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Methylene Blue Dosing and Products


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#1 niner

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Posted 03 February 2009 - 05:05 AM


I take MB and have for about half a year.

Geddarkstorm, how much MB do you take, and where do you get it?

#2 VespeneGas

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Posted 03 February 2009 - 05:16 AM

Just want to echo niner's query. I eagerly follow your posts (very informative, thank you btw), and am interested to hear that you've noted subjective benefits from MB.

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#3 geddarkstorm

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Posted 03 February 2009 - 05:18 PM

I take MB and have for about half a year.

Geddarkstorm, how much MB do you take, and where do you get it?


The ease or difficulty of finding MB seems to vary per region in the country, I'm afraid. For instance, it's sold over the counter at Walgreen's down in Florida as a 2% solution, and I have reports of the same in Kansas. Where I live, I could only find 1% MB at a science/hobby store, so there's a good chance any place like that will have it.

I take ~100 microliters of 1% MB in tea once every morning (I have a syringe, but this is approximately two drops from any standard eye dropper). This gives about ~1mg of MB, which if factoring in an absorbance percent in the gut of about 50% (actual aqueous solution studies have shown it's about 70% absorbed orally in humans, but I like to factor it down a little for reasons I'll explain in a second), gives about 300-500 nM in my blood (assuming the standard human has 5 liters of blood). We want to keep MB around 100 nM in the blood as long as possible, so by taking around 300 or 500 nM, since we have to be aware of absorption and excretion kinetics, that should keep levels around 100 nM for as long as possible without spiking up towards 1 uM where MB's mitochondrial effects are halved. This also should allow proper dosage of MB to filter into peripheral tissues.

Now, the studies done in rats showing significant mental improvements used 1mg/kg per day dosages. When following the recommended conversion to effective human dose from a rat, that gives us about 10mg of MB, or about 3 uM in the blood. That isn't so bad, but that does put us above the best dose that was seen for human cells in the paper the OP listed, by 30x. It could be though that in vivo effective concentrations are lower than in vitro due to the influence of serum agents that may prevent MB entry into cells (and elimination kinetics of course). Yet another reason why I set my limit roughly 3x that of the optimal dose found in the OP's paper.

The absolute minimal dosing scheme for MB is also detailed nicely here, in section [037] of the patent. I fully believe, however, that their dosage is far too low, considering 10 nM of MB did nothing in human cells. Moreover, the patent did not even take into consideration absorption percentages. There's no way 160 ug will get you at a sustained level of 100 nM - you'd be immensely lucky to even spike at that level. Still, the patent gives some nice ideas about dosage schemes as well for those who want to play around with it.

As an aside, I will tell you that the dosage level I recommend may at times, depending on how hydrated you are, slightly discolor the urine with a faint blue/green tint. Going to a 10 mg MB dosage will definitely discolor it, just so no one freaks out when it happens, it is not a bad thing as we'll see below.

On a final note, the amount of MB typically used to fight methylhemoglobinemia is ~240 mg, and according to the NIH toxicological studies, the lowest dose of MB needed to see the very slightest amount of toxicity is ~670mg or so for an average human. So the dosage I'm recommending is ~600x less than the lowest toxic dose, and ~200x less than that used medicinally in humans for over a century. The LD50 of MB in humans should be around 9 grams.

Just want to echo niner's query. I eagerly follow your posts (very informative, thank you btw), and am interested to hear that you've noted subjective benefits from MB.


It is hard for me to relay much subjective information, since I started taking quercetin and resveratrol a few months after MB. Nonetheless, I've seen marked improvements in my ability to retain and relate information in presentations and science talks; which has been very nice. There is no way I can say for certain it was MB, especially since my dose is a little lower than that seen for mental improvement in rats. The only other marked affect, which others have reported too, is improved healthy look to the skin, nails, and hair. That's highly subjective, but my skin has also been thoroughly tested by my new kitten, which has been lacerating the heck out of my fiancee, but does considerably less damage to me - my skin is apparently tougher now. But if it's due to MB or not, I cannot say for sure.

Edited by geddarkstorm, 03 February 2009 - 05:26 PM.

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#4 100YearsToGo

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Posted 03 February 2009 - 10:54 PM

You can buy it here:

http://www.amazon.co...rd_i=B000PDSJ5A

2.303% water solution

Edited by 100YearsToGo, 03 February 2009 - 10:58 PM.


