Methylene Blue for Cancer: What You Need to Know (2025)
What Is Methylene Blue?
Methylene blue is the parent molecule for hydroxychloroquine and chloroquine, off-patent drugs commonly used to treat not only malaria but also COVID-19. Best known as a fish tank antiseptic and textile dye for blue jeans, it was actually the first synthetic drug in modern history, developed in 1876. Since then, we’ve discovered it has many really important medicinal benefits.
The first medical application of methylene blue was for malaria. In 1890, Paul Ehrlich, a scientist at the famous Charité Hospital in Berlin, Germany, discovered methylene blue inhibits an enzyme that weakens the malaria parasite.
One of the first antipsychotic medications was also made from methylene blue. Other drugs developed from or with it include antibiotics and antiseptics. In the past, it was commonly used to treat urinary tract infections. It’s also been used as an antiviral agent in blood used for transfusions.
To this day, methylene blue is found in every hospital in the world, as it’s the only known antidote for metabolic poisons (any poison that interferes with oxygen transport or displaces oxygen, either from the blood or from the mitochondria).
For example, if you’re admitted for carbon monoxide poisoning, they’ll give you methylene blue intravenously. Cyanide is another example. The only known antidote for cyanide poisoning is methylene blue. It’s also been speculated that methylene blue might be useful in the treatment of acute lung infections such as SARS-CoV-2.
Importantly, methylene blue is a hormetic drug, which means that low doses have the opposite effect as high doses. For example, it’s primarily used in emergency rooms at the upper dosage limit (3 milligrams to 4 mg per kilo of bodyweight) for methemoglobinemia, which is when a metabolic poison interferes with the transport of oxygen in hemoglobin, by the iron in hemoglobin being oxidized to +3 rather than its normal reduced +2 state.
However, if you take too high a dose, you produce methemoglobinemia. At dosages in between, there’s no effect. Likewise, while low dosages have an antioxidant effect, high doses are pro-oxidative and can kill bacteria and tumor cells.
Basically, as an electron cycler, methylene blue acts like a battery, but unlike other compounds that do the same thing, it doesn’t cause damaging oxidation in the process. If anything interferes with oxygenation or cellular respiration, such as cyanide, methylene blue is able to bypass that point of interference through electron cycling, thus allowing mitochondrial respiration, oxygen consumption and energy production to function as it normally would.
One of the first antipsychotic medications was also made from methylene blue. Other drugs developed from or with it include antibiotics and antiseptics. In the past, it was commonly used to treat urinary tract infections. It’s also been used as an antiviral agent in blood used for transfusions.
To this day, methylene blue is found in every hospital in the world, as it’s the only known antidote for metabolic poisons (any poison that interferes with oxygen transport or displaces oxygen, either from the blood or from the mitochondria).
For example, if you’re admitted for carbon monoxide poisoning, they’ll give you methylene blue intravenously. Cyanide is another example. The only known antidote for cyanide poisoning is methylene blue. It’s also been speculated that methylene blue might be useful in the treatment of acute lung infections such as SARS-CoV-2.
Importantly, methylene blue is a hormetic drug, which means that low doses have the opposite effect as high doses. For example, it’s primarily used in emergency rooms at the upper dosage limit (3 milligrams to 4 mg per kilo of bodyweight) for methemoglobinemia, which is when a metabolic poison interferes with the transport of oxygen in hemoglobin, by the iron in hemoglobin being oxidized to +3 rather than its normal reduced +2 state.
However, if you take too high a dose, you produce methemoglobinemia. At dosages in between, there’s no effect. Likewise, while low dosages have an antioxidant effect, high doses are pro-oxidative and can kill bacteria and tumor cells.
Methylene Blue, an Antioxidant and Energy Producer
Gonzalez-Lima’s research has primarily focused on low-dose benefits for nonacute purposes over the longer term — such as neuroprotective benefits and cognitive enhancement. While it has several mechanisms of action, a unique feature is that it acts on the level of electrons. He explains:
“Our body uses electrons as part of the electron transport chain that happens inside mitochondria, and these electrons, moved along through the mitochondria, are generated from electron donors that we produce by the foods that we eat.
