Methylene Blue: A Guide for People with Cancer

Methylene Blue: A Guide for People with Cancer

What is Methylene Blue?

Methylene Blue (MB), also known as methylthionine chloride, is a synthetic compound initially developed as a dye but later discovered to have various medical applications. It has been used in cancer therapy to treat methemoglobinemia and neurodegenerative diseases and as a cancer treatment photosensitizer.[i]

Where Does Methylene Blue Come From?

Methylene Blue was first synthesized in the late 19th century and has been widely used in medical and scientific research. It is derived from phenothiazine and exists in oxidized (blue) and reduced (colorless) forms.

Anticancer Activity of Methylene Blue

Recent studies suggest that Methylene Blue has potential anticancer properties.

Oral Use of Methylene Blue for Cancer

Methylene Blue has been investigated for its oral application in cancer treatment, particularly in managing painful oral mucositis caused by chemotherapy and radiation therapy. Some studies suggest that Methylene Blue oral rinses may help alleviate pain and inflammation in cancer patients undergoing treatment.[ii] [iii] Oral use and absorption of methylene blue has not been well evaluated in animals and humans. 

Methylene Blue Potential Concerns and Side Effects

While Methylene Blue has therapeutic potential, it also carries risks. Some reported side effects include serotonin syndrome when combined with certain medications, discoloration of urine and skin, and potential neurotoxicity. Additionally, Methylene Blue has been associated with hemolysis and methemoglobinemia in high doses. Side effects can include:

• Serotonin Syndrome – Methylene Blue can interact with serotonergic medications, leading to excessive serotonin levels.
• Methemoglobinemia – High doses of Methylene Blue can paradoxically induce methemoglobinemia, reducing oxygen transport in the blood.

• Hemolytic Anemia – Methylene Blue may cause hemolysis, particularly in individuals with a deficiency of glucose-6-phosphate dehydrogenase (G6PD).
• Neurotoxicity – Some studies suggest Methylene Blue may contribute to neurotoxicity at high concentrations.
• Skin, Bowel, and Urine Discoloration – Methylene Blue can cause temporary blue discoloration of the skin, bowel movements (poop), and urine.
• Gastrointestinal Distress – Nausea, vomiting, and abdominal pain have been reported in some cases.
• Hypotension – Methylene Blue may lead to a drop in blood pressure, particularly when administered intravenously.
• Respiratory Distress – Rare cases of respiratory complications have been observed.

Potential Methylene Blue Medication Interactions

Warning: Serotonin Syndrome With and Without[iv] Concomitant Use of Serotonergic Drugs and Opioids.[v] Methylene blue may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Avoid using methylene blue with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors.

You can use this Drug Interaction Checker https://www.drugs.com/drug_interactions.html.

Dosage of Methylene Blue

Methylene Blue (MB) is administered orally or intravenously depending on the condition treated. Studies suggest that Methylene Blue may be an adjunctive therapy for cancer-related applications due to its potential to modulate oxidative stress and enhance mitochondrial function. The dosing strategy varies, but some research indicates that oral Methylene Blue is often taken in small doses ranging from 0.5 mg to 4 mg per kilogram of body weight, with frequency depending on individual tolerance and therapeutic goals. A typical adult dose is 1 mg/kg of body weight, administered twice daily.

In critical care settings, Methylene Blue has been used in bolus injections followed by continuous infusion, particularly for conditions like vasodilatory shock. However, excessive dosing—above 7 mg/kg—can paradoxically induce methemoglobinemia and hemolytic anemia.[vi]

Methylene Blue with Renal (kidney) Impairment Considerations

In people with kidney issues, methylene blue doses can be adjusted:

• Mild to moderate impairment: No dose change is typically needed
• Severe impairment: Use caution, consider dose reduction
• Dialysis patients: Give after dialysis sessions

Monitor renal function blood tests, including creatine and eGFR, and adjust as needed.

Methylene Blue with Hepatic (liver) Impairment Considerations

For people with liver problems, methylene blue dosages can be adjusted:

• Mild impairment: No dose adjustment required
• Moderate to severe impairment: Many practitioners reduce the dose by 50%
• Monitor liver blood AST and ALT tests regularly

Watch for signs of toxicity, such as nausea or confusion.

You should consult a healthcare professional before using Methylene Blue to ensure safe and effective administration.

Keith Bishop is available for Cancer Coaching Sessions, which provide additional information on integrating Methylene Blue into a treatment program. Click here to learn about cancer coaching sessions. 

