Patients have been asking us for more information about methylene blue, an antimicrobial drug that some Lyme doctors now prescribe for a variety of conditions. We asked LymeDisease.org board member Erica Lehman, MD, to explain more about it.

By Dr. Erica Lehman

Methylene blue (MB) is truly a fascinating compound and one of the most revolutionary medications to hit the functional medicine and tick-borne disease spheres.

It was first synthesized by a German chemist Heinrich Caro in 1876. Initially, it was known as methylthioninium chloride and later named methylene blue due to its distinctive color.

Its early applications include use as a dye and staining agent for biological tissue. It was used in histology and microscopy to enhance the visibility of cell structures because it can stain DNA. I used it early on in my ophthalmic surgery training to mark the sclera (the white part of the eye), for cataract and retinal detachment surgery.

In the late 19^th and early 20^th centuries, it gained popularity as an antiseptic and disinfectant. MB was used to treat wounds and prevent infections and in the early 1900s, it emerged as an effective drug for malaria. MB is a parent compound for hydroxychloroquine.

Mid-20^th century researchers explored its potential in neurological conditions like Alzheimer’s disease and Parkinson’s. Recently, it has been investigated as an antimicrobial for tick-borne diseases. The only FDA indication for MB is the treatment for a rare blood disorder called methemoglobinemia. This is a dangerous condition, where hemoglobin has a reduced oxygen-carrying capacity.

Chemical Structure

The core of MB structure is the phenothiazine ring, which consists of three benzene rings linked to a sulfur and nitrogen heterocyclic ring. This structural arrangement contributes to its unique proprieties. MB has two diethyl-amino groups which makes the compound polar and water soluble and gives the compound its signature color.

MB is metabolized by the liver and processed by the kidneys and excreted through urine. It crosses the blood brain barrier (BBB), enabling access to the central nervous system. This explains why it has applications for treatment of neurodegenerative diseases.

Mechanism of Action (MOA)

MB reroutes the pathway of the electron transport chain (ETC), which occurs in the inner membrane of the mitochondria, as an alternative electron carrier. It bypasses the complexes I-III and attenuates electron leakage and reactive oxygen species creation. The first complexes of the ETC have been hypothesized to create large amounts of reactive oxygen species leading to oxidative stress.

Oxidative stress has implications in many chronic illnesses including Lyme disease, long COVID, and ME/CFS. However, its mechanism of action to improve cognitive function in people with Alzheimer’s disease, Parkinson’s and other neurocognitive diseases is still unknown.

MB can be absorbed intravenously, orally, and transdermally. Its half-life is five hours, so it can be dosed twice a day. Its toxic effects are dose-dependent, making it a hormetic drug: therapeutic at low doses, damaging at high doses.

Properties

The antimicrobial, antioxidant and neuroprotective properties of MB make it so special. It is rare one single compound has all these properties, making it a triple threat. Animal model studies show MB stimulates autophagy (cell degradation and recycling, basically dead-cell housekeeping) and decreases neuroinflammation.

In addition, it requires the enzyme glucose-6-phosphate dehydrogenase (G6PD). 5% of the population has a G6PD deficiency. There are over 400 variants of this enzyme deficiency, usually inherited genetically via the X chromosome. 186 of these genetic variants are currently identified.

Adverse Effects

As with all medications, MB can bring potential adverse effects and drug interactions. For instance, MB may reduce renal blood flow and will definitely turn your urine blue.

It can also interact with prescribed antidepressants (including MAOIs, SSRIs or SNRIs) and potentially with high tyramine containing foods (including some cheeses, cured meats, and alcoholic beverages.) This can lead to serotonin syndrome—a possibly life-threatening condition. In addition, MB should not be taken by women who are pregnant.

With the compound’s reliance on G6PD, an individual with a G6PD deficiency should not take MB. It is important to be tested for this deficiency prior to taking the medication. If you do have a G6PD deficiency and take MB, it may cause hemolysis which is the rupturing of your red blood cells.

As always, consult your doctor.

Clinical applications

The most exciting aspects of MB are its clinical applications for tick-borne diseases. MB’s antimicrobial properties help your body fight against Bartonella, in a similar way to an antibiotic. It inhibits important metabolic processes, including biofilm formation, to prevent the bacteria from multiplying and spreading. Current published in vitro studies (Zhang et al, 2020) have only explored MB’s antimicrobial properties in Bartonella, alone and in combination with other antibiotics. Other antimicrobial properties are yet to be elucidated.

Another novel use of MB is for treating long COVID. Two more prominent symptoms of long COVID are fatigue and brain fog. Because MB helps to increase ATP production, and therefore increase overall body energy, it may ameliorate some of these symptoms. There have been many positive anecdotal case reports supporting the use of MB in long COVID.

MB can also treat cyanide poisoning.

Game Changer

This revolutionary medication has gained a positive reputation in the world of tick-borne diseases, similar to when disulfiram was repurposed for Lyme disease in 2016. I have found clinical success in using MB for many symptoms of Lyme disease, including fatigue, depression, brain fog, anxiety and much more. With its antimicrobial properties, using MB has enabled me to minimize the use of antibiotics and therefore avoid their potential side effects.

I truly think the benefits of MB outweigh the blue stain in your toilet!

Dr. Erica Lehman, an integrative physician, tick-borne disease specialist, board certified ophthalmologist, cornea specialist, and eye surgeon in Beverly Hills, California, serves on the board of LymeDisease.org. Click here for her website.