All the foods that we eat, the only way they contribute to energy is by producing electron donors. They donate these electrons to the electron transport inside the mitochondria. The ultimate electron acceptor in nature is oxygen. That's why the process of removing electrons from a compound is referred to as oxidation.
In mitochondria, this process is called oxidative phosphorylation. The electron transport is coupled with the phosphorylation of adenosine to eventually produce the adenosine triphosphate molecule (ATP). Methylene blue is an electron cycler. It's an autooxidizing compound.
So, methylene blue donates its electrons directly to the electron transport chain, it obtains electrons from surrounding compounds, and maintains oxygen consumption and energy production. By doing this, it helps oxygen to be fully reduced into water.
So, it becomes two things that are often not found together. It acts as an antioxidant, because oxygen is neutralized into water by donating electrons to the electron transport, and it produces energy, because when the electron transport pumps are moving along oxidative phosphorylation, you have an increase in ATP formation.
Oftentimes, we have things that improve energy metabolism, but then they lead to oxidative stress. In the case of methylene blue, that's not the case.
You can increase oxygen consumption rates, increase ATP production for energy metabolism, and at the same time reduce oxidative stress which, of course, will lead to reduction in oxidative damage at the level of mitochondria, then at the level of the other parts of the cells, and eventually membranes of the cells, and reactions that are cascades of this oxidative damage.”
“Our body uses electrons as part of the electron transport chain that happens inside mitochondria, and these electrons, moved along through the mitochondria, are generated from electron donors that we produce by the foods that we eat.
All the foods that we eat, the only way they contribute to energy is by producing electron donors. They donate these electrons to the electron transport inside the mitochondria. The ultimate electron acceptor in nature is oxygen. That's why the process of removing electrons from a compound is referred to as oxidation.
In mitochondria, this process is called oxidative phosphorylation. The electron transport is coupled with the phosphorylation of adenosine to eventually produce the adenosine triphosphate molecule (ATP). Methylene blue is an electron cycler. It's an autooxidizing compound.
So, methylene blue donates its electrons directly to the electron transport chain, it obtains electrons from surrounding compounds, and maintains oxygen consumption and energy production. By doing this, it helps oxygen to be fully reduced into water.
So, it becomes two things that are often not found together. It acts as an antioxidant, because oxygen is neutralized into water by donating electrons to the electron transport, and it produces energy, because when the electron transport pumps are moving along oxidative phosphorylation, you have an increase in ATP formation.
Oftentimes, we have things that improve energy metabolism, but then they lead to oxidative stress. In the case of methylene blue, that's not the case.
You can increase oxygen consumption rates, increase ATP production for energy metabolism, and at the same time reduce oxidative stress which, of course, will lead to reduction in oxidative damage at the level of mitochondria, then at the level of the other parts of the cells, and eventually membranes of the cells, and reactions that are cascades of this oxidative damage.”
Basically, as an electron cycler, methylene blue acts like a battery, but unlike other compounds that do the same thing, it doesn’t cause damaging oxidation in the process. If anything interferes with oxygenation or cellular respiration, such as cyanide, methylene blue is able to bypass that point of interference through electron cycling, thus allowing mitochondrial respiration, oxygen consumption and energy production to function as it normally would.
METHYLENE BLUE and Ovarian Cancer
According to Dr William Makis (X/Twitter):
"2024 Moreira - Methylene Blue Metabolic Therapy Restrains In Vivo Ovarian Tumor Growth" (source)
"Ovarian cancer remains a significant challenge, especially in platinum-resistant cases where treatment options are limited."
