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Alzheimer's Disease

Rember for Alzheimer’s: Methylene Blue’s Comeback

Today we take up the extremely interesting story of Rember, hailed in this week’s press as a potential wonder drug for Alzheimer’s. There are a lot of unusual features to this one.
To take the most obvious first, the Phase II data seem to have been impressive. It’s hard to show decent efficacy in an Alzheimer’s trial – you can ask Wyeth and Elan about that, although it’s a sore subject with them. But Rember, according to reports (this is the best I’ve seen), was significantly more effective than the current standard of care (Aricept/donezepil, a cholinesterase inhibitor). In light of some of the more breathless news stories, though, it’s worth keeping in mind that this was efficacy in slowing the rate of decline – not stopping it, and certainly not reversing it. Especially in the later stages of the disease, it’s extremely hard to imagine reversing the sort of damage that Alzheimer’s does to the brain (and yes, I know about the TNF-alpha reports – that subject is coming in a post next week). If Rember is twice as effective as Aricept, that’s great – except Aricept’s efficacy has never been all that impressive.
But that’s still something, considering how the drug is supposed to work. Its target is different than the usual Alzheimer’s therapy. Accumulation of amyloid protein has long been suspected as the cause of the disease, but there have always been partisans for another pathology, the neurofibrillary tangles associated with tau protein. Arguments have been going on for years – decades – about which of these has more to do with the underlying cause(s) of Alzheimer’s. Rember is the first clinical shot (that I’m aware of) at targeting tau. If the first attempt manages to show such interesting results, it’s a strong argument that tau must be important. (Other people are working in this area, too, of course, but my impression is that it’s nowhere near as many as work on amyloid).
That’s food for thought, considering the amount of time and effort that’s been expending on amyloid. It may be that both pathologies are worth targeting, or it may even be that these results with Rember are a fluke. But it’s also possible that tau is really the place to be, in which case the amyloid hypothesis will take its place in the medical histories as a gigantic dead end. I’m not quite ready to bet that way myself, but it’s definitely not something that can be ruled out. I wouldn’t put all my money on amyloid either, at this point. (Boy, am I glad I’m not still working in Alzheimer’s: this sort of stuff is wonderful to watch from the outside, but from the inside it’s hard to deal with).
Now, what about the drug itself? It’s coming from a small company called TauRx, whose unimpressive web site just went up recently. The underlying science (and the clinical data) all come from Dr. Claude Wischik of the University of Aberdeen, who has so far not published anything on the drug. The presentation this week has, by far, been the most that anyone’s seen of it (papers are said to be in the works).
And Rember itself is. . .well, it’s methylene blue. Now there’s an interesting development. Methylene blue has been around forever, used for urinary tract infections, malaria, and all sorts of things, up to treating protozoal infections in fish tanks. (For that matter, it’s turned up over the years as a surreptitious additive to blueberry pies and the like, turning the unsuspecting consumer’s urine greenish/blue, generally to their great alarm: a storied med school prank from the old days). What on earth is it doing for tau protein?
According to TauRx, the problem is that the aggregation of tau protein is autocatalytic: once it gets going, it’s a cascade. They believe that methylene blue disrupts the aggregation, and even helps to dissociate existing aggregates. Once they’re out in their monomeric forms, the helical tau fragments are degraded normally again, and the whole tau backup starts to clear out.
Now for another issue: there’s been some commentary to the effect that Rember can’t possibly make anyone any money, because it’s a known compound. Au contraire. While we evil pharmaceutical folks would much rather have proprietary chemical matter, there are plenty of other inventive steps worth a patent. For one thing, I suspect that formulation will be a challenge here (and that Medpage story seems to bear this out). I doubt if methylene blue crosses the blood-brain barrier so wonderfully, and I also believe that it’s cleared pretty well (thus that green urine). So TauRx had to dose three times a day, and their highest dose didn’t seem to work, probably because of absorption issues. (That’s also going to lead to gastrointestinal trouble). So formulating this ancient stuff so it’ll actually work well could be a real challenge: t.i.d with diarrhea is not the ideal dosing profile for an Alzheimer’s therapy, to put it mildly.
And for another, there’s always mechanism of action. I deeply dislike patent claims that try to grab hold of an entire area, but there’s so much prior art in tau that no one could try it. But use of a specific compound (or group of compounds) for a specific therapy: oh, yes indeed. It’s a complicated area, and the law varies between Europe and the US, but it definitely can be done. The people who say that this can’t be patented should check out the issued patents US7335505 or US6953794. Or patent applications US20070191352, WO2007110627, WO2007110629, and WO2007110630. There you go; that wasn’t hard. Mind you, there might be some prior art for using such compounds as cognition-improving agents: I’d start here if I were in the business of looking into that sort of thing.
Finally, is methylene blue (or some derivative thereof) actually going to be a reasonable drug? There’s that dosing problem, for one thing, but the long history in humans is encouraging (and is a key part of TauRx’s hopes not to spend so much money on toxicity testing in the clinic – talks with the FDA should be starting soon). There have been contradictory reports (plus, minus) on the effects of the compound on the brain in general, though, so they may have to do more work than they’re planning on. All in all, a fascinating story.

117 comments on “Rember for Alzheimer’s: Methylene Blue’s Comeback”

  1. Fred Cohen says:

    Out of curiousity, I took a look at the granted US patent covering the method and compositions for treating Alzheimer’s via tau aggregation disruption (the 695 patent).
    What I found interesting is that Methylene Blue wasn’t the best tau aggregation disruptor in vitro. The patent doesn’t make it clear why Methylene Blue was preferred as a lead by TauRx, but it does imply that there was at least as strong a rationale for selecting carbemazepine, pyridoxine (B6), or cobalamine (B12), among other comnpounds tested.
    As you might know, there has been a single RCT looking at supplementation that included 5 mg daily of pyridoxine and 500 mg of oral B12 (mecobalamin) plus 1 mg folate in mild/mod AD (Sun et al 2007, PMID: 18042476). The vitamins were studied under a different hypothesis of action: the homocysteine hypothesis. There was no benefit of the vitamins on top of ACHase inhibition. Observational data have been mixed, but there’s little evidence of a correlation between AD progression and intake or serum levels of pyridoxine or B12 (see for example Luchsinger 2007, PMID: 17210813).
    I couldn’t find any studies with carbemazepine specifically looking at cognition in AD.
    Although the results of the TauRx Phase 2 study appear promising at face value, I’d want to understand why MB was chosen over these other tau aggregation disruptors (just commercial considerations?) and why other compunds with the same tau MOA, namely pyridoxine and B12, appear to offer little or no benefit clinically before loosening the reins on my enthusiasm.

