Amazing Medicinal Properties Of Beta-lapachone (β-lapachone)

haidut · Jan 29, 2016

Dan W · Jan 29, 2016

Here's "title-ified" versions of the links.

Miscellaneous

Preclinical Pharmacokinetic Evaluation of β-Lapachone: Characteristics of Oral Bioavailability and First-Pass Metabolism in Rats.
Cancer therapy with beta-lapachone.
β-Lapachone attenuates mitochondrial dysfunction in MELAS cybrid cells.
Beta-lapachone inhibits pathological retinal neovascularization in oxygen-induced retinopathy via regulation of HIF-1α.
Beta-lapachone, a modulator of NAD metabolism, prevents health declines in aged mice.
β-lapachone accelerates the recovery of burn-wound skin.
Corpus cavernosal smooth muscle relaxation effect of a novel AMPK activator, beta-lapachone.
Beta-lapachone suppresses radiation-induced activation of nuclear factor-kappaB.
In vitro and in vivo wound healing-promoting activities of beta-lapachone.
Suppression of tumor necrosis factor-activated nuclear transcription factor-kappaB, activator protein-1, c-Jun N-terminal kinase, and apoptosis by ...

Cancer/Hypoxia

Cortisol/Diabetes/Obesity

Beta-lapachone, a specific competitive inhibitor of ligand binding to the glucocorticoid receptor.

Inflammation/CVD

Neurological/Mental/Mood

Endotoxin/Gastrointestinal/Liver/Pancreas/Kidney

Anti-viral/Anti-bacterial/Anti-parasitic/Anti-fungal

Blossom · Jan 29, 2016

That's so nice of you to type all of that out Dan!

Dan W · Jan 29, 2016

I'd like to take credit, but I just made a shoddily-constructed script to do it. So it's entirely possible the post will burst into flames at some point.

Blossom · Jan 29, 2016

Dan Wich said:
I'd like to take credit, but I just made a shoddily-constructed script to do it. So it's entirely possible the post will burst into flames at some point.

I'll keep the fire extinguisher on standby! I wish @firebreather was around.

firebreather · Feb 1, 2016

Blossom said:
I'll keep the fire extinguisher on standby! I wish @firebreather was around.

@Blossom

Makrosky · Feb 2, 2016

haidut,

When you compile lists of articles on pubmed to support your thesis, do you cherry pick them ? I mean, do you include only the ones that confirm your point of view or do you take into account also the ones that doesn't ? How do you do it ? I'm asking you this because I trust and value your work a lot but I'm concerned of a possible confirmation bias.

I'm asking you this because I almost never see you posting evidence against Ray Peat supps, and I'm pretty sure pubmed is big enough to hold studies from both sides.

Last week you posted something about antibiotics being bad for respiration, IIRC. But that's an exception I guess.

cantstoppeating · Feb 3, 2016

Dan Wich said:
I'd like to take credit, but I just made a shoddily-constructed script to do it. So it's entirely possible the post will burst into flames at some point.

Can you do this for Haidut's other supplement threads? Mods, can you help with this?

It's immensely helpful to see the title each pubmed link rather than the url.

charlie · Feb 3, 2016

cantstoppeating said:
Mods, can you help with this?

Yes, and the forum software is now setup to pull the page title for any link posted. Example: Cancer therapy with beta-lapachone. - PubMed - NCBI

haidut · Feb 4, 2016

Makrosky said:
haidut,

When you compile lists of articles on pubmed to support your thesis, do you cherry pick them ? I mean, do you include only the ones that confirm your point of view or do you take into account also the ones that doesn't ? How do you do it ? I'm asking you this because I trust and value your work a lot but I'm concerned of a possible confirmation bias.

I'm asking you this because I almost never see you posting evidence against Ray Peat supps, and I'm pretty sure pubmed is big enough to hold studies from both sides.

Last week you posted something about antibiotics being bad for respiration, IIRC. But that's an exception I guess.

We all have confirmation bias, it's an unavoidable side effect of being a human with unique experiences. My selection bias is largely based on how many times a study has been quoted and in what journals. Kind of like the Google pagerank algorithm, which btw was developed by looking at citations of scientific studies.
The benefit of quinones is fairly well-established and there aren't many studies refuting their effects. Of course, that does not mean the consensus is correct.
Anyways, if you like to see the opposite view try to find studies that speak negatively about these quinones. I guess it comes down to what you believe the evidence point to. If you believe bioenergetics evidence trumps genetics' then PubMed starts to look like a disjointed set of various schools of thought, so using evidence from one school to refute findings from another does not make much sense. For instance, there would not be much point in including counter-evidence for quinones from a geneticist that works on the premise that it is mutations cause cancer and very high doses of emodin are mutagenic. However, if I find evidence from the bioenergetic school of thought that says physiological doses of emodin inhibit respiration or cause hypoxia then of course I would be paying close attention to it. So far, there have been no such cases but if you are aware of such studies please post here.

