# Methylene blue

Category: Drugs & Compounds

Also known as: methylthioninium chloride

Methylene blue is a multifunctional dye that Peat identified as a potent blocker of nitric oxide production, acting through at least six distinct mechanisms including the prevention of excitotoxic damage and the inhibition of excess microtubule polymerization. He considered it…

11 passages · 3 authors · 2014–2023 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/methylene-blue

## Synthesis

**Methylene blue** is a multifunctional dye that Peat identified as a potent blocker of **nitric oxide** production, acting through at least six distinct mechanisms including the prevention of excitotoxic damage and the inhibition of excess microtubule polymerization. [Source 1] He considered it a valuable emergency substance for turning off the massive over-production of nitric oxide, alongside more commonly available substances like niacinamide and progesterone. [Source 3] Its core therapeutic action lies in its ability to act as an *electron cycling agent*, receiving electrons from carriers like NADH and passing them directly to functional parts of the mitochondrion, effectively bypassing damaged segments of the electron transport chain to restore energy production. [Source 3, 4]

At the molecular level, methylene blue oxidizes critical sulfur groups on glutamate receptors, turning off the excitotoxic process that otherwise leads to cell death through nitric oxide synthesis. [Source 4] Dinkov has elaborated that this oxidizing power is central to its benefit, noting that most people exist in an excessively *reduced state*, and that the oxidized form of methylene blue is required to restore proper electron flow and activate cytochrome C activity. [Source 9] He further explained that methylene blue can substitute for oxygen as the final electron acceptor, re-oxidizing NADH back to NAD and thereby lowering the expression of **lactate dehydrogenase**, a nonspecific biomarker overexpressed in every type of cancer. [Source 11] This allows the substance to reach cells in a state of chronic hypoxia that oxygen itself cannot adequately supply. [Source 6, 8]

Peat observed remarkably potent effects at very low doses, noting that a well-controlled study found **15 mg per day** sufficient to relieve severe depression, while he personally suspected that optimal doses might be analogous to thyroid hormone, in the range of 20 to 40 micrograms daily. [Source 3, 10] He reported that many people were experiencing powerful antidepressant effects from just one milligram per day, and that it could resolve insomnia by restoring mitochondrial energy production and lowering nitric oxide. [Source 2, 10] Toxicity studies have shown an extraordinary safety profile; lifespan studies in rodents using doses equivalent to several grams per day in humans showed no life-shortening effects, and in female mice, the highest doses actually extended maximum lifespan. [Source 3, 4]

Despite its safety, specific cautions exist. Peat warned that in an **iron overload** state, methylene blue, like ascorbic acid, can reduce ferric iron to the ferrous form, generating the most toxic free radicals. [Source 5] Dinkov has emphasized that methylene blue is a relatively strong *monoamine oxidase type A inhibitor*, which decreases serotonin degradation and can lead to dangerous serotonin syndrome when combined with SSRI drugs or other serotonergic substances, particularly at the high injected doses used for treating shock. [Source 7] For human use, sourcing a USP-grade product is recommended, as the substance is widely sold as a fish tank treatment and questions of heavy metal contamination in non-pharmaceutical grades have been raised. [Source 2, 6]

## People also ask

### How does methylene blue restore mitochondrial energy production?

Peat described it as an electron cycling agent that accepts electrons from carriers like NADH and passes them directly to the mitochondrion, bypassing damaged parts of the electron transport chain to restore energy production.

### What is a safe daily dose of methylene blue for depression?

Peat noted that a controlled study found 15 mg per day effective for severe depression, but he suspected optimal doses might be much lower, in the range of 20 to 40 micrograms daily, with many people experiencing benefits from just one milligram.

### Why is methylene blue dangerous to combine with SSRI drugs?

Dinkov emphasized that methylene blue is a relatively strong monoamine oxidase type A inhibitor, which decreases serotonin degradation and can lead to dangerous serotonin syndrome when combined with SSRIs or other serotonergic substances.

