Methylene Blue Review

Discussion in 'Blogs' started by noqcks, Jul 19, 2020.

  1. noqcks

    noqcks Member

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    Methylene Blue is beloved by everyone around here, but I couldn't find a concise summary of its benefits online.

    I wrote a blog post about the history of MB, mechanism of action, dosage, etc.

    Would love feedback.

    Methylene Blue: Cognitive Enhancer

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    Methylene Blue: Cognitive Enhancer

    Yes, I take an anti-malarial to help improve my memory. Let me explain.

    Methylene Blue (MB) was first formulated in 1876 and it was the first synthetic drug to be used in humans. It was originally used as a dye for cotton straining, and is still used as a dye in laboratory settings.

    It was experimentally used to treat schizophrenia in the early 19th century. At this time a peculiar side effect of Methylene Blue (MB) was noted. In high enough doses, MB will turn urine blue. Eventually it was used side by side with other psychiatric medications to ensure drug regimen compliance. If a patient wasn't peeing blue, they weren't taking their meds.

    The blue pee side effect is still quite useful in Africa where MB is used as an anti-malarial. With drug faking being common in Africa, blue pee is the best indication you're not taking a fake drug.

    It was also used extensively by World War II by allied forces in the south pacific for malaria, who used to joke "Even at the loo we see, we pee, navy blue".

    MB is now being researched for help in diseases such as cancer, Alzheimer's, Multiple Sclerosis, depression, and aging. It's quite an exciting dye. Let me review the mechanism of action, before discussing promising research, safety, and if one was inclined, dosage.

    Mechanism of Action

    You would think it impossible that one dye could be used to treat so many seemingly disparate diseases. It seems implausible.

    MB does not work on the receptor-ligand model, like many other drugs do, it works by directly increasing mitochondrial respiration through the Electron Transport Chain. The Electron Transport Chain is series of four proteins complexes that sit in the membrane of the mitochondria and are responsible for Oxidative Phosphorylation (OxPhos). OxPhos is the main method through which ATP is produced, the "energy currency" of the cell.

    MB can easily cross biomembranes, just as Nitric Oxide does. It permeates into the mitochondria, where it acts on the Electron Transport Chain as an electron transporter. It is first reduced to MBH2 by the NADH that comes from the Electron Transport Chain complex I and then re-oxidized back to MB by complex IV. The cycling between these two forms facilitates electron transportation for ATP synthesis and increases the performance of the Electron Transport Chain. This is true even in hypoxia.

    An increase in ATP from the mitochondria is beneficial, even in healthy individualsʳ. The cell is the foundation of life. The mitochondria powers the cell through ATP synthesis. You are comprised of a multitude of cells. The mitochondria powers you.

    Energy and structure are related at every level in the human organism, and mitochondrial impairment is implicated in many disease states (Diabetes, Multiple Sclerosis, Cancer, etc).

    "These findings provide evidence that methylene blue, the redox dye currently used as an antidote for encephalopathy associated with alkylating chemotherapy, uncouples oxidative phosphorylation and acts as an electron transfer mediator to stimulate mitochondrial respiration." (Visarius 1997)

    Medical Uses + Research

    Methylene Blue is medically approved for urinary tract infection, malaria, methemoglobinemia, cyanide poisoning, and hypoxia.

    I would like to highlight some of the interesting non-approved use cases and research.

    Septic Shock
    It is thought that the sudden release of Nitric Oxide is responsible for the cardiovascular problems associated with septic shock.

    Methylene Blue has been found to be a potent inhibitor of nitric oxide synthase, one of the three enzymes involved in nitric oxide synthesis.ʳ The exact impact MB can have in sepsis is inconclusive.

    Skin Aging
    As we age, the combination of accumulated Reactive Oxygen Species (ROS) and the bodys reduced ROS scavenging capacity leads to increased oxidative stress. Collagen is a protein responsible for providing skin structure and forming connective tissue. The overabundance of ROS decreases collagen synthesis and increases collagen breakdown.

    According to this ROS theory of skin aging, skin products with antioxidants are used to suppress or neutralize excess ROS. Vitamin C and Vitamin E being the most well known antioxidants in skin products. Methylene Blue, acting as an antioxidant, is able to deactivate superoxide, a potent ROS.ʳ ʳ

    Malaria
    As already mentioned, MB was heavily used for malaria before being replaced by other antimalarials which didn't turn urine blue.

    In 2014, a study showed that intravenous MB was just as effective as the standard malaria treatment method, intravenous artesunate.ʳ

    Cancer
    A study from 2017 shows that MB was able to differentially kill tumor cells in culture when used in conjunction with photodynamic (light) therapy.ʳ

    This is one of the only papers I've found on the effects of Methylene Blue on cancer. More research is needed, especially since Cancer may be a metabolic disease.

    Antimicrobial
    MB is often used as an anti-fungal in aquariums. It's often used to treat fish eggs to ensure they're not lost to fungal overgrowth.

    [​IMG]

    Alzheimer's

    The most promising research on MB is being done in Alzheimer's patients.

    MB seems to be able to "untangle" the neurofibrillary tangles that are a common hallmark of Alzheimer's disease. A researcher who noticed this, Claude Wischik, founded a company called TauRx, which created a modified and patentable form of MB called LMTX. In a recent drug trial, subjects taking LMTX deteriorated significantly more slowly than those on placebo, and in some cases had improved cognitive function.

    Cognitive Function
    Studies have shown that MB increases cellular oxygen consumption and glucose uptake in the brain. MB increases CMRO2 (the cerebral metabolic rate) through improved performance of the Electron Transport Chain.