SQu · Feb 4, 2016

"If you believe bioenergetics evidence trumps genetics"

You gave me a bit of a fright. What's he doing in this thread? I wondered. I'm trying to avoid him.

tara · Feb 4, 2016

SQu said:
You gave me a bit of a fright. What's he doing in this thread? I wondered. I'm trying to avoid him.

Tee hee.

Makrosky · Feb 4, 2016

haidut said:
We all have confirmation bias, it's an unavoidable side effect of being a human with unique experiences. My selection bias is largely based on how many times a study has been quoted and in what journals. Kind of like the Google pagerank algorithm, which btw was developed by looking at citations of scientific studies.
The benefit of quinones is fairly well-established and there aren't many studies refuting their effects. Of course, that does not mean the consensus is correct.
Anyways, if you like to see the opposite view try to find studies that speak negatively about these quinones. I guess it comes down to what you believe the evidence point to. If you believe bioenergetics evidence trumps genetics' then PubMed starts to look like a disjointed set of various schools of thought, so using evidence from one school to refute findings from another does not make much sense. For instance, there would not be much point in including counter-evidence for quinones from a geneticist that works on the premise that it is mutations cause cancer and very high doses of emodin are mutagenic. However, if I find evidence from the bioenergetic school of thought that says physiological doses of emodin inhibit respiration or cause hypoxia then of course I would be paying close attention to it. So far, there have been no such cases but if you are aware of such studies please post here.

haidut, thanks a lot for taking the time to reply. I agree we all have confirmation bias in ALL aspects of life. Regarding the different schools of thought... well.... What you said makes sense. I don't know that much to have an opinion about it, so I'll take your word on that.

I still think we all are caught in a confirmation bias in this forum like when we don't believe in the key/keyhole mechanical way of seeing the ligand/receptor interactions (after having read Peat theories) BUT we still use the keyhole idea and the papers to explain things and try supplements and construct hypothesis and stuff.

And no I'm not aware of such studies. I wasn't talking about quinones specifically, but more in general.

Regards

haidut · Feb 5, 2016

Makrosky said:
haidut, thanks a lot for taking the time to reply. I agree we all have confirmation bias in ALL aspects of life. Regarding the different schools of thought... well.... What you said makes sense. I don't know that much to have an opinion about it, so I'll take your word on that.

I still think we all are caught in a confirmation bias in this forum like when we don't believe in the key/keyhole mechanical way of seeing the ligand/receptor interactions (after having read Peat theories) BUT we still use the keyhole idea and the papers to explain things and try supplements and construct hypothesis and stuff.

And no I'm not aware of such studies. I wasn't talking about quinones specifically, but more in general.

Regards

I would have gladly used studies that do not use the key/receptor mechanism but there aren't many of them on PubMed. So, I guess we have to rely on the actual results (beneficial vs. not beneficial) to gauge what is good or not. Btw, many of these studies do talk about the effect of these quinones on things like NAD and lowering estrogen/serotonin/HIF/lactate so they are consistent with Peat's "bias" but stop short of crediting these bioenergetic effects as the main mechanism of action. It is unwritten rule that unless you find a key/receptor explanation the study won't have much practical (read financial) merit. As Peat mentioned in one of his articles, there is no study explaining the aspirin "receptor" yet everybody agrees that it is a very beneficial drug that works through "unexplainable" ways.

Parsifal · Feb 26, 2016

What effets do NAD have on metabolism?

haidut · Feb 28, 2016

Parsifal said:
What effets do NAD have on metabolism?

Without enough NAD you will be stuck in glycolysis and overproducing lactate. Also, if this leads to an excess of NADH all kinds of other nasty stuff can happen including neuroexcitotoxicity and even cancer.

David Chung · Mar 12, 2016

haidut said:
Without enough NAD you will be stuck in glycolysis and overproducing lactate. Also, if this leads to an excess of NADH all kinds of other nasty stuff can happen including neuroexcitotoxicity and even cancer.

In mice, beta-lapachone increases NAD/NADH ratio. NAD/NADH ratio affects metabolic rate. One consequence of the increased ratio, in one animal model, is the extension of lifespan.

