2255 replies to this topic

[Ethic]

Beta-Lapachone, a Modulator of NAD Metabolism, Prevents Health Declines in Aged Mice

 

http://www.ncbi.nlm....les/PMC3469505/

 

But again, here its a NR thread, we should open and discuss it in a more general thread since its offtopic

 

Edited by Ethic, 23 February 2016 - 06:49 PM.

[Bryan_S]

From what I have been told it is hard to keep the NAD levels up for a prolonged period due to feedback loops. It tends to readjust due to 

an underlying change in NAMPT with age. I am not a scientist but it seems that the NAD+/NADH ratio is more important than absolute levels of NAD.

The NQ01 gene drives this ratio.  Beta Lapachone drives influences NQ01.

 

Thanks for the enlightening contribution. We always look forward to your posts. If NQO1 gene expression is truly the key then we should look at some substances that induce NQO1 gene expression. Let's see what result we get with "Induction of NQO1 gene expression by" . . . Humm I see a familiar result, one being quercetin. That wasn't expected.

 

We've investigated the flavonoid quercetin pretty extensively in several other forums. In the upper righthand corner above the Longecity banner search "quercetin" and search "senolytics quercetin" where we've discussed this. In senolytics it was used to eliminate some varieties of senescence cells. If I remember correctly quercetin changes the NAD+ to NADH ratio by oxidizing NADH. This compound might have an indirect effect on NQO1 expression or there might be a more direct expression path.

 

Now as I look at each of these compounds I'm struck with a notion of cellular stress because each has been associated with some cellular toxicity. Each seems to become toxic at some dosage level and it appears Beta Lapachone can build up in the tissues over time so this might become a moving target with extended use. It's possible the NQO1 gene expression each compound is generating is in response to cellular stress and there may be other suitable long term NQO1 activators. JMHO

 

Safety Issues and Beta-Lapachone

http://www.beta-lapachone.com/safety/

 

The quercetin paradox

https://www.research...ercetin_paradox

 

Beta-Lapachone is found to inhibit the activity of topoisomerase. On the long term side quercetin has been linked to kidney damage. I think I'd put both of these compounds in the short term use category and both seem to have very good cancer treatment potential I just don't know about recreational long-term supplementation.

 

I'd like to find a compliment to Nicotinamide Riboside supplementation but I don't think either of these are my choice today and both seem better suited for other applications. I trust other NQO1 gene expression alternatives will emerge.

 

All insights are welcome.

Edited by Bryan_S, 24 February 2016 - 12:00 AM.

[to age or not to age]

I interviewed Irina Conboy at Berkeley this past fall and she said something that I believe goes to your point of possible downsides to Quercetin and

Beta Lapachone, even though she was speaking about substances that might influence adult stem cells to act younger.  Irina said in effect that 

dosing and administration of these substances (this goes to the rate of reversal) is the next hurdle because it is very much a dialing situation.  She was also speaking broadly about genes and mechanisms that are helpful in youth but were a black hat later on (think mtor) and influencing these various points of intervention. There is a much longer discussion here but I think that like NR, rapamycin, beta lapachone etc, this may be a cycling issue, or a combination issue.  Guarante believes that and increases in NAD might have an additive or even a multipole effect on the action of substances like pterostilbene and resveratrol. I myself am very interested in testing various combinations on groups of mice in different dosing regiments.   

 

[Bryan_S]

I myself am very interested in testing various combinations on groups of mice in different dosing regiments.   

Maybe if you haven't already spoken to Josh Mitteldorf you might want to hear his approach. It appears he's already spoken with Tom Andre on the Beta Lapachone front. I do still think this substance holds great promise being that it exerts a powerful genomic influence (i.e. cell cycle arrest, apoptosis and acts as a DNA topoisomerase cell division inhibitor) its just at this point it's not a casual consideration to add as a daily part of our supplement regimen.

 

Josh has written before on NAD+ boosting. However this does not appear to fall within his list of compounds for investigation, which is strange because he's interested in Pterostilbene but has not proposed pairing it with a NAD booster. He's posted his proposal in this link and I assume he's working towards that end.