  2. from_sgc says:

    But apparently methylene blue also inhibits the aggregation of amyloid with the same IC50 ~2uM:
    There might be no contradiction with amyloid hypothesis.

  3. pcr says:

    Assuming they generate sufficient efficacy and safety data to warrant approval, would FDA accept Rember as the brand name? Isn’t it too similar to “Remember”?

  4. satan says:

    One of the problems with companies based outside N. America is that those environments have no accountability (legal or otherwise).
    For all the problems with pharma companies here, reality ultimately triumphs. Asian cultures are often driven by names, personalities and “legends” as opposed to reality. Even japan is still stuck in modes of thinking that would not have been acceptable here in the 1950s.

  5. Just the fact that you can buy methylene blue off the shelf will make it difficult to maximize profits, even with US and EPO patents. I can easily imagine clinics in third world countries running the treatment themselves, even with the modifications that you suggest are needed.

  6. from_sgc says:

    The trial is claimed to be double-blinded.
    BUT the obvious sign of methylene blue in the body is a blue urine. It should immediately become obvious to doctor/patient who is on placebo and who is treated. Unless of course there is a blue-urine placebo pill.

  7. processchemist says:

    But if they patent a formulation for parenteral use and this one has the best effect, things should be different, I suppose

  8. Still Scared of Dinosaurs says:

    #7 is a good point. It’s hard to imagine a way to measure cognition that wouldn’t be susceptible to bias.
    Maybe they need to test the drug in patients with porphyria.

  9. natas says:

    #4 that’s an… interesting view. Perhaps you could back it up with something more than anecdote and spittle?

  10. anon says:

    #7, #9 – Nahh, one of the conditions of the trial was that you can only go to the bathroom blindfolded…with a nurse to make sure there’s no peeking!

  11. CMC guy says:

    I thought there were some drugs that caused “blue urine” and heard story of one drug development was halted becasue of this side effect. Google search hit two and suggested some foods. (I assume there is no Methylene Blue in the formulations).
    Triamterene – a mild diuretic and can cause a blue urine color.
    Rinsapin …antibiotic sometimes used to treat a staph infection and can cause you to see a blue or green urine color
    Don’t know how could use as Placebo but in addition to #11 anon suggestion could always make them wiz in the dark…

  12. Jose says:

    A web site for “” I think I see the horsemen of the Apocalypse headed this way….

  13. Retread says:

    “It’s hard to show decent efficacy in an Alzheimer’s trial” — not so at all — if the drug reversed the disability, we’d know in a flash. This just shows how low our expectations of this class of drugs has become.
    In 9/70 two great things happened: I finished my two years as a doc in the Air Force, and L-DOPA was released in the USA (having been used in Europe for years). The chief assigned me to run the L-DOPA clinic (set up because we had zero experience with the drug) in our residency program and I watched people get out of wheelchairs. Interestingly, just like the anti-depressants (which we thought and probably still think muck around with catecholamine neurotransmitters and serotonin) L-DOPA doesn’t work right away, the effects build over several weeks.
    While Aricept may be the standard of care — it is a lousy drug. I never saw significant improvement (this was how this class of drugs was initially touted), nor did any clinical neurologist I knew. We clearly need something better.
    Assuming Rember does help, the next thing would be to combine it with a drug in the Aricept class. Few, if any, cancers are beaten with a single drug.
    #9 — amusing idea, but porphyrics when not in an attack have normal looking urine. When they’re in an attack, they are very, very sick.
    As a clinician, I was exposed to some nasty bugs and once had to take prophylactic rifampicin for a while — which turns the urine orange. Unfortunately I went to a college football game while taking it and got some very strange looks in the john — which consisted of several 40 foot long urinals.

  14. Morten says:

    @#4 Um… wow. “One of the problems with companies based outside N. America is that those environments have no accountability (legal or otherwise).”
    @#7&9 I’m assuming that the placebo was just straight-up methylene blue since TauRX wanted to show efficacy for their formulation… or is that dumb?
    @Derek It’s called a Swiss-type claim when you use a known substance for new indications. Rather than those patent links you might want to just link here:

  15. Alan Hochberg says:

    The efficacy might be modest rather than stellar, but still it’s nice to see a drug on which there is decades of safety data, and that is benign enough for college students to slip into to their friends’ drinks as a joke without getting arrested. Let the formulation and derivatization begin.

  16. Still Scared of Dinosaurs says:

    “which turns the urine orange. Unfortunately I went to a college football game while taking it and got some very strange looks in the john — which consisted of several 40 foot long urinals.”
    Lemme guess – the ‘bama fans thought there was something seriously wrong with you and the Clemson fans wanted to know where they could get some.

  17. retread says:

    Nope — it was a Syracuse game. They are known as the Orangemen, whence I gave new meaning to their cheer “Go Orange”

  18. Still Scared of Dinosaurs says:

    I almost, ALMOST went with ‘cuse, but the last game I attended was Clemson at BC so I went with that. Dohhh!
    I guess people taking Rember can go to Giants games and shout “Go Big Blue!” Just trying to return the thread to the original topic.

  19. John Bosnitch says:

    The author and many posters on this topic seem to be professionals in this field.
    So here’s my question #1: With a family history of Alzheimer’s, an aged (89) father who is starting to become noticeably forgetful, and ‘rember’ promising to slow but NOT reverse the disease… why should I wait for further trials before getting my father on this apparently non-threatening drug by simply buying Methylene Blue.
    And the inevitable question #2: Where can I buy it and how should I administer the 60mg “effective” dose?
    I would appreciate any advice you have… either here in these postings or directly to me:
    John Bosnitch

  20. Spottymaldoon says:

    In terms of general import to humanity, this announcement is reminiscent of 1989 claim to have produced ‘cold fusion’ of deuterium using a palladium electrode! Quite on the same scale if it proves to be valid and, of course, it’s inevitable that many people are going to jump the gun and start dosing themselves well ahead of any clinical trials.
    I understand that methylene blue prices have already shot up – as did palladium in 1989.

