146 replies to this topic

[ceridwen]

I have a bad NQ01 gene. If I upregulate it would I increase my cancer risk?

[Tom Andre F. (ex shinobi)]

I have a bad NQ01 gene. If I upregulate it would I increase my cancer risk?

 

normally the opposite as beta lapachone was mainly studied as anti cancer drug: http://www.nature.co...icles/srep07769 or http://www.ncbi.nlm....pubmed/12188909

 

Seems cytotoxic only in cancer cell

 

 

[Tom Andre F. (ex shinobi)]

NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation

 

Oxygen and glucose deprivation (OGD) due to insufficient blood circulation can decrease cancer cell survival and proliferation in solid tumors. OGD increases the intracellular [AMP]/[ATP] ratio, thereby activating the AMPK. In this study, we have investigated the involvement of NQO1 in OGD-mediated AMPK activation and cancer cell death. We found that OGD activates AMPK in an NQO1-dependent manner, suppressing the mTOR/S6K/4E-BP1 pathway, which is known to control cell survival. Thus, the depletion of NQO1 prevents AMPK-induced cancer cell death in OGD. When we blocked OGD-induced Ca²⁺/CaMKII signaling, the NQO1-induced activation of AMPK was attenuated. In addition, when we blocked the RyR signaling, the accumulation of intracellular Ca²⁺ and subsequent activation of CaMKII/AMPK signaling was decreased in NQO1-expressing cells under OGD. Finally, siRNA-mediated knockdown of CD38 abrogated the OGD-induced activation of Ca²⁺/CaMKII/AMPK signaling. Taken together, we conclude that NQO1 plays a key role in the AMPK-induced cancer cell death in OGD through the CD38/cADPR/RyR/Ca²⁺/CaMKII signaling pathway.

 

http://www.nature.co...icles/srep07769

 

 

[Steve H]

Shame you need a truck load of BL :D A more permanent solution is needed.

[Tom Andre F. (ex shinobi)]

Well maybe no need for large dose, It deserve further data

 

 

[Nate-2004]

I was reading all the details about beta-lapachone from this page here: http://www.beta-lapachone.com/

 

I can't copy and paste it because the page owner protected it from being copied for some baffling reason, but that aside I wanted to comment on some of the issues and ask questions.

 

1) It says beta lapachone is said to kill a wide range of bacteria, fungus and viruses. Is that true? If so, would that not be a bad thing for the good bacteria in your gut's microbiota?

 

2) With regards to Tom's desire to get some of this expensive, rare stuff (available only from the tiniest corner of Nepal, high in the Himalayas, where only a few select, powerful monks with incredible martial arts skills guard the temple where the precious flower that contains this substance is kept), haha, it says the bioavailability is only 15% but that the half-life is beyond 24 hours. That is very interesting. If we could only get 1 gram, then taking 200mg per day may build up over time (30mg per day) over 5 days = 150mg at the end of the 5 days, staying in your system for who knows how long.

 

3) It also inhibits the telomerase enzyme, maybe I'm wrong, but wouldn't this make it so your telomeres in healthy cells continue to shorten rapidly or prevent your cells from dividing? I understand what it would do for cancer cells but what would this do exactly for healthy cells?

 

Edited by Nate-2004, 29 June 2016 - 02:13 PM.

[Tom Andre F. (ex shinobi)]

Nate,

 

the blog anti copy past is just because when people just copy past without the link of the source, then they dont realize they damage the SEO.

 

Normally beta-lapachone shouldnt damage telomerase in healthy cell, actually it should be the opposite and even give some telomerase activities, this is what was discussed in page 2 of this thread since it also activate PGC1a

 

beta lapachone is toxic only in cancer cell and cytoprotective in healthy one : http://www.ncbi.nlm....pubmed/24763872

 

this is what we see also for a wide range of herb extract, including resveratrol. Same for the anti fungus, virus.. effect. Since these (resveratrol, quercetin, pterostilbene..) are secondary metabolite from plant, their purpose was to protect the plant from parasite. But are you concerned about garlic, oignon ? they wouldnt touch your good bacteria in your gut.. even a study showed resveratrol is actually prebiotic and same for oignon.

 

also in the korean vivo studies you can clearly see that even better since they monitored a large range of biomarker. When you know how important is NAD+/NADH you understand its logical since its just opposed to the inflammatory state for instance. The mitochondria of the mice stayed very young.