[Logic]

Lest we forget:

The de novo pathway to NAD+ starts in the gut with Tryptophan. The levels of which decrease with age due to gut bacteria imbalances 

Minireview: Gut Microbiota: The Neglected Endocrine Organ

Manipulating the microbial composition of the gastrointestinal tract modulates plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Indirectly and through as yet unknown mechanisms, the gut microbiota exerts control over the hypothalamic-pituitary-adrenal axis. This is clear from studies on animals raised in a germ-free environment, who show exaggerated responses to psychological stress, which normalizes after monocolonization by certain bacterial species including Bifidobacterium infantis.

http://press.endocri...10/me.2014-1108

 

Metabolic Signatures of Extreme Longevity in Northern Italian Centenarians Reveal a Complex Remodeling of Lipids, Amino Acids, and Gut Microbiota Metabolism

With increasing age...profiling of blood serum displayed a marked decrease in tryptophan concentration, while an unique alteration of specific glycerophospholipids and sphingolipids are seen in the longevity phenotype. ... we also revealed that the longevity process deeply affects the structure and composition of the human gut microbiota ... a complex remodeling of lipid, amino acid metabolism, and of gut microbiota functionality are key regulatory processes marking exceptional longevity in humans.

http://journals.plos...al.pone.0056564

 

Functional metagenomic profiling of intestinal microbiome in extreme ageing
Among these, we observed an age-related increased abundance of genes involved in the tryptophan metabolism pathway (ko00380). This evidence is in agreement with the reduction of tryptophan found in serum of centenarians [22], although we cannot directly infer causality. Linking together the two observations, we advance the hypothesis that the potential increase of consumption of tryptophan by the gut microbiota affects its bioavailability within the host. A recent study showed patients with inflammatory diseases to have a significant depletion of serum levels of tryptophan compared to control population [23] and Huang et al. demonstrated a clear relationship between reduced serum tryptophan levels and an increase of immune activation [24]. In addition, the decrease of the serum level of tryptophan was associated with cognitive deficit in senile dementias [25-27], and Noristani et al. demonstrated that high triptophan diet lead to a reduction of the plaque pathology in Alzheimer's disease in mouse [28]. It is thus tempting to speculate that a microbiota-dependent reduction of tryptophan can nurture inflammaging in centenarians and could worsen the conditions of the patients affected by cognitive deficit.

http://www.impactagi...ull/100623.html

Also don't forget the increase in NF-kB etc with the increasing gut permeability that accompanies aging.

http://www.longecity...g-in-zebrafish/

 

Everybody! To the tune of Yellow Submarine! Sing after me: "We all live on bacteria shit! ...Bacteria shit! ...bacteria shit! ..."  

 

Edited by Logic, 24 February 2016 - 07:52 PM.

[bluemoon]

 

 

Josh has written before on NAD+ boosting. However this does not appear to fall within his list of compounds for investigation, which is strange because he's interested in Pterostilbene but has not proposed pairing it with a NAD booster. He's posted his proposal in this link and I assume he's working towards that end.

 

 

He has been skeptical of NR since late 2014 since he says the mouse trials didn't impress him at the time. In contrast, Guarente said in an interview a year ago that the mice studies with NR "hold great promise."

 

 

Nov 14, 2014

http://joshmitteldor...heres-the-beef/

 

 

Feb 13, 2015  

http://joshmitteldor...ls-in-the-news/

[Tom Andre F. (ex shinobi)]

 

From what I have been told it is hard to keep the NAD levels up for a prolonged period due to feedback loops. It tends to readjust due to 

an underlying change in NAMPT with age. I am not a scientist but it seems that the NAD+/NADH ratio is more important than absolute levels of NAD.

The NQ01 gene drives this ratio.  Beta Lapachone drives influences NQ01.