## Related concepts

- [Nitric oxide](https://bioenergeticoracle.com/md/concepts/nitric-oxide/index.md)
- [DMSO](https://bioenergeticoracle.com/md/concepts/dmso/index.md)
- [Erectile Dysfunction](https://bioenergeticoracle.com/md/concepts/erectile-dysfunction/index.md)
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## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — Nitric Oxide

Ray Peat · Interview · 2014 · http://l-i-g-h-t.com/files/herb-doctors-nitric-oxide.mp4

> **Andrew Murray:** OK, now I guess methylene blue is not an FDA controlled substance or anything, I thinks it's fairly widely available, it's just a dye isn't it, and typically it's known as a dye, I know it's a tissue stain...
>
> **Ray Peat:** And fish stores use it, I'm not sure how they use it, whether it's for sterilising aquariums or something and fish farmers use it to cure various fish infections.
>
> **Andrew Murray:** OK, well people listening perhaps might want to start looking up methylene blue and its implications in the treatment and/or the prevention of different degenerative conditions. So, extremely cheap I’m sure, not at all patented, not controlled, and if there’s some good studies coming out showing methylene blue's positive effects blocking nitric oxide, I think that could be well worth people looking at as an alternative to many of the drugs that people might be using for different conditions.
>
> **Ray Peat:** I've counted about 6 different ways that methylene blue stops or blocks the production of nitric oxide.
>
> **Andrew Murray:** OK, go on, do you want to share them or?

### Source 2 — Ray Peat Email Advice Depository — Post 914

Ray Peat · Email · Dec 8, 2022

> ## Thread 2
>
> **Question:** [2015] I've been interested in methylene blue since your newsletter and KMUD interview. Do you think the purity of some methylene blue could be a problem? I bought some that is used for fish and aquariums. I have read online that a lot of methylene blue is contaminated with heavy metals, but I don't know what to think, because the people making these claims were trying to sell their own methylene blue, which they claimed was free of heavy metals.
>
> **Ray Peat:** I suspect it all might be made at the same factory, but I haven't seen the analysis. The seller could tell you the metal content.
>
> **Question:** It's probably too early to really tell, but for the few weeks I've been taking methylene blue, I haven't had my normal insomnia ("circadian rhythm disorder"). I've been looking for information on nitric oxide and insomnia but haven't found anything good. My digestion is also better. Is there some reason methylene blue might help insomnia?
>
> **Ray Peat:** Yes, it restores mitochondrial energy production, and lowers nitric oxide. High nitric oxide seems to be involved in insomnia How much of it are you taking? Are you buying a prepared solution?

### Source 3 — Nitric Oxide

Ray Peat · Interview · 2014 · http://l-i-g-h-t.com/files/herb-doctors-nitric-oxide.mp4

> **Ray Peat:** Yeah, some of the toxicity experiments have been kind of ridiculous in which they feed rats the equivalent for a person, it would be, an ounce or two of crystalline methylene blue which it would, just that amount of concentrated any chemical is going to be harmful. But it’s been twenty-five years ago, someone did a very well-controlled study of severe depressed people, 15mg per day was all it took to relieve severe depression. The side effects of even many times higher doses than that are essentially zero. Two studies, one by the NIH, 6 years ago and one more recent, gave greater doses, up to what would be the equivalent of about 4 or 5 or 6 grams a day for a person of the crystalline material, many times higher than the curative, anti-depressive dose, and they did it for the whole lifespan of rats and mice and saw no life-shortening effects in either rats or mice but in female mice, in both studies, they saw an extension of the maximum lifespan with the highest dose. And so in these ridiculously high doses many times, I guess about, 5-10x higher than the dose Paul Ehrlich used more than a hundred years ago to treat malaria – and he cured two cases of malaria in a period of just a couple of weeks - giving 5 doses a day of 100mg each time orally. But with very much smaller doses you see changes in the brain and reduced stress and curing depression and so on. At several times higher doses than he used to cure malaria you still don't see any harmful effects and in animal experiments, it took one of the gigantic doses, equivalent to, I think it was about 8g a day for a person, before it stopped doing the simple anti-depressive actions.

### Source 4 — Nitric Oxide

Ray Peat · Interview · 2014 · http://l-i-g-h-t.com/files/herb-doctors-nitric-oxide.mp4

> **Andrew Murray:** Now do you think the effects of methylene blue, there are probably multiple effects, but I wonder if any of the electron quenching or electrical stabilising activity of methylene blue might be responsible for interacting with different proteins and that kind of...
>
> **Ray Peat:** Yeah, one of the known mechanisms is that it can receive electrons from the mediator that receives them from glucose, and NADH for example, can be oxidised, and then the methylene blue can pass those electrons on to the part of the mitochondrion that is still working bypassing damaged parts of the mitochondrion so it can act like the missing enzymes simply restoring mitochondrial function. In subtler ways it, for example, the receptor that causes excito-toxic damage from overdoses of glutamic acid for example, anything that is depleting the brain of energy while stimulating it, activates these glutamate receptors and there are two sulphur groups in those proteins that respond to excito-toxins, that methylene blue oxidises those, and turns off the receptor and stops the excito-toxic process. And that's one of the ways, the excito-toxic processes, one of the things that turns on nitric oxide production going ahead and killing the cell, that's why the excited state is toxic, largely because of the production of nitric oxide.