    Twenty-six healthy participants, between the ages of 22 and 62, were enrolled in a double-blinded, randomized, placebo-controlled clinical trial to measure the effects of MB on the human brain during working-memory and sustained-attention tasks. The participants were given a single low-dose of MB. Participants who took MB had a 7 % increase in correct responses during memory retrieval. This is an hour after only a single low-dose.ʳ

    Dosage
    Because Methylene Blue is still being studied in healthy humans for mitochondrial and memory enhancing effects, there's no recommended dosage (unless you have malaria).

    Methylene Blue exhibits a hormetic dose, with opposite effects at high and low doses. For example, high doses of MB can cause methemoglobinemia, while low doses of MB is the choice treatment for methemoglobinemia.

    There are a number of reasons to keep the dose low

    • MB can easily contain impurities of heavy metals like cadmium, mercury, and lead – even in USP grade. In small doses, these trace heavy metals are easily dealt with, but in large doses they can bioaccumulate. This is definitely why you should only purchase USP grade methylene blue. Never lab or chemical grade.
    • MB can exhibit effects at nanomolar ranges in cell cultures.
    • At high doses, MB can potentially "steal" electrons away from the electron transport chain complexes, disrupting the redox balance and acting like a pro-oxidant.ʳ
    • At high doses, MB exhibits its MAO inhibiting effects and can lead to serotonin syndrome, especially when eating tyramine rich foods or taking SSRIs.
    For this reason, the dosage of Methylene Blue should be around ~1-2mg per dayʳ. A lot of the studies in Alzheimer's and Malaria use high doses of 150mg+/day. I don't think this is needed in healthy organisms, especially because of the negative effects that can appear at high doses. I personally take around 1.2mg per day.

    Safety
    • It should not be taken with an SSRI.ʳ
    • It should not be given to babies.ʳ
    • If you have a G6PD deficiency.
    • Don't take the ones they sell at the fish store. Only purchase USP grade MB that has been analyzed for trace metals.
    Side Effects
    MB is quite safe at low doses, assuming no contraindications with SSRIs or presence of the user having a G6PD deficiency.

    Side effects are rare in doses under 2mg/kg, and especially rare at doses of 1mg.

    Rare symptoms can include stomach pain, chest pain, dizziness, headache, sweating, confusion, high blood pressure, shortness of breath, accelerated heartbeat, tremor, skin turning blue, urine turning blue or green, reduction of red blood cells, or jaundice (only reported in infants).

    Products
    These are the different places where you can find USP grade methylene blue. Not an exhaustive list.

    Personal Anecdote
    I've always felt like I had the brain of someone much older than myself, and not in a good way. I had trouble remembering events and things I'd learned. Sometimes I could remember going to a place, but not who I went there with. Bizzare.

    I started taking taking 1mg of methylene blue a day and my thinking cleared. I feel my memory is much better than it was. My verbal fluidity seems to have improved. This mirrors personal experience by people in the Nootropics community.

    I think Methylene Blue is really quite safe and I'll likely continue taking it long term for its mitochondrial benefits.
     
  2. Jessie

    Jessie Member

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    Interesting writeup. I've never tried MB because if it's anything like thyroid or high dose thiamine, my temps get so warm I can't sleep well at night. I suppose this is more of a atmospheric issue, but I live with other people that like the rooms a bit warmer (72 degrees at night). Personally I like the feeling thyroid and other stuff (like thiamine and potentially MB as well) gives me, but if I'm too hot to sleep good I'm a very grumpy person the next day. I've often thought about taking a cold shower before bed, or maybe sleeping in a damp shirt.
     
  3. milkboi

    milkboi Member

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    Very cool article, thanks for that!
     
  4. OP
    noqcks

    noqcks Member

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  5. Lollipop2

    Lollipop2 Member

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    Good overview! I can send this to people. Why didn’t you include IdeaLabs Oxidal? It seriously the best on the market.

    Oxidal
     
  6. OP
    noqcks

    noqcks Member

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    Excellent! That was the intent. I have family members I want to introduce to MB, which is why I made the write up.

    I didn’t include Oxidal because it contains more than just MB. I might include later with a note.
     
  7. Lollipop2

    Lollipop2 Member

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    Please include it now with a note as it is the one I tell people to buy. Read why he puts it in. It has a protective factor.
     
  8. Lollipop2

    Lollipop2 Member

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    Please consider including it now with a note. I have a bias as it is the one I tell people to buy. So understand my motivation - lol. Otherwise, I will have to say: “Ignore his recommendations and just read the overview.” Read why he puts it in. It has a protective factor.
     
  9. Twohandsondeck

    Twohandsondeck Member

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    @noqcks thank you kindly for this write-up. I jumped on the forum with the specific intent of finding much of the information you generously compiled together here and lo there's this on the front page fresh pressed. God bless!
     
  10. OP
    noqcks

    noqcks Member

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    :thumbright

    Tell me what you want written next
     
  11. Lejeboca

    Lejeboca Member

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  12. Lokzo

    Lokzo Member

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    Great write up, would be more than happy to have you post this on my site as a guest blog if you like!
     
  13. Marcine

    Marcine Member

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    It's really too bad you live with people who don't understand the benefits of sleeping cool. You might consider a product called a Chillipad, I believe is the name.
     
  14. Jessie

    Jessie Member

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    I did a quick google search for chillipad and I'm definitely interested in the idea, thanks for the suggestion! Yeah, I much prefer a good 67-68 degree environment for sleeping. The 70s get a bit much for me.
     
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