See the following reference (whose link you posted).

Beta-lapachone, a modulator of NAD metabolism, prevents health declines in aged mice.

The referenced article includes a graph comparing the survival rate of mice (1) under caloric restriction to (2) those given beta-lapachone. Beta-lapachone extends mice life more effectively than caloric restriction.

I have seen your post that indicates methylene blue also drives NAD/NADH ratio. Thus, I'd assume that methylene blue would have the same life-extending effect as beta-lapachone (in mice, of course).

This naturally raises the following questions:

(1) what would happen to NAD/NADH ratio if beta-lapachone and methylene blue are administered at the same time (combined)?

(2) Since niacinamide likely raises NAD level, what would be the health effect of co-administering niacinamide, methylene blue, and beta-lapachone?

===========

BTW, I have been using niacinamide for my personal health purposes for about 7 months. Very clear and positive effects on my body!

haidut · Mar 12, 2016

David Chung said:
In mice, beta-lapachone increases NAD/NADH ratio. NAD/NADH ratio affects metabolic rate. One consequence of the increased ratio, in one animal model, is the extension of lifespan.

See the following reference (whose link you posted).

Beta-lapachone, a modulator of NAD metabolism, prevents health declines in aged mice.

The referenced article includes a graph comparing the survival rate of mice (1) under caloric restriction to (2) those given beta-lapachone. Beta-lapachone extends mice life more effectively than caloric restriction.

I have seen your post that indicates methylene blue also drives NAD/NADH ratio. Thus, I'd assume that methylene blue would have the same life-extending effect as beta-lapachone (in mice, of course).

This naturally raises the following questions:

(1) what would happen to NAD/NADH ratio if beta-lapachone and methylene blue are administered at the same time (combined)?

(2) Since niacinamide likely raises NAD level, what would be the health effect of co-administering niacinamide, methylene blue, and beta-lapachone?

===========

BTW, I have been using niacinamide for my personal health purposes for about 7 months. Very clear and positive effects on my body!

Yes, both methylene blue and niacinamide raise NAD/NADH ratio. I posted a thread on methylene blue and NAFLD and the beneficial effects of methylene blue on that conditions were largely due to the elevation of NAD/NADH. Niacinamide also raises NAD/NADH (in humans) as shown by that case study I posted of a person whose NAD levels increased 20-fold by taking 4g niacinamide daily.
Finally, methylene blue and niacinamide are synergistic as there is another study I posted showing that niacinamide protects from the the excessive ROS methylene blue generates in higher doses. So, niacinamide + methylene blue would be a great and likely safe way to raise NAD and get the lifespan benefits. Beta-lapachone could be added as well but since it affects blood clotting I'd be careful adding it to methylene blue as together they may increase bleeding risk. But in terms of raising NAD levels even more, I think it would indeed be synergistic with niacinamide and MB.

David Chung · Mar 12, 2016

haidut said:
But in terms of raising NAD levels even more, I think it would indeed be synergistic with niacinamide and MB.

Do you think that beta-lapachone would be beneficial for dementia/Alzheimer's (as are niacinamide and MB)?

BTW, I heard your interview with Danny on dementia/Alzheimer. You referred to the disease as "diabetes type III." That was eye-opening - I had been trying to help my mom with memory issues, and I was struck by how well your characterization matched the symptoms my mom showed (e.g., high blood sugar level, her lack of appetite, high cholesterol, etc.). Very insightful.

haidut · Mar 13, 2016

David Chung said:
Do you think that beta-lapachone would be beneficial for dementia/Alzheimer's (as are niacinamide and MB)?

BTW, I heard your interview with Danny on dementia/Alzheimer. You referred to the disease as "diabetes type III." That was eye-opening - I had been trying to help my mom with memory issues, and I was struck by how well your characterization matched the symptoms my mom showed (e.g., high blood sugar level, her lack of appetite, high cholesterol, etc.). Very insightful.

I think there is are a few studies with beta-lapachone showing reductions in beta-amyloid. They are all animal studies, but the effects again seems to be raising NAD levels. Emodin from cascara has been shown to do the same.
However, in keeping with the hypothesis of AD being diabetes-like condition of the brain, niacinamide would in theory be much better, and indeed there are a few studies and a human clinical trial with 3g niacinamide daily. I emailed the human study PI and he told me that while he cannot discuss specific results, he think the effects he saw are better than anything else he has seen used for AD. See below.
Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr2... - PubMed - NCBI
Safety Study of Nicotinamide to Treat Alzheimer's Disease - Full Text View - ClinicalTrials.gov

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