#5 rubegoldberg

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Posted 04 February 2009 - 02:07 AM

http://www.methylene-blue.com/

Provepharm research results in the first cGMP Pharmacopoeial grade Methylene Blue (Methylthioninium chloride Ph.Eur) obtained using
  • New innovative synthetic pathway
  • Heavy-metal-free process
  • “Clean chemistry” process involving pharmaceutical grade reagents
Provepharm offers Methylene Blue with
  • Metal impurity concentrations up to 50 times lower than current pharmacopoeial limits
  • Full regulatory package in preparation including USDMF, EDMF and CEP including up to 12 months stability data under ICH conditions
  • Stock build to ensure future reliable supply
Provepharm Methylene Blue enables confidence to
  • Update and resume commercialisation of existing Marketing Authorisations containing methylene blue as drug substance in Europe
  • Ensure compliance with world best practice for existing products containing methylene blue as drug substance commercialised around the world
  • Undertake research for new therapeutic applications of Methylene Blue


#6 PWAIN

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Posted 04 February 2009 - 04:25 AM

http://www.methylene-blue.com/

Provepharm research results in the first cGMP Pharmacopoeial grade Methylene Blue (Methylthioninium chloride Ph.Eur) obtained using

  • New innovative synthetic pathway
  • Heavy-metal-free process
  • “Clean chemistry” process involving pharmaceutical grade reagents
Provepharm offers Methylene Blue with
  • Metal impurity concentrations up to 50 times lower than current pharmacopoeial limits
  • Full regulatory package in preparation including USDMF, EDMF and CEP including up to 12 months stability data under ICH conditions
  • Stock build to ensure future reliable supply
Provepharm Methylene Blue enables confidence to
  • Update and resume commercialisation of existing Marketing Authorisations containing methylene blue as drug substance in Europe
  • Ensure compliance with world best practice for existing products containing methylene blue as drug substance commercialised around the world
  • Undertake research for new therapeutic applications of Methylene Blue


Doesn't look like they will actually sell the stuff to an end user. Have you been able to buy from them?

#7 niner

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Posted 04 February 2009 - 04:37 AM

Provepharm raises the specter of heavy metal contamination. Depending on the exact nature of the metal, this may or may not be a problem at the doses being considered here. I lean toward "not", but this isn't the sort of thing that I would want to leave to chance. MB has been used as a human pharmaceutical; would that suggest a clean source? Someone with access to an analytical lab could run a sample of MB for metals, but having this done at a contract lab would run into some money. Another concern, FWIW, is

MB also induces phase-2 antioxidant enzymes in hepG2 cells.

This could impact the bioavailability of other supplements, but might not be a problem at the low doses being discussed here.

#8 gwgaston

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Posted 04 February 2009 - 07:27 AM

Here are 2 links for what is advertised as "UltraPure Grade":

http://www.bioexpres...200212000212260


http://search.anaspe...=methylene blue (Will have to select country and redo the search)


Those came from the comments that follow this article:

http://pipeline.cora...es_comeback.php

Note comment #61 geddarkstorm :)

#9 imhotep

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Posted 04 February 2009 - 04:24 PM

I tried finding Methylene blue in a Walgreens in Florida, The pharmacist went nuts, she acted like I was trying to buy LSD. Any idea where it is at?

#10 geddarkstorm

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Posted 05 February 2009 - 05:43 PM

I tried finding Methylene blue in a Walgreens in Florida, The pharmacist went nuts, she acted like I was trying to buy LSD. Any idea where it is at?


It was reported in the hispanic/ethnic remedy section. I'm not sure where in Florida that was, and since I don't live there, I can't say for sure. MB is used in a prescription drug combination for fighting urinary track infections, from my understanding, which might be why she freaked out, haha.

@niner: I've seen analytical reports on MB purity for the kind sold to consumers, and all the heavy metal levels where well below the strictest limits. Even if some metals like mercury or lead, for the sake of argument, were in the low ppb range, when you are taking just 100 microliters of that solution, you'll only be getting the equivalent of 100 parts per quadrillion amounts; well below detection, and you probably get an order of magnitude or two more than that in your drinking water. Furthermore, MB is used to treat fish of fungal diseases and other pests, and fish are more sensitive to heavy metals than us, from what I know.

My area of research is directly on a mouse/human metal sensor protein (for zinc), which also responds to heavy metals. Our bodies have a lot of heavy metal defenses. Metals just aren't quite as dangerous (nor is radiation) as we treat them, but better safe than sorry!

Still, I completely believe that company is creating a "false dilemma" to get people to buy their radically overpriced product - especially since they claim they are the new, and best process, and heavily imply all other processes are "inferior" and let in a lot of heavy metals. All I can say is, what? I highly, highly doubt that is the case since it's used in medicine, and I'm sure the FDA would throw a fit if everyone else were letting in a substantial amount of metals. After I saw their site, I worried quite a bit about this and went looked around everywhere to investigate, but no where could I, at least, find any evidence what so ever that there are substantial heavy metals in MB synthesis - except maybe the version used as an industrial fabric dye, but then that also has strict heavy metal limits (though not as strict) as you aren't allowed to put lead or mercury in consumer clothing. Getting back to it being used in people for 100 years without an apparent problem, all the way back when we didn't even have real heavy metal standards, and certainly not anywhere near as strict as now, I personally don't worry about this issue unless some reputable source showed otherwise.

