Methylene Blue Lyme Disease Protocol: What Experts Are Saying Now

Lyme disease is a tick-borne infection that can result in several clinical manifestations, such as fever, musculoskeletal pain, brain fog, etc. Antibiotics are considered a first-line treatment for Lyme disease. Is there an emerging alternative treatment option for Lyme disease? 

Methylene blue, an aniline-based dye was used as an effective treatment strategy for malaria, methemoglobinemia, and urinary tract infections. In this article, we will explore the case studies and role of methylene blue in managing the clinical symptoms of Lyme disease. 

What is methylene blue?

Methylene blue is a fascinating compound, that was first synthesized by German chemist Heinrich Caro in 1876. Earlier, this compound was known as methylthioninium chloride. Methylene blue was used as a dye for staining biological tissues.

Indications:

• MB is used to manage wounds and treat infections.
• It is used in the management of a complex blood disorder, called methemoglobinemia.
• Vasoplegic syndrome
• Mapping of lymph nodes

Mechanism of action:

Methylene blue acts as an alternative electron carrier and reroutes the electron transport chain pathway (ETC), which is located in the mitochondrial inner membrane. It can reduce the oxidative stress and help in restoring the mitochondrial function. 

MB inhibits the nitric oxide synthase and guanylate cyclase, resulting in vasoconstriction. As a result, there will be reduced neuroinflammation and improved cognitive function.

The antimicrobial properties of methylene blue helps the body to fight against bacteria and prevent their proliferation. It also helps in eliminating the bacterial biofilms and protects from infection. 

Can methylene blue cause drug interactions?

Yes, methylene blue can result in drug interactions. MB is associated with the increased risk of developing serotonin syndrome. Drug interactions occur when methylene blue interacts with drugs that affect serotonin and monoamine oxidase inhibitors (MAOIs). 

There are two types of MAOIs: MAO-A & MAO-B. MAO-A has an impact on deamination of epinephrine, serotonin, melatonin, etc. MAO-B breaks down benzylamine and phenethylamine. Due to the effect of MAO-A, intravenous administration of methylene blue is associated with the development of serotonin syndrome. 

• Increased heart rate
• Insomnia and confusion
• Restlessness
• Diarrhea
• Lack of muscle coordination
• Unconsciousness

How is methylene blue administered?

For many patients, a daily dose of 15 mg is administered. Methylene blue can be administered orally or intravenously, and is prescribed as 50 mg doses (twice daily). 

Depending on the clinical goals, and health condition, methylene blue (MB) can be administered through several routes. Oral route of administration is mostly preferred to treat chronic symptoms of Lyme disease. 

Oral route is associated with easy administration and consistent absorption. It can be used with antibiotics or mitochondrial support supplements to manage the condition. Methylene blue can be administered intravenously, particularly in emergency cases. MB can also be administered sublingually and must be taken under the guidance of a qualified healthcare professional. 

How methylene blue differ from antibiotic treatment?

Case studies:

A 55-year old female patient was experiencing clinical symptoms, such as memory loss, brain fog, and memory lapses. Upon testing, IgG bands were found to be positive. Instead of proceeding with antibiotics, she focused on enhancing mitochondrial and cognitive function. Hence, the methylene blue protocol was introduced to the patient. 

Before the treatment, the patient had developed cystitis and urinary tract infections. Laboratory tests confirmed the presence of E.coli bacteria that progressed to the upper urinary tract. After two weeks, the repeat urine culture didn’t show traces of the bacteria. After the completion of the MB protocol, all clinical symptoms resolved. All gut-related symptoms, such as diarrhea, and food intolerances, got better. She fully recovered after using two months of MB protocol. 

This case highlights the importance of innovative Methylene Blue treatment options for Lyme disease. Successful application of the MB protocol opens the way to further research in similar clinical cases.

What happens when methylene blue is combined with antibiotic treatment?

Methylene blue has the potential to eliminate the resistant forms of bacteria. MB has synergistic effect, when combined with antibiotics which eliminates both active and persistent forms of bacteria. MB along with antibiotics, such as doxycycline or amoxicillin can help in eliminating bacterial biofilms.

It can also reverse the fatigue and cellular disruption in chronic Lyme patients that increases recovery rate. MB also benefits patients with PTLDS, and contribute to enhanced energy levels. 
Methylene blue can possibly improve the efficacy of antibacterial medication in Lyme patients because it helps to focus on bacterial persistence, manipulate biofilms, and enable cellular recovery. 

Conclusion:

Methylene blue has emerged as a promising adjunctive therapeutic strategy for Lyme disease, especially for those who are struggling with persistent clinical symptoms of post-treatment Lyme disease. Due to the neuroprotective properties, MB can reduce the neurological manifestations of Lyme disease. Continued research can open the way to effective interventions in treating Lyme disease. 

References:

1. Lehman E. Methylene blue–a new/old drug for treating Lyme disease [Internet]. LymeDisease.org; 2024 Mar 27 [cited 2025 Jul 11]. Available from: https://www.lymedisease.org/methylene-blue-lyme-disease/
2. Project Lyme. Methylene Blue for Treating Lyme Disease, Bartonella, and Babesia [Internet]. ProjectLyme.org; 2022 Aug 30 [cited 2025 Jul 11]. Available from: https://projectlyme.org/methylene-blue/
3. Earlywine K. Methylene Blue: Understanding Drug Interactions [Internet]. Fagron Academy; 2025 Feb 13 [cited 2025 Jul 11]. Available from: https://www.fagronacademy.us/blog/methylene-blue-understanding-drug-interactions/
4. Mayo Clinic. Serotonin syndrome – Symptoms and causes [Internet]. Rochester (MN): Mayo Clinic; [updated 2024 Sep; cited 2025 Jul 11]. Available from: https://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes/syc-20354758
5. Mak RS, Liebelt EL. Methylene Blue: An Antidote for Methemoglobinemia and Beyond. Pediatric Emergency Care. 2021 Sep;37(9):474–7 [Internet]. [cited 2025 Jul 11]. Available from: https://europepmc.org/article/MED/34463662