  21. sharon says:

    Hi Satan,
    I’ll have you know that Singapore is near the very top of the world’s economic league and have zero debt as opposed to Mr. Bush’s sorry economic legacy so make you criticism of Asian countries carefully in the future. And by the way, the science of the rember™drug could well have been formulated in a world class university in Singapore but, as it is, the research was done mainly out of the University of Aberdeen in Scotland where Prof. Wischik is based.

  22. says:

    As an apprentice pharmacist in 1954 I dispensed many a bottle of ‘magic’ medicine for one of our local doctors in Durban South Africa. Apart form a ‘mess’ of ingredients, he used to include metylene blue and liquor sact (burnt sugar or dark caramel) so that the patient would swallow black medicine and pee blue. This was the magic, which probably did the patient as much good as the other ingredients!!

  23. says:

    As an apprentice pharmacist in 1954 I dispensed many a bottle of ‘magic’ medicine for one of our local doctors in Durban South Africa. Apart form a ‘mess’ of ingredients, he used to include metylene blue and liquor sact (burnt sugar or dark caramel) so that the patient would swallow black medicine and pee blue. This was the magic, which probably did the patient as much good as the other ingredients!!

  24. losingit2 says:

    Interesting discussion as I am a 58 year old early onset patient. I was diagnosed about 2 years ago and am currently on Aricept and Namemda.
    I appreciate the gallows humor, but I think this is a hoax.
    Based on what I see, I am amazed that he was allowed to present at ICAD

  25. EISERMANNS says:


  26. EISERMANNS says:


  27. Petros says:

    The patent position of Rember is discussed in this wek’s Current Patents GAzette. The author suggests that the filings published to date, assigned to WISTA LABORATORIES (now TauRx), offer little, if any, effective protection to Rember.

  28. bets says:

    Like a previous contributor I notice there are a few folks of a scientific ‘bent’ posting on this site. I wish to God this disease was only of academic interest to me. My father is 77 and was diagnosed a year ago ( there were some delays in getting specialist help) . To be honest I would give him dynamite if I thought it would blow this ‘worm’ out of his brain. ( I exaggerate but I really wouldn’t care what colour his pee was if this helped him.) He is on Arricept which helped initially but the effect has tailed off and the worm continues eating … Any advice gratefully received. Four years is too long to wait and watch a person revert to toddlerhood.

  29. eugene says:

    Even though most of us are of a scientific bent, most of us are chemists and not physicians, so we can’t give you any useful advice. Our choice on what to do by reading the info would be just as good as yours (with the difference that if I decided to dose myself, I’d read up on the formulation details used in the study or ask an insider if that was unavailable).
    And even if we were physicians, no physician who is not involved in this study would urge you to take a drug that hasn’t been fully tested or that at the end of the day could prove to offer no benefit. There is just no possible value to possibly misleading strangers over the internet no matter how bad their circumstances are. And I sympathize of course.
    Now if you put up an online poll of this blog’s readership asking: “If you had early Alzheimer’s yourself and knew the formulation details of Rember, would you dose yourself based on these perliminary results?”, the percentages who vote ‘yes’ or ‘no’ would serve as guidance for you. But giving advice from a single scientist (not a physician) to a single person with a devastating problem concerning an experimental drug over the internet? That is going to be very difficult here.

  30. dorothy says:

    #30 I am an R.N.,and yes, I would self administer. My Mother was diagnosed 10 yrs. ago and I would try rat shit if I thought it could stop her horrendous suffering. Thank you all for the work that you do .Please pray for those who are dying endlessly.

  31. Terence says:

    I feel so sad for the shareholders of TauRx and Prof wischik. He has spent more than 20 years of research and who knows how much money. Yet there are people in this blog that are suggesting using generics or breaking the patent. These same people insult Asians in the same breath. Shame on you.


    So methylene blue turns urine blue? Okay – beetroot turns urine purple. If this drug helps dementia sufferers those of us who care 7/24 for relatives who are becoming totally helpless and dependent would gladly accept the medicine for their suffering loved ones even if it caused striped urine with rainbow spots.

  33. sb2 says:

    Wow – speaking on behalf of Alzheimer’s patients who need your help and help you by donating to research – many of you should be ashamed of yourselves. Call me naive, but when is a patent worth more than a human life? When is blue urine a reason to halt a clinical trial? I’ll take blue urine over memory loss any day. I don’t know when the industry took this turn and I hope that your comments don’t reflect the true feelings of pharma and the researchers in the field.

  34. metame says:

    A couple questions for anyone who is game:
    1) When dealing with a disease that has essentially zero rate of spontaneous recovery, why bother with a placebo control group? Can’t we just take it as read that the disease would otherwise progress?
    2) I can’t tell from reading the patent what exactly they did to methylene blue to merit a new patent. And–the more urgent question for many–how is it any different from the stuff that’s been with us for years?
    My mother has corticobasal degeneration–another tauopathy that, briefly stated, does horrific things and nothing yet has been found to stop it.

  35. linda says:

    my mother has alzheimers….
    we tried all the medications
    namenda aricept excelon
    none of them work………
    i wish i could get some of
    this medicine right now to try
    i hate to see her regressing to
    a two year old…for thirty five
    years she was a business manager
    now she cant even make out a
    personal check………
    thanks to anyone researching this disease
    hope it wont be too late for mom…….

  36. Denise says:

    For those caring for loved ones with AD and other dementias, think about trying a more comprehensive approach. There is no “magic bullet” for these conditions. Current research suggests that AD involves inflammation and an underactive immune system. The best approach should include the current rx’s, treatment for nutritional deficiencies such as Bcomplex, B12, Vit D, Fish Oil, etc., and support for the immune system. Not to mention lifestyle changes; especially those that reduce stress for the patient. Good luck!