"In this study, we investigated the potential of methylene blue (MB) as a metabolic therapy and complementary treatment approach for ovarian cancer"
Methylene blue (MB), a well-known dye agent, has shown promising effects in stimulating mitochondrial electron transfer chain and oxidative phosphorylation (OXPHOS), leading to increased mitochondrial respiration and ATP production
MB has also been reported to have direct effects on cell and mitochondrial metabolism
Methylene blue metabolic therapy exerted a strong inhibitory effect on the proliferation of the TOV112D ovarian cancer cell line, where the cell proliferation reached 16% of the control
addition of carboplatin to MB-50 exhibited a slight impact on TOV112D proliferation compared to MB-50 alone, but this effect was not significant (adding chemo to methylene blue makes little difference)
DISCUSSION:
The anticancer effect of methylene blue has been known for over a century.
In 1893, Louis Rambaud published data on a series of end-stage patients who responded to a high-dose treatment of methylene blue. This was confirmed by Pursell in cancer treatments on dogs
The results presented in this study demonstrate the potential of methylene blue (MB) metabolic therapy as an effective treatment approach for ovarian cancer
“stronger reduction in proliferation observed in TOV112D (platinum resistant cancer) cells compared to ARPE-19 (normal ovarian) cells in response to the MB-50 treatment highlights the potential of methylene blue as a therapeutic agent that specifically targets ovarian cancer cells”
"addition of carboplatin to MB-50 exhibited a slight impact on the TOV112D proliferation compared to MB-50 alone, suggesting a potential additive effect of carboplatin in combination with methylene blue, albeit to a limited extent."
modest enhancement of the in vivo tumor response observed to the combination of MB and carboplatin (MB + carboplatin) raises the possibility of a synergistic effect between methylene blue and carboplatin
“it would be highly relevant to identify the metabolic pathways as well as the signaling pathways involved in the inhibition of cancer cell growth by methylene blue”
“In conclusion, this study provides crucial insights into the potential of methylene blue-guided metabolic therapy for treating ovarian cancer. The results underscore the promise of metabolic therapy in reducing tumor growth by addressing the mitochondria redox potential, akin to its role as an oxidative agent in bacterial diseases. However, there is a pressing need for further investigations into the specific impact of methylene blue on apoptotic signaling and metabolic pathways within cancer cells. These molecular mechanisms must be thoroughly elucidated to optimize the application of metabolic therapy and enhance the treatment outcomes, particularly in the context of chemoresistant ovarian cancers.
My Take…
I will be writing a series of articles on Methylene Blue and Cancer over the coming days.
In this paper, methylene blue had a dramatic effect on ovarian cancer cell proliferation, oxygen consumption rate in tumor cells and on tumor growth.
However, the pathways are unknown.
Interestingly, while MB slowed the tumor growth rate significantly (much better than chemo), it didn’t stop the tumor growth.
The authors admit they don’t really know exactly how methylene blue works against ovarian cancer."
Methylene Blue in Glioblastoma (Brain Cancer)
Dr William Makis shared on X/Twitter in Feb 2025:
2013 Poteet et al - Reversing the Warburg Effect as a Treatment for Glioblastoma (PubMed).
"Here, we documented that methylene blue (MB) reverses the Warburg effect evidenced by the increasing of oxygen consumption and reduction of lactate production in Glioblastoma cell lines"
"Methylene Blue decreases Glioblastoma cell proliferation and halts the cell cycle in S phase."
Methylene Blue inhibits cell proliferation in both temozolomide-sensitive and -insensitive GBM cell lines (wow!!!)
Methylene Blue
Methylene blue (MB), synthesized in 1876, has been in clinical application for more than a century in diagnostic procedures and as a treatment of multiple disorders such as methemoglobinemia, malaria, ifosfamide neurotoxicity, and cyanide poisoning
There is mounting evidence that MB enhances brain metabolism and exerts neuroprotective effects in multiple neurodegenerative disease models including Parkinson, Alzheimer, and Huntington disease
In the current study we tested the hypothesis that reversal of the Warburg effect by MB inhibits GBM cell proliferation.
