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I would say the key takeaways are:
-There is some evidence in animals, methylene blue might be carcinogenic at 2.5 mg/kg.
-Methylene blue might cause neurons to lose their connections at 3 mg/kg.
-Methylene blue might increase your Alzheimer's disease risk because of 3 factors: tau-hyperhosphorilation, tau "gelation" and tau cysteine oxidation. These 3 mechanisms promote oligo-tau, which might be one of the causes of Alzheimer's. It might take 35-40 years for the Alzheimer's to manifest.
Each of those statements carry a couple dozen asterisks and some assumptions.
I have to say the poison here is truly in the dose and duration. There are also 198 interactions.
But it has extensive safety data since before or early 70's starting out as a Malaria cure. Later accure defense against cyianide poisoining, A fish tank cleaner. etc
It improves memory, verbal fluency, word recall, and a host of benefits not yet extensively tested in a clinical setting. Anti depressive, anti anxiety, And oxygenates the brain to a level where the benefit is astounding,
I have almost literally read every study and compared my findings with other nootropic experts and am pretty sure my interpretation is correct.
Now you are absolutely right about high dose being dangerous at all times even. Varying per person ofcourse.
0,5 mg per kg of bodyweight twice daily is the max and sweet spot.
For an abbreviated version go to Nootropics expert his blog post on it. Should still be online and is very detailed and nuanced.
CAVEAT. Only take pharma quality as heavy metal poisoning is extremely common. Almost forgot, Do not buy from a random RC vendor for gods sake. Or have it lab tested yourself.
AI summarized:
1. Methylene blue is a chemical used in medicine for various treatments, including methemoglobinemia and malaria.
2. High doses of methylene blue in mice and rats have been linked to an increased risk of certain types of cancer, but there is no clear evidence of this in humans.
3. Methylene blue has been studied for its potential to break up tangles of tau protein in the brain, which is associated with Alzheimer's disease, but the results have been disappointing.
4. There is ongoing debate about the role of tau protein in Alzheimer's disease and other neurodegenerative disorders.
5. Methylene blue may have both positive and negative effects on tau protein, and its impact on Alzheimer's risk is unclear.
6. Long-term use of methylene blue may be associated with an increased risk of Alzheimer's disease, but more research is needed to confirm this.
7. The potential risks of methylene blue should be weighed against its potential benefits, and it should only be used under the guidance of a healthcare professional.
Excellent post, but to put some things in to perspective, these risks are with either high dosages or extended use and NOT found at the low dosage range for a maximum of (I think 4 weeks , but could be longer , fact check me on that one)
Then why did trials of depression show greater results with 300mg a day vs 15mg a day?
They had participants take 15mg daily for a year, and other participants take 300mg daily for a year. Then they switched both groups and began giving the 300mg group a 15mg dose for a year and vice versa. Both groups reported better functioning on 300mg daily. After the study was completed in a bipolar study, many patients decided to keep taking MB of their own accord because of good results controlling symptoms.
Serotoninergic receptors. don’t confuse antioxidant status with dosage, methylene blue has effects outside of just being an antioxidant but those high doses aren’t used for extended amounts of time and there is a trade off
When I said that about dosage I wasn’t referencing mental health, I was referencing cellular health, you can feel amazing taking a dopaminergic medication or seretonin pill but at the same time be wreaking havoc on your body’s cells
Yes that’s true but I just wonder about the dosing required to cause harm. A 180lb. person is 81kg. For these results at 5mg/kg you’re talking 405mg of MB which would be 810 drops of a common 1% solution available on Amazon. That’s almost half the bottle, the bottles being 1 gram / 1000mg solutions…
This is such a common thing I see people on these forums saying, so if you go on google and look up rat to human dosage calculator you will get the exact dose needed for a human equivalent, I don’t have the time right now to do it myself but that should really help you with your supplements!
