What Is Methylene Blue?

by Ryan Heeney / March 4th, 2022

In 1876, methylene blue was originally created as a dye to be used for textiles.  By 1891 its use in the treatment of malaria was pioneered by two gentleman named Paul Guttmann and Paul Ehrlich and became the first fully synthetic drug used in medicine. 

Why methylene blue was even chosen to treat malaria was actually completely by accident.  Ehrlich believed that colored dyes worked the same way that drugs used to treat disease were thought to work at the time—by “staining” the pathogen.  This was actually a common belief for the time, by staining the pathogens with the colored dye it was believed this somehow “destroyed” them.  In reality, changing the cell membrane of pathogens is in fact how various drugs work, so while the idea was quite simplistic, the theory was still partially right.

Although the medical community at the time still hadn’t figured out exactly how it worked, they discovered methylene blue in dosages of 100 mg daily reliably cured malaria.  This was a big deal at the time because of how widespread and lethal malaria had been.

Methylene blue eventually dropped out of favor in its treatment of malaria due to the fact that in the early 1900’s an anti-parasitic drug named “quinine” took over as the main treatment.  The main reason for this change was simply due to the fact that quinine could be patented (in other words, quinine could be more profitable for the medical industry).  After getting the patent, the company did a lot of publicizing and lobbying for quinine and eventually was successful in getting methylene blue replaced. Even though quinine is still the go-to for treatment of malaria, this did not stop methylene blue from remaining an often trusted second option.

Still to this day, if you go to a tropical region and contract malaria and for whatever reason quinine is not available, there is a good chance you will be treated with methylene blue instead.

Modern hospitals have also found other life-saving aspects of methylene blue.

If a patient comes into a hospital with severe blood loss and trauma and is experiencing shock and/or organ failure and an adrenaline injection does not work to increase blood pressure, large doses of methylene blue are administered.  Methylene blue is chosen under these circumstances because of it’s ability to blocking the effects and synthesis of nitric oxide, which initially raises blood pressure. Once the person has recovered and their carbon dioxide production rebounds (it is very low during shock due to high lactate) it actually has vasodilating effects and reverts the blood pressure back to normal. During shock doctors prefer higher blood pressure to avoid organ failure and if methylene blue usage is kept being administered for the next few days after the initial shock reaction, the increased carbon dioxide will gradually normalize blood pressure.

These properties are the reason methylene blue makes the World Health Organization’s list of essential medicines (which they consider to be the safest and most effective medicines needed in the healthcare system today). You can find the WHO’s list here:

https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-MVP-EMP-IAU-2019.06-eng.pdf

Okay, methylene blue can help me in times of emergencies but what can it do for me in everyday health?

If you look at the chemical structure of methylene blue, it is very similar to a number of other compounds called “quinones”.

Some common quinones you might be familiar with are CoQ10, emodin, vitamin K and the tetracycline family of antibiotics.  While the actual definition of a quinone is quite technical, the one property quinones share is their ability to accept electrons.

What does this mean and why is it important?

Something known as the “bioenergetic theory” (and is the main premise here at The Metabolic Lifestyle) says that the better your cell can turn the food you eat into the energy (ATP) your cells use, the healthier you will be. This is what having a high metabolism means.  Conversely, that same theory says that anything that interferes with metabolism will cause disruption in the organism, and will eventually lead to disease and death. This is what the philosophy of The Metabolic Lifestyle and for an in-depth recap, you can look back to my first article “What Is the Metabolic Lifestyle”.

If we assume metabolism is the most important aspect of our health, than we must put great importance on the most basic, fundamental part of metabolism and that is on the “transfer of electrons”.  The efficiency of the transfer of electrons from the food you eat, to the oxygen in the cell, is perhaps the most crucial and defining characteristic of living beings. It is this transfer of electrons that creates the energy (ATP) used to power all the cells in our body… keeping us alive and full of vitality.

From start to finish, this process of cellular metabolism is made up of over 40 different steps—all happening within the cell. Depending on an individuals health, diet, age, stress levels, the general health of their cell, etc., a “kink in the hose” can form. This causes a build up of electrons which are ideally supposed to be flowing seamlessly through these 40+ steps.

This problem will cause a malfunction within the cell and ultimately a malfunction in the organism.