 

But yeah its so bad this molecule is not so well developped and rare that only some very high martial art monk can get after some adventure in the mountain once every 10 year

[Tom Andre F. (ex shinobi)]

Another very interesting effect from beta lapachone on cardiovascular health:

 

Activation of NAD(P)H:Quinone Oxidoreductase 1 Prevents Arterial Restenosis by Suppressing Vascular Smooth Muscle Cell Proliferation

http://circres.ahajo...104/7/842.short

 

Abstract

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are important pathogenic mechanisms in atherosclerosis and restenosis after vascular injury. In this study, we investigated the effects of β-lapachone (βL) (3,4-Dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione), which is a potent antitumor agent that stimulates NAD(P)H:quinone oxidoreductase (NQO)1 activity, on neointimal formation in animals given vascular injury and on the proliferation of VSMCs cultured in vitro. βL significantly reduced the neointimal formation induced by balloon injury. βL also dose-dependently inhibited the FCS- or platelet-derived growth factor-induced proliferation of VSMCs by inhibiting G₁/S phase transition. βL increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase 1 in rat and human VSMCs. Chemical inhibitors of AMPK or dominant-negative AMPK blocked the βL-induced suppression of cell proliferation and the G₁ cell cycle arrest, in vitro and in vivo. The activation of AMPK in VSMCs by βL is mediated by LKB1 in the presence of NQO1. Taken together, these results show that βL inhibits VSMCs proliferation via the NQO1 and LKB1-dependent activation of AMPK. These observations provide the molecular basis that pharmacological stimulation of NQO1 activity is a new therapy for the treatment of vascular restenosis and/or atherosclerosis which are caused by proliferation of VSMCs.

 

[Tom Andre F. (ex shinobi)]

Another article about beta lapachone and brown fat : http://www.beta-lapa...-adipose-cells/

[Female Scientist]

Hi Folks, Just found you over here from the NR thread. BL looks very promising indeed. Sorry if this is a dumb question, but are there concerns about taking BL simply via Pau D'Arco -- Nature's Way on Amazon offers it 545 mg per cap $11.41 per 180 capsules?? And if this is a good way to get the BL, what would the suggested dose be? The bottle advises 2 caps twice daily with meals.... Thanks in advance for answers...

[Nate-2004]

Hi Folks, Just found you over here from the NR thread. BL looks very promising indeed. Sorry if this is a dumb question, but are there concerns about taking BL simply via Pau D'Arco -- Nature's Way on Amazon offers it 545 mg per cap $11.41 per 180 capsules?? And if this is a good way to get the BL, what would the suggested dose be? The bottle advises 2 caps twice daily with meals.... Thanks in advance for answers...

 

I'm curious about that too. I don't think it's the same thing.

 

I'm still curious as to why this isn't being manufactured yet.

[hamishm00]

No issues from my side with supplementing 3 x caps Pau D'arco + NR + 100mg pterostilbene as a stack.

 

There is potentially a decent amount of beta-lapachone in "Donny D'arco", perhaps enough to meaningfully facilitate the oxidation of NADH to NAD+ by NQO1. Of course there is a laundry list of other stuff in there: acetaldehydes, alpha-lapachone, ajugols, anisic acid, anthraquinones, benzoic acids, benzenes, carboxaldehydes, chromium, chrysanthemin, dehydro-alpha-lapachone, dehydroisolapachone, deoxylapachol, flavonoids, furanonaphthoquinones, hydrochlorolapachol, 2-hydroxy-3-methyl-quinone, 6-hydroxy-mellein, iso-8-hydroxy-lariciresinol, kigelinone, lapachenol, lapachenole, lapachol, lapachones, menaquinones, 4-methoxyphenol, naphthoquinones, paeonidin-3-cinnamyl-sophoroside, phthiolol, quercetin, tabebuin, tectoquinone, vanillic acid, vanillin, veratric acid, veratric aldehyde, and xyloidone.

 

A pure source of b-lapachone would be nice - any supplement companies out there reading this:  nudge nudge.

[Nate-2004]

No issues from my side with supplementing 3 x caps Pau D'arco + NR + 100mg pterostilbene as a stack.

