384 replies to this topic

[abelard lindsay]

Does anyone have any thoughts on how the MB would effect the gut microbes.

The same thing happens when taking anti-biotics. It's pretty easy to replace gut microbes with pro-biotics like acidophilus pills.

[aaCharley]

Does anyone have any thoughts on how the MB would effect the gut microbes.

The same thing happens when taking anti-biotics. It's pretty easy to replace gut microbes with pro-biotics like acidophilus pills.

Sure they can be replaced. I would expect to take antibiotics for a week or so. If the gut bacteria are reduced I can replace them.
The suggestions for the MB seem to be for fairly continuous use a seemingly low dose. How often should I try to replace the lost bacteria - if any are lost. There are something like 7,000 different bacteria in there. Which ones are reduced and which probiotic is used for replacing tht group?

I'm not suggesting that I have an answer. I'm not even really suggesting that there is a real problem. I certainly wonder though about whether the long term use would create a problem, even at low dose. If long term use at low dose can eventually bring about transport throughout the body and particularly effect the cells in the brain, then the point of first contact, the GI tract, should be the most effected.

[niner]

I can believe that MB can be effective in lots of ways, particularly as a fungal fighter. The effect on clearing the taus would be great and might not really require continual use. However what I do not see addressed is the effect that it may have on the beneficial microbes and bacteria that inhabit the gut. If the MB wipes out the beneficial organisims while accomplishing the good work in some other part of the body, it might not be wise to take it for any length of time. Does anyone have any thoughts on how the MB would effect the gut microbes.

At the concentrations that we're talking about here, I think you can forget about any anti-microbial activity.

[Lufega]

Might MB have anti-lyme activity at the higher doses that produce a blue sclera and urine??? Can someone pull studies on it's use as an anti-malarial in WWII? Any Side effects aside from aesthetics?? Any Guinea pigs???

wiki-
Methylene blue was identified by Paul Ehrlich about 1891 as a successful treatment for malaria. It disappeared as an anti-malarial during the Pacific War in the tropics, since American and Allied soldiers disliked its two prominent, but reversible side effects: turning the urine green, and the sclera (the whites of the eyes) blue.

It ain't that bad!!

[rwac]

There's newer stuff than that.

http://findarticles....6/ai_n32050344/

In vitro antimalarial activity of methylene blue against field isolates of Plasmodium falciparum from children in Southwest Nigeria
Background & objectives: Methylene blue (MB), a thiazine dye is used in the treatment of various methemoglobinaemias. However, sporadic reports have shown some antimalarial therapeutic effect when administered to patients with clinical manifestations of malaria. The inhibitory concentration of schizont maturation and antimalarial activity of MB have not been fully elucidated. The present study therefore aimed at determining the antimalarial activity of MB in Plasmodium falciparum isolates obtained from children with malaria using standard in vitro drug susceptibility test.

Methods: Twenty children (8 boys and 12 girls) within the age range 4.5-11.5 yr were enrolled into the study and 2 ml of blood withdrawn aseptically. The standard microtest technique of schizont inhibition assay was used to culture fresh isolates obtained from P. falciparum infected patients. Chloroquine (CQ) and quinine (QN) were used as reference standards for in vitro drug susceptibility tests.

Results: The mean 50 per cent inhibitory concentration ([IC.sub.50]) values were 9.59 [ or -] 3.25nM, 196 [ or -] 21.11nM and 607 [ or -] 27.41nM for MB, CQ and QN respectively. Ten of the 14 isolates were sensitive to MB, 11 were sensitive to CQ while nine were sensitive to QN. Three isolates were resistant to CQ, and of these, two were sensitive to MB and one was sensitive to QN.

http://www.malariajo.../content/5/1/84

Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine
AbstractThe development of safe, effective and affordable drug combinations against malaria in Africa is a public health priority. Methylene blue (MB) has a similar mode of action as chloroquine (CQ) and has moreover been shown to selectively inhibit the Plasmodium falciparum glutathione reductase. In 2004, an uncontrolled dose-finding study on the combination MB-CQ was performed in 435 young children with uncomplicated falciparum malaria in Burkina Faso (CQ monotherapy had a > 50% clinical failure rate in this area in 2003). Three serious adverse events (SAE) occurred of which one was probably attributable to the study medication. In the per protocol safety analysis, there were no dose specific effects. The overall clinical and parasitological failure rates by day 14 were 10% [95% CI (7.5%, 14.0%)] and 24% [95% CI (19.4%, 28.3%)], respectively. MB appears to have efficacy against malaria, but the combination of CQ-MB is clearly not effective in the treatment of malaria in Africa.

http://www.ncbi.nlm....pubmed/19415120

Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial.