Methylene Blue and Red Light Therapy

Light therapy is crucial in activating methylene blue (MB) and enhancing its therapeutic effects. Methylene Blue is a photosensitizer, meaning it absorbs specific wavelengths of light—primarily red and near-infrared (NIR) light—to produce reactive oxygen species (ROS), which can help target cancer cells and pathogens. Studies indicate that Methylene Blue has peak absorption around 635–670 nm, making it particularly effective when combined with low-level laser therapy (LLLT) or photodynamic therapy (PDT). [vii]

Research has explored the use of Methylene Blue in antimicrobial applications and cancer treatments, demonstrating that light activation significantly enhances its ability to induce oxidative stress in diseased cells. Additionally, Methylene Blue has been investigated for its role in root canal disinfection, where light activation enhances its penetration and effectiveness against bacterial biofilms.[viii] The combination of MB and light therapy continues to be studied for various medical applications, including neuroprotection and wound healing.[ix]

Infrared radiation (IR) penetrates the skin and tissues, generating heat at a cellular level. This process increases blood flow, reduces inflammation, and enhances cellular metabolism. IR therapy is commonly divided into three categories:

• Near-Infrared (NIR, 700–1400 nm): Deep tissue penetration, often used for mitochondrial stimulation.
• Mid-Infrared (MIR, 1400–3000 nm): Offers moderate penetration, making it beneficial for improving circulation and promoting detoxification.
• Far-Infrared (FIR, 3000–10000 nm): Surface-level heating, primarily used for relaxation and pain relief.

Most infrared (IR) saunas primarily use far-infrared (FIR) technology. FIR saunas operate at lower temperatures than traditional saunas and penetrate deeper into the body, promoting relaxation and detoxification. However, some saunas incorporate near-infrared (NIR) and mid-infrared (MIR) wavelengths, which may offer additional benefits such as improved circulation, skin rejuvenation, and interaction with methylene blue.

Cancers Studied with Methylene Blue

Caution: Although some preclinical studies have investigated the impact of methylene blue on mitochondrial metabolism or DNA interaction, these findings are not robustly linked to selective cancer cell killing without light exposure in peer-reviewed clinical or translational cancer research. There are no studies showing methylene blue does not work against cancer. It just hasn’t been well studied.

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Modulation of Mitochondrial Function in Cancer Cells

1. Reversal of the Warburg Effect: In glioblastoma cells, MB enhances mitochondrial oxidative phosphorylation, thereby counteracting the Warburg effect—a metabolic hallmark in which cancer cells favor glycolysis over oxidative phosphorylation. This shift leads to cell cycle arrest in the S phase and inhibits cell proliferation.[x]
2. Induction of Apoptosis via Mitochondrial Dysfunction: MB-mediated photodynamic therapy (MB-PDT) in melanoma cells triggers apoptosis through mitochondrial pathways. This process involves the generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, and activation of caspases.[xi]
3. Selective Targeting in Ovarian Cancer: In ovarian cancer models, MB disrupts mitochondrial energetics, resulting in reduced ATP production and subsequent proliferation. Notably, MB exhibits a differential effect, sparing normal cells while targeting cancerous ones.[xii]
4. MB Enhanced Chemotherapy in Ovarian Cancer: MB stimulated oxygen consumption, enhanced mitochondrial activity, and improved the chemotherapy response carboplatin. This provides a deeper understanding of mitochondria dysregulation and the metabolic impact on cancer cell proliferation.[xiii]

Mechanisms Underpinning MB's Mitochondrial Effects

• Electron Shuttling: MB can accept electrons from NADH and donate them to cytochrome c, bypassing damaged components of the electron transport chain and thereby restoring mitochondrial function.[xiv]
• ROS Generation: Upon light activation, MB produces singlet oxygen and other reactive oxygen species (ROS) in cancer cells, resulting in oxidative damage to mitochondria and promoting cell death.[xv]
• Activation of Antioxidant Pathways: MB induces the Nrf2/ARE signaling pathway, enhancing the expression of antioxidant genes and facilitating mitochondrial DNA repair mechanisms.[xvi]

🧪 Therapeutic Implications and Considerations

• Combination Therapies: MB's ability to modulate mitochondrial function suggests potential synergy with chemotherapeutic agents, especially in overcoming drug resistance.[xvii]

Hyperthermia and Methylene Blue

At the time of publication, there is very little research on the use of hyperthermia in combination with methylene blue.