 

There is potentially a decent amount of beta-lapachone in "Donny D'arco", perhaps enough to meaningfully facilitate the oxidation of NADH to NAD+ by NQO1. Of course there is a laundry list of other stuff in there: acetaldehydes, alpha-lapachone, ajugols, anisic acid, anthraquinones, benzoic acids, benzenes, carboxaldehydes, chromium, chrysanthemin, dehydro-alpha-lapachone, dehydroisolapachone, deoxylapachol, flavonoids, furanonaphthoquinones, hydrochlorolapachol, 2-hydroxy-3-methyl-quinone, 6-hydroxy-mellein, iso-8-hydroxy-lariciresinol, kigelinone, lapachenol, lapachenole, lapachol, lapachones, menaquinones, 4-methoxyphenol, naphthoquinones, paeonidin-3-cinnamyl-sophoroside, phthiolol, quercetin, tabebuin, tectoquinone, vanillic acid, vanillin, veratric acid, veratric aldehyde, and xyloidone.

 

A pure source of b-lapachone would be nice - any supplement companies out there reading this:  nudge nudge.

 

There are some people on here who might know how to isolate it.

[Black Fox]

Beta-lapachone may raise NAD+/NADH ratio .... But lapachenol, lapachenole, lapachol, lapachones are toxic, if not cancer promoter ...... Stay away from Pau d'arco at least for the long run or high doses

There ain't no affordable beta-lapachone source avail yet

[Tom Andre F. (ex shinobi)]

Unfortunately I already looked around to isolated beta-lapachone from pau darco and it looked very difficult. So as for pterostilbene, best is synthetic form to get it pure. I also dont want all the others compounds packaged in pau darco.

 

Maybe if we are enough we could get the price below the 250$ / 200$ per gram. Its really unfortunate as I see this as the best option to modulate NAD+. Especially the study show a real increase in energy in mice, better cognition, lifespan increase and weight control. I also like the effect on brown fat especially. Maybe someone can help to organize a group buy ?

[Nate-2004]

Unfortunately I already looked around to isolated beta-lapachone from pau darco and it looked very difficult. So as for pterostilbene, best is synthetic form to get it pure. I also dont want all the others compounds packaged in pau darco.

 

Maybe if we are enough we could get the price below the 250$ / 200$ per gram. Its really unfortunate as I see this as the best option to modulate NAD+. Especially the study show a real increase in energy in mice, better cognition, lifespan increase and weight control. I also like the effect on brown fat especially. Maybe someone can help to organize a group buy ?

 

We'd have to have a source to organize that with. I'm guessing nobody on the board works in the area of synthesizing it?

[hamishm00]

Beta-lapachone may raise NAD+/NADH ratio .... But lapachenol, lapachenole, lapachol, lapachones are toxic, if not cancer promoter ...... Stay away from Pau d'arco at least for the long run or high doses

There ain't no affordable beta-lapachone source avail

 

 

Lapachol was actually used to treat cancer, but the required doses were too high and caused side effects. Applying your thinking, you could also argue that Resveratrol, pterostilbene etc are also toxic (they're produced by plants to kill biological organisms). I would do a bit of research into Hormesis. Toxic isn't always bad. Hormesis is a biological phenomenon whereby a beneficial effect (improved health, stress tolerance, growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses.

Edited by hamishm00, 17 August 2016 - 04:43 AM.

[hamishm00]

Beta-lapachone may raise NAD+/NADH ratio .... But lapachenol, lapachenole, lapachol, lapachones are toxic, if not cancer promoter ...... Stay away from Pau d'arco at least for the long run or high doses

There ain't no affordable beta-lapachone source avail yet

 

Not sure how you reach the conclusion that lapachol or any lapachone is a cancer promoter - sources please? I would say the opposite is true. It appears to only be toxic to cancer cells or cell lines derived from cancers:

 

Lapachol as an anti-cancer/treatment drug: http://www.ncbi.nlm....pubmed/15643520
tumor growth inhibitory activity: http://www.sciencedi...960894X13014212

Beta-lapachone is lethal at micromolar concentrations against a variety of cancer cells and shows promise as an anti-cancer drug: http://www.ncbi.nlm....pubmed/12188909

and http://www.ncbi.nlm..../pubmed/7641181

Beta-lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cells: a p53-independent response.http://www.ncbi.nlm....0?dopt=Abstract

Cyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-kappaB-dependent XIAP up-regulation.http://www.ncbi.nlm....4?dopt=Abstract