Coulibaly B, Zoungrana A, Mockenhaupt FP, Schirmer RH, Klose C, Mansmann U, Meissner PE, Müller O.

Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso.

BACKGROUND: With the availability of new preventive and curative interventions, global malaria control has been strengthened significantly in recent years. Drugs effective in reducing malaria gametocytaemia might contribute to local elimination and possible long-term eradication. We here report on the effects of methylene blue (MB)-based malaria combination therapy on gametocytaemia during a randomised-controlled trial in Burkina Faso. METHODS: An open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria was conducted in Nouna, north-western Burkina Faso. Children were randomised to MB-artesunate (AS), MB-amodiaquine (AQ), and AS-AQ (local standard of care). Overall follow-up was for 28 days, follow-up for gametocytaemia was for 14 days. FINDINGS: The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. Compared to AS-AQ, both MB-containing regimens were associated with significantly reduced gametocyte carrier rates during follow-up days 3, 7, and 14. This effect was seen both in patients with and without P. falciparum gametocytaemia at baseline. INTERPRETATION: MB reveals pronounced gametocytocidal activity which appears to act against both existing and developing P. falciparum gametocytes. MB-based combination therapy thus has the potential to reduce transmission of P. falciparum malaria in endemic regions, which has important implications for future elimination and eradication strategies. TRIAL REGISTRATION: (ClinicalTrials.gov) NCT00354380.

So yes, MB is effective against malaria.

Edited by rwac, 09 November 2009 - 01:34 AM.

[Lufega]

There's newer stuff than that.

Thanks for those studies!

[abelard lindsay]

Some more interesting MB research:

Antiviral Res. 2004 Mar;61(3):141-51.
Methylene blue photoinactivation of RNA viruses.

Floyd RA, Schneider JE Jr, Dittmer DP.

Oklahoma Medical Research Foundation, Auburn University, Auburn, AL 36849, USA. robert-floyd@omrf.ouhsc.edu

We present a review of the current status of the use of methylene blue (MB) photoinactivation of viruses starting with the first early observations up to its current use to inactivate HIV-1 in blood products. Basic mechanism of action studies conducted with model bacteriophages indicate that MB-photomediated viral RNA-protein crosslinkage is a primary lesion and that oxygen, specifically singlet oxygen, is very important also. Basic studies on the mechanism of action with HIV are lacking; however, we do show new data illustrating that viral reverse transcriptase inactivation per se cannot account for MB-mediated photoinactivation. We also show data illustrating that MB photomediates the inactivation of West Nile Virus, a flavivirus, which poses a significant new threat to the continental US. MB photoinactivation of viruses show significant promise because the technology not only offers significant potency but the history of safe MB use in human therapy makes it attractive also.

PMID: 15168794 [PubMed - indexed for MEDLINE]

[curious_sle]

So yes, MB is effective against malaria.

That took me a bit by surprise and touched andother point of interest... maybe someone can PM me with more ideas... seems Methylene Blue could be used as a treatment option for chagas desease... as my former "significant other" has chagas i'm always looking for new treatment options. Seeing that there is only treatment for one strain and she hasn't that strain... all comments very welcome.

nice find.

[AgeVivo]

We are probably soon starting MPrize @ home with methylene blue.
...
We'll probably need a control food colorant that also turns the pee blue, such as Blue Brilliant FCF (E133)

I have some pharmaceutical methylene blue (1 mg in 1 ml). We chose to use 100 nM in the drinking water (a semi rationale for this dose is at the bottom of http://www.mfoundati...read.php?p=4119). Blue brilliant CFC is a very good control:
in the following picture, in one bottle i've put MB (dillution by approx 330 000 to reach 100 nM), in the other one blue FCF (dillution until the 2 bottles look the same):

Nice isn't it? Plus i have tasted both and did not find any taste. My petshop mice are drinking it and they do well (no diarhea contrary to what i was afraid of; it is some much dilluted ;-). While some here have started taking MB themselves, I am a lot more careful. I think i will start the real mprize at home in the beginning of 2010. Those who want to follow me then will be welcome.