  37. MTK says:

    sb2 and M. Hamilton,
    You two are misunderstanding the significance of the blue urine. No one is saying this should stop an effective medication being used. what they are saying is that it is a potential complication in designing a clinical trial and getting meaningful results.
    So the comments which you interpret as callous disregard for human suffering are anything but that. What they are saying is “How can we make sure that this works?” “How can we ensure that we are providing patients and their relatives real effective medicines and not false hopes?” “How can we assess this potential drug properly, so we can either make it better or move on to other leads with a real chance of making a difference?”
    I hope this helps you understand and appreciate what researchers and the pharma industry does.
    Believe it or not, everyone in the industry wants to help. We all have or have had family members afflicted with cancer, Alzheimer’s, heart disease, etc. That’s why many of us got in the business in the first place.

  38. Shawn says:

    My understanding is that the current treatment plan using methylene blue for Alzheimer’s and Parkinson’s, is that very small doses would be used, a la, “a few rain­drops in four Olym­pic-sized swim­ming pools” (ref.
    In fact, high doses of the drug can cause brain damage over time.
    If this is the case, the “blue urine” issue would probably be irrelevant as the doses are so low. As Derek pointed out, the dosing may be the critical potentially valuable/patentable aspect in addressing mitochondrial dysfunction in Alzheimer’s. Delivery of the drug is another issue, but many new and existing drug delivery mechanisms avoid ingestion and therefore the diarrhea issue.

  39. Jiff says:

    For those dealing with loved ones with this illness hang in there. Taking it one moment at a time works for me.
    #37 We have been doing all this and Mom’s progessive slide has been very slow (about one stage per year) No longer using Aricept (leg cramps) just namenda, B6, B12, vitamins and calm surrounding.

  40. Jiff says:

    For those dealing with loved ones with this illness hang in there. Taking it one moment at a time works for me.
    #37 We have been doing all this and Mom’s progessive slide has been very slow (about one stage per year) No longer using Aricept (leg cramps) just namenda, B6, B12, vitamins and calm surrounding.

  41. mike says:

    Another product claiming similar effects:
    Professor Kruzel (Regen Therapeutics)
    ‘In this presentation I will explain how such a low dose of Colostrinin™ can produce significant medical benefits in AD patients. I will focus on our findings from recent genomic microarray work, which shows that Colostrinin™ can favourably modulate the expression of several molecules involved in the pathology of Alzheimer’s disease (upregulation of bleomycin hydrolase, downregulation of APP and effect on Tau phosphorylation). This enables the body’s own multiple responses to reduce neuronal pathology and achieve homeostasis. The effect on Tau is said to be the reason for the response witnessed by the patients taking the drug Rember*. This data suggests that Colostrinin™, may be one of the first compounds with the potential to impact both Tau tangles and beta amyloid plaques, the two key pathologies of Alzheimer’s disease.’

  42. Thank you for all of the interesting articles you have written on Alzheimer’s.

  43. jtwiz7 says:

    After Dorothy and Denise’s comments, I discussed it with wife and after ten days,there’s a new person in our house.

  44. kathy phillips says:

    Why didn’t you post my commentsof France being able to come up with cures for certaind diseases as Cancer and Alzheimers diseases but the USA hasn’t approved them, are you afraid to post this, it’s a money making business, and I believe, the government has more to do in hiding the cures for these diseases, so they can pocket money. I want answers.

  45. Derek Lowe says:

    Your comment showed up about nine times, actually. Could you provide any examples at all of a French cancer or Alzheimer’s cure? Name, company, when it was approved by the EU regulatory authorities – any of those? I’m not aware of a single one, and I’ve worked in both areas.
    Drug discovery is indeed a money making business, both here and in Europe. But how the government is pocketing money by “hiding cures” is a mystery to me. Believe me, drug companies would love to find some of these, because they’d make a mint.

  46. lisa says:

    Seem to recall methylene blue being used to treat bipolar disorder. Interesting that Lithium also seems to interfere with tau formation (GSK inhibition) and is currently being tested in ALzheimer’s. If lithium prevents phosphorylation and methylene blue breaks down tangles, the combo should be especially effective…assuming tau is the culprit.

  47. Damitha Edirisinghe says:

    It is very exiting to know that there is hope for alzheimer sufferers. A cure or something that improves memory matters immencely to me for personal reasons and hence would like to know when these trial drugs would be available ? and if there are any clinical trials going on at the moment where patients can obtain these on trial basis?

  48. ltdem says:

    To #44. jtwiz7. When you say theirs a new person in the house, are you saying that you tried the methelyne blue (Rember)? If so, what dosage? How much improvement? How was it administered?

  49. Daniel Crespin says:

    A molecular weight of 320 for MB suggested, after some estimations, to interpret the “few rain­drops in four Olym­pic-sized swim­ming pools” metaphor as one part per billion (ppb) or 10^(-9) order of magnitude.
    Since a close relative has been ravaged by Alzheimer for several years, I diluted and administered the usual 2% commercial MB. It was hard to measure the possible mild improvement in the patient.
    More recently I had access to one of the original articles on MB and found their most effective concentration was actually 100 ppb. With this datum, some Web search on MB pharmacokinetics/ pharmacodynamics and given that the volume of blood plasma in adults is about three liters, I arrived at the following practical dose formulation:
    Dilute twenty-fold commercial 2% MB in water.
    For example, add water to 25 ml of 2% MB to complete 500 ml, or half liter. At 20 drops per ml this contains 10000 drops at 0.1% dilution.
    This MB at 0.1% is given one drop three times a day, preferably in half glass of water (to avoid blue tongue). I am trying this on myself as well.
    I am 62. Assuming no placebo effects, and not being —as far as I know— an Alzheimer person, the following seem to take place:
    1.-Skin become smooth
    2.- Nails grow faster
    3.-Physical activity goes on rather well.
    Of course, I have not subjected myself to any sophisticated cognitive or clinical tests.
    My Alzheimer relative, an extremely fragile a 93 years old person, seems to be improving as well.

  50. Daniel Crespin says:

    Sorry, in my previous comment, where it says 100 ppb it should say 100 nanomol. The final 0.1 % dilution is OK.

  51. Ken Gillman says:

    Methylthioninium chloride (methylene blue) is an monoamine oxidase inhibitor (MAOI), see my web site for details, and paper in Brit J Pharmacol.

