significant holdings².  Press releases are not given much heed. 

 

1) "For the three months ended October 1, 2016 (“Q3 2016”), ChromaDex reported net sales of $5.0 million, a decrease of 20% as compared to $6.3 million for the three months ended October 3, 2015 (“Q3 2015”)."

 

https://globenewswir...al-Results.html

 

2) http://www.nasdaq.co...tional-holdings

[bluemoon]

But then you could say the same thing about Chromadex crashing in June after the short-sell report. Apparently there are investors paying attention even if volume is usually low. 

 

I would have guessed a bump up but there are of course many factors involving the price.The fun starts if NMN can be sold at competitive prices to NR or if a pharmaceutical starts to sell a drug by 2018 or 2019 as David Sinclair thought in 2013 that would compete with NR.

 

  

[Thell]

 

Dietary proanthocyanidins boost hepatic NAD+ metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats

http://www.nature.co...es/srep24977#f3

 

rReceived 21 October 2015

Accepted: 08 April 2016

Published online: 22 April 2016

 

Abstract

 

"Proanthocyanidins (PACs) have been reported to modulate multiple targets by simultaneously controlling many pivotal metabolic pathways in the liver. However, the precise mechanism of PAC action on the regulation of the genes that control hepatic metabolism remains to be clarified. Accordingly, we used a metabolomic approach combining both nuclear magnetic resonance and mass spectrometry analysis to evaluate the changes induced by different doses of grape-seed PACs in the liver of healthy rats. Here, we report that PACs significantly increased the hepatic nicotinamide adenine dinucleotide (NAD+) content in a dose-dependent manner by specifically modulating the hepatic concentrations of the major NAD+ precursors as well as the mRNA levels of the genes that encode the enzymes involved in the cellular metabolism of NAD+. Notably, Sirtuin 1 (Sirt1) gene expression was also significantly up-regulated in a dose-response pattern. The increase in both the NAD+ availability and Sirt1 mRNA levels, in turn, resulted in the hepatic activation of SIRT1, which was significantly associated with improved protection against hepatic triglyceride accumulation. Our data clearly indicates that PAC consumption could be a valid tool to enhance hepatic SIRT1 activity through the modulation of NAD+ levels."

 

So Proanthocyanidins might be another route to increasing NAD+.

 

 

It looks like there is now a discussion thread for a grape seed extract product whose extract was used in this study. I'm not sure if it will be an 'open' discussion on the merits and efficacy or a 'sales' thread but I know that I'm definitely interested in another pathway.

[bluemoon]

I've been curious about Elysium's trial compared to Chromadex's trial. Elysium limited the age of participants from 60 to 80 years old while Chromadex's 12 participants were not, right? 

 

250 mg of NR with 50 mg of pterostilbine increased NAD+ in blood by 40%. Chromadex showed 100 mg of NR alone increased NAD+ by 30%.  If both studies used the same ages then it would be reasonable for someone to take just 125 mg of NR (what I take) and no pterostilbine for $0.75 a day to get nearly the same boost as taking Elysium's Basis 250 mg of NR with 50 mg of pterostilbine for $1.70 a day. Yet, the age group isn't the same so...

 

I've wondered ever since Guarente told reporters what he was taking, Basis, along with 250 mg of resveratrol and 2500 IU of vitamin D, if he was taking a double dose of Basis or the dose that his company recommends. To get the 90% increase in NAD+ at $3.30 a day is well beyond what most will pay among those who are willing to try NR in the first place unless the results come back are a health home run, which I doubt - but maybe. 

  

Edited by bluemoon, 09 December 2016 - 05:16 PM.

[Oakman]

I've been curious about Elysium's trial compared to Chromadex's trial. Elysium limited the age of participants from 60 to 80 years old while Chromadex's 12 participants were not, right? 

 

250 mg of NR with 50 mg of pterostilbine increased NAD+ in blood by 40%. Chromadex showed 100 mg of NR alone increased NAD+ by 30%.  If both studies used the same ages then it would be reasonable for someone to take just 125 mg of NR (what I take) and no pterostilbine for $0.75 a day to get nearly the same boost as taking Elysium's Basis 250 mg of NR with 50 mg of pterostilbine for $1.70 a day. Yet, the age group isn't the same so...