 

Thanks for the enlightening contribution. We always look forward to your posts. If NQO1 gene expression is truly the key then we should look at some substances that induce NQO1 gene expression. Let's see what result we get with "Induction of NQO1 gene expression by" . . . Humm I see a familiar result, one being quercetin. That wasn't expected.

 

We've investigated the flavonoid quercetin pretty extensively in several other forums. In the upper righthand corner above the Longecity banner search "quercetin" and search "senolytics quercetin" where we've discussed this. In senolytics it was used to eliminate some varieties of senescence cells. If I remember correctly quercetin changes the NAD+ to NADH ratio by oxidizing NADH. This compound might have an indirect effect on NQO1 expression or there might be a more direct expression path.

 

Now as I look at each of these compounds I'm struck with a notion of cellular stress because each has been associated with some cellular toxicity. Each seems to become toxic at some dosage level and it appears Beta Lapachone can build up in the tissues over time so this might become a moving target with extended use. It's possible the NQO1 gene expression each compound is generating is in response to cellular stress and there may be other suitable long term NQO1 activators. JMHO

 

Safety Issues and Beta-Lapachone

http://www.beta-lapachone.com/safety/

 

The quercetin paradox

https://www.research...ercetin_paradox

 

Beta-Lapachone is found to inhibit the activity of topoisomerase. On the long term side quercetin has been linked to kidney damage. I think I'd put both of these compounds in the short term use category and both seem to have very good cancer treatment potential I just don't know about recreational long-term supplementation.

 

I'd like to find a compliment to Nicotinamide Riboside supplementation but I don't think either of these are my choice today and both seem better suited for other applications. I trust other NQO1 gene expression alternatives will emerge.

 

All insights are welcome.

 

 

Bryan,

 

The more I study beta-lapachone, the more i found it safe. Look at the life extension onn mice using beta-lapachone and the dosage they used : 70 to 80mg /kg. And the scientific think this dosage can be improved. The mitochondria study in the study show a real protective effect as well. I think BL is toxic only in vitro on some cancer cells.

 

Beta-lapachone increases NQO1 enzyme activity and quercetin increases Nrf2-mediated gene expression of NQO1. I dont know any study which show a vivo effect using quercetin but the one using beta-lapachone is complete and we see a NAD+ enhancement + sirt 1 and 3 increase thats why i was so excited about this compound.

 

[Logic]

I did a site search for Nrf2:

https://cse.google.c...ab=0&gsc.q=Nrf2

 

Sulforaphane and Nrf2 caught my eye:

http://www.longecity...phane-and-nrf2/

due to possible AGE clearance which may be its MOA!?:

http://www.longecity...ster-than-fn3k/

[Ethic]

Actually Sulforaphane is the most promising supplement after Nicotinamide Riboside, IMHO. (atm)

 

NQO1 modulator, anti-cancer and according to Agingsciences blog it may alleviate Progeria symptoms. http://www.anti-agin...ative-splicing/

 

Ofc ruthless company "Monsanto" took notice already and patented a non genetically-modified broccoli cultivar (high in Sulforaphan) over here in Europe....

 

But luckily there's an affordable large-dose Sulforaphane (50mg/capsule) and I will add it to my stack in two months, out of curiousity.

 

Just in case you're interested, it's from "Hirundo Products" and costs around 50€ on Amazon Austria. http://nutri-store.l...apseln-120-stk/

[pleiotropic]

David Sinclair has launched a crowdfunding campaign to investigate the effects of NMN in mice further:

 

https://www.lifespan...-aging-in-mice/

 

 

 

The first long-term lifespan study in mice involving supplementation with NMN, a precursor of NAD+ metabolism, which has been shown to reduce aging markers and increase SIRT1 activity. We propose to conduct a longevity study using NMN in the drinking water of control laboratory mice and a novel model of accelerated aging mice known as the ICE mouse (Induced change in Epigenetics).

 

 

 

•  

 

[bluemoon]

This is seems odd to me.

 

Why would a leading laboratory at Harvard need to crowd source chump change like $30,000 (and another $30,000 later)? How much is a publicity stunt? Maybe a good one....