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What This Means for Cancer Treatment

While Methylene Blue shows promise, it's not a standalone cancer cure. Instead, many healthcare practitioners see it as part of a larger treatment toolkit. Perhaps the most exciting potential lies in combining it with PDT (photodynamic therapy) treatments to improve their effectiveness.

Methylene blue is not currently approved for cancer treatment but is being studied as:

• A diagnostic tool (e.g., tumor staining in surgeries),
• An adjunct to photodynamic therapy, and
• A possible modulator of redox and mitochondrial dynamics.

Its application depends on dose, light exposure, cancer type, and redox context. Further clinical trials are needed to clarify its therapeutic window and safety.

I will update this blog as more research becomes available.

 Photodynamic Therapy with Methylene Blue

A study published in Molecular Pharmaceutics explored the use of a methylene blue-bound nanoplatform for targeted imaging and combined photodynamic-photothermal therapy of prostate cancer cells. The research demonstrated that, upon activation with near-infrared (NIR) light, the nano platform could selectively induce cytotoxic effects in LNCaP human prostate cancer cells. Importantly, no significant cytotoxicity was observed in the absence of NIR light, highlighting the specificity of the treatment.[xviii]

Methylene Blue Diagnostic Applications

Beyond therapeutic uses, methylene blue has also been explored as a diagnostic aid. Its staining properties can aid in the early detection of malignant lesions, although further research is required for its specific application in cancer diagnostics.

Methylene Blue Limitations and Considerations

• Light Activation Requirement: The efficacy of methylene blue in inducing cytotoxic effects is contingent upon activation by specific wavelengths of light.
• Clinical Translation: Although preclinical studies are promising, further clinical trials are needed to establish the safety and effectiveness of methylene blue-based therapies in prostate cancer patients.

Methylene Blue Medical Disclaimer

The information provided in this article about Methylene Blue and cancer treatment is for educational purposes only. This content is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding your medical condition.

Never disregard professional medical advice or delay seeking it because of something you have read in this article. This information should not be used to diagnose or treat any health condition. If you suspect you have a medical problem, contact your healthcare provider immediately.

Research findings discussed in this article are based on scientific studies but may not be conclusive or applicable to all situations. Treatment outcomes can vary between individuals. Any application of the information provided is at your own risk.

The authors, publishers, and distributors of this content take no responsibility for any liability, loss, or risk, personal or otherwise, which is incurred as a direct or indirect consequence of accessing, using, or applying any of the contents of this article.

References

[i] Seitkazina A, Yang JK, Kim S. Clinical effectiveness and prospects of methylene blue: A systematic review. Precision and Future Medicine. Published online September 29, 2022. doi: https://doi.org/10.23838/pfm.2022.00079   

[ii] Horace R, Roldan SP, Roldan CJ. Methylene Blue Oral Rinse: An Effective Alternative for the Treatment of Pain in Oral Mucositis During Head and Neck Cancer Treatment. J Exp Pathol. 2024;5(1):24-30. https://www.scientificarchives.com/article/methylene-blue-oral-rinse-an-effective-alternative-for-the-treatment-of-pain-in-oral-mucositis-during-head-and-neck-cancer-treatment  

[iii] Roldan, C. J., Chung, M., Feng, L., & Bruera, E. (2021). Methylene Blue for the Treatment of Intractable Pain From Oral Mucositis Related to Cancer Treatment: An Uncontrolled Cohort. Journal of the National Comprehensive Cancer Network, 19(5), 521-527. Retrieved May 9, 2025, from https://doi.org/10.6004/jnccn.2020.7651  

[iv] Wolvetang T, Janse R, Ter Horst M. Serotonin Syndrome After Methylene Blue Administration During Cardiac Surgery: A Case Report and Review. J Cardiothorac Vasc Anesth. 2016;30(4):1042-1045. doi:10.1053/j.jvca.2015.11.019 https://linkinghub.elsevier.com/retrieve/pii/S1053-0770(15)00953-2

[v] Zuschlag ZD, Warren MW, K Schultz S. Serotonin Toxicity and Urinary Analgesics: A Case Report and Systematic Literature Review of Methylene Blue-Induced Serotonin Syndrome. Psychosomatics. 2018;59(6):539-546. doi:10.1016/j.psym.2018.06.012 https://www.sciencedirect.com/science/article/pii/S0033318218303190?via%3Dihub