Nonetheless, it is something to think about, and everyone needs to be aware.

Edited by geddarkstorm, 05 February 2009 - 05:47 PM.

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#11 tham

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Posted 05 February 2009 - 06:27 PM

You can find methylene blue at aquarium shops.
Not sure of the concentration though.

I used quite a bit during my fish rearing days as a kid.
Dripped in till the aquarium turned all bluish, whenever
the fish fell sick. Never really worked anyway.

#12 tham

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Posted 05 February 2009 - 06:34 PM

Looks like 2.3 %.

http://www.americana.../Quickcure.html

http://www.everythin...6253.dept.1131/

http://www.aquariumg...hyleneblue.html

Edited by tham, 05 February 2009 - 06:35 PM.


#13 tintinet

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Posted 09 February 2009 - 05:40 PM

I ordered some of the fish tank variety. It arrived in a plastic bag, within which the bottle had leaked. Opening the bag resulted in a wide splatter of MB in my kitchen, impelling me into frenzied cleaning before the stains set in. Handle with care!

#14 bgwithadd

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Posted 09 February 2009 - 06:22 PM

it's not so much general health as mental health. There's a very high correlation between violent crime and lead exposure, for example. Even tiny amounts of lead can screw you up, but as you say it's very likely in your water supply and house in similar levels as any drug you consume.

#15 geddarkstorm

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Posted 11 February 2009 - 06:07 PM

it's not so much general health as mental health. There's a very high correlation between violent crime and lead exposure, for example. Even tiny amounts of lead can screw you up, but as you say it's very likely in your water supply and house in similar levels as any drug you consume.


And in older paints, and electronics, and on toys (from China that is), haha. Lead is everywhere.

One of the main reasons free, ionized lead is dangerous (the metallic form is inert and not dangerous) is because it kicks out zinc from the prophobilinogen synthase, inactivating the enzyme. This enzyme is part of the heme synthesis pathway and one of the rate limiting steps, at that. Its loss will lower heme production, but worst yet, its substrate, aminolevulinic acid (ALA), looks very much like GABA! Loss of prophobilinogen synthase causes a massive build up of ALA, and can lead to ALA poisoning. Since ALA looks so much like GABA, it can trick the brain into misregulating GABA and other glutamate signaling systems. This can lead to all sorts of craziness, in a literal sense, as the brain cannot easily get rid of ALA, as it isn't a true neurotransmitter and neurons don't have systems to deal with it.

Still, minute amounts of ionized lead, like we all have in our water, aren't going to do this, and as long as there's sufficient metallothionines around, it'll be bound up by those and sequestered away from the cell. It's only once you ingest enough free lead to overwhelm your natural heavy metal defenses that trouble starts, and only once you have enough lead to inhibit a sufficient number of prophobilinogen synthases to poison yourself with ALA. It's why the Romans didn't go crazy overnight despite having lead plumbing, plates, utensils, and lead based medicine. It took years upon years of heavy lead leaching into their bodies to finally cook things up to levels enough to cause insanity.

#16 malbecman

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Posted 11 February 2009 - 07:36 PM

Yes, its a wonderful dye, even at 1-2%, and often used in biology for that purpose (in addition to the treatment of fish fungal diseases). Sorry to hear of your troubles, Tintinet.


I ordered some of the fish tank variety. It arrived in a plastic bag, within which the bottle had leaked. Opening the bag resulted in a wide splatter of MB in my kitchen, impelling me into frenzied cleaning before the stains set in. Handle with care!



#17 tintinet

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Posted 14 February 2009 - 09:57 PM

Trivial as troubles go- mostly just comical, even in the midst of the event. I posted it mostly as a warning to others so they might avoid this mishap.

Edited by tintinet, 16 February 2009 - 03:46 PM.


#18 tintinet

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Posted 17 February 2009 - 12:28 AM

Works (esthetically) quite well in blueberry smoothies, FWIW.
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#19 stephen_b

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Posted 11 March 2009 - 07:38 PM

Any thoughts on this source? It costs $30.50 for 25g in a 1% aqueous solution.

It's made by

Acros Organics N.V.
One Reagent Lane
Fair Lawn, NJ 0741

and has CAS# 61-73-4.

StephenB

Or for the aquarist, there's Kordon bethylene blue, at $3.49 for a 4 oz 2.303% aqueous solution.

Edited by stephen_b, 11 March 2009 - 08:22 PM.