### Source 5 — Ray Peat Email Advice Depository — Post 628

Ray Peat · Email · Feb 9, 2021

> **Question:** an email I send about MB: Hello Dr Peat, I was hoping you would be able to answer this question regarding methylene blue. Would methylene blue be dangerous or beneficial in an iron overload state ?
>
> **Ray Peat:** Like ascorbic acid , it can reduce ferric iron to the ferrous form, which creates the most toxic free radicals.

### Source 6 — Georgi Dinkov - Biohacking Mitochondria and Hormone Health for men and women - part 2

Georgi Dinkov · Interview · Jan 17, 2018

> **Georgi Dinkov:** It's like no matter how healthy you are, there is always a section of yourself, like a group of yourself somewhere in the body that's not getting enough oxygen. getting enough nutrition, that is not respiring properly, it's not producing sufficient ATP. And when you give them methylene blue, which distributes pretty evenly and absorbs pretty well throughout the body, you basically reach every single one of these cells, unlike oxygen. So you can basically take care of even that last step, that last mile that oxygen itself cannot reach, even if you're not exercising.

### Source 7 — Crucial Facts About Your Metabolism - Discussion Between Georgi Dinkov & Dr. Mercola

Georgi Dinkov · Interview · Sep 17, 2023

> **Georgi Dinkov:** Methylene blue is a relatively strong monoamine oxidase type A inhibitor. And in combination, which means it's going to decrease the degradation of serotonin, which means it's going to increase the buildup of serotonin. So if you're taking anything that contributes to the serotonergic tone, it's potentially dangerous. Multiple case studies published of people going to the hospital in shock, and methylene blue is the preferred treatment for shock because it rapidly recovers the blood pressure and the perfusion of the tissues, which are dying because there's no blood supply. But they noticed that since they give a very high dose, between 100 and 400 milligrams as a single injection, they had cases where people went into serotonin syndrome and Because they didn't know, because when somebody comes in critical through the door, you don't always know what medication they're taking, right? Then people went into serotonin syndrome and there's a known interaction of methylene blue with SSRI drugs. And if you go to like even CVS or like Rite Aid Pharmacy and tell them, hey, what medication should I not take together with methylene blue? The first thing they'll say is SSRIs. I've already tried it at the local pharmacy.

### Source 8 — Georgi Dinkov - Biohacking Mitochondria and Hormone Health for men and women - part 2

Georgi Dinkov · Interview · Jan 17, 2018

> **Kevin Cottrell:** And that's an interesting thing because, you know, the other thing for listeners, you've probably, if you have a fish tank, have seen methylene blue, haven't you, right? You know, it's a common substance that's out there, isn't it, Georgi?
>
> **Georgi Dinkov:** Yeah, it is. Actually, you can buy it from Amazon. You can buy it from pretty much any place online. If you type metal in blue in Google, but probably better to type metal in blue USP. In other words, you want to buy the one that's licensed for human use. The USP stands for United States Pharmacopeia. So you can actually buy it in powder. You can buy it in solution. It's already dissolved, so you can just take the drops that you need. And most of the ones that are being sold, they're actually sold for, just like I said, for people that have fish and they have aquariums. So methylene blue, in addition to being a great oxidant, in other words, acting like oxygen and being able to replace oxygen in metabolism, is actually a very potent antifungal, antibacterial, and antiviral substance. As a matter of fact, methylene blue is the first, as far as I know, at least that's how it's been described, it is the first official commercial drug that was introduced for use in the Western world. And its original designation was to treat malaria. But its effects are not just limited to destroying the plasmodium that causes malaria. It actually kills pretty much any virus that it gets into contact with. There are studies on PubMed showing that it inhibits both the infection and the replication with HIV. with the JC virus, with the Epstein-Barr virus, which some people think is the cause of multiple sclerosis, with the herpes virus, with the enterovirus, which are causing these acute cases of gastroenteritis, people vomiting, especially ones going on cruise ships, because the environment there is... teeming with bugs. So methylene blue is a very versatile substance and it has such systemic effects that I don't think there's a cell in the body that would not benefit from having a little bit of extra methylene blue.