 

 

[bluemoon]

The crowdfundig for Sinclair page was taken down today. It's too soon to know if temporary, but it is possible Harvard didn't want Sinclair involved in something like that just as they told him to stop promoting Shaklee's  resveratrol product a few years ago. Or maybe GSK saw a conflict of interest and told Sinclair to knock it off. Or maybe the men in the black suits... 

[stefan_001]

The crowdfundig for Sinclair page was taken down today. It's too soon to know if temporary, but it is possible Harvard didn't want Sinclair involved in something like that just as they told him to stop promoting Shaklee's resveratrol product a few years ago. Or maybe GSK saw a conflict of interest and told Sinclair to knock it off. Or maybe the men in the black suits...

My guess is that Sinclair doesn't have a lot of support for this study and tries to push ahead regardless. Not surprising as also people on this forum concluded this is a somewhat pointless effort given the fact it first needs to ho back to NR before it can enter the cell.

[Bryan_S]

I've been watching this conversation for a number of days just scratching my head over this approach.

 

This website is still announcing his crowdfunding as coming soon. 

 

https://www.lifespan.io/

 

JMHO plus substantial speculation, I see conventional funding/grant time scales moving much slower than Sinclair wants. The 2016 Symposium on Aging Now may also be at play here but it's doubtful this study endeavor could be launched by the time Sinclair hosts this symposium in June. Also if it's truly been withdrawn than maybe someone (an investor) offered him funding with some caveats.

 

I also see Sinclair wanting to differentiate his work from the current Nicotinamide Riboside work being done by Charles Brenner, PhD and others which I believe David feels has encroached on his work. Somehow NR and NMN work has fused together through product marketing. Neither side has completed research saying these precursors extend the lives of test animals so the race is on to begin to produce results suggesting NAD+ boosting as a path to longevity.

 

I also see a battle between preventive medicine and longevity. Longevity results are a hot button to attract further funding where preventive medicine results don't attract as much funding interest. It's all about headlines and between researchers in this field David Sinclair understands and knows how to exploit this.

 

I'm a stickler for the details and although extracellular NMN and NAD+ seems to be converted to NR at the cell membrane I don't think its right to attribute all of David's NMN results to Nicotinamide Riboside without reproducing those same results independently. Conversely I also look at this from Brenner's standpoint and he appears to have mapped out the precursor relationships slightly ahead of Sinclair and his own research may have originally spurred David to launch his mouse NMN study as a competitive headline approach. Both labs have contributed much to one another without question. I believe competition between researchers is a great thing. Results that differ and those that match further our understanding and insights.

 

Back the the crowdfunding. The SENS Mitosens Mitochondrial Repair Project has already surpassed its crowdfunding goal and I think this funding approach has already proven itself and I want to see more!!! I'm just pleased at the activity surrounding NAD+ boosting and sirtuin research to date. These insights have already branched out into so many other areas of research. However at its core I'm beginning to see a stagnation developing in the release of corporately funded study results where corporate marketing is spoon feeding us select study quotes. This is where I find corporate study funding in conflict with pure academic grant funded research. Money pollutes the scene when study insights begin to map out medical applications. By its very nature corporate funding is designed to horde study information and confound the competition. (Positive study results spur competition and poor study results hurt corporate product sales.) So from my standpoint I'm not holding my breath any longer for ChromaDex funded research to reach the surrounding research community and trickle down to us.

 

On the other hand I have my eye out for the non-corporate projects to fill in our understanding about NAD+ Boosting. I would like to see more publicly funded projects overall.

 

I also fear crowdfunded studies are no guarantee those study results will be published either. We've moved from the OMG is this the way it really works phase to a commercialization phase. So if David Sinclair provides a statement guaranteeing full study disclosure helping to move the research community ahead I'd support it, otherwise why fund him in such an endeavor?

 

JMHO

Edited by Bryan_S, 01 March 2016 - 07:50 PM.

[midas]

Just my thought on this.....I think Sinclair is concentrating on NMN purely because NR is trademarked. I also would not be surprised if the same was to happen with NMN in the near future.