More than 90 years ago, Warburg hypothesized that cancers may be caused by increased glycolysis and impaired respiration based on observations that tumor tissue actively metabolizes glucose and produces excessive lactic acid while exhibiting a comparably low respiratory rate
Recent findings suggest that reinstating normal oxidative phosphorylation in cancer cells may not only inhibit cell growth and proliferation but also impair the metastatic capacity of malignant cells
Acute Methylene Blue treatment dramatically increases oxygen consumption rate (OCR) and decreases extracellular acidification rate (ECAR) in U87 Glioblastoma cells.
Reversal of the Warburg effect was associated with a reduction of U87 cell proliferation, evidenced by the cell growth curve, liquid colony formation, and soft agar colony formation assays
CANCER NEEDS:
Glioblastoma cells, like other cancers, face two major metabolic challenges, bioenergetic and biosynthetic demands of rapid cell proliferation
It has been proposed that the fundamental metabolic switch may confer to cancer cells a selective advantage during growth and proliferation
Glucose not only provides the major fuel for ATP synthesis through glycolysis and mitochondrial oxidative phosphorylation
but glucose also provides the backbone for intermediates needed in biosynthetic pathways, including ribose sugars for nucleotides, glycerol and citrate for lipids, nonessential amino acids, and NADPH through the oxidative pentose phosphate pathway
Besides serving as the major bioenergetic hub, mitochondria also provide metabolites for macromolecule synthesis to meet the biosynthetic demand of a proliferating cancer cell
We predict that Methylene Blue reverses the Warburg effect and switches mitochondria from a biosynthetic hub back to a predominantly bioenergetic hub in GBM cells, thus decreasing metabolic intermediates and inhibiting cancer proliferation. This notion is supported by our data that MB increases ATP production, decreases NADPH, and arrests cancer cells in S phase (!!!)
MB enhances oxygen consumption rate and extracellular acidification rate in glioma cells immediately after treatment
TEMOZOLOMIDE
TMZ is currently one of the primary chemotherapies for GBM
TMZ is a prodrug that decomposes into a drug which disrupts GBM cell division by heavily alkylating and methylating DNA
Resistance to TMZ develops when cells increase expression of certain enzymes.
We tested the effect of MB on both TMZ-sensitive and TMZ-resistant GBM cell lines, U87 and T98G, respectively.
As predicted, TMZ arrests U87 cell cycle at M phase.
Methylene Blue induced cell cycle arrest in S phase and inhibited cell proliferation of both U87 and T98G cells.
Similarly, Methylene Blue increased OCR, decreased ECAR, and activated the AMPK signaling pathway in T98G cells.
These data suggested that Methylene Blue might be effective in both TMZ-sensitive and -resistant GBMs.
Our study indicated that MB and TMZ arrest GBM cells at different stages of the cell cycle; thus, an additive effect on GBM proliferation might be achievable with a combination therapy of MB and TMZ.
A slight additive action was indeed observed in the combination therapy of MB and TMZ in the liquid colony formation assay; therefore, we predict that combination therapy of MB and TMZ might be able to decrease the necessary dose of each drug, reducing the side effects while still achieving the maximal inhibitory effect on GBM progression.
CONCLUSION:
Our current study demonstrated that Methylene Blue exerts profound action on GBM bioenergetics.
Methylene Blue inhibits GBM cells proliferation and arrests the cell cycle in S phase
The effect of MB on GBM proliferation intertwined with the activation of AMPK and its downstream signaling of ACC and cyclin expression
By reversing the Warburg effect, Methylene Blue switches the mitochondria from a biosynthetic hub to bioenergetic hub and inhibits GBM cell proliferation.
Although the inhibitory action of Methylene Blue on cancer proliferation needs further verification in vivo using different treatment paradigms, our in vitro data provide the proof of concept that reversal of Warburg effect might be a novel therapy for Glioblastoma (!)
This is a very interesting study from a mechanistic view point of how Methylene Blue works on Cancer!
