471 replies to this topic

[Tom Andre F. (ex shinobi)]

Bryan,

 

So in our current best strategy do you think we should come back with C60 as well to protect mitochondria disfunction ? a top 3 would be: 100mg pterostilbene twice a day (total 200mg) + 100mg per day pure NR (niagen) (to slowly increase NAD+ without the bad side of the niacinamide metabolite) + few drops of C60oo (from sarah vaugler)

 

We need also to reply to some aging "paradox" such as noise and ears growth though aging.. Fight wrinkles and white hair or brain amyloid is a thing, but this is another one..

[Asor]

My doctor just emailed me that the recently released clinical trial by Chromadex is not the one they are expecting data from (about toxicity at higher dosages).

 

The trial she's reffering to is not completed yet.

 

That's all i know / she told me about it.

 

 

[Bryan_S]

Bryan,

 

So in our current best strategy do you think we should come back with C60 as well to protect mitochondria disfunction ? a top 3 would be: 100mg pterostilbene twice a day (total 200mg) + 100mg per day pure NR (niagen) (to slowly increase NAD+ without the bad side of the niacinamide metabolite) + few drops of C60oo (from sarah vaugler)

 

We need also to reply to some aging "paradox" such as noise and ears growth though aging.. Fight wrinkles and white hair or brain amyloid is a thing, but this is another one..

 

Some tissues are just going to continue to grow. I touched briefly on hypertrophy and hyperplasia in the BPH thread. These are different in nature but in hyperplasia the cell count rises over time enlarging a particular tissue mass. Wether programed cell death has some how faltered I'm not qualified to comment but their may prove to be interventions to cull out the old cells.

 

I think we have the mechanisms for repair within us. Discovering the paths that "malfunction/or get turned off" gives insights in how to find and address these unknown mechanisms. I believe many of the things like our NAD decline has an upstream action manifesting its slow decline. In fact the gene responsible for the production of glycine (CGAT and SHMT2) might be involved but I suspect their is something further up stream than those as well. The article about the epigenome switching off and ramping down the cellular protection mechanisms at the moment of sexual maturity is a good place to investigate and see what streams from it.

 

As far as intervention, NAD boosting is a stopgap measure while the upstream causes of its decline are not totally identified. If Professor Hayashi is correct then glycine supplementation may also be an additional stopgap measure but I would like to see some scientific agreement to strengthen his idea and see further research as to its mechanisms and what kind of dosages would be realistic or perhaps harmful. Its one thing to do research in a petri dish and another to supersaturate an adult organism. 

 

What ever we do in the meantime lets read listen and learn. Also I know we have a few lurkers watching the show unfold on this thread, in fact there are exponentially more of you than the people posting. NAD boosting appears to be relatively safe but from time to time we may introduce conversation about substances that have the potential to harm you. So some self restraint is advised when the next bleeding edge compound arrives in this or a forum near you.

Edited by Bryan_S, 20 August 2015 - 08:24 PM.

[albedo]

My apologizes if this is off topic here but always wondered about the double role of sirtuins in cancer (I particularly look at prostate cancer because of my increased risk). What is you view and should we strive to keep a good balance between an over activation and under activation of sirtuins?

 

“…. Sirt1 has been shown to be overexpressed in several cancers, including prostate [53], acute myeloid leukaemia [54], colon cancer [55], and some nonmelanoma skin cancers [56]. Sirt1 has also been observed to be repressed in many other cancers, including glioblastoma, bladder, ovarian, and prostate cancers [57]. This duality of purpose indicates the pivotal role this Sirtuin exerts in the cell. Overexpression of Sirt1 can lead to deacetylation of p53 [58, 59] and reduction of many tumour suppressor genes, thus promoting genomic instability by reducing the cell’s ability to respond to DNA damage and stress. Conversely, it can also deacetylate B-catenin causing the oncogenic formof this protein to translocate to the cytoplasm, thus reducing the growth of tumours [60]…. »

 

Sirtuins, Bioageing, and Cancer

http://www.ncbi.nlm....les/PMC3134127/

 

Also here: Sirtuin inhibitors as anticancer agents

http://www.ncbi.nlm....les/PMC4384657/

 

 

 

[sthira]

Did you post this one, Brian?

The role of sirtuins in cardiac disease.