 

At first, around 2 years ago, I had a lot of respect for Sinclair, now, not so much. Something is eating at me about the guy and I don't trust him anymore.

[bluemoon]

"Something is eating at me about the guy, and I don't trust him anymore" is a bit on the vague side.

 

Sinclair is a scientist so all one has to do is look at his publications. If they are sound, then great; if not, then not so great. In the past three years, he has made some very strong statements at how close the world is to taking a pill that would slow down an aspect, two or three of aging and delay the onset of diseases. I think he will be shown to be correct in part because the statements of others in the field back that claim up to different degrees.

 

 

     

[Bryan_S]

Interesting to see some new study's https://clinicaltria...e&Search=Search

[midas]

Interesting to see some new study's https://clinicaltria...e&Search=Search

 

https://clinicaltria...e&Search=Search

[malbecman]

 Well, only the last trial, #5, looks to be of interest.  The others are just pharmacokinetics/safety studies.  

 

Below are the outcomes to be measured in trial #5 but since it just went up on the website a few days ago, the results are going to be awhile.  It ends in June but who knows how long it will take

them to publish results.

 

https://clinicaltria...Riboside&rank=5

 

Further study details as provided by Elysium Health:

Primary Outcome Measures:

• Blood pressure [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  Assessment of blood pressure
• Safety Blood Parameters [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  Assessment of safety blood parameters: CBC, electrolytes (Na, K, Cl), kidney function (creatinine), liver function (AST, ALT, GGT and bilirubin)
• Heart Rate [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  Assessment of heart rate

Secondary Outcome Measures:

• Physiological Performance [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  6 Minute Walk Test
• Physiological Performance [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  30 Second Chair Stand Test
• Physiological Performance [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  Physical Activity Scale for the Elderly
• Body Weight [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Blood Pressure [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Serum Glucose [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Lipid Profile [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Quality of Life and Sleep Quality [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  Health Assessment Questionnaire
• Quality of Life and Sleep Quality [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  Older People's Quality of Life Questionnaires
• Blood NAD+ [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:

• Expression Profile of Peripheral Blood Mononuclear Cells [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Pain Assessment [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  VAS Pain Scale
• Endothelial Function [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  EndoPat

Estimated Enrollment: 120 Study Start Date: January 2016 Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
 

[lumia]

Just a pretty newbie question. If you can only choose one between resveratrol and NR for sirtuin activation, which one would you choose?

[Bryan_S]

NR certainly works by raising NAD+ levels which the sirtuins need as an energy source to work, (sirtuins are NAD+ dependent) however among the "activators" i.e. resveratrol and Pterostilbene, its "claimed" Pterostilbene is a better sirtuin activator.

 

There is a debate about the effectivness in some circles. I take Pterostilbene because MIT biologist Leonard Guarente feels this is currently our best option and he has examined this subject closely. Here some links pointing to points both pro and con.

 

http://www.pterostilbene.com/

http://joshmitteldor.../pterostilbene/

http://www.pterostil...vs-resveratrol/

 

http://biopharmconso...rtris-founders/

 

I also take grape seed extract and magnolia bark extract "Honokiol" as a sirtuin activator. So I'm covering the bases and I take NR.

 

Here is one more interesting artical on pterostilbene and cancer:

https://www.umc.edu/...cer_growth.aspx

 

So if you are interested in stimulating sirtuin production remember they need the energy substrate NAD+ to work as pointed out by Sinclair. So I see this supplement story as a dual path, take your sirtuin simulator but also add your NAD+ booster to fuel the enzymes to work.

 

 

 

Edited by Bryan_S, 07 March 2016 - 01:10 AM.

[bluemoon]

  I take Pterostilbene because MIT biologist Leonard Guarente feels this is currently our best option and he has examined this subject closely. 

 

 

Right, but in this February 2014 interview with MIT Technology Review, the writer states: "Guarente also says he takes Basis every day, along with 250 mg of resveratrol, the red-wine compound."                            