### Source 9 — IdeaLabs Forum Q&A — Oxidal

Georgi Dinkov · Forum Q&A · May 8, 2015

> **Georgi Dinkov:** (2017-04-12) I have mentioned this in oher threads - for long term administration and benefits (including lifespan extension) about 1mg MB single daily dose is needed to produce 100nM/L concentrations shown to be optimal in the animal studies. Ray has mentioned similar doses as well. As far as the reduced/oxidized form - the quote from your study says oxidized MB is rapidly reduced in the body. The primary benefits of MB are as an oxidizing agent and for that the oxidized form is needed. As I said, most people are in an excessively reduced state, so oxidizing agents are what stimulates metabolism and promotes health. The reduced form may have some special effects on tau proteins but why would you take the reduced form is the study itself says taking oxidized MB gets rapidly reduced in the body, so it would be able to get to the brain. So, with oxidized MB you get both the benefits of the oxidizing effects and reduced MB as a result, which can then cross the BBB and do what it needs to. Btw, I am not really convinced about that argument for reduced MB being more effective. I think the primary benefit of MB in neurodegenerative disorders is precisely the oxidizing power, the ability to lower NO and ativate cytochrome C activity, and the ability to bypass ETC if some are damaged or not functioning well. Remember, all disease is due to disturbed electron flow and for restoring the electron flow and for restoring that flow the oxidized version is needed. These things are discussed in other threads so if you use Google to search the forum you will find a lot of info. Just Google for "site:raypeatforum.com methylene blue ETC".

### Source 10 — Politics & Science: Evolution

Ray Peat · Interview · Mar 4, 2015 · https://www.youtube.com/watch?v=WoeHU0qEZbc

> ## Methylene Blue
>
> **John Barkhausen:** A follow-up on methylene blue from Duncan: "Have you tried methylene blue? How does it feel versus progesterone or caffeine?"
>
> **Ray Peat:** I've only been using it transdermally. My approach to understanding new chemicals is to find what the smallest amount does and then work up. So far, I see it as a good anti-inflammatory. Quite a few people are having very powerful antidepressant effects from it with just one milligram a day. But I think it's probably going to be effective at doses analogous to thyroid hormone—20, 30, or 40 micrograms per day might be the optimal dose. It's known that it can bypass mitochondrial defects, and I think that's a big part of why it can cure serious depression at such a small dose.

### Source 11 — Nitric Oxide and Methylene Blue [Generative Energy #11]

Danny Roddy · Interview · Nov 1, 2015 · https://www.youtube.com/watch?v=GgeZJoir70w

> **Georgi Dinkov:** I guess the main reason why it's so useful is because it acts like it can act as a substitute to oxygen. In other words... as the final electron acceptor in the entire metabolic chain. So whenever you have cases of hypoxia, which now we're finding that virtually every disease can be characterized as a chronic hypoxic state. In other words, metabolism is not working well. Oxygen is not getting to the cells. They're not properly oxygenated. They're in a chronic state of hypoxia. Glucose is upregulated. There's too much NADH being produced. The cell is in a reduced state. And all this is because of inability of oxygen to do its good by extracting these electrons and basically re-oxidizing the NADH back to NAD. Well, it looks like, well, no, it looks like, but it's been proven that methylene blue can do the same. In other words, if you have too much glucose, let's say in a cancer cell, and you're producing too much NADH, the way the body gets rid of it is by using pyruvate to oxidize NADH in the process, create lactate. Well, if you take methylene blue, you'll actually substitute for pyruvate and you'll basically, you'll avoid this creation of extra lactate. So it has been shown that taking some methylene blue lowers the levels of the enzyme called lactate dehydrogenase, which is overexpressed in every single type of cancer. If you go to Google, and go to the Wikipedia page of lactate dehydrogenase, you will see modern medicine likes to call it a nonspecific biomarker, both for diagnosis, but that's what makes it so powerful. Whenever you hear nonspecific, it means something good is going on. It is a nonspecific biomarker, both for diagnosing cancer and for prognosis. In other words, how long these people will live. Just go. It's incredible. Like basically right now, three pharmaceutical companies are doing everything possible to come up with an LDH inhibitor when several of them naturally already exist. Methylene blue is one of them.

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