To visualize just how many opportunities there are for the flow electrons to hit a "kink in the hose”, the diagram below illustrates the amount of steps which are involved in cellular respiration from start to finish:

Quite a few opportunities for a clog, huh? But what exactly happens when this backup of electrons occurs?

When this back up of electrons occurs at a certain point listed above, parts of the cell’s “machinery” will begin to malfunction. To better understand the consequences of one of these traffic jams, let’s look at a specific example in a simpler diagram…

A very common place for this to occur is at the end of a step labeled “glycolysis”.  This location can be seen below circled in red:

Pyruvate is the “output” of the metabolism of glucose during glycolysis and is the form which is now able to enter the mitochondria of the cell. When the build up of electrons occurs here, it throws a wrench into the gears of glycolysis and pyruvate itself begins to build up.

This causes many processes to malfunction and even begins causing disruptions of things like the ratios between molecules NAD+ and NADH (which is a very important topic and worth another article of it’s own in the future) but the main detrimental result of this pyruvate buildup is increased levels of lactic acid in the body.

This is not good.

Lactic acid has many systemic, anti-metabolic, toxic effects in the system.  Probably the most well-known of these is its role in cancer. Not only is lactic acid overproduced as a product of the cancer metabolism, but lactic acid itself promotes cancerization.

Lactic acid also promotes angiogenesis. Angiogenesis is associated with cancer because of the fact that cancers require the formation of new blood vessels to grow and metastasize.

It doesn’t stop there, lactic acid also exacerbates existing hypoxia. This is because that when the concentration of lactic acid is high, the concentration of carbon dioxide will be low.  These two have an inverse relationship—when one goes high, the other goes low. When carbon dioxide is low, hemoglobin cannot release the oxygen in your blood. This process depends on carbon dioxide and when you have low carbon dioxide levels in the blood, you exacerbate this hypoxic, low metabolic state. This relationship between carbon dioxide and oxygen’s ability to be used is the metabolism is called “the Bohr effect”.

Remember, this is what can happen when the traffic jam of electrons happens just at this point. There are still 40+ more places for this to happen.

Let’s say this build up or “clog” happens somewhere in the Krebs cycle, this could cause an excess of citric acid, oxaloacetate or a number of other byproducts which can also lead to cancerization (especially if the build up is citric acid).

If the traffic jam of electrons happens in the electron transport chain, you can have a dramatic increase in the amount of something called superoxide ions which attack the unsaturated fats in your cells, creating lipid peroxidation (a very toxic process).

These are just a few examples of the many possibilities and inevitable effects one can expect from various kinks in the metabolic hose.

Okay, I can see what happens when there’s a backup of electrons in the metabolic process, but how can methylene blue help?

One of the most amazing things about Methylene blue is the fact that is an extremely powerful electron acceptor.  Just like with oxygen, electrons flock to methylene blue like a magnet.  When you ingest methylene blue, you might as well be ingesting the next best thing to pure oxygen. This is where methylene blue’s true value lays is and is the reason it’s often referred to as a “promiscuous electron acceptor”.

Methylene blue immediately makes it’s way into your cells after entering the blood stream and if there is a build up of electrons anywhere in the cell, it will begin to clear those blockages out.  It doesn’t discriminate and takes electrons from any spot they are found in excess. 

Now, if you do not have much of a build up anywhere, methylene blue won’t do much of anything—but more importantly, if you don’t need it it will not harm you. 

But as we all know, life isn’t stress free and most likely we all have build ups of electrons somewhere in our chain.

What else can methylene blue do?

As you might have guessed from its ability to treat malaria, methylene blue is a potent antiparasitic—but that’s only the beginning when it comes to fighting pathogens.  Methylene blue is an extremely effective antiviral, antifungal and antibacterial substance.

But if methylene blue kill pathogens, won’t it harm us too?

Nope. And there’s two reasons for that.

First, methylene blue works through the creation of something called “reactive oxygen species” or ROS for short.  ROS are molecules containing highly reactive oxygen and are byproducts of the mitochondria.  This is really what takes the pathogens out. The reason these reactive oxygen species don’t harm us is that the amount created isn’t enough to harm us, but more importantly is the fact that our cells have antioxidant defense systems (including the powerful glutathione) which protects us, but allows the pathogens to be destroyed. If methylene blue created ROS beyond what it did in reasonable does (1-2 mg a day), an increase in ROS might be a problem, but at a level at 1-2 mg a day, the harm is put only on the unwanted pathogens.

