Why Is Everyone Dramatically Under-dosing Methylene Blue?

[bodacious]

Saw this post on Reddit today:

Why is everyone dramatically under-dosing Methylene Blue?!? • /r/Nootropics

Thought you might be interested in reading

 

[Peatit]

I heard RP saying that according to him the best dosage should be around 5 mcg/day ,ATM I'm not sure about the actual figure, but it was a very low dose anyway

 

[Makrosky]

I think in this board the concerns are related to MB properties as IMAO at high doses. Don't know why people "out there" underdose it.

 

[BobbyDukes]

I heard RP saying that according to him the best dosage should be around 5 mcg/day ,ATM I'm not sure about the actual figure, but it was a very low dose anyway

Surely you mean 5mg, and even if it were 5mg, I pretty sure that isn't the figure that's been quoted by Peat.

 

[Such_Saturation]

He said 100mcg to 1mg

 

[Peatit]

He said 100mcg to 1mg

Do you remember in which interview he discusses this? I'm pretty sure I heard it in an Herb Doctor show but I can't remember which one it was.
And I'm of course probably wrong but I remember having mentally noted that the dose he talked about was really tiny.

 

[Such_Saturation]

Emails I think.

 

[jb116]

I don't like how I feel above .5mg
so 100mcg to 1mg sounds right to me.

 

[haidut]

The optimal in-vitro and vivo concentrations have repeatedly been shown to be around 100nM/L. This concentration is achievable by taking around 1mg MB daily, so Peat's recommendation is spot on. Keep in mind that despite the low dose, MB has very long half-life in tissues and especially the brain, so taking even 1mg over the course of a few weeks will build up.

 

[Elephanto]

Have you seen this study haidut :
Methylene blue induces macroautophagy through 5′ adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation

This one graph shows a reverse-U relation with "akt" and "mtor". So those two if raised high are thought to be beneficial for alzheimer, which is probably where they found the "100nm ideal dose" as it raises akt and mtor the most. But they are also cancer-promoting, or at least "growth promoting". I think you may get a lot of good effects from methylene blue without raising akt so much, like using much larger or smaller doses.

-

Anyway from personal experience, I've had success with 1ml / 23 mg solutions. Lots of energy without nervousness, feeling of lightness and absence of inflammation. With large doses I suspect the most apparent effects you get are from nitric oxide scavenging and the antimicrobial effect. I've also been told that my (black) hair look way darker when I've been using it.

 

[haidut]

Have you seen this study haidut :
Methylene blue induces macroautophagy through 5′ adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation

This one graph shows a reverse-U relation with "akt" and "mtor". So those two if raised high are thought to be beneficial for alzheimer, which is probably where they found the "100nm ideal dose" as it raises akt and mtor the most. But they are also cancer-promoting, or at least "growth promoting". I think you may get a lot of good effects from methylene blue without raising akt so much, like using much larger or smaller doses.

-

Anyway from personal experience, I've had success with 1ml / 23 mg solutions. Lots of energy without nervousness, feeling of lightness and absence of inflammation. With large doses I suspect the most apparent effects you get are from nitric oxide scavenging and the antimicrobial effect. I've also been told that my (black) hair look way darker when I've been using it.

I have never seen any study (in vivo or in vitro) showing MB to have pro-carcinogenic effect at any dose. Do you know of such a study? Just because something promotes mTOR does not mean it is pro-carcinogenic. Eating almost any protein promotes mTOR and it is a signal that the organism is well-fed. Antagonizing mTOR is the mechanism of starvation and caloric restriction and resveratrol is one of the most potent mTOR inhibitors. It also happens to be carcinogenic. The whole idea behind starving being somehow good for us is bunk, aside from the restriction of a few anti-metabolic substances like PUFA, tryptophan, methionine, cysteine, etc.

 

[Elephanto]

I have never seen any study (in vivo or in vitro) showing MB to have pro-carcinogenic effect at any dose. Do you know of such a study? Just because something promotes mTOR does not mean it is pro-carcinogenic. Eating almost any protein promotes mTOR and it is a signal that the organism is well-fed. Antagonizing mTOR is the mechanism of starvation and caloric restriction and resveratrol is one of the most potent mTOR inhibitors. It also happens to be carcinogenic. The whole idea behind starving being somehow good for us is bunk, aside from the restriction of a few anti-metabolic substances like PUFA, tryptophan, methionine, cysteine, etc.

