Methylene Blue AD Cure Celebration Thread!

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HomesteadGal
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Re: Methylene Blue AD Cure Celebration Thread!

Post by HomesteadGal »

I would feel better about the possibilities if Dr. Bredesen had recommended this at all in his book. He has been at this research for a long time and could have included it in the protocol. And methylene blue has been experimented with in humans for over a century. If someone like TauRX wants to do a study where the subjects are properly diagnosed and have the same ongoing treatments for the same confounding factors throughout the study period and they started at similar states of health, etc, I will look forward to seeing the result. I am a diabetic APOE 3/4 and can use all the help I can get.
However, the subjects not on the usual Alzheimer's pills may have been very slow to progress, so their doctors/families may have not bothered with pharmaceuticals early on. These people would show a slow disease progession in the study because they were slow to progress even before they started the study. Was any of it controlled for? So many variables...
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Re: Methylene Blue AD Cure Celebration Thread!

Post by J11 »

Homesteadgal, yes I had these same concerns at the time of ICAD in July of 2016. However, after reading the article for the second phase 3 with LMTX, the first phase 3 with LMTX, the phase 2 trial with MB, I am becoming more confident that this is for real.

The phase 2 trial with Methylene Blue which was first announced ten years ago was a strong result. There were over 300 patients who remained randomized for up to 2 years. The blinding was mostly kept. None of these patients received standard of care dementia medications. The overall results for this study were strong. Those with AD did not progress during a year of treatment. It is difficult to find glaring deficiencies in this trial. While the reported numbers might be smallish in some of the important subgroups, a significant number of patients carried forward into the blinded randomized extensions. The trial hit its primary endpoints.

There are only a few aspects of this trial that one can quibble over. When you read this phase 2 trial carefully (assigned reading on the other Methylene Blue thread) you realize that this result was solid.

The problem with this trial related mostly to an unforeseen issue with pharmacokinetics which obscured the result somewhat. However, the other assigned reading in the other thread explains why this dosing problem arose. When considered together one has a better insight into why the trial turned out as it did. It also adds yet more credibility to the bottom line that the phase 2 trial provided substantial evidence of MB's anti-dementia effect.
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Re: Methylene Blue AD Cure Celebration Thread!

Post by Orangeblossom »

I'm still not sure how it works, what is the mechanism behind it. I can't help thinking that due to the name it turns the brain blue (!) :? (sorry, I'm sure it doesn't).

Maybe I would be more interested if I knew how it actually worked.
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Re: Methylene Blue AD Cure Celebration Thread!

Post by J11 »

Orangeblossum, I have stayed away from answering the question about the mechanism of action because
with human biology as it is and the methods available to investigate it as they are, it might not be possible to
unambiguously establish such an MOA.

Human biology is so highly interconnected that changing one part of the network can have cascading effects
that ultimately might achieve the therapeutic objective. Frequently the proximal explanation has turned out to
be erroneous. We should not be mislead by nM potent drugs targeting some biological pathway when the true
effect might result from downstream effects on other pathways.

A serious derailing of the entire scientific process can occur when the MOA is pursued instead of first going through
a series of highly precise replications of the original result. It has been almost ten years since the first phase 2 trial
with Methylene Blue was first reported and there continues to be question of whether this result was in fact definitive.

It is morally outrageous that this uncertainty continues!

Ten years later there should be no uncertainty!
The phase 2 trial reported stopping the progression of neurodegeneration for two years or more!
Such an extravagant claim should be simple to prove or disprove.

Tens of millions of people are now coping with severe neuro-degenerating dementing illness. We are their guardians. It is our responsibility as ethically guided humans to provide them the best care and conduct the best possible research on their behalf. Those in authority who do not sincerely pursue such an objective should not continue to hold such authority. By not conducting the replication studies for Methylene Blue, we have failed those with dementia and we have failed at a profound level as human beings and more generally as a species.

A randomized phase 3 replication of Methylene Blue with perhaps a few hundred mild/moderate AD patients who
are not on current AD medications with 50-70 weeks of on treatment at a dose of 120-150 mg/day for active treatment
and 10-20 mg/day placebo dose is the moral minimum to fulfill our obligations.

This reminds me of a similar circumstance with cancer in the 1970s with regards to vitamin C. The original research with
high dose prolonged dosing of iv vitamin C found extremely large anti-cancer effects. In fact nearly 10% of the treated
patients developed fatal tumor lysis syndrome responses due to overwhelmingly massive tumor destruction. Most of the other
patients also did reasonably well. Yet, after all of these decades and numerous flawed replications attempts the enormous
potential of vitamin C in cancer therapy continues to be largely unrealized.

We cannot allow this same limbo to develop in dementia. Most of the developed world would be financially ruined if this were
to happen. If we first faithfully replicate the results that have already been demonstrated, then we will have made a large step towards an effective treatment for Alzheimer's.
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Re: Methylene Blue AD Cure Celebration Thread!

Post by Tincup »

J11 wrote:Phase 2 a.PNG

Welcome to the party! :D
After listening to Peter Attia's podcast with Francisco Gonzalez-Lima and Lima's comments about Methylene Blue, I decided to test Kordon Methylene Blue-General Disease Prevention Treatment for Aquarium, which is available off Amazon for fish. I sent a bottle ($4.49US) to a chemist friend who has a mass spectrometry machine to test for heavy metals & mercury.

Here are the results.
methylene blue.pdf
I am not a chemist, but here is my friend's interpretation, " the only metals that were high were Copper at 573 ug/l which is below the drinking water limit. Zinc at 862 ug/l no limit for Zinc."

