Methylene Blue Review

[CastorTroy]

2023 The photodynamic and direct actions of methylene blue on mitochondrial energy metabolism: A balance of the useful and harmful effects of this photosensitizer - PubMed

This is rather useless if no dosing is disclosed. Do you have access to the full paper to have a look about the doses used?

 

[Kray]

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.

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.

• MitoLab
• Health Natura

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.

Thank you so much for the effort in researching and posting this information. Very helpful, and I appreciate you sharing your own experiences with it!

 

[area51puy]

View: https://youtu.be/XhgGGbdw4zE?si=9fg-Oj4w6O45gTxs

 

[mostlylurking]

2023 The photodynamic and direct actions of methylene blue on mitochondrial energy metabolism: A balance of the useful and harmful effects of this photosensitizer - PubMed

MB is also an MAO inhibitor, something you would want to avoid if you have a problem with serotonin.

Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction - PubMed

MB is a potent reversible inhibitor of MAO A with implications for gut uptake of amines when administered orally. At concentrations reported in the literature after intravenous administration, MAO B would be partially inhibited but MAO A would be completely inhibited. This inhibition of MAO A...

pubmed.ncbi.nlm.nih.gov

 

[mostlylurking]

This is rather useless if no dosing is disclosed. Do you have access to the full paper to have a look about the doses used?

There's a link to the full paper provided. It links to this:

The photodynamic and direct actions of methylene blue on mitochondrial energy metabolism: A balance of the useful and harmful effects of this photosensitizer

According to the literature, methylene blue (MB) is a photosensitizer (PS) with a high affinity for mitochondria. Therefore, several studies have expl…

www.sciencedirect.com

 

[area51puy]

View: https://youtu.be/XhgGGbdw4zE?si=9fg-Oj4w6O45gTxs

Listen to the whole two hours and goes into a lot of detail and studies , but ultimately recommends mb in you have impairments in complex 3 or 4 in the electron transport chain , but not 1 or 2. And says mb reduces atp if you have a healthy electron transport chain, but helps produce more atp if you have impairment in it.


And says mb is more hormesis effect where 11 percent of mb is converted into hydrogen peroxide and stays around 2.5 longer then normally which is helpful for the anti viral and anti microbial effects especially with light and with increased hydrogen peroxide in the cell which will lead to increased glutathione was his theory. So may be beneficial for some but could be detrimental for others especially the higher the dose for other and brings up some examples with the dementia studies.

@haidut might interests in this and I wonder what his take would on this video.

 

[area51puy]

View: https://youtu.be/RPSFy9doSrA?si=T5q9RZss7xHjKfTP


Here is a condensed version of his thoughts on methylene blue.

I discovered Pete work because of methylene blue. I was into health and longevity and in Ben greenfield book he talked about MB and I eventually gave it a try and no single thing I ever took gave me the energy and overall well being that MB did, so I did more research on it and found Georgi talking about it on some podcasts and started listening to the bioenergetic podcast.

But masterjon recommends it if you have problems in complex 3 or 4.

Now when I first started taking MB I was misinformed and thought sugar was the devil and was on keto and carnivore for years, but taking MB gave me great energy and my overall wellbeing. As I transitioned into peats work and my overall health improved greatly , so now when I take it occasionally I don’t feel any benefits from it. It may or may not but I don’t feel it like I did when I first started MB when I avoided sugar like the plague. I really thought I was being healthy eating kale salads with tons of PUFAs salad dressing on it. At least a year before I discovered Pete l was istening to Paul Saladino before he discovered Pete’s work and I eliminated PUFAs ,but it was mostly carnivore.

So maybe MB is beneficial if your metabolism is damaged from PUFAs or keto or whatever but as you improve your metabolism through Pete’s work the benefit may diminish . Masterjon say if your metabolism is healthy MB reduces atp production in the cell.

 

[Ismail]

2023 The photodynamic and direct actions of methylene blue on mitochondrial energy metabolism: A balance of the useful and harmful effects of this photosensitizer - PubMed

“The main conclusion that can be drawn from this study is that MB can interact with mitochondria, and, when photoactivated, it is capable of damaging specific structures and molecules even at low oxygen concentration condition, compromising mitochondrial energy metabolism. However, without photoactivation, MB also interacts with mitochondrial structures and negatively interferes in mitochondrial respiration, acting predominantly as an uncoupler of oxidative phosphorylation. Consequently, MB is also able to perturb the liver metabolism, altering several metabolic pathways related to energy metabolism.”

 

[charlie]

“The main conclusion that can be drawn from this study is that MB can interact with mitochondria, and, when photoactivated, it is capable of damaging specific structures and molecules even at low oxygen concentration condition, compromising mitochondrial energy metabolism. However, without photoactivation, MB also interacts with mitochondrial structures and negatively interferes in mitochondrial respiration, acting predominantly as an uncoupler of oxidative phosphorylation. Consequently, MB is also able to perturb the liver metabolism, altering several metabolic pathways related to energy metabolism.”

Imagine that.

 

[Ismail]

Imagine that.

Why do you say it like that? Genuinely asking.

I’m a little taken aback by this study, as everything else I’ve read about MB has been positive; to the point whereby I just tried it for the very first time last week and felt like my brain was super focused and I didn’t feel exhausted for the first time in a long time. I was getting things done and became extremely proactive and procrastination was nowhere to be found

However that feeling unfortunately hasn’t lasted, so not sure whether MB needs to be cycled. But having read the above summary (albeit the abstract and the discussion at the end), I’m unsure now.

 

[Donna57]

Listen to the whole two hours and goes into a lot of detail and studies , but ultimately recommends mb in you have impairments in complex 3 or 4 in the electron transport chain , but not 1 or 2. And says mb reduces atp if you have a healthy electron transport chain, but helps produce more atp if you have impairment in it.


And says mb is more hormesis effect where 11 percent of mb is converted into hydrogen peroxide and stays around 2.5 longer then normally which is helpful for the anti viral and anti microbial effects especially with light and with increased hydrogen peroxide in the cell which will lead to increased glutathione was his theory. So may be beneficial for some but could be detrimental for others especially the higher the dose for other and brings up some examples with the dementia studies.

@haidut might interests in this and I wonder what his take would on this video.

This was a very informative video. Thank you for sharing. I have a blockage on the electron chain transport system Cytochrome lll. Im using it to assist the electron chain transport system to assist in creating more ATP energy. I can tell you Ive used it along with colloidal silver when i got COVID and it wiped it out within 24 hours.

 

[Ismail]

I have a blockage on the electron chain transport system Cytochrome lll

What test(s) did you do to identify you have this blockage? Thanks