 

https://www.technolo...nti-aging-pill/

 

 

In another interview in April Guarente said he takes NR and pterostilbene (his product) and discussed  activating SIRT1:

  

 

Q. How do dietary supplements help with regards to sirtuins? 

 

A. 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

. 

 

So any idea why Guarente is taking (or was taking in early 2014) both resveratrol and pterostilbene? 

[Logic]

Just a pretty newbie question. If you can only choose one between resveratrol and NR for sirtuin activation, which one would you choose?

 

Watch out for this type of thinking Lumnia!
Wanting to simplify down to a simple answer of one thing does not work and understanding the basics is not as difficult (require the study time and mental capacity) as many may think/choose.

NAD+ can be thought of as energy (electricity) required for SIRT (toaster), PARP (stove), CD38 (washing machine), etc in your body(house).
Pt and R etc is the switch that switches on the toaster (SIRT), but without electricity (NAD+)  switching the switch has no effect.
Also where are you going to get the electricity?  Just connect to the grid (NR) or install a solar system? (NCQ etc)

The 'one pill' is 'the blue pill'. Welcome to the Matrix! Or just take 'the red pill'...

 

 

[lumia]

 

Just a pretty newbie question. If you can only choose one between resveratrol and NR for sirtuin activation, which one would you choose?

 

Watch out for this type of thinking Lumnia!
Wanting to simplify down to a simple answer of one thing does not work and understanding the basics is not as difficult (require the study time and mental capacity) as many may think/choose.

NAD+ can be thought of as energy (electricity) required for SIRT (toaster), PARP (stove), CD38 (washing machine), etc in your body(house).
Pt and R etc is the switch that switches on the toaster (SIRT), but without electricity (NAD+)  switching the switch has no effect.
Also where are you going to get the electricity?  Just connect to the grid (NR) or install a solar system? (NCQ etc)

The 'one pill' is 'the blue pill'. Welcome to the Matrix! Or just take 'the red pill'...

 

 

 

 

Logic,

 

I know Reseveratrol and NR work on completely different mechanisms; it's just I haven't state it clear why I asked this in the first place. It is one of the two possibilities:

1. I practice intermittent fasting, which I believe would activate some sirtuins. I wonder if I should just forgo Res and go NR instead.
2. As the alternative, I'm asking which is a better substance in activating the sirtuins, in case I can only afford one or the other. NR is not cheap, and good Res isn't that cheap either.
    

[Logic]

 

  I take Pterostilbene because MIT biologist Leonard Guarente feels this is currently our best option and he has examined this subject closely. 

 

 

Right, but in this February 2014 interview with MIT Technology Review, the writer states: "Guarente also says he takes Basis every day, along with 250 mg of resveratrol, the red-wine compound."                            

 

https://www.technolo...nti-aging-pill/

 

 

In another interview in April Guarente said he takes NR and pterostilbene (his product) and discussed  activating SIRT1:

  

 

Q. How do dietary supplements help with regards to sirtuins? 

 

A. 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

. 

 

So any idea why Guarente is taking (or was taking in early 2014) both resveratrol and pterostilbene? 

 

 

I'm guessing that like anybody, Guarente's stack changes as more is learned.
In this case:

• That Pt gives the in vitro results of R, in vivo. (more or less) Plus many other positive effects.
• That the in vivo results of R, caused mainly by its metabolites, are also desirable. Which means he probably swallows his R with a large cup of Green Tea... but has omitted saying so.

I'm trying to engender a culture of research amongst members again, as in the old days here.

 

https://cse.google.c...-8&q=#gsc.tab=0
http://www.ncbi.nlm.nih.gov/pubmed

 

 

[stefan_001]

 

Just a pretty newbie question. If you can only choose one between resveratrol and NR for sirtuin activation, which one would you choose?

 

Watch out for this type of thinking Lumnia!
Wanting to simplify down to a simple answer of one thing does not work and understanding the basics is not as difficult (require the study time and mental capacity) as many may think/choose.