Well you should ask Peat about mtor then... You know well about the benefits of methionine restriction and it does lower IGF1/mtor. Ive also never talked about fasting which is not beneficial because it activates sirt1 and even augments growth hormone in short-term. Despite that, Peat acknowledges the benefits of calorie restriction. Lastly, the graph doesn't show a major effect about mtor, I thought the most interesting point was the substantial raise of akt, which does not happen at lower or higher dose. But no, I don't have proof that it can be pro-cancer, it probably still has a net positive effect. You just don't want akt so high because that would make you acromegalic, it's the same point as Peat not liking growth hormone. alzheimer really is a problem of old age, you wouldn't expect your akt to be too low when you're young and restricting it in moderation probably leads to higher longevity.

 

[DaveFoster]

I think in this board the concerns are related to MB properties as IMAO at high doses. Don't know why people "out there" underdose it.

*MAOI

It's a MAOI. That's why.

 

[haidut]

Well you should ask Peat about mtor then... You know well about the benefits of methionine restriction and it does lower IGF1/mtor. Ive also never talked about fasting which is not beneficial because it activates sirt1 and even augments growth hormone in short-term. Despite that, Peat acknowledges the benefits of calorie restriction. Lastly, the graph doesn't show a major effect about mtor, I thought the most interesting point was the substantial raise of akt, which does not happen at lower or higher dose. But no, I don't have proof that it can be pro-cancer, it probably still has a net positive effect. You just don't want akt so high because that would make you acromegalic, it's the same point as Peat not liking growth hormone. alzheimer really is a problem of old age, you wouldn't expect your akt to be too low when you're young and restricting it in moderation probably leads to higher longevity.

OK, do you have something from Peat on that topic (mTOR, akt, etc)?

 

[Elephanto]

OK, do you have something from Peat on that topic (mTOR, akt, etc)?

Whenever he talks about methionine restriction or the bad effects from growth hormone. Those are synonyms, he never mentions "igf-1" I think but caution about growth hormone which directly raise igf-1. If you follow his logic and most supplements/dosage he recommends, you'll see that most of them tend to minimize akt, igf-1, mtor etc. Unsaturated fatty acids supress PTEN (tumor supressor restricting growth) and raise mtor, saturated fatty acids do the opposite; free fatty acids in general also raise mtor/suppress pten. I find that Peat rarely uses those scientific parameters to explain stuff but most of the time you'll find studies with those terms to corroborate his views.

 

[Makrosky]

*MAOI

It's a MAOI. That's why.

Sorry it is called IMAO in my language and that's why.

 

[haidut]

Whenever he talks about methionine restriction or the bad effects from growth hormone. Those are synonyms, he never mentions "igf-1" I think but caution about growth hormone which directly raise igf-1. If you follow his logic and most supplements/dosage he recommends, you'll see that most of them tend to minimize akt, igf-1, mtor etc. Unsaturated fatty acids supress PTEN (tumor supressor restricting growth) and raise mtor, saturated fatty acids do the opposite; free fatty acids in general also raise mtor/suppress pten. I find that Peat rarely uses those scientific parameters to explain stuff but most of the time you'll find studies with those terms to corroborate his views.

Yeah, I have seen him write about insulin and IGF-1 but not always in a bad light. He wrote that insulin activates PDH and has even been used in cancer therapy. On the other hand, he did write against being in an excessively anabolic state chronically. Then again, he also said having large muscle mass is very beneficial for health and that si hard to achieve without IGF-1 and mTOR. So, if would be nice if he can clarify what is good in what context.

 

[jb116]

Yeah, I have seen him write about insulin and IGF-1 but not always in a bad light. He wrote that insulin activates PDH and has even been used in cancer therapy. On the other hand, he did write against being in an excessively anabolic state chronically. Then again, he also said having large muscle mass is very beneficial for health and that si hard to achieve without IGF-1 and mTOR. So, if would be nice if he can clarify what is good in what context.

My thought would be any process that increases IGF-1/mTor but is also stressful is probably the context that it is undesired i.e. fasting, caloric restriction, unsaturated fats.
Regarding caloric restriction benefits, even that had context I think that it was the cutting out of certain foods, like pufa for example that was the benefit.

 

[tara]

Regarding caloric restriction benefits, even that had context I think that it was the cutting out of certain foods, like pufa for example that was the benefit.

That's how I read him too. And maybe restricting iron and particular amino acids like methionine.

 

[haidut]

That's how I read him too. And maybe restricting iron and particular amino acids like methionine.

Yes, he addresses that in a few of his articles. There is nothing beneficial about restricting calories per se, but it is a collateral benefit due to restricting PUFA, tryptophan, methionine, cysteine, iron, etc. There are quite a few studies showing restricting any of these substances but keeping caloric intake normal (or even increased) has the at least the same lifespan extension results (and sometimes more, in cases of tryptophan and iron).