Article written by: Dr. Scott Sherr
The History Behind Methylene Blue (MB)
MB has a very colorful (blue?) history. It was initially developed in the late 1800’s as a dye for use in textile manufacturing (fun fact: it was the dye initially used to stain blue jeans blue) but soon after it was synthesized, several medical applications were discovered, the first of which was for the treatment of malaria(1). MB was also used effectively as an antifungal, antiviral, and antibacterial agent before prescription antimicrobials became available in the 1950’s (2). It is still used as an antifungal agent in fish tank cleaners.(3)
In the mid 20th century, MB was discovered to have antipsychotic and mood enhancing properties (4). It was also added to other drugs to ensure medication compliance. Beginning early in the 20th century, MB was regularly used as a bacteriologic stain, a cellular stain, as an indicator dye, and for surgical and medical marking (5). Its use continues to the present day.
Recently, there has been significant interest in MB because of several studies showing that it may improve learning, memory, and be neuroprotective. It is also re-emerging as a possible treatment of malaria because of drug resistant strains and as a way to fight other infections as well, especially when combined with certain spectrums of light (6).
Methylene Blue Cellular Mechanisms
Methylene Blue is an electron cycler (7). At low doses (0.5 to 4mg/kg in most studies), MB accepts electrons. At higher doses, MB donates electrons. After absorption in the buccal mucosa (e.g. in a troche), oral ingestion, or IV administration, MB concentrates in tissues with the most mitochondria (e.g the brain where it readily crosses the blood brain barrier, the heart, the liver, and kidneys) (8).
At low doses, MB makes (blue) magic happen: Here are the 8 most promising ways it works:
- MB acts just like oxygen in the mitochondria. It accepts electrons at the electron transport chain (ETC) and increases ATP production (9). This effect can occur in the presence or absence of oxygen. Forgot how the ETC works? Watch this video (start at the 1-minute mark).
- Enhances the function of cytochrome oxidase (complex IV), making it work faster and more efficiently (10). This leads to increased oxygen consumption and increased ATP production, especially in the most metabolically active cells like the nerve cells in memory regions of the brain (11)!
- Stimulates glucose metabolism in conditions without oxygen and increases the amount of NAD + produced by mitochondria (12). The greater amount of NAD+, the younger your cells remain/become due to sirtuin activation (see David Sinclair’s book Lifespan for more information).
- In red blood cells, low dose MB changes the configuration of the iron (heme) in hemoglobin, the molecule in a red blood cell that carries oxygen (13). This improves the oxygen carrying capacity of hemoglobin which leads to increased ATP production from the ETC.
- Low dose MB also functions as a powerful antioxidant as it scavenges the mitochondria and cytosol for free electrons to accept and neutralize (14). On the macro level, this is how MB may be neuroprotective and even reverse skin damage (see below).
- Low dose MB also has antidepressant effects, functioning as a monoamine oxidase (MAO) inhibitor (15). Inhibiting MAO prevents monoamine neurotransmitter breakdown (dopamine, melatonin, and serotonin) which leads directly to increases in these neurotransmitters.
- Low dose MB may also function as a cholinesterase inhibitor, increasing the amount of acetylcholine available, a neurotransmitter in the brain responsible for arousal, attention, memory and motivation (16, 17).
- Low dose MB, combined with certain spectrums of light (UV, primarily) may be anti-infective against viruses, including coronaviruses (18).
Amazingly, there are 4 distinct ways MB increases cellular energy (ATP) production, three of which are related to its direct effects on the mitochondria.
Moderate to high doses of Methylene Blue
At moderate doses (4mg to 10mg/kg in most studies), MB becomes an electron donor and a pro-oxidant and facilitates the generation of singlet oxygen and peroxide radicals, especially in the presence of certain spectrums of light (19). This is likely the way MB works septic shock (via nitric oxide synthase inhibition) and possibly in cancer treatment synergy (20).
At high doses (>10mg/kg), MB can have harmful oxidative effects.
Methylene Blue Research and Potential Indications
The only FDA approved treatment of MB is for a condition called methemoglobinemia where MB helps oxygen bind to hemoglobin. If hyperbaric oxygen therapy isn’t available, or if there are delayed symptoms, MB is also used for carbon monoxide poisoning secondary to its antioxidant and energy enhancing effects in the mitochondria (21).
Outside of the FDA, MB has been shown in several non-human studies to be neuroprotective and improve many aspects of learning and memory. There is a wealth of animal data showing the impressive learning upgrades possible with MB.
In a recent human study, a single low dose of oral MB was shown to increase functional Magnetic Resonance imaging activity during sustained attention and short-term memory tasks. It also improved memory retrieval. In short, it made study participants more focused and smarter. Kind of awesome, eh? More human trials are underway…and many n=1 studies too!
One of the most promising areas of MB research is in neurodegenerative disease. Recent studies in animal models of Alzheimer’s Disease have shown that MB may slow the formation of amyloid plaques and neurofibrillary tangles (21). A pharmaceutical drug derived from MB has also shown benefit in both Alzheimer’s disease and fronto temporal dementia (Lewy Body Disease) and is currently in late phase trials.
There have also been several studies recently on the combination of MB and UV Light killing various viruses including Coronaviruses although not specifically COVID-19. There is, however, a study looking at MB for COVID-19 as well. In addition, there is ongoing research in MB for brain injury, for cancer, malaria, Hepatitis C, various skin conditions like psoriasis, and much more.
Methylene Blue Safety
MB is a very safe drug, especially when taken at low doses and when purity/potency tested. The most common (and harmless….and awesome?) side effect of MB is blue urine. Because of the potential risk of Serotonin Syndrome (a life threatening condition) do not combine MB of any dose with SSRIs, SNRIs or drugs that increase serotonin levels. For all you psychonauts out there considering MB, certain psychedelic substances like MDMA and psilocybin increase serotonin and the vine in ayahuasca ceremonies has MAO-I properties like MB…so be mindful of what you are stacking/ingesting!
Are you pregnant or breastfeeding? Please don’t take MB because it is contraindicated.
At high doses (>10mg/kg), MB may cause a litany of potential side effects including hypertension, methemoglobinemia (a condition it actually treats at low doses), dizziness, GI distress, affect readings of a pulse oximeter, induce hemolytic anemia in patients with a genetic condition called G6PD, and more.
Whatever you do…please do NOT drink fish tank cleaner. Although it has MB in it to treat fish fungal infections, it also contains tons of impurities including heavy metals like arsenic, aluminum, cadmium, and lead plus other badness too. Industrial grade MB has up to 11% impurities as well.
Your safest choice is USP (pharmaceutical grade) Methylene Blue that documents its purity and potency. Troscriptions, for example, founded and pioneered by Dr. Ted Achacoso, has two nootropic troches (Blue Cannatine and Just Blue) that are made with USP (and purity/potency tested) Methylene Blue.
Blue Cannatine is formulated with 5mg of methylene blue + nicotine, caffeine, and hemp crystals for a wide focus that launches your brain into git-er-done “limitless mode”. All ingredients in this formula (and in all Troscriptions products) are precision dosed, physician formulated, and purity/potency tested.
At the request of biohackers like you, Just Blue was developed. It is a 16mg pure methylene blue troche made with USP potency/purity tested MB. Dr. Ted likes to say that Just Blue functions as a brain health optimization supplement. It “powers you up like a gentle wind that lifts the glider wings of your brain for long and BRIGHT focus”. Translation: Your brain is ON and it’s a smooth blue ride.
Wherever you decide to get your methylene blue, make sure that it’s USP and purity/potency tested!