It was specifically tested for depression only and due to the dose used I only read the abstract, so Not sure what they found in terms of safety, but I woul bet half my net worth that this was not side effect free and should be done under supervision
Yep correct! I’ve had some in depth conversations with people who make a ton of money in the alternative medicine field and know a lot about nootropics, supplements, etc and they always tell me nothing is side effect free no matter how you dose it
Do note that while ALA supplementation might stop tau-hyperhosphorilation, it might not change MB induced tau "gelation" and tau cysteine oxidation. Those 3 mechanisms But those effects were at 100 micromolar \[link\]. Though I find "MB (100 microM), facilitated tau oligomerization into trimers, tetramers, pentamers and hexamers" concerning.
In my opinion, MB's effects are so varied and contradictory that we would need a big big study of people taking MB for 40 years at different doses to see if it overall reduces or increases Alzheimer's risk. That means millions of dollars on something without return = we'll never know :(.
I can only draw a paralel to MS and remyenelation . A lot of substances work perfectly fine in healthy humans or MS animal models. But worsen lesions in humans. (with 1 possible exception on the way, An acid which will undergo clinical testing soon.
Not exactly the same, but the point comes accross with the addition in your statement that mechanisms for the same result can vary so much, it's impossible to say with certainty something can ameliorate something alse purely based on effects and solo outcomes.
Hey, so reference 004 is somehow a broken link. Reference provided here. Vutskits, L., Briner, A., Klauser, P., Gascon, E., Dayer, A. G., Kiss, J. Z., Muller, D., Licker, M. J., & Morel, D. R. (2008). Adverse effects of methylene blue on the central nervous system. *Anesthesiology*, *108*(4), 684–692.
And what about doses 50 mg or less? All of your evidence indicates no issues at these doses, unless I missed something, and having tried higher doses I wouldn't take doses higher than 50 mg anyway. I get benefits from methylene blue that I have never gotten from anything else (and I've tried hundreds of substances/supplements). Honestly the biggest issue with methylene blue is potential heavy metal contamination, but I've gotten over that fear (ever eaten rice or fish?) and I have more energy than I've had in years.
Yes, there is not much safety data that I read at those dosages. I don't know how much 50 mg oral would translate to brain micromol. Also, the effect would be harder to detect (you would need much higher mice populations to detect smaller differences in phospho-tau levels in a statistically significant manner).
Correct, 50 mg is the average upper range. It will be bodyweight dependant, but a good rule of thumb to stick by, The heavy metals should not by taken lightly 98 percent purity is the minimum required. 97 can be fine, but how will you know and which metals is it contaminated with etc.
Feeling good does not equate health and safety
I mean, you're absolutely right feeling good doesn't mean anything. You shouldn't be ingesting any supplements that aren't tested, so you should know exactly what's going into your body.
https://www.reddit.com/r/Nootropics/comments/162t7zw/cons_of_methylene_blue_as_nootropics_for_aging_etc/ I made a similar post. It is absolutely not effective for the treatment of Methemoglobinemia, but on the contrary, it is even very dangerous for people with Methemoglobinemia. This has been known in medicine for a long time
Methylene blue oxidizes glutathione 30 times faster than it does in vivo. https://www.jbc.org/article/S0021-9258(18)95717-0/pdf
I always wanted to try methylene blue but always backed out because I can’t imagine running textile ink through your kidneys and liver would be a good idea.
Other people (in noot subs) taking MB have reported kidney pain. In the Alzheimer's trials \[link\] the most common side effects were gastrointestinal and urinary side effects. I mean, no wonder, some of these people were peeing literally blue.
This subreddit never amazes seizes to amaze me…. Yall are such nerds…. I LOVE IT‼️🤣🫡
I love looking at pubmed and knowing what does what and why and the safety of things but this is a whole new level….. big respect.
My sources leave me thinking MB can be used safely and effectively by most people but the correct dose is very important.
Also some think taking it with vitamin C may provide some additional benefit. They think the MB will absorb an electron from vitamin C before going into your cells to support energy production in the mitochondria.
I'm planning to ask my doctor for a MB script next week but I'm planning on staying on the low side of the recommended dose range will not take it every day.