Edited by AgeVivo, 14 November 2009 - 06:41 PM.

[rwac]

Blue brilliant CFC is a very good control:

Actually, Brilliant Blue has it's own biological effects. It blocks the P2X(7) receptor, which makes it suitable for use as an analgesic!
How likely is it that Brilliant Blue has it's own life extension properties ?

Brilliant Blue G Selectively Blocks ATP-Gated Rat P2X7 Receptors
Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain.

[AgeVivo]

This post is about the supposed absence of lifespan effects of brilliant blue FCF, a blue colorant
The next post about the effect of conjoint use of MB and vitamin C, that would allow to use a colorless control

Blue brilliant CFC is a very good control:

Actually, Brilliant Blue has it's own biological effects. It blocks the P2X(7) receptor, which makes it suitable for use as an analgesic!
How likely is it that Brilliant Blue has it's own life extension properties ?

Brilliant blue FCF (CFC was a typo error) is the blue colorant that you will use if you want to make a blue cake for children; it might be in your toothpaste, shampoo, etc. Therefore it has been studied much and many health questions have been raised. Allergy, analgesia or even spinal lesion recovery and safety studies are discussed here: http://en.wikipedia....lliant_Blue_FCF .

While I haven't measured it, i believe that the dose i used to match the color of 100nM MB is considerably smaller than in corresponding studies, in particular than 8kg/kg/day. 8kg/kg/day is the "non-observed-adverse-effect" dose estimated in mouse lifetime toxicity/carcinogenicity studies (http://dx.doi.org/10...6915(90)90034-K). I can't find it now but i also had seen that a lifespan of bbFCF-treated mouse and control were virtually the same; this is why i expect it not to affect the control lifespan; although the doses should be clearly compared to be more sure.

[AgeVivo]

This post is about the effect of conjoint use of MB and vitamin C

So yes, MB is effective against malaria.

That took me a bit by surprise and touched andother point of interest... maybe someone can PM me with more ideas...

Indeed MB may have effects against malaria (http://www.springerl...325w203570l582/ : "Methylene blue [and] mefloquine [] caused a rapid decline in percent parasitaemia, whereas menadione caused a delay in maturation of the infection [] but could not cure the mice")

In some *non-scientific* places on the Internet i found that MB should be complemented with vitamin C, with some obscure explanations: http://www.earthclin...ES/malaria.html :

You might never heard of methylene blue, but it was used during the Vietnam war to cure malaria. The reason for it's disuse is that taken in very high dose, it causes the urine to be blue. However, there's a cure for blue urine, it's called vitamin C sodium ascorbate! So the reason for disuse was that the doctors simply didn't give the GI's vitamin C sodium ascorbate when they injected methylene blue, or perhaps taken internally. Even so, it can easily be proven that methylene blue will become colorless. Just add drops of methylene blue in vitamin C, it will instantly become colorless. Interestingly, methylene blue works better with vitamin C, as both are related to negative hydrogen, as evidenced by the fact that if you did use ORP meter, the resultant measurement is likely to be -200 millivolts or up to -300 millivolts, which is a negative charge. Methylene blue is a negative hydrogen carrier, while vitamin C sodium ascorbate, preferably is a producer of that and is a reducing agent.

Sincerely i do not trust this text nor its date (2008), it could well have been invented and posted by someone who read this thread. Anyway, is someone able to understand and clarify those (pseudo-?)scientific explanations?

Edited by AgeVivo, 14 November 2009 - 11:24 PM.

[niner]

Interestingly, methylene blue works better with vitamin C, as both are related to negative hydrogen, as evidenced by the fact that if you did use ORP meter, the resultant measurement is likely to be -200 millivolts or up to -300 millivolts, which is a negative charge. Methylene blue is a negative hydrogen carrier, while vitamin C sodium ascorbate, preferably is a producer of that and is a reducing agent.

