#F023 Misuse and misinformation surrounding methylene blue

What is the subject ?

The misuse and misinformation surrounding methylene blue, presented without any factual basis as a miracle cure for cancer by a number of publications and media aimed at the general public

Why are we addressing this subject ?

Methylene blue is presented as a miracle cure for cancer in several newspapers and books aimed at the general public and relayed by social networks.
Methylene blue is a chemical compound used in the treatment of methaemoglobinaemia, a disease affecting haemoglobin.
In medicine, methylene blue is also used as a dye for bacteriological analyses or to differentiate certain tissues during surgery.
Experimental research has shown that methylene blue could have an effect on ovarian cancer cell cultures due to its effects on the mitochondria of these cells (1). However, the concentration of methylene blue that enables these effects to be observed in vitro is 50 micro-molar (µM), more than ten times the concentration that could be obtained by doses usable in humans.
It should be remembered that when used in humans, methylene blue can induce serious adverse effects, including death.

For more information

Methylene blue is a chemical compound used in the treatment of methaemoglobinaemia. These are situations where an abnormally high proportion of haemoglobin is in the form of methaemoglobin, a type of haemoglobin unable to carry oxygen efficiently. This can lead to symptoms such as breathing difficulties, bluish discolouration of the skin (cyanosis), fatigue and, in severe cases, heart or neurological complications. This phenomenon can be caused by certain medicines or chemicals (pesticides, nitrites, chlorites, carbon monoxide poisoning).

Methylene blue activates a normally inactive reductase enzyme system which transforms methylene blue into leuco-methylene blue. The latter enables methaemoglobin to be converted into haemoglobin, which is then able to bind oxygen efficiently and transport it to the body's tissues.

The theory that cancer is primarily a metabolic disease linked to an alteration in the energy management of tumour cells has been put forward in a number of popular books. Although this hypothesis has been explored in fundamental research, it has not been clinically validated. The use of methylene blue, proposed in this context as an inhibitor of cell fermentation, remains an unproven hypothesis based on cellular data at high doses which, as is often the case, cannot be used in humans. In this context, methylene blue is proposed indiscriminately and unscrupulously, and presented as an 'old' and 'risk-free' treatment.

Experimental research has shown that methylene blue could have an effect on the mitochondria of cancer cells at very high doses of at least 50 µM (1). By stimulating the mitochondrial electron transport chain and oxidative phosphorylation, it is thought to improve the energy efficiency of mitochondria, leading to a reduction in the production of lactate, a by-product of glycolysis that is often elevated in cancer cells. This process could disrupt the cancer cells' dependence on glycolysis for survival. The study, carried out in vitro, showed that when combined with treatments such as carboplatin, methylene blue can help to reduce the resistance of ovarian cancer cells (such as the OV1369-R2 lines) to certain anti-cancer drugs, particularly platinum-derived anti-cancer drugs. It was on the basis of these experimental cellular data that the hypothesis of a benefit of methylene blue in cancer emerged (1). In addition to the lack of clinical data, it should be emphasised once again that the concentration of methylene blue tested to observe these cellular effects is at least ten times higher than the concentration that can be obtained during use in humans with acceptable toxicity.

Methylene blue can cause serious adverse reactions in humans. In the worldwide pharmacovigilance database (Vigibase, WHO), there have been 63 observations of adverse reactions, all in the context of off-label use, including 9 deaths (14%), 14 cases (22%) with a life-threatening prognosis and 35 cases (56%) with hospitalisation or prolongation of hospitalisation. There has also been an increase in the number of cases reported to pharmacovigilance over time, with around 40% of cases reported in the last three years. The effects reported were serotonin syndromes (13 cases, 21%), unspecified comas (7 cases, 11%), encephalopathies (7 cases, 11%), hypotension (7 cases, 11%) and acute renal failures (6 cases, 10%).  Around 22% of the patients concerned were aged between 18 and 44, and 37% between 45 and 64. These findings suggest that the unadapted use of this product, outside the scope of international recommendations, could have serious health consequences.

Reference

(1) Moreira J. , Schwartz L., Jolicoeur M. In Vitro Methylene Blue and Carboplatin Combination Triggers Ovarian Cancer Cells Death. Int. J. Mol. Sci. 2024, 25, 11005. https://doi.org/10.3390/ijms252011005