Why this is unique and so important is the fact that there’s no known way a pathogen can defend itself from this increase of reactive oxygen species.  When someone has been infected with a virus or bacteria and they are being treated with some type of antiviral or antibacterial, often that pathogen will develop a resistance to the drug or treatment—this does not seem to happen with methylene blue. Methylene blue acts on such a fundamental pathway that none of these pathogens are capable of evolving to a point in which they can get past it. This is also the reason methylene blue is commonly used in aquariums—its antiviral, antibacterial, and antifungal properties make it a perfect choice for keeping fish safe while clearing harmful pathogens.

For what it’s worth, other substances that can generate these levels of reactive oxygen species include aspirin, caffeine, DHEA and progesterone.

Secondly, methylene blue also wipes out pathogens in a “round about way” by improving our metabolism. In this way, pathogens are killed off almost as a side effect.  Whenever your metabolism improves, your immune system also improves.  Whatever methylene blue is not able to take care of directly, the fact that your immune system has been given a “boost” gives it a opportunity to step in and take care of the rest.

Some may argue that nitric oxide has the same pathogen killing properties as methylene blue, but when analyzed further you begin to see why nitric oxide falls short.  Yes, it can kill pathogens directly, but it is heavily immunosuppressant.  This is the reason taking nitric oxide promoting drugs seem be to linked to infectious diseases, cancer, cardiovascular disease, etc.

But wait, I thought I heard nitric oxide can be good for you?

In the body nitric oxide really has two main functions.

1. It is the emergency vasodilator when carbon dioxide is not available.

2. Levels of nitric oxide rise when you have some kind of an infection. It is the cardinal tool the body uses to kill pathogens invading yourself and is very toxic to living organisms.

The problem is it is also toxic to us too, as we are living organisms too.

And this seems to follow an ongoing theme in health, and biology specifically.  Yes, we need our “stress system” in short bursts to keep us alive, but when this stress system runs chronically for long periods of time, health problems and disease will ultimately occur.

Remember, the stress system is good in emergency situations, but only for very short periods of time.

This is why drugs like Viagra are actually quite unhealthy.  Viagra promotes the production of nitric oxide to dilate blood vessels, but it does so everywhere—not just in a certain intended area.  Drugs like this affect the brain, the heart and other organs not originally intended.  They increase the chances of heart attacks, strokes, melanoma, pancreatic cancer and even neurological diseases.

In every case, methylene blue can get done what nitric oxide can do too… but in a much safer way.

Methylene blue seems to be good for almost everything, how about with aging?

There was a study done with skin cells from a subject who was 90 years old.  In one petri dish there was a solution of saline, glucose and a sample of the subject’s skin cells. In the other petri dish there was saline, glucose, a sample of the skin cells plus methylene blue. 

The only difference between the two petri dishes was the methylene blue.

The petri dish with the methylene blue got the amount which would be equivalent to 1-2 mg for an average sized person.

The results were pretty surprising…

The dish that contained the 90 year old skin cells with the methylene blue miraculously reverted to a metabolic state of someone estimated in their 20’s!

Remember, the only difference was the methylene blue—and while some might read this and find it hard to believe, this is that actual study:

I will post a link to the full study here.

The scientists involved in this study liked the results so much they immediately spun a separate company selling a skincare product that has methylene blue as the active ingredient.  In theory, this might be a great product, but unfortunately they included many harmful ingredients and also set the retail price for over $100 a bottle.

What’s one way methylene blue could help skin outside of a petri dish?

Well, one way could be the elimination of age spots.

Age spots are composed of something called lipofuscin.  Lipofuscin is brownish pigment in the skin which is a combination of iron, lipid peroxidation from polyunsaturated fats and some various lipid-like molecules like cholesterol esters. It’s a prominent sign of aging skin.  Lipofuscin isn’t just skin deep though, it accumulates inside of cells and blocks many of energetic pathways mentioned above resulting in the build of free electrons.  Like we discussed above, methylene blue does a great job at clearing these specific build ups of electrons, which in theory could clear age spots as well.

What about aging in general?

There was another study done with methylene blue on a living animal, specifically a type of fly.  For all intents and purposes this type of fly is thought to age the same way us humans do. The dose used in the experiment was a dose that would be the equivalent of 1-2 mg daily dose for an average sized person.  This dose was given for a duration of about 10% of the fly’s lifespan.  The results of this experiment were as equally surprising as the one done with the skin cells.  All signs of aging in the fly model had appeared to reverse.