Matsushima S, Sadoshima J.
Am J Physiol Heart Circ Physiol. 2015 Jul 31:ajpheart.00053.2015. doi: 10.1152/ajpheart.00053.2015. [Epub ahead of print]
PMID: 26232232

Abstract

Modification of histones is one of the important mechanisms of epigenetics, in which genetic control is determined by factors other than an individual's DNA sequence. Sirtuin family proteins, which are class III histone deacetylases (HDACs), were originally identified as gene silencers that affect the mating type of yeast, leading to the name 'silent mating type information regulation 2 (SIR2)'. They are characterized by their requirement of nicotinamide adenine dinucleotide (NAD+) for their enzyme activity, unlike other classes of HDACs. Sirtuins have traditionally been linked to longevity and the beneficial effects of calorie restriction and DNA damage repair. Recently, sirtuins have been shown to be involved in a wide range of physiological and pathological processes, including aging, energy responses to low calorie availability, and stress resistance, as well as apoptosis and inflammation. Sirtuins can also regulate mitochondrial biogenesis and circadian clocks. Seven sirtuin family proteins (Sirt1-7) have been identified as mammalian SIR2 orthologs, localized in different subcellular compartments, namely, the cytoplasm (Sirt1, 2), the mitochondria (Sirt3, 4, 5), and the nucleus (Sirt1, 2, 6, 7). Sirt1 is evolutionarily close to yeast SIR2 and has been the most intensively investigated in the cardiovascular system. Endogenous Sirt1 plays a pivotal role in mediating the cell death/survival process and has been implicated in the pathogenesis of cardiovascular disease. Downregulation of Sirt2 is protective against ischemic/reperfusion injury. Increased Sirt3 expression has been shown to correlate with longevity in humans. In addition, Sirt3 protects cardiomyocytes from aging and oxidative stress and suppresses cardiac hypertrophy. Sirt6 has also recently been demonstrated to attenuate cardiac hypertrophy, and Sirt7 is known to regulate apoptosis and stress responses in the heart. On the other hand, the roles of Sirt4 and Sirt5 in the heart remain largely uncharacterized.

KEYWORDS:
FoxO; Longevity; Sirtuin-activating compounds; cell death/survival

[Bryan_S]

Did you post this one, Brian?
http://www.ncbi.nlm....pubmed/26232232
The role of sirtuins in cardiac disease.

Matsushima S, Sadoshima J.
Am J Physiol Heart Circ Physiol. 2015 Jul 31:ajpheart.00053.2015. doi: 10.1152/ajpheart.00053.2015. [Epub ahead of print]
PMID: 26232232

Abstract

Modification of histones is one of the important mechanisms of epigenetics, in which genetic control is determined by factors other than an individual's DNA sequence. Sirtuin family proteins, which are class III histone deacetylases (HDACs), were originally identified as gene silencers that affect the mating type of yeast, leading to the name 'silent mating type information regulation 2 (SIR2)'. They are characterized by their requirement of nicotinamide adenine dinucleotide (NAD+) for their enzyme activity, unlike other classes of HDACs. Sirtuins have traditionally been linked to longevity and the beneficial effects of calorie restriction and DNA damage repair. Recently, sirtuins have been shown to be involved in a wide range of physiological and pathological processes, including aging, energy responses to low calorie availability, and stress resistance, as well as apoptosis and inflammation. Sirtuins can also regulate mitochondrial biogenesis and circadian clocks. Seven sirtuin family proteins (Sirt1-7) have been identified as mammalian SIR2 orthologs, localized in different subcellular compartments, namely, the cytoplasm (Sirt1, 2), the mitochondria (Sirt3, 4, 5), and the nucleus (Sirt1, 2, 6, 7). Sirt1 is evolutionarily close to yeast SIR2 and has been the most intensively investigated in the cardiovascular system. Endogenous Sirt1 plays a pivotal role in mediating the cell death/survival process and has been implicated in the pathogenesis of cardiovascular disease. Downregulation of Sirt2 is protective against ischemic/reperfusion injury. Increased Sirt3 expression has been shown to correlate with longevity in humans. In addition, Sirt3 protects cardiomyocytes from aging and oxidative stress and suppresses cardiac hypertrophy. Sirt6 has also recently been demonstrated to attenuate cardiac hypertrophy, and Sirt7 is known to regulate apoptosis and stress responses in the heart. On the other hand, the roles of Sirt4 and Sirt5 in the heart remain largely uncharacterized.