METHYLENE BLUE in PROSTATE CANCER (androgen-dependent and androgen-independent)
According to Dr William Makis (X/Twitter):
A few years ago there was an abstract presentation at the 2019 AACR Annual Meeting - American Association for Cancer Research
Shanti et al, looked at Methylene Blue in Prostate Cancer (source).
Highlights:
Methylene Blue effectively reduced the viability of androgen-dependent (LNCaP) and androgen-independent (PC3 and DU145) Prostate Cancer cells
Methylene Blue inhibited the colony forming ability of Prostate Cancer cells in-vitro suggesting its tumor suppressive potential
Methylene Blue treatment disrupted the migration potential of Prostate Cancer cells in a wound healing assay indicating the anti-metastatic function of MB
Methylene Blue effectively targeted the Prostate Cancer cell lines by inducing apoptotic cell death
Key apoptotic molecules such as Bax, TRAIL R2/D5, and phospho p53 (Serine 15, Serine 46, Serine 392) were robustly upregulated in androgen-dependent LNCaP cells following MB treatment.
“In conclusion, our findings suggest that MB induces apoptosis in Prostate Cancer cells and thus could serve as a potential anticancer agent for treating both hormone-dependent and -independent Prostate Cancer”
My Take…. Although this was an abstract presentation, it was nonetheless a very interesting one. We are still learning about the mechanisms of action of methylene blue on cancer cells but as we’ve seen with Ivermectin and Fenbendazole, it appears that numerous mechanisms are in play.
How to Select a High-Quality Product
Last but not least, selecting the correct product is of crucial importance, in addition to getting the dosing right. There are three basic types of methylene blue: industrial, chemical and pharmaceutical-grade.
The only version you’ll want to use medicinally is pharmaceutical-grade. Do not ingest methylene blue from the pet store that is meant for fish tanks. Industrial-grade methylene blue has lots of impurities, and typically contain only 10% to 25% methylene blue.
Chemical or laboratory grade, which is used for staining purposes on laboratories, has a much higher purity, but it’s still not suitable for medicinal purposes as it typically has heavy metal contaminants like lead, cadmium and arsenic. Over time, the impurities can accumulate in your body, resulting in toxicity.
Pharmaceutical grade is 99%+ pure. This is the kind used when injected intravenously for antidote purposes, or used orally. These products will be marked USP, which stands for United States Pharmacopeia.
According to Gonzalez-Lima, USP is better in terms of purity than the European pharmaceutical grade, which has fewer requirements. Taking the methylene blue with some ascorbic acid (vitamin C) facilitates absorption. You won’t find methylene blue at your local pharmacy but many compounding pharmacies can obtain the pharmaceutical grade.
“Ascorbic acid is a way to facilitate the cycling of methylene blue by promoting its reduction,” he explains. Considering the importance of mitochondrial health, methylene blue appears to be a simple and remarkably effective way to improve your overall health and cognitive function.
The only version you’ll want to use medicinally is pharmaceutical-grade. Do not ingest methylene blue from the pet store that is meant for fish tanks. Industrial-grade methylene blue has lots of impurities, and typically contain only 10% to 25% methylene blue.
Chemical or laboratory grade, which is used for staining purposes on laboratories, has a much higher purity, but it’s still not suitable for medicinal purposes as it typically has heavy metal contaminants like lead, cadmium and arsenic. Over time, the impurities can accumulate in your body, resulting in toxicity.
Pharmaceutical grade is 99%+ pure. This is the kind used when injected intravenously for antidote purposes, or used orally. These products will be marked USP, which stands for United States Pharmacopeia.
According to Gonzalez-Lima, USP is better in terms of purity than the European pharmaceutical grade, which has fewer requirements. Taking the methylene blue with some ascorbic acid (vitamin C) facilitates absorption. You won’t find methylene blue at your local pharmacy but many compounding pharmacies can obtain the pharmaceutical grade.