Sincerely i do not trust this text nor its date (2008), it could well have been invented and posted by someone who read this thread. Anyway, is someone able to understand and clarify those (pseudo-?)scientific explanations?

He's talking about MB having a low redox potential, so it's easy to switch it back and forth between oxidized and reduced forms. Or he might be. It sounds pretty muddled and it's probably wrong. An "ORP meter" i think stands for Oxygen Reduction Potential or something like that. Vitamin C will reduce MB to its colorless form, but I wouldn't be surprised if it was re-oxidized in the body and still gave you blue pee. (and made the whites of your eyes blue.) I don't think there would be any benefit to combining C and MB as far as the effects we are interested in.

[niner]

Blue brilliant CFC is a very good control:

Actually, Brilliant Blue has it's own biological effects. It blocks the P2X(7) receptor, which makes it suitable for use as an analgesic!

A control with biological effects is a problem. There might be no need for a color control anyway, if the animals' water is delivered from one of those hanging bottles. Just cover the bottle so they can't see what's inside. Do mice even see color? I don't think of rodents as being particularly aesthetic eaters anyway...

[AgeVivo]

A control with biological effects is a problem. There might be no need for a color control anyway, if the animals' water is delivered from one of those hanging bottles. Just cover the bottle so they can't see what's inside. Do mice even see color? I don't think of rodents as being particularly aesthetic eaters anyway...

As explained just above, if the doses and studies are confirmed it should be a control without biological effects.
The goal of the blue control is to make a blind test: i would receive two blue solutions (A and B), give solution A to cage A and solution B to cage B, i won't know which solution is MB (A or B?) and which one is the control so i won't be able to cheat (voluntarily or not) by better taking care of one cage. Such a blind test is absolutely essential for objectiveness.

[wolfeye]

Are there any rat life extension studies on Brilliant Blue G?

[AgeVivo]

I think the quest for life extension gets a little desperate when one considers drinking a pet store chemical, especially one cooked up from some guy in his garage that he then sells on ebay.

Methylene Blue has been used for long in humans but indeed not ebay-perstore-methylene-blue. Asking the pharmacist for MB is better, but wait for results first (Rember Phase III trials against Alzheimer, mprize at home, etc).

[Sillewater]

So for someone that seems to be progressing towards Alzheimer's would 60mcg 3x a day be sufficient? or do they have to play around with the dosages.

Edited by Sillewater, 21 December 2009 - 11:16 AM.

[AgeVivo]

Great news: the Intervention Testing Program (part of the National Institute of Aging) has decided to study the effet of methylene blue on the lifespan of mice. http://www.mfoundati...read.php?p=8327

It will be tested at the concentration of 28 ppm in food (not sure whether this is a lot or not compared to the 100nM that we were planning to give in the drinking water, or compared to what people consider trying?) and starting at 4 months old mice (young adults...). Based on their calendar i imagine that the results should be known by mid or late 2012.

[suprdupracetam]

In looking at the msds posted by Stephen b for the
Kordon product, I see that methylene blue was positive for inducing
DNA mutations in the ames test.

My guess is that this is due to its pro oxidant
effect at higher levels of methylene blue.
Particularly when you look at an abstract like
this russian study which showed a protective
effect at low levels.

Genetika. 2009 Mar;45(3):349-53.
[Methylene blue as a supressor of the genotoxic effect of ultraviolet radiation with a wavelength of 300-400 nm]
PMID: 19382686 [PubMed - indexed for MEDLINE]




On the other hand there are many
papers that state methylene blue
does cause DNA strand breaks.

Mutagenesis. 2009 May;24(3):253-8. Epub 2009 Feb 13.
Removal of red light minimizes methylene blue-stimulated DNA damage in oesophageal cells: implications for chromoendoscopy.
PMID: 19218330 [PubMed - indexed for MEDLINE]

Also, this paper concludes "In addition, reducing the concentration of MB 10-fold markedly reduced the DNA-damaging effect of MB in vitro. The results show that photoactivation of MB by red light is responsible for the majority of DNA damage"

Doesn't that imply that some DNA damage occurs from methylene
blue that isn't a result of oxidation and will still occur at very low doses?
Can someone who's more familiar with the
ames mutagenic test comment...