 

I've wondered ever since Guarente told reporters what he was taking, Basis, along with 250 mg of resveratrol and 2500 IU of vitamin D, if he was taking a double dose of Basis or the dose that his company recommends. To get the 90% increase in NAD+ at $3.30 a day is well beyond what most will pay among those who are willing to try NR in the first place unless the results come back are a health home run, which I doubt - but maybe. 

 

It is a bit of a problem to try to equalize these different studies to get a consistent picture. As far as cost, right now I take 375mg Niagen w/150mhg Pterostilbene in the morning, then 125mg Niagen in the evening for $1.83/day. You just need to dig a bit for deals, it's still not cheap, but gets more reasonable. 

 

Lower cost gives greater flexibility for adjusting dosing to see what happens. As we're all N=1 studies, as no one really knows (yet) what's most effective at any age...we're all longevity explorers. As always, many more studies are needed, esp. segregated as to age group, IMHO

[mrkosh1]

If we want to go into maximum NAD+ boosting, I think a supplement that was a combination of NR, R-ALA, and ALCAR would give basis a run for its money. When my financial situation improves, this is the stack I want to try. Although it may be irrational, I trust R-ALA and ALCAR more so than anything like resveratrol.

[Oakman]

If we want to go into maximum NAD+ boosting, I think a supplement that was a combination of NR, R-ALA, and ALCAR would give basis a run for its money. When my financial situation improves, this is the stack I want to try. Although it may be irrational, I trust R-ALA and ALCAR more so than anything like resveratrol.

 

If it helps you mrkosh1, with what I mentioned above, I take also (among others):

 

500 mg ALCAR, 150 mg R-ALA, 500 mg trans-Resveratrol

 

Unsure what my NAD+ levels are or if they've changed, trusting they've gone up  . What I can say is that in the week since I upped my dose of NR to 500 mg from 375mg (not changing anything else), I'm absolutely stronger at the gym, wake up earlier and feel more refreshed. Also, I feel the resveratrol is helping a lot since starting it.  It's all good together, and I strongly feel that these compounds are synergistic together.

Edited by Oakman, 09 December 2016 - 06:53 PM.

[bluemoon]

 It's all good together, and I strongly feel that these compounds are synergistic together.

 

 

This is what Lenny Guarente also said in a 2015 interview as well as he takes 250mg of resveratrol and either 50mg or 100mg of  pterostilbine with NR:

 

 I would expect both polyphenols and NAD+ precursors, both of which comprise Elysium’s initial product BASIS, to activate SIRT1.  In this regard, the polyphenol pterostilbene shows promise and may be more bioavailable than resveratrol, meaning the body is more readily able to absorb and utilize the product.  The combination of pterostilbene and NR might be particularly effective by providing sirtuin activation via two different mechanisms.  This is the rationale for BASIS, which contains pure forms of both NR and pterostilbene. 

 

 

I wonder why he also adds the 250 mg of resveratrol.

 

Finally, Elysium could do what Chromadex did and put the results of its 8 week trial up beyond just how much NAD+ is raised in blood since they have known the results for four months. Any idea why they aren't doing this apart from maybe the results are 1) not great at either 250mg NR or 500mg NR or 2) good results for the higher dose but now wonder how they market BASIS at the much higher price.

[Daniel Cooper]

 

 It's all good together, and I strongly feel that these compounds are synergistic together.

 

 

This is what Lenny Guarente also said in a 2015 interview as well as he takes 250mg of resveratrol and either 50mg or 100mg of  pterostilbine with NR:

 

 I would expect both polyphenols and NAD+ precursors, both of which comprise Elysium’s initial product BASIS, to activate SIRT1.  In this regard, the polyphenol pterostilbene shows promise and may be more bioavailable than resveratrol, meaning the body is more readily able to absorb and utilize the product.  The combination of pterostilbene and NR might be particularly effective by providing sirtuin activation via two different mechanisms.  This is the rationale for BASIS, which contains pure forms of both NR and pterostilbene. 

 

 

I wonder why he also adds the 250 mg of resveratrol.

 

Finally, Elysium could do what Chromadex did and put the results of its 8 week trial up beyond just how much NAD+ is raised in blood since they have known the results for four months. Any idea why they aren't doing this apart from maybe the results are 1) not great at either 250mg NR or 500mg NR or 2) good results for the higher dose but now wonder how they market BASIS at the much higher price.

 

 

 

He could just be covering his bases.  There has been a lot more studies on resveratrol.  We *think* that pterostilbene does the same thing only better, but we actually don't have as much concrete evidence for that as we'd like.

