Methylene Blue – Existing and Future Research

Methylene Blue


Molecular Formula:


Appearance and Structure

Methylene blue, also known as methylthioninium chloride, is a compound made up of very dark green-blue crystals or powder, which typically has a bronze lustre to it.

Methylene blue dissolves readily in water or alcohol.

History of Use

Methylene blue was first formulated in 1876 by Heinrich Caro. This was a landmark formulation and Methylene blue has since been called the first fully synthetic drug used in medicine (R).

In the late 19th Century, Methylene blue saw its first use in the treatment of malaria. At this time, researchers believed that drugs and dyes both worked by selectively staining pathogens and damaging them somehow (R).

Methylene blue was used as an antimalarial during the Second World War, but it soon fell out of favour as soldiers complained about it turning their urine blue (R).

It was this urine-colouring effect that gave rise to Methylene blue being used as a way to check whether psychiatric patients were adhering to their pharmaceutical regimen. Clinical effects were soon noticed in those psychiatric patients taking methylene blue, sparking interest in the drug’s antidepressant and other psychotropics (R).

Contemporary research has sparked a revival of interest in the use of Methylene blue as an antimalarial (R).

In 1933, researchers found that Methylene blue was an effective antidote to carbon monoxide poisoning and cyanide poisoning (R).

Methylene Blue can be found on the World Health Organization’s List of Essential Medicines; widely regarded as a list of the world’s safest and most effective medicines (R).

In addition to it’s clinical uses, Methylene blue is also used as a bacteriologic stain, an indicator dye, and for surgical and medical marking.


Methylene Blue – Existing Research


A 2017 study showed Methylene Blue to be a potent antioxidant for connective tissue cells, like skin, regardless of the patient type e.g. healthy or unhealthy (R).

Methylene blue generated connective tissue and slowed cellular death at a greater rate than other selective mitochondrial antioxidants (R).

Interestingly, Methylene blue was found to alter the expression of genes coding for proteins in the skin. For example, the production of collagen and elastin, both important proteins in determining skin health, was increased (R).

This study determined that dosage of 0.5 μM Methylene Blue “significantly increased cell viability in comparison to the control”. Importantly, Tissues treated with 5.0 μM and 10.0 μM actually showed a loss in cell viability (R).

It seems that low concentrations of Methylene blue (less than 2.5 μM) are the safest and most efficacious for long-term use. Until more research is done, we think that 0.5 μM is a solid starting point for future research.


Methylene Blue, combined with light, effectively reduced the infectivity of SARS-CoV in blood samples (R).

BX1, a treatment based on mehtylene blue, was found to eradicate COVID-19 in blood samples within just 2 minutes. (R).

A clinical trial administering Methylene Blue, Vitamin C and NAC found that the majority of subjects experienced a marked improvement in COVID symptoms, with improvements in key biological markers (R).

Another paper  highlighted the mechanisms by which Methylene Blue might treat Corona Virus. Specifically, MB can “abort effects of Bradykinin by inhibition of Nitric Oxide synthase inhibitor and promote oxygen saturation”  (R).

Finally, Methylene Blue combined with light was found to “robustly and consistently” inactivate corona virus when sprayed onto personal protective equipment. This effect was noted at a concentration of 10uM (R)


Monoamine oxidase enzymes break down certain neurotransmitters like noradrenaline and serotonin. Monoamine oxidase inhibitors (MAOIs) are used to reduce the activity of these enzymes in an attempt to fix a disrupted balance of neurotransmitters seem in those with depression.

Methylene Blue is a monoamine oxidase inhibitor (MAOI) (R).

At low-medium doses, Methylene blue reduces the activity of MAO-A more than MAO-B, but the degree of inhibition levels out at higher doses (R).

Caution must be used at doses greater than 5mg/kg as Methylene blue may cause a fatal build-up of serotonin – a particular risk when combined with SSRI medications (R).


Methylene blue was first identified as a possible treatment for malaria by Paul Ehrlich in 1891. It quickly became one of the first synthetic antimalarial drugs ever used (R).

Methylene blue fell out of favour as an antimalarial due to the undesirable effect of turning patients’ urine blue or green and having a similar effect on the whites of the eye.

However, there has been a recent resurgence of interest in its use as an anti-malarial, with a number of clinical trials in progress (R).

In fact, a 2014 study found that Intravenous methylene blue was just as effective as the standard malaria treatment method, intravenous artesunate. This study found that 20 mg per kg was the minimum effective daily dose (R).


