Methylene Blue: Evaluating an Old Drug with a New Indication


Author: Bob Brensel | President, Pharmacist | ScriptWorks

Bob Brensel, RPh, earned his Pharmacy Degree at University of the Pacific in Stockton, California in 1980. He was honored as a student with the Longs Drugs Stores, “Outstanding Intern Scholarship” in 1977. Read More →

The Potential Benefits of Methylene Blue and More

Lately, our pharmacists have been getting lots of calls about Methylene Blue. I thought we should discuss this in our blog this month.

Brief History of Methylene Blue

Methylene Blue has been a component of an FDA-approved drug and has been around since 1876.

The first medical use of this drug was used on soldiers suffering from malaria during World War II. It’s actually the first synthetic medicine used to address illnesses in human patients. It is still being used in some cases of malaria today.

So why are we getting so many calls?

In recent years, researchers have explored the idea that oxidative stress is linked with systemic aging of various tissues including those in the brain and on the skin. Methylene blue (MB), a well-established drug used for other conditions, is now being investigated to relieve this oxidative stress.

MB has a small molecular weight with both hydrophilic and lipophilic properties. This allows it to be easily delivered into the tissues and, once absorbed, MB can stimulate mitochondrial respiration and diminish oxidative stress.

Neurological Disease

Methylene blue has a direct effect on Mitochondria (the powerhouse of the cell). Mitochondrial dysfunction and oxidative stress have been observed in systematic aging that affects many tissues, including the brain and skin. Drugs that improve mitochondrial function and reduce oxidative stress may be appropriate ways to address cognitive decline and neuroprotection. It is the increase in oxygenation in the cells that is the mechanism by which methylene blue provides support.

Previous studies indicate that methylene blue (MB) has been shown to stimulate mitochondrial respiration and diminish oxidative stress. There is potential for it to be used as neuroprotection against mitochondrial dysfunction.

Methylene blue crosses the blood-brain barrier and, at low doses, serves as an electron cycler in the mitochondrial electron transport chain.

This interview by Dr. Peter Attia, MD and Francisco Gonzalez Lima, PhD from the University of Texas discusses the complexity of the brain and the cognitive benefits of MB.

Lyme Disease and Bartonella

Researchers at Johns Hopkins University Department of Molecular Microbiology and Immunology completed a drug screen to identify effective medications against the stationary phase Bartonella. Their research discovered 110 drug candidates from an FDA-approved library that had better activity against Bartonellla than Ciprofloxacin. The researchers confirmed their findings by performing a MIC study, and Methylene blue performed very well.

Helping Patients

A majority of patients can be maintained at a daily dose of 15 mg in capsule form. A dose of 50 mg taken twice daily has been used to address Lyme disease. A starting dose of 200 mg has been used in patients with COVID.

Methylene blue is best taken in the morning because it can be a mild stimulant and disrupt sleep patterns.

Clinical Considerations

Clinical considerations include not using methylene blue in patients on MAO inhibitors, or patients taking SSRIs or SNRIs. Methylene blue should not be taken with dapsone and is contraindicated in patients with renal disease or patients with hypersensitivity to methylene blue. It is also contraindicated during pregnancy.

Methylene Blue and Serotonin

Because of the potential risk of a life-threatening condition called Serotonin Syndrome, methylene blue should not be used when a patient is on SSRIs, SNRIs, or drugs that increase serotonin levels.

Methylene Blue: Some Possible Indications, Side Effects, Warnings

  • Arm or leg pain
  • Blue or green urine
  • Skin discoloration
  • Altered taste
  • Dizziness
  • Headache
  • Nausea
  • The sensation of feeling hot
  • Anemia
It is essential to follow the instructions provided by healthcare professionals or product labels when using methylene blue to ensure safe and appropriate use. If you have any concerns or questions about its safety or usage, consult with a healthcare professional.

Quality of Compounded Methylene Blue Capsules is Important

Methylene blue is prescribed in various dosage forms for different conditions in medicine, yet when practitioners want to prescribe capsules, patients have a hard time finding them. The capsule form of methylene blue isn’t commercially manufactured by a drug company, therefore, it won’t be found at standard “big box” retail pharmacies.
Methylene blue should be compounded at a high-quality compounding pharmacy, one that is PCAB accredited. It’s important to use a pharmacy that is experienced in compounding and uses the highest quality chemicals in compounding, meaning you should verify they are using methylene blue, USP grade, not another technical grade of methylene blue. At ScriptWorks, methylene blue is currently available in oral capsules.

If you’re a California medical practitioner interested in MB got your patients, please connect with our experts and we’ll help provide the best experience for your patients


Xue, H., Thaivalappil, A., & Cao, K. (2021). The Potentials of Methylene Blue as an Anti-Aging Drug,  Cells. 2021 PMID: 34943887. Published online 2021 Dec 1. doi: 10.3390/cells10123379 National Library of Medicine.

Auchter, A., Williams, J., Barksdale, B., Monfils, M.H., & Gonzalez-Lima, F. (2014). Therapeutic Benefits of Methylene Blue on Cognitive Impairment during Chronic Cerebral Hypoperfusion. Journal of Alzheimer’s disease : JAD. 42. 10.3233/JAD-141527.

Sloan, M. (2021). The Ultimate Guide to Methylene Blue. Accessed March 2023 at

Tucker, D., Lu, Y., & Zhang, Q. (2018). From Mitochondrial Function to Neuroprotection — An Emerging Role for Methylene Blue. Mol Neurobio, 55(6), 5137–5153. Accessed March 2023 at

Rojas, J.C., Bruchey, A.K., & Gonzalez-Lima, F. (2012). Neurometabolic Mechanisms for Memory Enhancement and Neuroprotection of Methylene Blue. Prog Neurobio, 96(1), 32–45. Accessed March 2023 at

Kayabasi, Y. & Erbas, O. (2020). Methylene Blue and Its Importance in Medicine. D.J. Med Sci 2020;6(3):136-145. Accessed April 2023 at

Schirmer, R.H., Coulibaly, B., Stich, A., et al. (2003). Methylene Blue as an Antimalarial Agent. Redox report : communications in free radical research, 8(5), 272–275. Accessed April 2023 at

Gonzalez-Lima, F. & Auchter, A. (2015). Protection Against Neurodegeneration with Low-dose Methylene Blue and Near-infrared Light. Front Cell Neurosci, 9, 179. Accessed April 2023 at

Atamna, H., Nguyen, A., Schultz, C., et al. (2008). Methylene Blue Delays Cellular Senescence and Enhances Key Mitochondrial Biochemical Pathways. FASEB J. 22(3):703-712. Accessed April 2023 at

Biju, K.C., Evans, R.C., Shrestha, K., et al. (2018). Methylene Blue Ameliorates Olfactory Dysfunction and Motor Deficits in a Chronic MPTP/Probenecid Mouse Model of Parkinson’s Disease. Neuroscience. 2018;380:111-122. Accessed April 2023 at

Zheng, X., Ma, X., Li, T. et al. (2020). Effect of Different Drugs and Drug Combinations on Killing Stationary Phase and Biofilms Recovered Cells of Bartonella henselae in vitro. BMC Microbiol 20, 87 (2020).

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