  52. Ken Gillman says:

    Daniel, can you send me the references you refer to. Basically its very uncertain trying to extrapolate from such information to what an effective human dose might be at the effector site: a CNS enzyme, receptor etc. In the end analysis its clinical effects that are the proof of pudding. MB definitely causes serotonin toxicity ( serotonin syndrome) if mixed w serotonin reuptake inhibitors. The earlier work re depression / MDP averred to isnt good enough to say much, but of course MAO-A inhib like moclobemide are thought by some to be mild antidepressants. Youdims 2006 review is useful re MAOIs which may indeed be helpful for dementia.

  53. Barbarawanda says:

    Where are folks sourcing methylene blue? Chemical companies (eg Sigma Aldrich) only sell “GPR” grade – which is likely to have heavy metal contamination.

  54. Barbara says:

    Sourcing MB
    Anaspec claims to produce “ultrapure” MB. I don’t know what criteria they use – insufficient info on website. Hopefully may be better than the GPR grade which is certain to have significant heavy metal contamination.
    Here’s another one:-
    If anyone tries to find out more about the quality of their MB from these websites, please post.

  55. rina says:

    I have been using MB from American Regent, but the urine is not turning blue.?wrong dose or wrong MB, I diluted it according to your instructions to .1%.
    please, respond, thank you.

  56. says:

    Rina and Daniel – I don’t know where you are getting your figures from, but MB was used at 60 mg per day in the clinical trial. A 0.1% (weight/volume) solution will only contain 100 mg in 100 ml by definition – you would need to drink 60 ml of this to get the therapeutic dose. A few drops would be not much more than homeopathic! Also see my suggestion for sourcing MB if you are intent on self-dosing – most MB suppliers are selling stuff that is likely to be contaminated with heavy metals.

  57. Daniel Crespin says:

    Answers below for several persons
    For Ken Gillman
    I wanted to attach the article to this message but neither this web page, nor yours, seem to give me the option. The article is:
    Atamna et al. Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways. The FASEB Journal, 2007; 22 (3)
    and is quoted in
    Extrapolating clinical doses from in vitro experiments is not the most scientifically sound procedure nor a clinically strict method, but MB has a long story of folk use since its discovery. Accordind to the FDA —I checked a few weeks ago— there has not been any report on MB toxicity.
    As you certainly know soldiers during WWII used it as antimalarial in doses high enough to give then blue urine, feces and sclerotic tissue. No toxicity report ever surfaced. Also, during my childhood —1950’s— it was used as topic for tonsillitis, we swallowed it and it produced similar effect. The risk/benefit rate for Alzheimer and Parkinson patients is therefore rather small. The few I know take it seem to be improving.
    Had Jenner or Pasteur been restricted by today pharmaceutical standards they would have not benefited humanity the way they did. Such standards, useful as they are, are also enforced by the big pharmaceutical companies to corner the market. If MB is really effective, a strong attack from the companies against OTC MB can be expected.
    A friend with advanced type 1 diabetes had a persistent infection in a foot for longer than one year. He decided to take MB three weeks ago and today informed me over the phone that his foot is cured, with only a scar left. Was it MB or some other cause?
    As for serotonin toxicity, is it true that even aged cheese has such effect?
    Perhaps the FDA does not consider serotonin toxicity to be a relevant form of toxicity. After all common salt is so toxic that Romans often used it to commit suicide. In large enough doses Yellow number 5 —tartrazine— has a behavioral effect in children, probably mediated via neural mechanism, hence could be considered neurotoxic but is still found in many foods. Alcohol is a commonly used toxic substance, and is not, apparently, a cure for Alzheimer, Parkinson, etc.
    Please let us know your opinion.
    For Barbarawanda and Barbara:
    I use standard 2% MB as sold over the counter in many pharmacies (like Walgreen’s) in South Florida. It is usually found in the “Hispanic Medicines” stand.
    For Rina:
    At such low concentration no coloring effect will appear in urine/stools or sclerotic tissue.
    A 60 mg dose is too large to conform the Olympic pool methaphor. For the moment I will stay with the “one drop of .1% dilution three times a day”.
    Since MB is often used to add to aquariums as a cure for some diseases of fish and fish are very susceptible to heavy metals I would expect these chemicals to be very-very low in MB.
    Regards to all,

  58. Scott says:

    After viewing all the comments: (1) it is still not clear what the commonded dosage is for improved mental acuity, (2) is this number greater or smaller than the amoung that will cause discolored urine, (3) where can I buy it (I tried a CVS and they never heard of it), (4) how can TauRx get a patent on a drug that is available over the counter (it’s like getting a patent on electricity)? Whenever TauRx gets this approved by the FDA (they tell me at the earliest by 2012), will doctors then start writing prescriptions for it? Why do they need to write a prescription for a drug that is available over the counter?

  59. Ken Gillman says:

    This discussion will benefit from a bit more understanding of the interface of science with clinical medicine. No-one seems to have noted that, apart from having nano-mol potency as an MAOI (ie like moclobemide, which has also been claimed to help dementia) it is also a potent NO synthase inhibitor.
    If anyone wishes to contact me thro’ my website I will explain it, pref via skype.
    Also fairly comprehensive refs are in my ‘paper’ about MB, pdf on website.
    NB I have no commercial interested of any sort

  60. John Bosnitch says:

    I am returning to this list after being contacted by quite a few readers who asked me whether I had found any more information about dosing and administration of MB.
    I discovered what appears to be a good estimate of what needs to be prepared in the form of instructions that almost anyone could prepare. Here is the source, which also includes other good advice:
    If you are not in Florida (where you can buy Methylene Blue over the counter, I have a friend there who can send it out at cost.
    I have one other suggestion. Since there is not supposed to be any negative effect whatsoever from taking MB, I suggest that if you are planning to give it to an older relative who is in serious need, you should still administer it to yourself at the same time so that you don’t need to do any guessing about side effects on a person who might not be a cognant as you are about what they are experiencing.
    I give this advice not as a professional and I welcome any and all comments here by scientists/doctors who might have better ideas. No matter what though, we need to assemble reports on all results and or side effects and publish them on the Net to get around the system’s embargo on this very needed therapy…
    I look forward to hearing of your results, as well as any better advice… please keep in touch with me directly as well…
    John Bosnitch