#20 stephen_b

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Posted 13 March 2009 - 01:46 AM

Scratch Acros Organics:

You have item(s) in your shopping cart which are considered hazardous materials. These item(s) cannot be shipped to residential addresses or sold to private individuals.


StephenB

#21 niner

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Posted 13 March 2009 - 02:22 AM

Scratch Acros Organics:

You have item(s) in your shopping cart which are considered hazardous materials. These item(s) cannot be shipped to residential addresses or sold to private individuals.

I'm kinda surprised that MB is considered hazardous, but Cole Parmer also had this to say:

Chemicals will only be sold to businesses, institutions, full-time educators, and other professionals with valid Cole-Parmer accounts.


This is standard for all the big chemical houses. They don't want to be responsible if you're whipping up a batch of bathtub PCP or if you kill yourself with some sort of misguided self-medication. It's probably more a function of the War On Drugs than anything else. It used to be possible to buy all kinds of chemicals, back in the day...
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#22 stephen_b

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Posted 15 March 2009 - 02:36 AM

The Kordon methylene blue product "Contains zinc free, chloride salt of Methylene Blue. Provided as a 2.303% water solution." Is that the same chemical as in the Ames' patent?

StephenB

#23 niner

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Posted 15 March 2009 - 03:43 AM

The Kordon methylene blue product "Contains zinc free, chloride salt of Methylene Blue. Provided as a 2.303% water solution." Is that the same chemical as in the Ames' patent?

I don't know if it's the same thing that Ames used, but is zinc the "heavy metal" that we're worried about in MB? I was expecting something a bit more... hazardous? Anyone know the typical synthetic route to MB, and what we might expect to see as a contaminant?

#24 s123

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Posted 15 March 2009 - 12:25 PM

The Kordon methylene blue product "Contains zinc free, chloride salt of Methylene Blue. Provided as a 2.303% water solution." Is that the same chemical as in the Ames' patent?

StephenB


Ames used MB from Fluka, Buchs, Switzerland.

A patent for the synthesis of MB: http://www.freepaten...08/0207603.html (I don't know if this one is used to produce MB today).
Most used process according to the Merck index: http://www.scribd.co...r-Dye-Chemistry (page 311)

#25 stephen_b

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Posted 17 March 2009 - 12:11 AM

I emailed Kordon for the MSDS for their Methylene Blue product, and they were quick to send it to me. It is CAS 61-73-4. Any comments?

StephenB

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#26 niner

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Posted 17 March 2009 - 12:34 AM

I emailed Kordon for the MSDS for their Methylene Blue product, and they were quick to send it to me. It is CAS 61-73-4. Any comments?

Would they be able to provide a COA? The MSDS doesn't say anything about purity. Will they sell it to random people such as ourselves?

#27 stephen_b

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Posted 17 March 2009 - 02:58 AM

Will they sell it to random people such as ourselves?

Sure. It's sold in pet stores to treat fungal infection in tropical fish. I bought mine here for $3.24.

#28 Lufega

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Posted 17 May 2009 - 12:11 AM

Today, I tried one drop MB in a glass of water. I am using the Kordon methylene blue product which did not come equipped with a dropper function so I had to improvise. It's been 1 hour since my first dose and I feel very drowsy. 1 drop is much higher than the 0.125 mg needed so I will adjust the dose for tomorrows dose and so on.

How should I dilute this to obtain the right amount from 2% solution???

#29 niner

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Posted 17 May 2009 - 04:10 AM

Today, I tried one drop MB in a glass of water. I am using the Kordon methylene blue product which did not come equipped with a dropper function so I had to improvise. It's been 1 hour since my first dose and I feel very drowsy. 1 drop is much higher than the 0.125 mg needed so I will adjust the dose for tomorrows dose and so on.

How should I dilute this to obtain the right amount from 2% solution???

A 2% solution is 2gm MB per 100gm solution, or 20mg MB per gram solution. To a good approximation, 1ml = 1gm here. To get 0.125mg, you might want to do two dilutions, depending on your ability to measure small volumes. If you have a dropper or syringe that's calibrated to deliver 1ml, for example, then you could take 1ml of the 2% solution and have 20mg. If you dilute this to 160ml, then one ml of it will contain 0.125mg. (20mg/160 = 0.125mg) You can work with larger or smaller amounts depending on the tools you have available for measuring small volumes.

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#30 rwac

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Posted 17 May 2009 - 05:22 AM

Today, I tried one drop MB in a glass of water. I am using the Kordon methylene blue product which did not come equipped with a dropper function so I had to improvise. It's been 1 hour since my first dose and I feel very drowsy. 1 drop is much higher than the 0.125 mg needed so I will adjust the dose for tomorrows dose and so on.

How should I dilute this to obtain the right amount from 2% solution???


I thought 1mg was the proper dose. where did you get the 0.125mg from ?




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