[bluemoon]

 

 

He could just be covering his bases.  There has been a lot more studies on resveratrol.  We *think* that pterostilbene does the same thing only better, but we actually don't have as much concrete evidence for that as we'd like.

 

 

I thought at first he is covering his bases as well but then remembered resveratrol and ptersotilbine do have some different effects as well. David Sinclair is known to take 1,000 mg of resveratrol and "a NAD precursor". He says it isn't NR  but would be very tempted to take it if not taking the other NAD+ precursor molecule, which is almost certainly NMN, right?

 

With respect to resveratrol studies on humans, I've only seen very small trials and at relatively small doses of 100 mg. For example, a few years ago 11 obese men were given 100 m of resveratrol for 4 or 6 weeks and no weight loss was reported, although it may have lowered glucose levels - I forget. Still, I don't recall any extensive resveratrol study like what Elysium did this summer where I think we will know much more when the results are made available. 

 

 

[trakker]

I've been curious about Elysium's trial compared to Chromadex's trial. Elysium limited the age of participants from 60 to 80 years old while Chromadex's 12 participants were not, right? 

 

250 mg of NR with 50 mg of pterostilbine increased NAD+ in blood by 40%. Chromadex showed 100 mg of NR alone increased NAD+ by 30%.  If both studies used the same ages then it would be reasonable for someone to take just 125 mg of NR (what I take) and no pterostilbine for $0.75 a day to get nearly the same boost as taking Elysium's Basis 250 mg of NR with 50 mg of pterostilbine for $1.70 a day. Yet, the age group isn't the same so...

 

I've wondered ever since Guarente told reporters what he was taking, Basis, along with 250 mg of resveratrol and 2500 IU of vitamin D, if he was taking a double dose of Basis or the dose that his company recommends. To get the 90% increase in NAD+ at $3.30 a day is well beyond what most will pay among those who are willing to try NR in the first place unless the results come back are a health home run, which I doubt - but maybe. 

 

My thought is the single dose of Basis probably raised NAD+ more than 40% initially, but by the 4 week point it had dropped down to 40%.

 

Note that the double dose of 500mg NR in Elysium trial raised NAD+ 90% at 4 weeks, but that wasn't maintained throughout - they state it remained "significantly higher" than 40%.  They would have stated the number if it was good.

 

So the bodies tendency to homeostasis is limiting the long term increase in NAD+ somewhat, but "significantly higher" than 40% is not bad imo.

 

The Chromadex/Brenner trial didn't measure the long term NAD+ increase.

 

Edited by trakker, 10 December 2016 - 08:37 AM.

[bluemoon]

Thanks for reminding me that the Chromodex trial only measured for a day, something I remembered while reading the Elysium report but then forgot when posting above.

 

That "significantly higher than 40%" also got my attention since a percentage wasn't given.  

 

If the detailed results on blood pressure, serum glucose and lipid profile, etc. were very good, you'd think they would release that information now.  

[Bryan_S]

 

 

Dietary proanthocyanidins boost hepatic NAD+ metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats

http://www.nature.co...es/srep24977#f3

 

rReceived 21 October 2015

Accepted: 08 April 2016

Published online: 22 April 2016

 

 

 

It looks like there is now a discussion thread for a grape seed extract product whose extract was used in this study. I'm not sure if it will be an 'open' discussion on the merits and efficacy or a 'sales' thread but I know that I'm definitely interested in another pathway.

 

 

Thanks Thell for digging that out of the archives.

 

I think there are more avenues to reenforce our NAD pathways and we've talked about Grape Seed Extract for awhile now. The discussion you reference is a sales thread but there is plenty of information to support this notion. I firmly believe polyphenols in general offer us a route to epigenetic and disease targets as can be seen in this search. Plants offer us a chance to investigate a host of epigenetic activating and silencing compounds. 

[Iporuru]

The Circadian NAD+ Metabolism: Impact on Chromatin Remodeling and Aging
Yasukazu Nakahata and Yasumasa Bessho

 

https://www.hindawi....i/2016/3208429/

 

 

Also this mentions nicotinamide riboside:

  [PDF] Natural Products of Fungal Endophytes and their Therapeutic Potential: A Fo-cus on Cardiovascular Disease

Edited by Iporuru, 10 December 2016 - 05:41 PM.