  61. Joe Pesec says:

    I am trying to get in on a clinical trial of Rember. Could anyone suggest the fastest way to do this? 216-481-0787
    Thank you and Happy Holidays
    Joe Pesec

  62. Scott says:

    In response to Joe’s desire to get in on a clinical trial for Rember, I sent and email to TauRx on this subject. They responded that you cannot get on a clinical trial by applying. The system is that they will contact neurologists and the neurologists will recommend subjects for such trials. You can get their email on their web site which is

  63. Zarabeth says:

    @John Bosnitch:
    1) My understanding is that the effective dose is approximately 60mg three times per day, not the microscopic quantities listed in that article.
    2) Methylene Blue is a powerful MAOI and thus should not be taken along with any SRI (which includes the SSRIs such as Celexa, Prozac, etc.) – doing so could very well be fatal upon the first dose.

  64. Ignacio says:

    Herpes labial asociado a Altzheimer.
    Tratamiento herpes= Azul de metileno.
    Tratamiento hongos= Azul de metileno
    Tratamiento Altzeimer= !!!¿ Azul de metileno ?!!!

  65. PV says:

    Some people take a medication called Prosed/DS for urinary problems. It contains MB and it turns the urine blue but not right away. Even after you stop taking it the urine remains blue for a few days. I don’t know why. There are people taking this drug for chronic urinary conditions such as interstitial cystitis even though the drug comes with the warning that it hasn’t been tested long term. It is a compound drug with probably more dangerous ingredients than MB. I’d like to think that it helps AD as a side effect!

  66. jtwiz7 says:

    To #49, Itdem, and others; yes, after discussion we have been using MB since last August. Approximately 150mg twice/day with lots of tlc, very healthy diet, zero sugar and soda, lots of water and vitamins B3, B6, and B12, exercise and crossword puzzles. Filled empty #2 gelatin capsules with nettle-nose tweezers and rubber gloves. Amazing immediate improvement. Sorry for delay in responding. Hope this helps.
    To #44. jtwiz7. When you say theirs a new person in the house, are you saying that you tried the methelyne blue (Rember)? If so, what dosage? How much improvement? How was it administered?

  67. Scott says:

    There still seems to be a lot of discussion about dosages, etc. The big question remains: is MB the silver bullet or not?

  68. chasmears says:

    Where did you get the methylene blue? Is it in liquid form? Where did you get the capsules? How do you know that the dosage you are using is 150mg? How long ago was person diagnosed with altzheimer’s?

  69. Scott says:

    In response to chasmears, I have not obtained any methylene blue. There has been a lot of chat saying that it was avaiable over the counter. I have not found that to be the case. My person was diagnosed with Alzheimer’s about one year ago. The fundamental quations about methylene blue do not seem to be available. Dosage is not the top priority question. The top priority question is whether it will work or notl

  70. Scott says:

    In response to chasmears, I have not obtained any methylene blue. There has been a lot of chat saying that it was avaiable over the counter. I have not found that to be the case. My person was diagnosed with Alzheimer’s about one year ago. The fundamental quations about methylene blue do not seem to be available. Dosage is not the top priority question. The top priority question is whether it will work or not.

  71. Dan says:

    My son is participating in an “unoffical” trial of MB for autism. Taking a daily dose of 1.0 ml per day. Although we were hoping for gains in speech – we primarilly have found less agitation, grimacing, muscle rigidity. We are going to cycle off and see if these return.

  72. mike says:

    Methylene blue kills fungus in fish tanks…maybe fungus has something to do with Alzheimers ? Fungus might be the “train ” that the tangled tao rides on ??

  73. mike says:

    Methylene blue kills fungus in fish tanks…maybe fungus has something to do with Alzheimers ? Fungus might be the “train ” that the tangled tao rides on ??

  74. mike says:

    Methylene blue kills fungus in fish tanks…maybe fungus has something to do with Alzheimers ? Fungus might be the “train ” that the tangled tao rides on ??

  75. agghouse says:

    to 67. jtwiz7, I care for my precious mother who I have watched decline rapidly and significantly over the last couple of years. Exelon & Namenda are not working. She is healthy as an ox;take her to silversneakers @YMCA 3x/wk;yrs of taking fish oil, b complex, vitD etc. WHERE CAN I GET THE METHELYNE BLUE? & how did you know what dosage?

  76. agghouse says:

    tl 67. jtwiz7, I also give my mother a puzzle every day; find a word, simple math problems, mazes etc. she has been unofficially diagnosed with alzheimers since feb 09;started treatment for mild dementia w/exelon nov ’07;started namenda 3 ’09. decline, decline.pls respond.

  77. Scott says:

    Here is an interesting finding. There is a disease called methemoglobinemia. It is the failiure of the blood system to deliver oxygen to the brain. It has many things in common with Alzheimer’s. First, it results in the loss of mental acuity. It results from common things like Tylenol and prservatives in food. It can be genetic. Most importantly it is treatable. Its standard treatment is MB the same chenical shown to be effective for Alzheimer’s. Is it possible that this disease can be misdiagnosed as Alzheimer’s?

  78. Retread says:

    Scott — the chance of methemoglobinemia being misdiagnosed as Alzheimer’s disease is quite remote. Here’s why. Methemoglobin is hemoglobin with the iron in a ferric oxidation (+++) state, rather than the ferrous state (++). In the ferric state hemoglobin can’t carry oxygen. This has a profound effect on the MRI as methemoglobin is paramagnetic and has a profound effect on the approach of the disturbed hydrogen nuclei returning to equilibrium (called T1 relaxation). Any hemorrhage into the brain results in the formation of metHemoglobin from hemoglobin which makes T1 images look very different (usually dark) around any metHemoglobin which has formed (even a small amount).
    Alzheimer patients NEVER show a pattern of this type on MRI.
    ” It is the failiure of the blood system to deliver oxygen to the brain. It has many things in common with Alzheimer’s. First, it results in the loss of mental acuity.” True enough but ANY failure of the blood system to deliver oxygen to the brain will have significant cognitive effects. Remember, our 3 pound brains are consuming 20% of the oxygen we breathe as we sit and look at the screen.