KEYWORDS:
FoxO; Longevity; Sirtuin-activating compounds; cell death/survival

 

No I didn't good find. SIRT3 is one of the things I've been following on the heart. Your article is similar reading to another I've been looking at http://eurheartj.oxf...urheartj.ehv290

[Bryan_S]

My doctor just emailed me that the recently released clinical trial by Chromadex is not the one they are expecting data from (about toxicity at higher dosages).

 

The trial she's reffering to is not completed yet.

 

That's all i know / she told me about it.

 

There is another one completed and one in the wings here. 

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

 

Chromadex also announced a second human study on nicotinamide riboside with a much longer time scale and another one at the University of Colorado in Boulder. We should have all sorts of data points in the next year.

[Bryan_S]

Horizontal transfer of mitochondria in sickness and in health August 20, 2015 by John Hewitt

 

http://medicalxpress...ess-health.html

 

 

I had a feeling this might be the case. "(Medical Xpress)—Two of the most enticing ideas in cells biology have recently converged to create a paradigm shift of epic proportions. The first is that not only is it possible for mitochondria to emigrate from their host cell, they are in fact exchanged among cells much more regularly than has ever been imagined. The second is that while happenstance mutations are clearly associated with different aspects of a litany of cancers, the canonical force consistently driving tumor initiation, progression, and metastasis is now broadly understood to be the metabolic fickleness of their mitochondria."

http://www.ncbi.nlm....pubmed/26224121

 

 

Also see http://medicalxpress...rogramming.html

[stefan_001]

My apologizes if this is off topic here but always wondered about the double role of sirtuins in cancer (I particularly look at prostate cancer because of my increased risk). What is you view and should we strive to keep a good balance between an over activation and under activation of sirtuins?

“…. Sirt1 has been shown to be overexpressed in several cancers, including prostate [53], acute myeloid leukaemia [54], colon cancer [55], and some nonmelanoma skin cancers [56]. Sirt1 has also been observed to be repressed in many other cancers, including glioblastoma, bladder, ovarian, and prostate cancers [57]. This duality of purpose indicates the pivotal role this Sirtuin exerts in the cell. Overexpression of Sirt1 can lead to deacetylation of p53 [58, 59] and reduction of many tumour suppressor genes, thus promoting genomic instability by reducing the cell’s ability to respond to DNA damage and stress. Conversely, it can also deacetylate B-catenin causing the oncogenic formof this protein to translocate to the cytoplasm, thus reducing the growth of tumours [60]…. »

Sirtuins, Bioageing, and Cancer
http://www.ncbi.nlm....les/PMC3134127/

Also here: Sirtuin inhibitors as anticancer agents
http://www.ncbi.nlm....les/PMC4384657/

So this would indicate that Sirt1 stimulation may be the wrong path to go. Sirt3 still promising. Is there more data on this possible dual role of sirt1?

[stefan_001]

 

My apologizes if this is off topic here but always wondered about the double role of sirtuins in cancer (I particularly look at prostate cancer because of my increased risk). What is you view and should we strive to keep a good balance between an over activation and under activation of sirtuins?

“…. Sirt1 has been shown to be overexpressed in several cancers, including prostate [53], acute myeloid leukaemia [54], colon cancer [55], and some nonmelanoma skin cancers [56]. Sirt1 has also been observed to be repressed in many other cancers, including glioblastoma, bladder, ovarian, and prostate cancers [57]. This duality of purpose indicates the pivotal role this Sirtuin exerts in the cell. Overexpression of Sirt1 can lead to deacetylation of p53 [58, 59] and reduction of many tumour suppressor genes, thus promoting genomic instability by reducing the cell’s ability to respond to DNA damage and stress. Conversely, it can also deacetylate B-catenin causing the oncogenic formof this protein to translocate to the cytoplasm, thus reducing the growth of tumours [60]…. »

Sirtuins, Bioageing, and Cancer
http://www.ncbi.nlm....les/PMC3134127/

Also here: Sirtuin inhibitors as anticancer agents
http://www.ncbi.nlm....les/PMC4384657/

So this would indicate that Sirt1 stimulation may be the wrong path to go. Sirt3 still promising. Is there more data on this possible dual role of sirt1?

 

New research showing that Sirt1 is not contributing to cancer development?

HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism

http://www.nature.co...cdd201575a.html

 

[Tom Andre F. (ex shinobi)]

 

My apologizes if this is off topic here but always wondered about the double role of sirtuins in cancer (I particularly look at prostate cancer because of my increased risk). What is you view and should we strive to keep a good balance between an over activation and under activation of sirtuins?

“…. Sirt1 has been shown to be overexpressed in several cancers, including prostate [53], acute myeloid leukaemia [54], colon cancer [55], and some nonmelanoma skin cancers [56]. Sirt1 has also been observed to be repressed in many other cancers, including glioblastoma, bladder, ovarian, and prostate cancers [57]. This duality of purpose indicates the pivotal role this Sirtuin exerts in the cell. Overexpression of Sirt1 can lead to deacetylation of p53 [58, 59] and reduction of many tumour suppressor genes, thus promoting genomic instability by reducing the cell’s ability to respond to DNA damage and stress. Conversely, it can also deacetylate B-catenin causing the oncogenic formof this protein to translocate to the cytoplasm, thus reducing the growth of tumours [60]…. »

Sirtuins, Bioageing, and Cancer
http://www.ncbi.nlm....les/PMC3134127/

Also here: Sirtuin inhibitors as anticancer agents
http://www.ncbi.nlm....les/PMC4384657/

So this would indicate that Sirt1 stimulation may be the wrong path to go. Sirt3 still promising. Is there more data on this possible dual role of sirt1?

 

No, definitely not.. and the way we want to activate SIRT1 is pretty safe: pterostilbene or resveratrol are both very potent anti cancer / tumor suppressor.

 

We need both activate SIRT1 AND SIRT3

 

[albedo]

...

So this would indicate that Sirt1 stimulation may be the wrong path to go. Sirt3 still promising. Is there more data on this possible dual role of sirt1?

 

Stefan, I do not think the papers say so. They indicate a possible therapeutic benefit of SIRT1 inhibitors in cancer though. I am trying to get hold of this extensive review paper which will describe the 7 sirtuins and their impact on diseases of aging (bold is mine):

 

Seven sirtuins for seven deadly diseases of aging.

http://www.ncbi.nlm....ubmed/23104101/

 

Abstract

Sirtuins are a class of NAD(+)-dependent deacetylases having beneficial health effects. This extensive review describes the numerous intracellular actions of the seven mammalian sirtuins, their protein targets, intracellular localization, the pathways they modulate, and their role in common diseases of aging. Selective pharmacological targeting of sirtuins is of current interest in helping to alleviate global disease burden. Since all sirtuins are activated by NAD(+), strategies that boost NAD(+) in cells are of interest. While most is known about SIRT1, the functions of the six other sirtuins are now emerging. Best known is the involvement of sirtuins in helping cells adapt energy output to match energy requirements. SIRT1 and some of the other sirtuins enhance fat metabolism and modulate mitochondrial respiration to optimize energy harvesting. The AMP kinase/SIRT1-PGC-1α-PPAR axis and mitochondrial sirtuins appear pivotal to maintaining mitochondrial function. Downregulation with aging explains much of the pathophysiology that accumulates with aging. Posttranslational modifications of sirtuins and their substrates affect specificity. Although SIRT1 activation seems not to affect life span, activation of some of the other sirtuins might. Since sirtuins are crucial to pathways that counter the decline in health that accompanies aging, pharmacological agents that boost sirtuin activity have clinical potential in treatment of diabetes, cardiovascular disease, dementia, osteoporosis, arthritis, and other conditions. In cancer, however, SIRT1 inhibitors could have therapeutic value. Nutraceuticals such as resveratrol have a multiplicity of actions besides sirtuin activation. Their net health benefit and relative safety may have originated from the ability of animals to survive environmental changes by utilizing these stress resistance chemicals in the diet during evolution. Each sirtuin forms a key hub to the intracellular pathways affected.

 

[APBT]

Stefan, I do not think the papers say so. They indicate a possible therapeutic benefit of SIRT1 inhibitors in cancer though. I am trying to get hold of this extensive review paper which will describe the 7 sirtuins and their impact on diseases of aging (bold is mine):

 

Seven sirtuins for seven deadly diseases of aging.

http://www.ncbi.nlm....ubmed/23104101/

 

 

FULL TEXT:

Attached Files

•  Seven sirtuins for seven deadly diseases ofaging.pdf   1.71MB   19 downloads

[stefan_001]

Thanks for comments Tom Andre and Albedo. So I didn't order that Honokiol for nothing :-)

Edited by stefan_001, 21 August 2015 - 08:44 PM.