Yes it was a fly, but here we have evidence in both a petri dish AND a living animal model that exhibits methylene blue’s abilities to reverse both the signs of aging, and aging itself.

What does this experiment mean for humans?

Let’s think about that…

Say the average person lives 80 years.  If we try to mimic the duration factor of the second experiment which used 10% of the fly’s lifespan, and applied that to an average human’s life span of say 80 years, then we get 8 years.  That would mean administering 1-2 mg of methylene blue daily for 8 years could hypothetically reverse signs of aging as it did in the animal model. It is very hypothetical, but interesting nonetheless.

Does this mean that someone could take methylene blue and reverse their biological age?

A fly is much smaller that a human, containing much less cells, and in the skin cell experiment there were probably something like only like 1,000 or so cells in the petri dish; while on the other hand the average person is made up of about 37 trillion cells. So while the differences in term of magnitude are very large, nothing can be ruled out. I think once dosages and duration are factored in in terms of a human trial, who who really knows what could be possible? 

If methylene blue was taken consistently throughout someone’s life and for a long enough duration (equivalent to the studies mentioned above) could the above experiments be mimicked?

Well it hasn’t really been studied enough, but it seems that not only looking younger but also being younger could be possible given the results of the other experiments.  The general process and theory seems to be valid.

But how could stopping or reversing the aging process even be possible?

Well, aging is a multi-factored process or “problem” if you want to look at it that way.  It’s a systemic issue.

Mainstream medicine will say that there is a heavy genetic component to aging. They often explain it through an evolutionary lens and to quote researcher Georgi Dinkov they might say something to the effect of:

“Beyond a very narrow set of reproductive years there is really no benefit to an organism surviving longer. This is because your genes are really controlling the show and your genes are just using you as a host or vehicle for propagation”… or “they will say we tend to age because this is a signal that your genes no longer need you, after reproduction they now have a younger host and a younger host has a better chance of survival with a better chance at further propagating those genes”.

But most people reading this will intuitively notice that with aging, comes a general slow down of bodily functions—anything from feeling a bit more tired during the day to a wound healing more slowly.

The bioenergetic theory and the theory here centered at The Metabolic Lifestyle says that aging is a cellular energetic slow-down and that stresses over time cause the cellular machinery to break down, therefore causing the cells of the bod to produce less and less energy—eventually leading to disease and death. The key here though is, here at The Metabolic Lifestyle we believe we have the power to not only stop the slowdown of the metabolism, but reverse it as well.

In my opinion this makes methylene blue one of the most effective anti-aging substances that I know of.

While the topic of methylene blue and aging is quite interesting, methylene blue offers an even more impressive punch at disease in the area of photodynamic therapy.

What is photodynamic therapy?

Photodynamic therapy is a treatment that uses special drugs or substances, that when combined with light, makes that drug or substance more effective than it was before.

The way methylene blue is used in this context is, it’s given to a human subject (by injection or taken orally) and after it has disseminated into tissues, red light is then shined onto the person.  In these experiments, the source of red light they typically use are through lasers.  This is because they want to make it more targeted and location specific.  While red light from the sun or from red light lamps will work just as well, you just can’t concentrate it at a certain area if you wanted to like you could from lasers.

The reason they are so interested in shining light at a specific area with methylene blue therapy is that they are currently treating tumors this way.  Methylene blue is administered, allowed to disseminate into the body and then the red light laser is focused on the area where the tumor is located. These experiments are yielding very impressive results.

How does this work?

When the red light and the methylene blue react, they release a high amount of reactive oxygen species in that specific area.  This changes the tumor environment to be very heavily oxidized—and tumors don’t like that.  Tumors like an anaerobic, oxygen free, environment. This flood of reactive oxygen species is what kills the tumor cell.

During experiments they will draw blood from subjects sitting under red light after receiving methylene blue and can observe the immediate effects this therapy has.  Real time tests show that carbon dioxide increases, nitric oxide decreases, lactic acid decreases, etc.  These are all potent signals of an internal environment which is anti-cancer and pro-health.

Does this even higher increase in reactive oxygen species from light therapy make it an even more potent pathogen killer?