  79. Denise says:

    Dr Jacob Teitelbaum writes,
    “Methylene blue will have an interesting time getting a patent (it is older than I am), but the drug company will probably patent the delivery system. It is worth keeping an eye out for, for use with those with Alzheimer’s. Although it will be 4-5 years before the FDA process is completed, so it can be approved for Alzheimer’s and available in pharmacies, the optimal dose is 60 mg 3 x day (more is not better) and it can be prescribed by Holistic Physicians and made by compounding pharmacies”
    I use Cape Apothecary in Annapolis Maryland for other compounded remedies, 410-757-3522. They can ship to anywhere.
    Take Care!

  80. Jim Tower says:

    My wife has been on MB since Feb 09 after 7 years since first symtoms noticed at age 55. The jury is still out; after a few weeks there seemed to be greater awareness of herself and surroundings and functional inprovement. Sleep highly important. Rx 60mg 3 x daily.
    Also,namenda,exelon,quercetin,vit E and fish oil. Any other results out there to report?

  81. jtwiz7 says:

    To 69. chasmears et al:
    Sorry for delay in responding, but as you know, it’s not easy.
    I will provide all info I have to anyone who e-mails me at we have been blessed and it seems to be working well.

  82. Boo says:

    Jim Tower, please get in touch with me via e mail. My address is cccbaxter at hotmail dot com. That is 3 Cs, not two.
    My Mother has Alzheimer’s, and has not yet forgotten her loved ones. While she is yet in fair mental condition, we are looking for whatever works. I wish to correspond with you about specifics. Thanks. 🙂

  83. Fran says:

    Info for Boo – Is your Mom by any chance taking a statin (cholesterol lowering) drug? All statins are capable of causing memory loss which can mimic AD.

  84. Jinny says:

    Hi, I hope this makes it to you or any one that can help us. Our history probably takes the cake, so to speak. My husband was diagnosed with early-onset alz last year at the age of 54. It is so sad to watch this man who had been a sgt. in law enforcement for 34 years, dwindle away. I am 48, and we have a precious little girl who is 7. Can you imagine what goes through her head at just watching her daddy? This is not the worst part. My sister was also diagnosed with early-onset alz at 46. She is now in last stages, living with a feeding tube. Her kids have had several tests performed, and learned that that she has genetically-chromosomed type of AD. They said 1-2 out of every five siblings will also suffer her same fate. There are seven of us. Can you imagine the horror and urgency i experience every day. Chances are more than high that our little girl will have neither parent at her graduation. I live everyday with two huge boulders on my my shoulders amidst a black cloud. This all is going on while trying to be the best care giver and mommy I can be. He can’t be accepted into any trials because he had malignant melonoma last year.-even though it was found in it’s earliest stage, requirng no treatment. He said dying from the cancer would have been so much easier. Is there anyone out there that can save my family?

  85. Boo says:

    Thanks, Fran. 🙂 I hope you got my email.

  86. James says:

    My Mother has suffered from AD for the last two years. She takes Aracept which I believe helped but made her more anxious. In the past six months she has declined sharply.
    I would like to try MB. I showed her doctor some material on MB and he did not react negatively.
    From what I have read the big thing is getting the MB to the brain without stomach, liver and kidneys getting in the way.
    It seems that TauRX will patent a delivery system since they cannot patent the drug. Would a nebulizer be able to transport the MB more directly to the brain?

  87. J A J says:

    You can purchase MB online at science shops. I bought a 1% solution and have followed the instructions as I have understood from previous writings in this string. I am not a science person, but I basically mix a drop of the liquid solution to 10 drops of water. Then take 1 drop of that solution in a small glass of water. My wife in her 50’s has AD. My entire immediate family feels that it helps her. I have stopped to see if it made a diff, and she seemed to do better when she had the MB. Not perfect, but it helps her to be more relaxed, and enjoying herself more. Sometimes give her 3 servings per day, but felt that two seems to have better results. We have been doing it for about 8 months now. It doesn’t heal or reverse, but it sure seems to make things more tolerable at this stage of AD.
    Also, websearching for MB and Rember, found that a company in Ellisville, MO, suburb of ST. Louis named Tocris. They have the MB, and earlier in the year had comments about rember. Their hq is in England. I tried to buy some MB from them, with a CC, but they said that since I was not a reg customer, I needed to do a financial or credit review. Sure wanted to see what their MB, or rember was all about.

  88. Scott says:

    I am interested in the comment that statins can mimic AD. Is there general agreement on this? If my wife is taking a statin (simvastatin), should she stop?

  89. Debra says:

    My mother has AD. She is taking Celexa. I just read that taking MB while taking Celexa could kill with just the first dose. My goodness !!
    I am glad i read that. I was thinking about giving my mother MB. I want to help her not hurt her in anyway. She is in denial that she has AD. Her 12 brothers and sister all had AD and she took care of them until they died. She has this fear on her face when i try to talk to her about it and she will get mean with me about it. So, I drop the subject. It is killing me to see her decline like she is. She broke her shoulder about 5 weeks ago and i am taking care of her and since then i have seem a big decline in her memory. I would love to see if she would try MB but since she is on the Celexa that is out of the question. Why is celexa dangerous to take with MB? Do you think that taking B-12 shots could help her with her memory? Along with other vit? Thank you

  90. Boo says:

    Hey there, Debra.
    If you want to give your Mom b12 shots, make sure that it is methylcobalamin. Cyanocobalamin and hydroxocobalamin would be no good for AD, and may even hurt. But methylcobalamin is supposed to be good for it.
    Methylcobalamin is expensive in injectible solution. If you actually convince a compounder to cut you some powder so you can mix your own shots, make sure to use a whatman filter and bacteriostatic water. It is also very important to make an absolutely sterile environment when mixing the solution.
    The shots should be given subcutaneously instead of intramuscular. Insulin needles/syringes will be good for this.
    Also, methylcobalamin in unstable in aqueous solution. Comb this thread for details. Look for the names Freddd, and kevinmillhill.
    Other things to look into are lithium, cannabis, huperzine-A, MSM, DMSO, RAW vegan diet, nicotinamide, methylfolate, vitamin k…
    Good luck to you and your family. AD is a bit*h.
    Good luck to you.