An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by beta-lapachone.http://www.ncbi.nlm....0?dopt=Abstract

beta-Lapachone-induced apoptosis is associated with activation of caspase-3 and inactivation of NF-kappaB in human colon cancer HCT-116 cells. http://www.ncbi.nlm....0?dopt=Abstract

Beta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell lines: Eye. 2008 Mar;22(3): Shah HR, Conway RM, Van Quill KR, Madigan MC, Howard SA, Qi J, Weinberg V, O'Brien JM. Department of Ophthalmology, University of California at San Francisco, San Francisco, CA, USA.
To investigate the cytotoxicity of beta-lapachone, a potent agent that may selectively target tumour cells, in retinoblastoma cell lines. Growth inhibitory effects of beta-lapachone were evaluated in Y79, WERI-RB1, and RBM human retinoblastoma cell lines. Pro-apoptotic effects of beta-lapachone were evaluated in Y79 cells. Beta-lapachone induced significant dose-dependent growth inhibitory effects in all three retinoblastoma cell lines. Beta-lapachone also induced proapoptotic effects in retinoblastoma cells. Beta-lapachone induced potent cytotoxic effects in retinoblastoma cell lines at low micromolar concentrations, suggesting this agent could be useful in the clinical management of retinoblastoma.

 

[Black Fox]

Beta-lapachone may raise NAD+/NADH ratio .... But lapachenol, lapachenole, lapachol, lapachones are toxic, if not cancer promoter ...... Stay away from Pau d'arco at least for the long run or high dosesThere ain't no affordable beta-lapachone source avail yet

Not sure how you reach the conclusion that lapachol or any lapachone is a cancer promoter - sources please? I would say the opposite is true. It appears to only be toxic to cancer cells or cell lines derived from cancers:Lapachol as an anti-cancer/treatment drug: http://www.ncbi.nlm....pubmed/15643520tumor growth inhibitory activity: http://www.sciencedi...960894X13014212Beta-lapachone is lethal at micromolar concentrations against a variety of cancer cells and shows promise as an anti-cancer drug: http://www.ncbi.nlm....pubmed/12188909and http://www.ncbi.nlm..../pubmed/7641181Beta-lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cells: a p53-independent response.http://www.ncbi.nlm....0?dopt=AbstractCyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-kappaB-dependent XIAP up-regulation.http://www.ncbi.nlm....4?dopt=AbstractAn NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by beta-lapachone.http://www.ncbi.nlm....0?dopt=Abstractbeta-Lapachone-induced apoptosis is associated with activation of caspase-3 and inactivation of NF-kappaB in human colon cancer HCT-116 cells. http://www.ncbi.nlm....0?dopt=AbstractBeta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell lines: Eye. 2008 Mar;22(3): Shah HR, Conway RM, Van Quill KR, Madigan MC, Howard SA, Qi J, Weinberg V, O'Brien JM. Department of Ophthalmology, University of California at San Francisco, San Francisco, CA, USA.To investigate the cytotoxicity of beta-lapachone, a potent agent that may selectively target tumour cells, in retinoblastoma cell lines. Growth inhibitory effects of beta-lapachone were evaluated in Y79, WERI-RB1, and RBM human retinoblastoma cell lines. Pro-apoptotic effects of beta-lapachone were evaluated in Y79 cells. Beta-lapachone induced significant dose-dependent growth inhibitory effects in all three retinoblastoma cell lines. Beta-lapachone also induced proapoptotic effects in retinoblastoma cells. Beta-lapachone induced potent cytotoxic effects in retinoblastoma cell lines at low micromolar concentrations, suggesting this agent could be useful in the clinical management of retinoblastoma.

Beta-Lapachone and Lapachol are two things way different and both present in Pau d'arco.As just said to stay away from high doses of Pau d'arco as lapachol at high doses is toxic.There were references in NR discussion group. And believe it was toxicology study in rats as well.Sorry I'm kinda really busy to be looking for it http://www.beta-lapachone.com/safety/

Edited by Black Fox, 19 August 2016 - 08:04 AM.