[rwac]

OE33 cells were treated with MB (0.015–15 mM) and exposed to white light (WL). Cells were also illuminated with WL fractions (580–700, 480–580, 350–480, <575, <610 and <688 nm) in the presence of MB. At clinically relevant concentrations, WL illumination of MB (15 mM) caused significant DNA damage in vitro (P < 0.001).

They're talking about 15uM to 15mM concentration. We're dealing with something like 100nM at most, so two orders of magnitude lower than what they tested.

[suprdupracetam]

rwac, do you know if anyone has done the Ames test
at these lower concentrations?

[aaCharley]

A couple of pretty nice articles on Mehtylene Blue. These seem to indicate that the Rember study used three doses daily of either 30mg, 60mg, or 100mg for each dose. Not micrograms. But perhaps I'm reading it incorrectly or the reports are off.

Vienna (and Burkina Faso): What's New With Methylene Blue?

Essay on the Medical History of Methylene Blue

ICAD 2008: Tau-Targeted Therapy Slows Alzheimer's Progression for 19 Months

[maxwatt]

A couple of pretty nice articles on Mehtylene Blue. These seem to indicate that the Rember study used three doses daily of either 30mg, 60mg, or 100mg for each dose. Not micrograms. But perhaps I'm reading it incorrectly or the reports are off.

Vienna (and Burkina Faso): What's New With Methylene Blue?

Essay on the Medical History of Methylene Blue

ICAD 2008: Tau-Targeted Therapy Slows Alzheimer's Progression for 19 Months

Ames' study used what I believe was the equivalent of 60 micrograms for a 70 kg human. Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways

[curious_sle]

Please pardon my ignorance but has anyone an idea if taking methylene blue together with benagene does interact potentiate or cancel each others efects out? I already tak Benagene now that it i quite affordable and would like to add methylene blue (though not into mixing it down myself but yeah. maybe someone enterprising will provide a usefull supplement sometime soon?).

Thank you for enlightening remarcs.

[Sillewater]

Vienna (and Burkina Faso): What's New With Methylene Blue?

Russian Journal of Genetics Volume 45, Number 3 / March, 2009
Methylene blue as a suppessor of the genotoxic effect of ultraviolet radiation with a wavelength of 300–400 nm
V. A. Chistyakov1 , M. A. Sazykina1, M. A. Kolenko1, G. G. Chervyakov2 and A. V. Usatov1
(it doesn't seem to me that the effects of MB due to light at sea level is warranted)

Neurobiol Dis. 2010 Apr 8. [Epub ahead of print]
Methylene blue fails to inhibit Tau and polyglutamine protein-dependent toxicity in zebrafish.
van Bebber F, Paquet D, Hruscha A, Schmid B, Haass C.

Neurodegener Dis. 2010;7(1-3):99-102. Epub 2010 Feb 18.
Transgenic zebrafish as a novel animal model to study tauopathies and other neurodegenerative disorders in vivo.
Paquet D, Schmid B, Haass C.

Nitric Oxide. 2010 May 15;22(4):275-80. Epub 2010 Jan 28.
A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock.
Juffermans NP, Vervloet MG, Daemen-Gubbels CR, Binnekade JM, de Jong M, Groeneveld AB.

Metabolic mapping of rat brain activity associated with conditioned fear extinction and renewal, and improvement of extinction memory by the metabolic enhancer methylene blue

This one seems important:
CNS toxicity involving methylene blue: the exemplar for understanding and predicting drug interactions that precipitate serotonin toxicity
Peter Ken Gillman*
Psychotropical Research, Bucasia, Queensland

Neurotox Res. 2009 Apr;15(3):260-73. Epub 2009 Feb 24.
Methylene blue provides behavioral and metabolic neuroprotection against optic neuropathy.
Rojas JC, John JM, Lee J, Gonzalez-Lima F.

Neuroscience. 2009 Oct 20;163(3):877-89. Epub 2009 Jul 24.
Striatal neuroprotection with methylene blue.
Rojas JC, Simola N, Kermath BA, Kane JR, Schallert T, Gonzalez-Lima F.