[Tom Andre F. (ex shinobi)]

 

...

So this would indicate that Sirt1 stimulation may be the wrong path to go. Sirt3 still promising. Is there more data on this possible dual role of sirt1?

 

Stefan, I do not think the papers say so. They indicate a possible therapeutic benefit of SIRT1 inhibitors in cancer though. I am trying to get hold of this extensive review paper which will describe the 7 sirtuins and their impact on diseases of aging (bold is mine):

 

Seven sirtuins for seven deadly diseases of aging.

http://www.ncbi.nlm....ubmed/23104101/

 

Abstract

Sirtuins are a class of NAD(+)-dependent deacetylases having beneficial health effects. This extensive review describes the numerous intracellular actions of the seven mammalian sirtuins, their protein targets, intracellular localization, the pathways they modulate, and their role in common diseases of aging. Selective pharmacological targeting of sirtuins is of current interest in helping to alleviate global disease burden. Since all sirtuins are activated by NAD(+), strategies that boost NAD(+) in cells are of interest. While most is known about SIRT1, the functions of the six other sirtuins are now emerging. Best known is the involvement of sirtuins in helping cells adapt energy output to match energy requirements. SIRT1 and some of the other sirtuins enhance fat metabolism and modulate mitochondrial respiration to optimize energy harvesting. The AMP kinase/SIRT1-PGC-1α-PPAR axis and mitochondrial sirtuins appear pivotal to maintaining mitochondrial function. Downregulation with aging explains much of the pathophysiology that accumulates with aging. Posttranslational modifications of sirtuins and their substrates affect specificity. Although SIRT1 activation seems not to affect life span, activation of some of the other sirtuins might. Since sirtuins are crucial to pathways that counter the decline in health that accompanies aging, pharmacological agents that boost sirtuin activity have clinical potential in treatment of diabetes, cardiovascular disease, dementia, osteoporosis, arthritis, and other conditions. In cancer, however, SIRT1 inhibitors could have therapeutic value. Nutraceuticals such as resveratrol have a multiplicity of actions besides sirtuin activation. Their net health benefit and relative safety may have originated from the ability of animals to survive environmental changes by utilizing these stress resistance chemicals in the diet during evolution. Each sirtuin forms a key hub to the intracellular pathways affected.

 

 

 

So bad that still no one who tested the potential lifespan extension of NR for exemple.. NAD+ seems more and more the ultimate way to go.

 

very Small dose of beta lapachone could also be an idea.. i will come back into that topic later through another blog dedicated
 

[Tom Andre F. (ex shinobi)]

 

Stefan, I do not think the papers say so. They indicate a possible therapeutic benefit of SIRT1 inhibitors in cancer though. I am trying to get hold of this extensive review paper which will describe the 7 sirtuins and their impact on diseases of aging (bold is mine):

 

Seven sirtuins for seven deadly diseases of aging.

http://www.ncbi.nlm....ubmed/23104101/

 

 

FULL TEXT:

 

 

Hey thanks, im reading this paper and page 14 you can read this: Fig. 8. The action of resveratrol leading to increased SIRT1activity. Some consider
 that resveratrol or its metabolites act on mitochondria as a mild ‘‘poison.’’ This then reduces ATP synthesis. As a result,the ratio of ATP to AMP decreases. The increase in  AMP activates AMP kinase, which in turn increases NAD+, which activates SIRT1. This then leads to the various effects of SIRT1.

 

Can someone tell me if they indeed explain resveratrol can act first act negativ and THEN ONLY being positive in the loop ?

[hamishm00]

An interesting piece from Vince Giuliano at Anti-Aging Firewalls http://www.anti-agin...-interventions/

 

Cherry picking a quote from Vince:

 

"I am now confident that supplementation with a NAD+ precursor like NMN or NR transiently increased the ratio of NAD+ to NADH (NAD/NADH), but the ratio returns to normal in the course of continued supplementation".

 

 

[Tom Andre F. (ex shinobi)]

I dedicated a special blog to speak about the interesting coumpound beta-lapachone: http://www.beta-lapachone.com/

 

and I just made an article to focus on the beta-lapachone effect on NAD+ and possible lifespan extension molecule: http://www.beta-lapa...f-healthy-life/

 

just tell me what you think guys. I didnt mention in the article, but the researcher of the main study on mice about BL and NAD+ think we should focus on dosage to found the best way to use it as a supplement. They said its safe and used for cancer also. Personally I dont know yet but I will next time focus and investigate on some possible dosage and also about the safety if you want ?