[hamishm00]

 

 

Beta-lapachone may raise NAD+/NADH ratio .... But lapachenol, lapachenole, lapachol, lapachones are toxic, if not cancer promoter ...... Stay away from Pau d'arco at least for the long run or high dosesThere ain't no affordable beta-lapachone source avail yet

Not sure how you reach the conclusion that lapachol or any lapachone is a cancer promoter - sources please? I would say the opposite is true. It appears to only be toxic to cancer cells or cell lines derived from cancers:Lapachol as an anti-cancer/treatment drug: http://www.ncbi.nlm....pubmed/15643520tumor growth inhibitory activity: http://www.sciencedi...960894X13014212Beta-lapachone is lethal at micromolar concentrations against a variety of cancer cells and shows promise as an anti-cancer drug: http://www.ncbi.nlm....pubmed/12188909and http://www.ncbi.nlm..../pubmed/7641181Beta-lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cells: a p53-independent response.http://www.ncbi.nlm....0?dopt=AbstractCyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-kappaB-dependent XIAP up-regulation.http://www.ncbi.nlm....4?dopt=AbstractAn NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by beta-lapachone.http://www.ncbi.nlm....0?dopt=Abstractbeta-Lapachone-induced apoptosis is associated with activation of caspase-3 and inactivation of NF-kappaB in human colon cancer HCT-116 cells. http://www.ncbi.nlm....0?dopt=AbstractBeta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell lines: Eye. 2008 Mar;22(3): Shah HR, Conway RM, Van Quill KR, Madigan MC, Howard SA, Qi J, Weinberg V, O'Brien JM. Department of Ophthalmology, University of California at San Francisco, San Francisco, CA, USA.To investigate the cytotoxicity of beta-lapachone, a potent agent that may selectively target tumour cells, in retinoblastoma cell lines. Growth inhibitory effects of beta-lapachone were evaluated in Y79, WERI-RB1, and RBM human retinoblastoma cell lines. Pro-apoptotic effects of beta-lapachone were evaluated in Y79 cells. Beta-lapachone induced significant dose-dependent growth inhibitory effects in all three retinoblastoma cell lines. Beta-lapachone also induced proapoptotic effects in retinoblastoma cells. Beta-lapachone induced potent cytotoxic effects in retinoblastoma cell lines at low micromolar concentrations, suggesting this agent could be useful in the clinical management of retinoblastoma.

Beta-Lapachone and Lapachol are two things way different and both present in Pau d'arco.As just said to stay away from high doses of Pau d'arco as lapachol at high doses is toxic.There were references in NR discussion group. And believe it was toxicology study in rats as well.Sorry I'm kinda really busy to be looking for it http://www.beta-lapachone.com/safety/

 

 

Yes I am aware tha Lapachol and Beta-Lapachone are two different things, but they're not that different (please see the beginning of the same link that you actually pasted where it says: "similar molecules with similar modes of action"). So the concern was that in drug trials it was noted that high doses of lapachol caused significant side effects, but otherwise was an anti-tumor/cancer agent (I refer to the two studies I quoted above on Lapachol).

 

Your position that these compounds might cause cancer isn't backed up by the material I have been able to find on either Lapachol or beta lapachone, and I'd really appreciate it if you could cast further light on this. I do agree that there is a reason to be cautious when taking Pau D'arco and certainly not in high doses otherwise you might suffer from the already documented side effects.

[Tom Andre F. (ex shinobi)]

Well more than the debate lapachol / beta lapachone, since we dont know what is the % of beta lapachone inside pau d'arco, (especially when it comes dried powder...) I would not use it as a reliable source. There is also no standarized extract since it seems the process is hard and costly. For the recall, the korean studies used the pure synthetic version.

 

Thats why I think we should maybe give a try to very low dose such as 10mg per day to decrease the cost. Still also the problem to make the dosage at home, we will need an electronic and reliable balance since fda would not allow to make it a dietary supplement bottle.

 

 

 

[stefan_001]

We have contributed to this field by uncovering the effect of β-lapachone on DUBs, by demonstrating that the mechanism of inhibition by β-lapachone proceeds via ROS generation and irreversible oxidation of the catalytic Cys moiety to the sulfinic acid form (Fig. 1).¹⁴ Of particular interest is USP2, due to its association with aggressive prostate cancer and triple negative breast cancer.¹⁷ 

......

Incubation at 6 μM concentration for two hours resulted in 3.92% apoptosis for the DMSO control, 50% for β-lapachone, ∼51% for 12, 13% for 9 and 9% for 7 (Fig. 6). 