“Ascorbic acid is a way to facilitate the cycling of methylene blue by promoting its reduction,” he explains. Considering the importance of mitochondrial health, methylene blue appears to be a simple and remarkably effective way to improve your overall health and cognitive function.
How to Use Methylene Blue
Most experts recommend relatively high doses for longer-term treatments, including dementia prevention and treatment, post-stroke care, cognitive enhancement and overall health optimization.
The doses they advise are 0.5 milligram (mg) to 1 mg per kilogram of body weight. I believe these doses are highly excessive and unnecessary. Please understand that doses of more than 3 to 5 mg are likely never needed unless you are undergoing treatment for some life-threatening conditioning like carbon monoxide or cyanide poisoning or a resistant urinary tract infection.
Selecting the right product is also important, and there are three types typically sold — industrial-grade, chemical-grade (laboratory-grade) and pharmaceutical-grade. The only one you should use is the pharmaceutical-grade variety. Other types of methylene blue, such as the one found in pet stores, are meant for keeping aquariums clean. Industrial-grade methylene blue contains impurities, and should never be used for any biological purposes.
There are several important considerations to consider when using methylene blue. Firstly, while you can easily and cheaply purchase methylene blue online, this is rarely a pharmaceutical grade product, and I strongly recommend never using these products because of the risk of heavy metal contamination.
Secondly, it is a prescription drug and can only be used with a prescription from a doctor. If you’re considering it, I encourage you to speak with your doctor about whether it might be appropriate for your needs.
Thirdly, it’s best to get your prescription filled by a compounding pharmacy. The only form of methylene blue available at conventional pharmacies is for IV use and a 10 ml vial contains 100 mg and costs over $200.
The dose of methylene blue that Dr Joseph Mercola recommends is 3 to 5 mg once a day (regardless of your weight). It has a half-life of 12 to 13 hours, so taking it once a day is sufficient and will increase your levels over time. It’s also best to take a day off once a week if you are taking it long term.
The doses they advise are 0.5 milligram (mg) to 1 mg per kilogram of body weight. I believe these doses are highly excessive and unnecessary. Please understand that doses of more than 3 to 5 mg are likely never needed unless you are undergoing treatment for some life-threatening conditioning like carbon monoxide or cyanide poisoning or a resistant urinary tract infection.
Selecting the right product is also important, and there are three types typically sold — industrial-grade, chemical-grade (laboratory-grade) and pharmaceutical-grade. The only one you should use is the pharmaceutical-grade variety. Other types of methylene blue, such as the one found in pet stores, are meant for keeping aquariums clean. Industrial-grade methylene blue contains impurities, and should never be used for any biological purposes.
There are several important considerations to consider when using methylene blue. Firstly, while you can easily and cheaply purchase methylene blue online, this is rarely a pharmaceutical grade product, and I strongly recommend never using these products because of the risk of heavy metal contamination.
Secondly, it is a prescription drug and can only be used with a prescription from a doctor. If you’re considering it, I encourage you to speak with your doctor about whether it might be appropriate for your needs.
Thirdly, it’s best to get your prescription filled by a compounding pharmacy. The only form of methylene blue available at conventional pharmacies is for IV use and a 10 ml vial contains 100 mg and costs over $200.
The dose of methylene blue that Dr Joseph Mercola recommends is 3 to 5 mg once a day (regardless of your weight). It has a half-life of 12 to 13 hours, so taking it once a day is sufficient and will increase your levels over time. It’s also best to take a day off once a week if you are taking it long term.
From sharper thinking to stronger cells, Methylene Blue enhances how your brain and body perform by enhancing mental clarity and focus, supporting blood flow, and increasing ATP production.
Urolithin A promotes healthy aging by activating mitophagy. Mitophagy helps the body to recycle and rebuild mitochondria (the powerhouses of your cells) and enhances the benefits of Methylene Blue.
Urolithin A promotes healthy aging by activating mitophagy. Mitophagy helps the body to recycle and rebuild mitochondria (the powerhouses of your cells) and enhances the benefits of Methylene Blue.
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