[Bryan_S]

An interesting piece from Vince Giuliano at Anti-Aging Firewalls http://www.anti-agin...-interventions/

 

Cherry picking a quote from Vince:

 

"I am now confident that supplementation with a NAD+ precursor like NMN or NR transiently increased the ratio of NAD+ to NADH (NAD/NADH), but the ratio returns to normal in the course of continued supplementation".

 

That is what the aim of the next round of clinical testing is to prove or disprove. "This placebo controlled double blind randomized crossover study will assess the potential benefits of daily NIAGEN supplementation over a course of six weeks." I also believe the mouse studies were conducted over the course of several weeks so if there are falling levels after boosting levels there should already be evidence of that.

[Tom Andre F. (ex shinobi)]

 

An interesting piece from Vince Giuliano at Anti-Aging Firewalls http://www.anti-agin...-interventions/

 

Cherry picking a quote from Vince:

 

"I am now confident that supplementation with a NAD+ precursor like NMN or NR transiently increased the ratio of NAD+ to NADH (NAD/NADH), but the ratio returns to normal in the course of continued supplementation".

 

That is what the aim of the next round of clinical testing is to prove or disprove. "This placebo controlled double blind randomized crossover study will assess the potential benefits of daily NIAGEN supplementation over a course of six weeks." I also believe the mouse studies were conducted over the course of several weeks so if there are falling levels after boosting levels there should already be evidence of that.

 

 

Well we need to actually control ourself the study result because I notice chromadex publish always result they like.. its logical for such business corporation but not a good thing for us.

For exemple, if there is a maximal boosting effect at week 4, and then decrease, they will cut the result at the time they want nor publish as a before / after.. Thats the problem. We need pure independent studies
 

[BigLabRat]

Well we need to actually control ourself the study result because I notice chromadex publish always result they like.. its logical for such business corporation but not a good thing for us.

For exemple, if there is a maximal boosting effect at week 4, and then decrease, they will cut the result at the time they want nor publish as a before / after.. Thats the problem. We need pure independent studies.

 

I don't disagree--independent studies would be great.

 

But independent studies almost never happen in the drug or supplement business, so I'm not exactly holding my breath!

 

(btw, thanks for the beta-lapachone info.)
 

[stefan_001]

 

An interesting piece from Vince Giuliano at Anti-Aging Firewalls http://www.anti-agin...-interventions/

 

Cherry picking a quote from Vince:

 

"I am now confident that supplementation with a NAD+ precursor like NMN or NR transiently increased the ratio of NAD+ to NADH (NAD/NADH), but the ratio returns to normal in the course of continued supplementation".

 

That is what the aim of the next round of clinical testing is to prove or disprove. "This placebo controlled double blind randomized crossover study will assess the potential benefits of daily NIAGEN supplementation over a course of six weeks." I also believe the mouse studies were conducted over the course of several weeks so if there are falling levels after boosting levels there should already be evidence of that.

 

 

I find that statement doubtfull. If you take it once a day then the boost will be gone in couple hours so how would the system adjust to that? If it were non stop supplementation then I could imagine that to be the case. If I eat sweet my blood sugar level will go up temporarely. I am eating sweet since I was born and the body regulation system is still not fast enough to get rid of the increase instantly.......

 

Edited by stefan_001, 23 August 2015 - 07:23 PM.

[Bryan_S]

 

 

An interesting piece from Vince Giuliano at Anti-Aging Firewalls http://www.anti-agin...-interventions/

 

Cherry picking a quote from Vince:

 

"I am now confident that supplementation with a NAD+ precursor like NMN or NR transiently increased the ratio of NAD+ to NADH (NAD/NADH), but the ratio returns to normal in the course of continued supplementation".

 

That is what the aim of the next round of clinical testing is to prove or disprove. "This placebo controlled double blind randomized crossover study will assess the potential benefits of daily NIAGEN supplementation over a course of six weeks." I also believe the mouse studies were conducted over the course of several weeks so if there are falling levels after boosting levels there should already be evidence of that.

 

 

Well we need to actually control ourself the study result because I notice chromadex publish always result they like.. its logical for such business corporation but not a good thing for us.