 

http://pubs.rsc.org/...6/sc/c6sc02758j

[Tom Andre F. (ex shinobi)]

We have contributed to this field by uncovering the effect of β-lapachone on DUBs, by demonstrating that the mechanism of inhibition by β-lapachone proceeds via ROS generation and irreversible oxidation of the catalytic Cys moiety to the sulfinic acid form (Fig. 1).¹⁴ Of particular interest is USP2, due to its association with aggressive prostate cancer and triple negative breast cancer.¹⁷ 

......

Incubation at 6 μM concentration for two hours resulted in 3.92% apoptosis for the DMSO control, 50% for β-lapachone, ∼51% for 12, 13% for 9 and 9% for 7 (Fig. 6). 

 

http://pubs.rsc.org/...6/sc/c6sc02758j

 

Interesting, it seems that beta-lapachone kind of regulate the over expression in cancer. DUbs is necessary for ubiquitin recycling and homeostasis maintenance. But these start to be over complicated topic to me.

 

Its also interesting to see the mechanism where the difference is made between high ROS condition where cancer cell survive and generate ROS through redox cycling
 

[to age or not to age]

 

Unfortunately I already looked around to isolated beta-lapachone from pau darco and it looked very difficult. So as for pterostilbene, best is synthetic form to get it pure. I also dont want all the others compounds packaged in pau darco.

 

Maybe if we are enough we could get the price below the 250$ / 200$ per gram. Its really unfortunate as I see this as the best option to modulate NAD+. Especially the study show a real increase in energy in mice, better cognition, lifespan increase and weight control. I also like the effect on brown fat especially. Maybe someone can help to organize a group buy ?

 

We'd have to have a source to organize that with. I'm guessing nobody on the board works in the area of synthesizing it?

 

Nate over the past year, I have worked with two chemists who undertook synthesizing it (BL) for me.

We made a bit under ten grams.  The cost of the raw materials was 200 dollars per gram.  two weeks ago I had a proton NMR done on this sample. It is >97% pure.  The chemists attribute any small impurity to the vial I shipped it inn to the testing lab.  I gave samples to Lenny Guarante (MIT) and David Sinclair (Harvard) both of whom I know and filmed for my movie To Age or Not To Age.  They were both impressed with the purity.

My chemists have worked out the kinks of producing Beta Lapachone, as the NMR reports highlights.

So, my big question is: what is a reasonable and conservative dosage? To give some perspective.  A doctor I contacted is himself taking 6mg of Rapamycin once a week, and will do so for one year.  It could be that beta lapachone, like rapamycin, should be cycled, and at small doses.  Any ideas? Finally, I could supply a group buy, but we need to discuss dosage. 

[Nate-2004]

Nate over the past year, I have worked with two chemists who undertook synthesizing it (BL) for me.

 

We made a bit under ten grams.  The cost of the raw materials was 200 dollars per gram.  two weeks ago I had a proton NMR done on this sample. It is >97% pure.  The chemists attribute any small impurity to the vial I shipped it inn to the testing lab.  I gave samples to Lenny Guarante (MIT) and David Sinclair (Harvard) both of whom I know and filmed for my movie To Age or Not To Age.  They were both impressed with the purity.

My chemists have worked out the kinks of producing Beta Lapachone, as the NMR reports highlights.

So, my big question is: what is a reasonable and conservative dosage? To give some perspective.  A doctor I contacted is himself taking 6mg of Rapamycin once a week, and will do so for one year.  It could be that beta lapachone, like rapamycin, should be cycled, and at small doses.  Any ideas? Finally, I could supply a group buy, but we need to discuss dosage. 

 

 

Yeah I'd love to know what the dosage would be, I'd be interested in a group buy. Might be useful to sell some of that to some researchers and help crowd source some human studies if it's not hard or expensive to get approval for phase 1. Unfortunately with the FDA you have to treat a specific disease, and they won't classify aging as a disease. It's utterly obnoxious because that not only makes it more expensive but it's like shooting randomly into the dark, trying to hit a bullseye and then presuming that if you miss your mark, the gun is broken rather than just testing on healthy subjects over 45, measuring everything and seeing what happens. I guess the best first target is patients with diabetes or obesity?

[to age or not to age]

 

Nate over the past year, I have worked with two chemists who undertook synthesizing it (BL) for me.