NAD+ can be thought of as energy (electricity) required for SIRT (toaster), PARP (stove), CD38 (washing machine), etc in your body(house).
Pt and R etc is the switch that switches on the toaster (SIRT), but without electricity (NAD+)  switching the switch has no effect.
Also where are you going to get the electricity?  Just connect to the grid (NR) or install a solar system? (NCQ etc)

The 'one pill' is 'the blue pill'. Welcome to the Matrix! Or just take 'the red pill'...

 

 

 

 

:-)  Great post!

 

[Ethic]

I also take grape seed extract and magnolia bark extract "Honokiol" as a sirtuin activator. So I'm covering the bases and I take NR.

 

Hey Bryan, thank you for your comments!

Grape seed extract modulates NAMPT and improves skin blood flow (stated by many OPC consumers) and I see skin and hair as good indicators for general state of health.

 

So, how happy are you with the results of your current stack and do you want to share any changes to your skin condition?

 

NAD+ can be thought of as energy (electricity) required for SIRT (toaster), PARP (stove), CD38 (washing machine), etc in your body(house).

Pt and R etc is the switch that switches on the toaster (SIRT), but without electricity (NAD+)  switching the switch has no effect.

Also where are you going to get the electricity?  Just connect to the grid (NR) or install a solar system? (NCQ etc)

 

Hey Logic, thank you for your comments aswell, what do you mean by NCQ?

Edited by Ethic, 07 March 2016 - 10:31 AM.

[Logic]

 

 

Just a pretty newbie question. If you can only choose one between resveratrol and NR for sirtuin activation, which one would you choose?

 
Watch out for this type of thinking Lumnia!
Wanting to simplify down to a simple answer of one thing does not work and understanding the basics is not as difficult (require the study time and mental capacity) as many may think/choose.

NAD+ can be thought of as energy (electricity) required for SIRT (toaster), PARP (stove), CD38 (washing machine), etc in your body(house).
Pt and R etc is the switch that switches on the toaster (SIRT), but without electricity (NAD+)  switching the switch has no effect.
Also where are you going to get the electricity?  Just connect to the grid (NR) or install a solar system? (NCQ etc)

The 'one pill' is 'the blue pill'. Welcome to the Matrix! Or just take 'the red pill'...
 

 

 
Logic,
 
I know Reseveratrol and NR work on completely different mechanisms; it's just I haven't state it clear why I asked this in the first place. It is one of the two possibilities:

•  
• I practice intermittent fasting, which I believe would activate some sirtuins. I wonder if I should just forgo Res and go NR instead.
• As the alternative, I'm asking which is a better substance in activating the sirtuins, in case I can only afford one or the other. NR is not cheap, and good Res isn't that cheap either.
   

"Should I get the 'toaster' or 'electricity' for my 'house'?" is what you are asking Lumia... 
 

Personally, amongst other things, I take:

 

SIRT:
http://www.solal.co....als/resveratrol

NB: composition.

NAD+:
Niacin

 

NB that this, and NR, is a 'Candida kickstarter  kit' and some types of Candida are NAD+ auxotrophs (uses what you have produced), so precautions need to be taken!

For a start:
http://www.ncbi.nlm....pubmed/24514088
Do you see your 'one or the other door' closing and another reason or its being in...  (whatever those NR pills are called)!?  
Also Ribose is a powerful AGE (Advanced Glycation Endproducts) promoter..!

 

I am afraid there is just no substitute for reading the thread and using the different search functions in the search drop-down menu to come up with a stack of your own.
Plz use GoogleSiteSearch in that Search dropdown menu to look up NAD+, candida, auxotroph Advanced Glycation Endproducts etc.

 

Edited by Logic, 07 March 2016 - 11:51 AM.

[Logic]

Hey Logic, thank you for your comments aswell, what do you mean by NCQ?

 

 

Oops!  I meant NQ01.  Thx for catching that.

 

https://cse.google.c...ab=0&gsc.q=NQO1

[Bryan_S]

 

I also take grape seed extract and magnolia bark extract "Honokiol" as a sirtuin activator. So I'm covering the bases and I take NR.