Very good discussion of MB and effects of neurotransmitter systems.
Biochem Pharmacol. 2009 Oct 15;78(8):927-32. Epub 2009 May 9.
Methylene blue and Alzheimer's disease.

Bioavailability seems to be at 70%:
Eur J Clin Pharmacol. 2009 Feb;65(2):179-89. Epub 2008 Sep 23.
High absolute bioavailability of methylene blue given as an aqueous oral formulation.
Walter-Sack I, Rengelshausen J, Oberwittler H, Burhenne J, Mueller O, Meissner P, Mikus G.
Oz M, Lorke DE, Petroianu GA.

Neurocrit Care. 2009;11(1):88-93. Epub 2009 Mar 5.
Methylene blue-associated serotonin syndrome: a 'green' encephalopathy after parathyroidectomy.
Rowley M, Riutort K, Shapiro D, Casler J, Festic E, Freeman WD.

J Neurosci. 2009 Sep 30;29(39):12079-88.
Chemical manipulation of hsp70 ATPase activity regulates tau stability.
Jinwal UK, Miyata Y, Koren J 3rd, Jones JR, Trotter JH, Chang L, O'Leary J, Morgan D, Lee DC, Shults CL, Rousaki A, Weeber EJ, Zuiderweg ER, Gestwicki JE, Dickey CA.

J Biol Chem. 2010 Mar 26. [Epub ahead of print]
Inhibition of Hsp70 by methylene blue affects signaling protein function and ubiquitination and modulates polyglutamine protein degradation.
Wang AM, Morishima Y, Clapp KM, Peng HM, Pratt WB, Gestwicki JE, Osawa Y, Lieberman AP.

Based on my amateur reading of most of these papers high doses of MB should be used with care because of its effect on neutrotransmitter systems (a la reports of neurotoxicity) and that methylene blue definitely seems to protect the brain. Its effect on zebrafish tau proteins is questioned (this is also discussed in the article I posted at the top, What's new with MB). Also prophet mentioned in the beginning of the thread about HSP70 and there's lots of studies coming out on that which seems interesting.

Anyways my tilt was towards AD not life-extension. I think I'll continue with the 60mcg doses for my grandfather.

[rwac]

Anyways my tilt was towards AD not life-extension. I think I'll continue with the 60mcg doses for my grandfather.

So would you say it's helping him ? Have you tested larger doses to see if they work ?

[Sillewater]

That I can't be too sure of myself. I'm not home often enough to be able to notice a difference. However my grandmother has said his memory has improved a bit since he started taking it. Like many times he could not remember family member names or would get them mixed up but now he seems to be able to recall most. However couldn't that just be because he has had practice?

No I have not tried higher dosages. After a couple more weeks at 60mcg I think I'll try 1mg to see if there is a difference. What dosage would you recommend? From my readings it seems that 60mg was used in the TauRx trial, but based on the report of neurotoxicity at higher doses I am wary of going that high.

Edited by Sillewater, 12 May 2010 - 09:35 PM.

[rwac]

No I have not tried higher dosages. After a couple more weeks at 60mcg I think I'll try 1mg to see if there is a difference. What dosage would you recommend? From my readings it seems that 60mg was used in the TauRx trial, but based on the report of neurotoxicity at higher doses I am wary of going that high.

Thats a good sign. I suggest increasing it gradually. How about trying 120 mcg next.

On the other hand, it has other effects at larger doses like antimicrobial effects, so that may be worth trying too.

Have you considered a ketogenic diet for your grandfather, it might help quite a bit.

[Sillewater]

What are the anti-microbial dosages? I ask because my grandfather has been experiencing constipation. His feces are dense and hard which I take to mean that his gut bacteria is missing. So I have been giving him some probiotics (Ultimate Flora by Renew Life) and it seems to work (I'm looking into getting some of Funk's tried and tested probiotics e.g. VSL#3, also Activia, Goodbelly, Align however I'm wary of the sugar content because his A1c came back a bit high). So for now I would rather keep it under the anti-microbial dosage.

Sure maybe I'll do 120mcg and see if there is a difference but I think 1mg would be the highest I want to go.