 

We made a bit under ten grams.  The cost of the raw materials was 200 dollars per gram.  two weeks ago I had a proton NMR done on this sample. It is >97% pure.  The chemists attribute any small impurity to the vial I shipped it inn to the testing lab.  I gave samples to Lenny Guarante (MIT) and David Sinclair (Harvard) both of whom I know and filmed for my movie To Age or Not To Age.  They were both impressed with the purity.

My chemists have worked out the kinks of producing Beta Lapachone, as the NMR reports highlights.

So, my big question is: what is a reasonable and conservative dosage? To give some perspective.  A doctor I contacted is himself taking 6mg of Rapamycin once a week, and will do so for one year.  It could be that beta lapachone, like rapamycin, should be cycled, and at small doses.  Any ideas? Finally, I could supply a group buy, but we need to discuss dosage. 

 

 

Yeah I'd love to know what the dosage would be, I'd be interested in a group buy. Might be useful to sell some of that to some researchers and help crowd source some human studies if it's not hard or expensive to get approval for phase 1. Unfortunately with the FDA you have to treat a specific disease, and they won't classify aging as a disease. It's utterly obnoxious because that not only makes it more expensive but it's like shooting randomly into the dark, trying to hit a bullseye and then presuming that if you miss your mark, the gun is broken rather than just testing on healthy subjects over 45, measuring everything and seeing what happens. I guess the best first target is patients with diabetes or obesity?

 

 

[to age or not to age]

 

 

Nate over the past year, I have worked with two chemists who undertook synthesizing it (BL) for me.

 

We made a bit under ten grams.  The cost of the raw materials was 200 dollars per gram.  two weeks ago I had a proton NMR done on this sample. It is >97% pure.  The chemists attribute any small impurity to the vial I shipped it inn to the testing lab.  I gave samples to Lenny Guarante (MIT) and David Sinclair (Harvard) both of whom I know and filmed for my movie To Age or Not To Age.  They were both impressed with the purity.

My chemists have worked out the kinks of producing Beta Lapachone, as the NMR reports highlights.

So, my big question is: what is a reasonable and conservative dosage? To give some perspective.  A doctor I contacted is himself taking 6mg of Rapamycin once a week, and will do so for one year.  It could be that beta lapachone, like rapamycin, should be cycled, and at small doses.  Any ideas? Finally, I could supply a group buy, but we need to discuss dosage. 

 

 

Yeah I'd love to know what the dosage would be, I'd be interested in a group buy. Might be useful to sell some of that to some researchers and help crowd source some human studies if it's not hard or expensive to get approval for phase 1. Unfortunately with the FDA you have to treat a specific disease, and they won't classify aging as a disease. It's utterly obnoxious because that not only makes it more expensive but it's like shooting randomly into the dark, trying to hit a bullseye and then presuming that if you miss your mark, the gun is broken rather than just testing on healthy subjects over 45, measuring everything and seeing what happens. I guess the best first target is patients with diabetes or obesity?

 

 

I also gave a sample to researchers at Buck during the SENS conference. They will test it on worms (not exactly what I need) I have been thinking about having it tested on healthy middle aged mice, alone and in conjunction  with rapamycin, and again with resveratrol. Both rapamycin and beta lapachone partially overlap the gene impacts of calorie restriction.  Further, rapamycin seems to impact the gut bacteria, while beta lapachone impacts the NAD ratio and the key NQOi gene. So, it is possible that these are substantially different pathways, both very important, and possibly complimentary.

[to age or not to age]

 

 

 

Nate over the past year, I have worked with two chemists who undertook synthesizing it (BL) for me.

 

We made a bit under ten grams.  The cost of the raw materials was 200 dollars per gram.  two weeks ago I had a proton NMR done on this sample. It is >97% pure.  The chemists attribute any small impurity to the vial I shipped it inn to the testing lab.  I gave samples to Lenny Guarante (MIT) and David Sinclair (Harvard) both of whom I know and filmed for my movie To Age or Not To Age.  They were both impressed with the purity.

My chemists have worked out the kinks of producing Beta Lapachone, as the NMR reports highlights.

So, my big question is: what is a reasonable and conservative dosage? To give some perspective.  A doctor I contacted is himself taking 6mg of Rapamycin once a week, and will do so for one year.  It could be that beta lapachone, like rapamycin, should be cycled, and at small doses.  Any ideas? Finally, I could supply a group buy, but we need to discuss dosage. 