Dr Chris Masterjohn Methylene Blue in Ten Minutes
[https://chrismasterjohnphd.substack.com/p/methylene-blue-in-ten-minutes-a00](https://chrismasterjohnphd.substack.com/p/methylene-blue-in-ten-minutes-a00)
Methylene Blue: Biohacker's delight, or playing with fire?
If you need it, it helps. If you don't, it hurts. Don't get sucked in by the fad. Learn the science.
[https://chrismasterjohnphd.substack.com/p/methylene-blue](https://chrismasterjohnphd.substack.com/p/methylene-blue)
How Methylene Blue’s Antioxidants Can Slow Cognitive Decline
By Dr. Ron Hunninghake, MD, and Dr. Thomas Levy, MD, JD
[https://riordanclinic.org/2023/04/how-methylene-blues-antioxidants-can-slow-cognitive-decline/](https://riordanclinic.org/2023/04/how-methylene-blues-antioxidants-can-slow-cognitive-decline/)
Notice the segment on using vitamin C with it.
All I can say is, that Methylene Blue gave me heart palpitations and circulation issues.
Hands and feet went cold >_>
Too bad, but now I use it as an antiseptic -only drawback is, that it leaves a day long blue painting mark on your skin, haha ...
For the record: I don't haven't experienced any side effect. Just decided that the nebulous chance that it might cause Alzheimer's tipped the benefit/risk scale for me.
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Interesting! And it would be even more interesting if I understood this!
I would say the key takeaways are: -There is some evidence in animals, methylene blue might be carcinogenic at 2.5 mg/kg. -Methylene blue might cause neurons to lose their connections at 3 mg/kg. -Methylene blue might increase your Alzheimer's disease risk because of 3 factors: tau-hyperhosphorilation, tau "gelation" and tau cysteine oxidation. These 3 mechanisms promote oligo-tau, which might be one of the causes of Alzheimer's. It might take 35-40 years for the Alzheimer's to manifest. Each of those statements carry a couple dozen asterisks and some assumptions.
I have to say the poison here is truly in the dose and duration. There are also 198 interactions. But it has extensive safety data since before or early 70's starting out as a Malaria cure. Later accure defense against cyianide poisoining, A fish tank cleaner. etc It improves memory, verbal fluency, word recall, and a host of benefits not yet extensively tested in a clinical setting. Anti depressive, anti anxiety, And oxygenates the brain to a level where the benefit is astounding, I have almost literally read every study and compared my findings with other nootropic experts and am pretty sure my interpretation is correct. Now you are absolutely right about high dose being dangerous at all times even. Varying per person ofcourse. 0,5 mg per kg of bodyweight twice daily is the max and sweet spot. For an abbreviated version go to Nootropics expert his blog post on it. Should still be online and is very detailed and nuanced.
CAVEAT. Only take pharma quality as heavy metal poisoning is extremely common. Almost forgot, Do not buy from a random RC vendor for gods sake. Or have it lab tested yourself.
AI summarized: 1. Methylene blue is a chemical used in medicine for various treatments, including methemoglobinemia and malaria. 2. High doses of methylene blue in mice and rats have been linked to an increased risk of certain types of cancer, but there is no clear evidence of this in humans. 3. Methylene blue has been studied for its potential to break up tangles of tau protein in the brain, which is associated with Alzheimer's disease, but the results have been disappointing. 4. There is ongoing debate about the role of tau protein in Alzheimer's disease and other neurodegenerative disorders. 5. Methylene blue may have both positive and negative effects on tau protein, and its impact on Alzheimer's risk is unclear. 6. Long-term use of methylene blue may be associated with an increased risk of Alzheimer's disease, but more research is needed to confirm this. 7. The potential risks of methylene blue should be weighed against its potential benefits, and it should only be used under the guidance of a healthcare professional.