If reactive oxygen species kill pathogens, larger amounts from light therapy will get the job done even more effectively.  If you wanted to quickly knock out a certain pathogen, you could use this temporary at-home protocol:

Since the concentration of methylene blue used in fish tanks to fight pathogens is usually about 5 mg per liter.  Assuming we have about 6 liters of blood in our body, this means 25-30 mg of methylene blue could be taken in a single dose (hat tip to Georgi Dinkov for the math). This would then be followed by sitting in bright sunlight or a different source of red light for a certain period of time. With this concentration of methylene blue in the blood and the red light penetrating the tissue, this should have the same effectiveness of a very potent antiviral, antibiotic or antifungal.  This would also be a very effective way to “detox” as well. This level of methylene blue dosage should only be used sporadically and only in times of wanting to kick a cold or virus.

Photodynamic therapy with methylene blue could even have some life-saving applications and could be an effective therapy for candida—and while some might not think candida is life threatening, certain types of candida can indeed be very lethal.

Pharma companies are currently all over photodynamic therapy; they are filing patents as we speak and it’s no surprise to see why.

Along with red light, is there anything we can do to make methylene blue work even better?

There are two substances that seem to work really well with methylene blue; making it absorb better and work more efficiently.  Those are caffeine and benzoic acid.

Caffeine:

Studies done in the 1950’s and 1960’s show that when you administer caffeine with anything else, it not only increases the bioavailability (absorption from the intestines into the blood) of the substance, it also increases the cellular uptake of the substance.  In other words it makes the cells in your body much more permeable to that specific chemical that you ingested with caffeine.  Caffeine can do this in even very small amounts.  Caffeine is also known to specifically increase methylene blue’s effects once inside the cell as well.  There are a lot of similar chemicals that will do this and many of those are actually found in coffee and chocolate—theobromine, theophylline, theacrine and uric acid to name a few.

If you would like to know the mechanism on how caffeine does this exactly, the study below describes it very well.

https://pubmed.ncbi.nlm.nih.gov/331090/

Benzoic Acid:

A chemical very similar to aspirin, benzoic acid has a very potent, pro-metabolic effect if combined with something that can oxidize it. Well, methylene blue is a powerful oxidizing agent.  When you combine methylene blue with benzoic acid, it gets turned into a powerful pro-metabolic agent similar to a chemical known as dinitrophenol or DNP for short.  Some of those in the health and fitness industry know DNP as probably the most effective fat loss drug there is (and it really probably is). It was banned by the FDA but you can get around that with next best thing—benzoic acid with methylene blue.  So not only could methylene blue be used as a powerful oxidizing agent, but also a potentially very effective fat loss tool as well.

Interesting note: ECA, a popular fat loss drug in the United States using ephedrine, caffeine and aspirin, was banned in 2004.  Some could argue that a combination of methylene blue, caffeine and aspirin would accomplish something similar to ECA without all of the negative effects ephedrine had on things like blood pressure.  In my opinion, the methylene blue/caffeine/aspirin combination is a much safer, more benign option.

Are there any products on the market that combine these substances into one?

Yes. A product called “Oxidal” from a company called IdeaLabs combines methylene blue, caffeine and benzoic acid into one.  The company uses USP grade methylene blue (the highest grade) and the price is good.  I have no affiliation or connection to the company, I just believe the product is of high quality.  You can find that product here.  The amount of caffeine in Oxidal is 0.4 mg per drop and is not enough for you to experience any stimulating effects—but is enough to synergize with the methylene blue.

How about any pure methylene blue products?

CZTL makes a great powdered form of methylene blue that you can mix with liquid. They ship the powder with detailed instructions (it ships in 1g vials so it's easy to mix); so even if a person purchases 50g, he gets 50 vials of 1g each. They also provide chat support post-purchase to help the users. Dr. Mercola endorses the product and I respect his opinion on many things. For full transparency I am affiliated with this product but did my research and found it to be a great option. I asked for a heavy metals report on the product and they provided one; tested third party which can be seen here:

A link to that product can be found here: CZTL Methylene Blue

A company called Botany makes a good methylene blue product that is USP grade, but they have recently changed their droplet container which has made it not that easy to use. I’m hoping they change it back because it is a good, pure product. If they solve the problem, I’ll be sure to post about it. Also, as of writing this they are sold out. Hopefully they restock. I have no affiliation to this product.