For exemple, if there is a maximal boosting effect at week 4, and then decrease, they will cut the result at the time they want nor publish as a before / after.. Thats the problem. We need pure independent studies
 

 

 

I'm sure ChromaDex filters the data to some extend but were are talking about peer reviewed studies. Not the sort of thing you want flying back into your face where you have to eat your words. I don't see anything suspicious.

 

For those who have their doubts and can afford to test your metabolites/NAD levels I contacted Genova Diagnostics some months back on the behalf of some other members wanting to set up some testing. They said they could do it. As far as I could tell there were no takers. Maybe one of you that looked into this can relate to the board how much money Genova wanted? Today I might wait long enough to see the human study parameters and work out what testing you'd need, so you'll know what to ask Genova Diagnostics to do.

 

http://www.longecity...e-5#entry720226

[albedo]

Thank you Brian, I like the idea to test. I would like to know exactly which marker can/should be tested but it can be expensive. I can maybe check my lab in Europe and see if they offer something. Anybody knows a similar test in EU? Of course I cannot to this in US unless visiting over there which nevertheless I do regularly. Will try to look into this and report something if worth.

[Bryan_S]

I'm sure we can find other labs that are capable.

[Bryan_S]

ACTIVATION OF AMP-PROTEIN ACTIVATED KINASE BY OXALOACETATE COMPOUNDS

 

United States Patent Application 20150238450 http://www.freepaten...15/0238450.html

 

Not sure if anyone else noticed this on the radar today, I think it deserves a little side research. Oxaloacetate also seems to be listed as a Caloric restriction mimetic and a AMPK Booster. There were some studies done on oxaloacetate and C. elegans. Now Caenorhabditis elegans are a rather easy organism to work with. It seems like we see a number of compounds increasing their life span. However it appears later studies included mouse models so there might be something to take note of after all.

 

I also found a little discussion on it here on LongeCity but it seems to have lost momentum.

 

At any rate anything that activates mitochondrial biogenesis and acts as a AMPK booster is topic on this thread.

 

[resveratrol_guy]

 

ACTIVATION OF AMP-PROTEIN ACTIVATED KINASE BY OXALOACETATE COMPOUNDS

 

United States Patent Application 20150238450 http://www.freepaten...15/0238450.html

 

Not sure if anyone else noticed this on the radar today, I think it deserves a little side research. Oxaloacetate also seems to be listed as a Caloric restriction mimetic and a AMPK Booster. There were some studies done on oxaloacetate and C. elegans. Now Caenorhabditis elegans are a rather easy organism to work with. It seems like we see a number of compounds increasing their life span. However it appears later studies included mouse models so there might be something to take note of after all.

 

I also found a little discussion on it here on LongeCity but it seems to have lost momentum.

 

At any rate anything that activates mitochondrial biogenesis and acts as a AMPK booster is topic on this thread.

 

 

Oxaloacetate seems to enhance endurance by increasing the rate at which latic acid can be recycled. This sounds good because the muscles and particularly the heart love to run on lactic acid. But by doing so, are we not simply allowing our bodies to operate more vigorously under hypoxic conditions than they would otherwise be capable of? Would this not foster cancer, which thrives in such conditions, utilizing glycolysis? I'm encouraged by your study entitled "Oxaloacetate Activates Brain Mitochondrial Biogenesis, Enhances the Insulin Pathway, Reduces Inflammation, and Stimulates Neurogenesis", and Lesson 8 on this blog page which applies to humans, but what about cancer?

 

Also, Bulletproof has some heady claims about its own oxaloacetate supplement, with links to a pile of research.

 

It deserves repeating: bitter gourd is a cheap and gastonomically unique way to hit AMPK, not that there aren't plenty of other options.

Edited by resveratrol_guy, 27 August 2015 - 11:07 PM.

[Supierce]

BIDMC Researchers Identify New Vitamin B3 Pathway

http://www.bidmc.org...reMedicine.aspx

[Tom Andre F. (ex shinobi)]

Here is the patent list regarding niagen: https://chromadex.co...ts/Patents.html

 

does that mean that no one else can synthesis NR without being under the patent law ??

[Asor]

Here is the patent list regarding niagen: https://chromadex.co...ts/Patents.html

 

does that mean that no one else can synthesis NR without being under the patent law ??

 

I think they patented their own particular process to make NR.

Others can eventually come up with a different process.