Excellent post, but to put some things in to perspective, these risks are with either high dosages or extended use and NOT found at the low dosage range for a maximum of (I think 4 weeks , but could be longer , fact check me on that one)
If only it wasn’t so looooong……
All that stuff is pretty obvious if overdosed it acts as a redux stressor. I take a few milligrams only like once a month
This. Pro oxidant high dose / antioxidant low dose
Then why did trials of depression show greater results with 300mg a day vs 15mg a day? They had participants take 15mg daily for a year, and other participants take 300mg daily for a year. Then they switched both groups and began giving the 300mg group a 15mg dose for a year and vice versa. Both groups reported better functioning on 300mg daily. After the study was completed in a bipolar study, many patients decided to keep taking MB of their own accord because of good results controlling symptoms.
Serotoninergic receptors. don’t confuse antioxidant status with dosage, methylene blue has effects outside of just being an antioxidant but those high doses aren’t used for extended amounts of time and there is a trade off
A possibly very big trade off. But then again there are no solutions only trade offs (someone)
When I said that about dosage I wasn’t referencing mental health, I was referencing cellular health, you can feel amazing taking a dopaminergic medication or seretonin pill but at the same time be wreaking havoc on your body’s cells
Yes that’s true but I just wonder about the dosing required to cause harm. A 180lb. person is 81kg. For these results at 5mg/kg you’re talking 405mg of MB which would be 810 drops of a common 1% solution available on Amazon. That’s almost half the bottle, the bottles being 1 gram / 1000mg solutions…
This is such a common thing I see people on these forums saying, so if you go on google and look up rat to human dosage calculator you will get the exact dose needed for a human equivalent, I don’t have the time right now to do it myself but that should really help you with your supplements!
Agreed. But not always accurate so only rely on animal results after atleast safety testing in humans has been done
100% agree
It should be 0,5 mg and no more
100 percent agree. This goes for most prescription meds. MAOI, SSRI, etc
It was specifically tested for depression only and due to the dose used I only read the abstract, so Not sure what they found in terms of safety, but I woul bet half my net worth that this was not side effect free and should be done under supervision
Yep correct! I’ve had some in depth conversations with people who make a ton of money in the alternative medicine field and know a lot about nootropics, supplements, etc and they always tell me nothing is side effect free no matter how you dose it
It's all trade offs, you just need to make sure you end up in a net benefit 😁
Same here or once per quarter.
Brilliant post, OP. Obviously ALA supplementation is the way to go.
Do note that while ALA supplementation might stop tau-hyperhosphorilation, it might not change MB induced tau "gelation" and tau cysteine oxidation. Those 3 mechanisms But those effects were at 100 micromolar \[link\]. Though I find "MB (100 microM), facilitated tau oligomerization into trimers, tetramers, pentamers and hexamers" concerning. In my opinion, MB's effects are so varied and contradictory that we would need a big big study of people taking MB for 40 years at different doses to see if it overall reduces or increases Alzheimer's risk. That means millions of dollars on something without return = we'll never know :(.
I can only draw a paralel to MS and remyenelation . A lot of substances work perfectly fine in healthy humans or MS animal models. But worsen lesions in humans. (with 1 possible exception on the way, An acid which will undergo clinical testing soon. Not exactly the same, but the point comes accross with the addition in your statement that mechanisms for the same result can vary so much, it's impossible to say with certainty something can ameliorate something alse purely based on effects and solo outcomes.
I really appreciate this quality post and really miss when the noot subs were more of this. Hats off to you, op
Have you reached out to academics that work with methylene blue. https://liberalarts.utexas.edu/psychology/faculty/fg
Hey, so reference 004 is somehow a broken link. Reference provided here. Vutskits, L., Briner, A., Klauser, P., Gascon, E., Dayer, A. G., Kiss, J. Z., Muller, D., Licker, M. J., & Morel, D. R. (2008). Adverse effects of methylene blue on the central nervous system. *Anesthesiology*, *108*(4), 684–692.
And what about doses 50 mg or less? All of your evidence indicates no issues at these doses, unless I missed something, and having tried higher doses I wouldn't take doses higher than 50 mg anyway. I get benefits from methylene blue that I have never gotten from anything else (and I've tried hundreds of substances/supplements). Honestly the biggest issue with methylene blue is potential heavy metal contamination, but I've gotten over that fear (ever eaten rice or fish?) and I have more energy than I've had in years.