  91. Boo says:

    Dang. I left out omega 3 fatty acids. Hempseed oil and Udo’s oil are good sources, and AD sufferers need it more than the rest of us.

  92. Rich says:

    I purchased 1% MB from an online lab. I’m ready to dilute it to .1%
    I then noticed the “Fatal upon 1st dose” comment by Zarabeth, and am holding off.
    Can someone substantiate that comment ??? My mother is taking Zoloft, which is an SRI. I don’t understand how something can be used for 100 years, but in conjunction with one med. be fatal.
    Thank you…. You can also email me at

  93. Zarabeth says:

    This doctor has done a bit of research into MB toxicity. His contention is that almost every mysterious death from MB is attributable to the patient being on SRIs at the time:
    He cites a number of cases (24 or something) where a patient died on the operating table due to MB injection (where it’s used to dye organs for easier identification during surgery).

  94. Boo says:

    Injection is dangerous. Can cause rotting flesh and so forth, so must be injected by medical professionals in a medical setting only.
    Oral ingestion is different. College kids trick each other into drinking it all the time as a joke. Makes their pee turn green or blue and stains the mouth blue (temporary), and they often use more than 60 mg. **If no one is taking a SRI**, I’m not worried too much about giving the 3 doses of 60 mg a day in juice, personally. Especially when they have dementia.

  95. Rich says:

    Zarabeth & Boo
    Thanks so much for your responses! I’ll certainly read through the information on the link you provided Zarabeth. I would be dosing her the 60mg three times per day in water or juice, but it looks like oral would also be a danger given that she is also taking a SRI, correct?
    I’ll be talking to her Neurologist about this in a couple weeks as well. Hopefully he’ll have a suggestion or two.
    Again – thanks so much !!!

  96. Boo says:

    Rich: yes, methylene blue is extremely dangerous for a person to take if they are also on an SRI. Can be fatal. What the chances are, and what exactly makes it dangerous, I cannot say, as I don’t understand the processes in play.

  97. H Fisher says:

    Has anybody tried this in conjunction with trehalose or any other autophagy inducing regimin?

  98. rose says:

    A woman named Anita Scoggins claims that phosphatidylserine (not sure of spelling) brought her husband back from severe dementia. Try, a physician who works with her, or google her to find out more. I’m about to order it myself for my own dear mother. Hope Jenny gets this.

  99. zanet says:

    good my dad has Alzheimer’s’ and I len54 years and I would somehow help him: I would be interested in this product where I buy it …. Greeting zaneta

  100. nitrosonium says:

    anyone know much about tetrazine as an amide substitution (isostere???) in SAR?

  101. C says:

    Try 60 mcg of MB – NOT 60 mg. You can argue, or don’t believe me, but that’s my anecdotal comment.

  102. George says:

    My vision become much better after I started consume methylene blue 1-2 drops 0,1% (standard solution advised) 2-3 times a day!!! Vision become clear and with no vision noise in the centre of vision. Amazing! I worried about that problem 12 years along. I am 53 y.o.

  103. Scott says:

    It sounds as if Rember has fallen off the radar screen. Is that accurate?

  104. Scott says:

    It sounds as if Rember has fallen off the radar screen. Is that accurate?

  105. Todd says:

    Vitamin C will render the methylene blue transparent. No need to worry about blue urine for testing here, people!

  106. SHARONEC says:

    Here is the link to the October 30, 2012 webinar describing the phase 3 clinical trial of second generation Rember/methylene blue.
    The drug, LMTX, targets tangles of tau protein in the brain, dissolving them to halt their harmful effects on memory, closely held TauRx said in a statement today. LMTX also works on precursors to fully formed tau tangles, the Singapore-based company said. The trials, part of the last of three phases of human testing usually needed for regulatory approval, will involve more than 1,300 people in more than a dozen countries.

  107. Inclineal says:

    I have been infusing my wife with Baxter Gammagard -20gmq 2 weeks. She has had 20 infusion to date, well-tollerated etc. Her AD appears to be stable and she has show some improvement.
    Trying to get into LMTX clinical trial but may not get in.
    Understand there are sources for pure MB in India. Does anyone have contact info they will shre with me?

  108. LIsa says:

    I have found a straight forward website that indicates dilution and dosage.
    refer to

  109. Picks says:

    Acouple of questions for anyone who might know the answers.
    1. Can the diluted MB be used to make coffee, tea and fruit juices without impacting the efficacy of the MB?
    2. I’m concerned about where to source the MB from (I’m in the UK). Getting it from the pet shop, where it’s sold for fish diseases, just doesn’t sound good.

  110. LUCKYGUYS says:

    I have been taking MB for 6 months with 1000mg vitamin C. Concerned that the vitamin c may be
    interfering and reducing the benefits of MB. Anyone know the answer to this?

  111. Hopeful says:

    Scott wonders whether Rember has fallen off the screen. No. Trials are halfway through in England

  112. Ken says:

    Hi all, my wife has AD and we would like to try the MB solution. Can anybody tell me how long would it be after stopping taking citalopram before the MB could be safely taken?
    Thank you.

  113. Anon says:

    Please do not take MB. I know someone who was in the Wischik study. She was verbal, communicative and emotionally responsive prior to taking it. Within just a few months of taking this (for the study) she became minimally verbal and communicative, with very little emotional responsiveness. We’re talking just months here. She also lost coordination and balance ability. On top of all that, significant diarrhea episodes and sickness were very common- blue stain was everywhere (they ask you to use powder vitamin C to clean it up- total nightmare). This is a horrible agent that is neurotoxic and causes the dementia to get much worse over a short period of time. These guys should be arrested for the quackery they are unleashing onto the public. The doctors in the study have no bedside manners, so to speak, nor could they care less about the side effects. I wish I could give you more details about my experiences with the company and their quacks, but I assure you this is NOT a good drug, even if it is claimed to be ‘generally accepted as safe’. It makes dementia worse in a short time, hands down. I wanted it to be a possible treatment and high hopes, but it isn’t. Avoid this. Please. I have no affiliation to any competitorof the company, lab, or Pharma. I know this from witnessing it first hand. Avoid it, please.

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