Studies show that Methylene blue causes cancer cell apoptosis (cell death) by the generation of cellular oxidative stress via the NQO1-dependent (R).

Methylene Blue is being explored for its role in the photodynamic treatment of cancer (R).

A very recent study found that Methylene blue when used as part of photodynamic therapy (more on this below), causes “massive cell death of tumor cells”. Furthermore, malignant cells were far more susceptible to the therapy compared to healthy cells (R).


Recent research has demonstrated that Methylene blue has the potential to reduce the formation of amyloid plaques and neurofibrillary tangles seen in Alzheimer’s disease (R).

Studies have also demonstrated that by inhibiting acetylcholinesterase, Methylene blue can increase levels of acetylcholine. treat Alzheimer’s

Methylene blue also has the ability to repair mitochondrial function and cellular metabolism – both of which are often damaged in Alzheimer’s (R).

Methylene blue’s neuroprotective effects are mediated by autophagy (an intracellular degradation system) through activation of AMPK signalling. This makes it a potentially useful treatment for conditions such as Huntington’s (R).


A 2017 study investigated the effects of Methylene blue on adult neural stem cells in mice. Although no differences in the ability of the stem cells to multiply were identified, there was a general potential of MB to increase the migratory capacity of adult neural stem cells i.e. neural mobility. Methylene blue made it easier for the brain to “re-wire” itself (R).

In 2012, a study investigating the mechanisms of Methylene blue’s neuroprotective effects found that Methylene blue could reduce superoxide (potent free radical) production by acting as an alternative mitochondrial electron transfer carrier, as well as a recyclable anti-oxidant in mitochondria (R).

Methylene blue inhibits GABA receptor function by interacting with the GABA binding site (R). This could explain the compound’s positive effect on the CNS (R).


It is thought that the sudden release of nitric oxide is responsible for cardiovascular problems associated with septic shock.

Methylene blue has been found very effective in improving the arterial pressure and cardiac function in septic shock. Most likely because it is a potent inhibitor of guanylate cyclase, an enzyme involved in the nitric oxide-mediated relaxation of the blood vessels (R).


Methemoglobinemia is a potentially fatal condition that is characterized by the inability of haemoglobin to carry oxygen due to the ferrous part of the heme molecule being oxidized to a ferric state (R).

Methylene Blue, which reacts with red blood cells to form leukomethylene blue, acts as a reducing agent of oxidized haemoglobin, converting the ferric ion back to its oxygen-carrying ferrous state (R)

The dose range of Methylene blue used to treat Methemoglobinemia is 1-2mg/kg of 10mg/ml solution (R, R2).


Methylene blue has a long history of being used to treat cyanide poisoning but has now been replaced by other treatments (R).


Methylene Blue combined with light treatment is an effective way to control oral lichen planus (R).

Photodynamic using Methylene blue and non-coherent light was found to be an effective treatment for the leishmaniasis infection (R)

Similarly, Methylene blue can be combined with a LED device to create and effective photodynamic antifungal therapy against chromoblastomycosis (R).

A 2010 study found that Methylene blue-mediated photodynamic therapy, in combination with low-level light therapy, is a suitable treatment protocol for recurrent herpes (R).

Methylene blue, in combination with light, also inactivates the viral nucleic acid of hepatitis-C and HIV (R).

Researchers of a 2009 study found that photodynamic therapy, using Methylene blue as the photosensitizer, is a potential solution to cases of drug-resistant psoriasis (R).

Methylene Blue Safety

Methylene blue is a very safe drug when used in therapeutic doses (<2mg/kg) (R). The following negative effects are all attributable to very high dosages.

Toxicity has been reported with high doses. Side effects of Methylene blue toxicity include cardiac arrhythmias, coronary vasoconstriction, decreased cardiac output and blood flow in different parts of the body (R).

Large quantities of Methylene blue can also turn the urine a greenish blue (RR2).

In newborn babies, Methylene blue can cause excess bilirubin, meth-Hemoglobin formation, hemolytic anaemia, respiratory distress and swelling of the lungs (RR2R3).

Be aware that taking Methylene Blue can interfere with the reading of a pulse oximeter and create a falsely low oxygen saturation reading (R).

As discussed above, Methylene blue is a monoamine oxidase (MAO) inhibitor. This property can cause extreme serotonin toxicity at doses >5mg/kg (very high dose) (R).

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