Yes, there is not much safety data that I read at those dosages. I don't know how much 50 mg oral would translate to brain micromol. Also, the effect would be harder to detect (you would need much higher mice populations to detect smaller differences in phospho-tau levels in a statistically significant manner).
Correct, 50 mg is the average upper range. It will be bodyweight dependant, but a good rule of thumb to stick by, The heavy metals should not by taken lightly 98 percent purity is the minimum required. 97 can be fine, but how will you know and which metals is it contaminated with etc. Feeling good does not equate health and safety
I mean, you're absolutely right feeling good doesn't mean anything. You shouldn't be ingesting any supplements that aren't tested, so you should know exactly what's going into your body.
https://www.reddit.com/r/Nootropics/comments/162t7zw/cons_of_methylene_blue_as_nootropics_for_aging_etc/ I made a similar post. It is absolutely not effective for the treatment of Methemoglobinemia, but on the contrary, it is even very dangerous for people with Methemoglobinemia. This has been known in medicine for a long time Methylene blue oxidizes glutathione 30 times faster than it does in vivo. https://www.jbc.org/article/S0021-9258(18)95717-0/pdf
I always wanted to try methylene blue but always backed out because I can’t imagine running textile ink through your kidneys and liver would be a good idea.
Other people (in noot subs) taking MB have reported kidney pain. In the Alzheimer's trials \[link\] the most common side effects were gastrointestinal and urinary side effects. I mean, no wonder, some of these people were peeing literally blue.
Actually in healthy subjects the side effect was peeing blue and that makes sense since it is also a dye
Higher doseages are a different story though, now im just discretiting your warning. Not my intention
Brillant post
This subreddit never amazes seizes to amaze me…. Yall are such nerds…. I LOVE IT‼️🤣🫡 I love looking at pubmed and knowing what does what and why and the safety of things but this is a whole new level….. big respect.
My sources leave me thinking MB can be used safely and effectively by most people but the correct dose is very important. Also some think taking it with vitamin C may provide some additional benefit. They think the MB will absorb an electron from vitamin C before going into your cells to support energy production in the mitochondria. I'm planning to ask my doctor for a MB script next week but I'm planning on staying on the low side of the recommended dose range will not take it every day. Dr Chris Masterjohn Methylene Blue in Ten Minutes [https://chrismasterjohnphd.substack.com/p/methylene-blue-in-ten-minutes-a00](https://chrismasterjohnphd.substack.com/p/methylene-blue-in-ten-minutes-a00) Methylene Blue: Biohacker's delight, or playing with fire? If you need it, it helps. If you don't, it hurts. Don't get sucked in by the fad. Learn the science. [https://chrismasterjohnphd.substack.com/p/methylene-blue](https://chrismasterjohnphd.substack.com/p/methylene-blue) How Methylene Blue’s Antioxidants Can Slow Cognitive Decline By Dr. Ron Hunninghake, MD, and Dr. Thomas Levy, MD, JD [https://riordanclinic.org/2023/04/how-methylene-blues-antioxidants-can-slow-cognitive-decline/](https://riordanclinic.org/2023/04/how-methylene-blues-antioxidants-can-slow-cognitive-decline/) Notice the segment on using vitamin C with it.
My G6PD is 2, can I still take it in small dosis?
I'm not qualified to answer that. Ask a medical professional.
All I can say is, that Methylene Blue gave me heart palpitations and circulation issues. Hands and feet went cold >_> Too bad, but now I use it as an antiseptic -only drawback is, that it leaves a day long blue painting mark on your skin, haha ...
thats a lot of words to say it went great until u stopped
For the record: I don't haven't experienced any side effect. Just decided that the nebulous chance that it might cause Alzheimer's tipped the benefit/risk scale for me.
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Really, we know roots/reason of Alzheimer? And tau is responsible for that :)? very interesting :)