 

 

Yeah I'd love to know what the dosage would be, I'd be interested in a group buy. Might be useful to sell some of that to some researchers and help crowd source some human studies if it's not hard or expensive to get approval for phase 1. Unfortunately with the FDA you have to treat a specific disease, and they won't classify aging as a disease. It's utterly obnoxious because that not only makes it more expensive but it's like shooting randomly into the dark, trying to hit a bullseye and then presuming that if you miss your mark, the gun is broken rather than just testing on healthy subjects over 45, measuring everything and seeing what happens. I guess the best first target is patients with diabetes or obesity?

 

 

I also gave a sample to researchers at Buck during the SENS conference. They will test it on worms (not exactly what I need) I have been thinking about having it tested on healthy middle aged mice, alone and in conjunction  with rapamycin, and again with resveratrol. Both rapamycin and beta lapachone partially overlap the gene impacts of calorie restriction.  Further, rapamycin seems to impact the gut bacteria, while beta lapachone impacts the NAD ratio and the key NQOi gene. So, it is possible that these are substantially different pathways, both very important, and possibly complimentary.

 

So my question is: if for instance, a 25mg dose is taken each day for a week, does anyone have any insight into how much beta lapachone would remain in the plasma after one week. And if beta lapachone is discontinued after one week, how much BL would remain in the blood plasma after two weeks?

[to age or not to age]

 

I think there is plenty to find out. This is one the graphs that creates doubts in my mind from the earlier cited papers.You can see that in the cisplatin treated mice BL helps recover SIRT1 and SIRT3. But the impact of BL on healthy mice SIRT levels is more or less zero. So the claim that it acts like the CR mechanism is not supported by that graph at least for the healthy mice.The mice used were only 8 weeks old so perhaps the effect may be different in aging mice that have declining SIRT levels.

 

 

This is a reasonable conclusion. Very young mice at 8 weeks are unlikely to benefit from it as they already presumably have optimal levels. We have found this working in Senolytics too, very old mice benefit but very young mice do not because they have not developed the declines associated with aging so there is nothing to treat. I would not be at all surprised to see exactly the same with BL here because again a young mouse does not need repairing. 

 

The graphs also show that the SIRT levels dont recover to the heathy mice level with BL treatment. Why is that? Still not enough NAD+ in the cell? Another rate limiting mechanism? This is one of the reasons I would love to see graphs showing the absolute values of NAD+ instead of the ratio's.

 

 

It may be as simple as not enough induction from the dosage. Bearing in mind the optimal dosage and frequency are yet to be established. So increasing the dose could well increase that NAD+ ratio. This is very easy to investigate and I could design a test group to estalish the dosage rapidly. 

To conclude there is in my view sufficient data to suggest that BL may be able to upregulate the master controller NQ01 and as it is a primary target far upstream worth investigating. 

 

 

[to age or not to age]

 

 

I think there is plenty to find out. This is one the graphs that creates doubts in my mind from the earlier cited papers.You can see that in the cisplatin treated mice BL helps recover SIRT1 and SIRT3. But the impact of BL on healthy mice SIRT levels is more or less zero. So the claim that it acts like the CR mechanism is not supported by that graph at least for the healthy mice.The mice used were only 8 weeks old so perhaps the effect may be different in aging mice that have declining SIRT levels.

 

 

This is a reasonable conclusion. Very young mice at 8 weeks are unlikely to benefit from it as they already presumably have optimal levels. We have found this working in Senolytics too, very old mice benefit but very young mice do not because they have not developed the declines associated with aging so there is nothing to treat. I would not be at all surprised to see exactly the same with BL here because again a young mouse does not need repairing. 

 

The graphs also show that the SIRT levels dont recover to the heathy mice level with BL treatment. Why is that? Still not enough NAD+ in the cell? Another rate limiting mechanism? This is one of the reasons I would love to see graphs showing the absolute values of NAD+ instead of the ratio's.

 

 

It may be as simple as not enough induction from the dosage. Bearing in mind the optimal dosage and frequency are yet to be established. So increasing the dose could well increase that NAD+ ratio. This is very easy to investigate and I could design a test group to estalish the dosage rapidly. 

To conclude there is in my view sufficient data to suggest that BL may be able to upregulate the master controller NQ01 and as it is a primary target far upstream worth investigating.