 

Hey Bryan, thank you for your comments!

Grape seed extract modulates NAMPT and improves skin blood flow (stated by many OPC consumers) and I see skin and hair as good indicators for general state of health.

 

So, how happy are you with the results of your current stack and do you want to share any changes to your skin condition?

 

Its evolved over time but back to the beginning. I'm old school, Primarily I believed if we ate right there was no need for supplementation. I started my career in the health occupations as a LMT for 16-years. For 8 of those years I was a manager at a 5 star health resort and I helped administrate exercise, nutrition and spa treatment plans for our clients. Other than the exercise and spa activities I felt most of the supplementation we threw at them was crap and driven by high markups and commissions. Oh sure we'd send them packing with ample supplements to carry them to their next visit but I couldn't discern any benefit when I'd see them next. Also a short 1-3 week stay wasn't long enough to change long-term eating and exercise behaviors and most would revisit us months later with the same problems . . . unless they hired a personal Chef and Exercise Trainer in the interim as a bridge. So you could say my view of just the supplementation world was tainted from having an insiders view. 

 

Fast forward a few years and I'm working in television and reading the daily science and Medical Journal Articles because I'd never lost my original interest in physiology. Also I had a parent beginning to lose his faculties and some of the first NR studies began to emerge and the idea of supplementation with a medical purpose began to emerge to help stressed and dying nerve cells. Meanwhile the sirtuin research looked promising but appeared to have stalled and failed. We've we've all read how that unfolded. But then the sirtuin work began to cross over into the NR world after their NAD+ dependency was uncovered and I really got interested in the work of David Sinclair and Leonard Guarente as the epigenetics landscape began to unfold.

 

So that's the background that brought me here. I'm driven by lower leg and foot inflammation (Skydiving accident where I crushed my legs) and I was recently debilitated by a huge inflammatory episode in 2013-14 when I could no longer participate in skydiving activities and extra video & staging work I used to supplement my income. About that time NR became available in 2013 thru ChromaDex and by the spring of 2014 I was back on my feet again after starting my NR regiment. Now mind you I did all the obvious physical therapy, DMSO, anti-inflammatory's, limb elevation, cold treatments. I did a combination or some or all these for 6-months with no relief. It wasn't until I added NR to that my situation that my condition changed and reversed. 

 

I also wasn't at first sure NR had made the difference. This stuff is expensive and my wife talked me into discontinuing it and the inflammation soon returned. To be honest She's still a skeptic. However I'd made note of some other benefits I hadn't expected like a mental fog that had been been lifted and a skin-condition (Rosacea) that got better, both of those conditions and the leg and foot inflammation also returned after discontinuing the NR. So I resumed the NR regiment, then began researching the over 100-year B3 history and became a believer as much of what I'd experienced had been previously documented.

 

Nicotinamide Riboside  inflammation 

Nicotinamide Riboside Vascular inflammation

There are more and these affects may be attributable to increased SIRT1 or SIRT3 activity.

 

I've added various things to my stack to enhance what benefits I've gotten from the Nicotinamide Riboside. I've dropped the Nicotinamide. It helped my skin-condition when I took lower amounts of NR but as I increased my dosage and began the Grape Seed Extract, Honokiol and Pterostilbene (I did not start all these at once) these seemed to increase the affects of my NR. My blood pressure has dropped (Grape Seed Extract) and my BPH has all but disappeared (Honokiol). I also take Glycine but haven't noticed anything stunning from it but I feel very calm and sleep great but that could be the Honokiol as both have calming affects along with the B3's. Keep in mind I'm still a firm believer in exercise and a varied diet low in red meat. I attribute my personal recovery to becoming more active again and focusing on the B3 science that has been decades in the making as the bridge.

 

Got to head in to work. I'll add some study links for the plant Polyphenols that help with the sirtuins when I get a moment. 

Edited by Bryan_S, 08 March 2016 - 01:13 AM.
Updated with links