[vi] Sari-Yavuz S, Heck-Swain K-L, Keller M, Magunia H, Feng Y-S, Haeberle HA, Wied P, Schlensak C, Rosenberger P and Koeppen M (2022) Corrigendum: Methylene blue dosing strategies in critically ill adults with shock—A retrospective cohort study. Front. Med. 9:1094735. doi: 10.3389/fmed.2022.1094735 https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.1094735/full

[vii] Giannelli, M., Bani, D. Appropriate laser wavelengths for photodynamic therapy with methylene blue. Lasers Med Sci 33, 1837–1838 (2018). https://doi.org/10.1007/s10103-018-2566-x

[viii] Taldaev A, Terekhov R, Nikitin I, et al. Methylene blue in anticancer photodynamic therapy: systematic review of preclinical studies. Front Pharmacol. 2023;14:1264961. Published 2023 Sep 28. doi:10.3389/fphar.2023.1264961 https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1264961/full  

[ix] George S, Kishen A. Photophysical, photochemical, and photobiological characterization of methylene blue formulations for light-activated root canal disinfection. Journal of Biomedical Optics. 2007;12(3):034029. doi: https://doi.org/10.1117/1.2745982    

[x] Yang SH, Li W, Sumien N, Forster M, Simpkins JW, Liu R. Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots. Prog Neurobiol. 2017;157:273-291. doi:10.1016/j.pneurobio.2015.10.005 https://www.sciencedirect.com/science/article/abs/pii/S0301008215300605?via%3Dihub

[xi] Chen Y, Zheng W, Li Y, Zhong J, Ji J, Shen P. Apoptosis induced by methylene-blue-mediated photodynamic therapy in melanomas and the involvement of mitochondrial dysfunction revealed by proteomics. Cancer Sci. 2008;99(10):2019-2027. doi:10.1111/j.1349-7006.2008.00910.x https://pmc.ncbi.nlm.nih.gov/articles/PMC11159616/

[xii] da Veiga Moreira J, Nleme N, Schwartz L, et al. Methylene Blue Metabolic Therapy Restrains In Vivo Ovarian Tumor Growth. Cancers (Basel). 2024;16(2):355. Published 2024 Jan 13. doi:10.3390/cancers16020355 https://pmc.ncbi.nlm.nih.gov/articles/PMC10814748/

[xiii] da Veiga Moreira J, Schwartz L, Jolicoeur M. In Vitro Methylene Blue and Carboplatin Combination Triggers Ovarian Cancer Cells Death. Int J Mol Sci. 2024;25(20):11005. Published 2024 Oct 13. doi:10.3390/ijms252011005 https://pmc.ncbi.nlm.nih.gov/articles/PMC11507203/

[xiv] Yang SH, Li W, Sumien N, Forster M, Simpkins JW, Liu R. Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots. Prog Neurobiol. 2017;157:273-291. doi:10.1016/j.pneurobio.2015.10.005 https://pmc.ncbi.nlm.nih.gov/articles/PMC4871783/

[xv] da Veiga Moreira J, Schwartz L, Jolicoeur M. Singlet Oxygen-Induced Mitochondrial Reset in Cancer: A Novel Approach for Ovarian Cancer Therapy. Metabolites. 2024;14(12):648. Published 2024 Nov 21. doi:10.3390/metabo14120648 https://pmc.ncbi.nlm.nih.gov/articles/PMC11677997/

[xvi] Samoylova NA, Gureev AP, Popov VN. Methylene Blue Induces Antioxidant Defense and Reparation of Mitochondrial DNA in a Nrf2-Dependent Manner during Cisplatin-Induced Renal Toxicity. Int J Mol Sci. 2023;24(7):6118. Published 2023 Mar 24. doi:10.3390/ijms24076118 https://pmc.ncbi.nlm.nih.gov/articles/PMC10094522/

[xvii] da Veiga Moreira J, Schwartz L, Jolicoeur M. In Vitro Methylene Blue and Carboplatin Combination Triggers Ovarian Cancer Cells Death. Int J Mol Sci. 2024;25(20):11005. Published 2024 Oct 13. doi:10.3390/ijms252011005 https://pmc.ncbi.nlm.nih.gov/articles/PMC11507203/

[xviii] Fan Z, Dai X, Lu Y, et al. Enhancing targeted tumor treatment by near IR light-activatable photodynamic-photothermal synergistic therapy. Mol Pharm. 2014;11(4):1109-1116. doi:10.1021/mp4002816 https://pmc.ncbi.nlm.nih.gov/articles/PMC3983349/