I'm looking at this for a person with memory loss from other than AD. My reasoning to select this product is that my understanding is that fish are very sensitive to toxins, so anything you use to treat them with has to be pretty "clean."
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Re: Methylene Blue AD Cure Celebration Thread!

Post by J11 »

tincup, ask your chemist friend about reducing MB. From what I understand MB can be reduced by simply adding vitamin C. After it has been reduced, it would then be in the LMTX form that they used in the phase 3 trials and the Lucidity extension.

taurx is going to make a fortune off of this!
I told someone about the results of the plasmapheresis trial and how it would slow dementia progression by up to 70% for at least over a year or two. Even though this person probably could benefit right now from an anti-dementing treatment and could afford the up to $100,000 per year cost if pressed, they plead poverty. All these million dollar treatments typically help few people and generate marginal returns for the pharma companies.

Though LMTX could be a blockbluster! Pretty much everyone might start taking it for most of their life span. It would be a statin for the brain: consumer medicine, cheap, possibly over the counter and a printing press for the company. Going for a mass market product really is the sweet spot in pharmaceuticals. It is hard for people to complain when they can pay very reasonable prices for a well tested and effective pharmaceutical product. If the company plays it smart and doesn't try to gouge the public, they'll do great! There would be an enormous amount of good will for a company that could provide such a bargain. When this all lines up properly, I wouldn't be going to the fish store any more. It's basically homeopathic scale dosing! I hope that I will be able to simply buy it online.

By the way how many mg of MB are there in each ml of the Kordon product? I can't quite remember. An 8 mg dose should not need much of the Kordon product.

Looking at the Lucidity trial on clinical trials gov, I can hardly believe that enrollment has still not picked up yet. There are only a handful of sites recruiting in the States (e.g., California, Florida, etc). No other nation in the world is recruiting! This is unconscionable! A few decades ago it was such a big joke to give gram scale doses of MB and watch people's pee turn blue.
This was a great joke for doctors to be. Here we are now and giving MG scale doses to those with approaching irreversible neurodegenerative illness no longer is sufficient to warrant hasty clinical development. Of course, it is not as if current drugs are somehow harmless.

Our loved one's geriatric psychiatrist straight out lied when we asked about the potential risks of anti-psychotics in AD; oh, no, these drugs are completely harmless. Really? Our loved one was admitted to hospital and was immediately dosed with anti-psychotics. Pharmaceutical companies paid the largest fine in FDA history for encouraging the prescribing of resperidone etc. to those with dementia even when it was known that such drugs sometimes produced fatal side-effects.

It is almost 2 1/2 years into the Lucidity trial, why are so few of the sites recruiting?
What about the extension trial for the phase 3s?
More timely reporting of the progress of results should be mandatory.
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Re: Methylene Blue AD Cure Celebration Thread!

Post by aphorist »

I have some pharmaceutical grade MB and it works pretty well. You can probably get some lab/pharmaceutical grade off Ebay.

The biggest problem I have is that MB is so, so messy. The stain is so strong. I got some on my countertops and it's still there 6 months later. Everything becomes blue and it's a nightmare. Get it on your hands, get it on your clothes, it practically never goes away.

Additionally, I don't think there is any evidence of actual lifespan extension, so I question its usefulness, even though mechanistically it should be advantageous, particularly for E4 genotypes.

See ITP papers on Methylene Blue:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954939/

I would only take it 3-4 days a week and cycle on/off.
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Re: Methylene Blue AD Cure Celebration Thread!

Post by Tincup »

aphorist wrote:
See ITP papers on Methylene Blue:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954939/
.
I could not find the doses used in the above paper and according to Francisco Gonzalez-Lima, dose is crucial. Too much, no bueno.
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Re: Methylene Blue AD Cure Celebration Thread!

Post by J11 »

Tincup, the article mentioned an MB dose of 27 mg/kg in the mice. This is roughly equal to 2 mg/kg in humans which would translate into approximately 100-200 mg dosing. This is the dosing that was used in the taurx phase 2 MB trial and this did find substantial anti-dementing effects in those not receiving other AD drugs.
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Re: Methylene Blue AD Cure Celebration Thread!

Post by aphorist »

Tincup wrote:
aphorist wrote:

I could not find the doses used in the above paper and according to Francisco Gonzalez-Lima, dose is crucial. Too much, no bueno.
Starting at 4 months of age, UM-HET3 mice were fed 27 mg MB per kg diet. Survival curves for pooled male or female data were not changed significantly by MB (Fig. 5E,F). Male survival was not affected at any of the three sites, although there was a suggestion (P = 0.07) of a negative effect at TJL, with a 13% decline in median survival.
27 mg/kg * 3/37 = ~2.19 mg/kg

A prior human MB trial had 60 mg 3x a day which is approximately 2.57 mg/kg/day at a 70 kg body weight.
The 280-mg dose selection was estimated as 4 mg/kg for an average body weight of 70 kg. Methylene blue is a memory-enhancing drug in animals and humans after a single dose in the low-dose range of 0.5–4 mg/kg, but it has opposite effects at doses greater than 10 mg/kg and displays a hormetic dose response (15)
0.5 mg/kg - 4.0 mg/kg is supposedly a hormetic dose response range.

Typically 2-3 mg/kg is given intravenously.

I think I targeted like 1.5-2.0 mg/kg. If you skew in any direction, you want to skew lower, because it is lipophilic and targets high respiring tissue, which means it targets nerve cells and the brain at higher concentration rates than elsewhere in the body. It is not a uniform tissue distribution.

Half life is 12 hours.
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