Understanding Methylene Blue: Safety, Side Effects, and More
- Dr. Joshua Lamers

- Aug 5
- 4 min read
Updated: Oct 19
Methylene blue (MB) has gained significant attention for its mitochondrial, cognitive, and antimicrobial benefits. However, before you consider adding it to your wellness routine, it's crucial to understand how to use it safely and responsibly. While MB has a long history of medical use and is generally safe at appropriate doses, it does come with some risks. Understanding these risks is essential for anyone considering this compound. So, is Methylene Blue safe? What are the side effects, dosages, and potential drug interactions?

The Most Important Safety Concerns
1. Serotonin Syndrome: The Most Critical Interaction
Methylene blue is a reversible MAO-A inhibitor. This means it can increase levels of serotonin, dopamine, and norepinephrine in the brain. This can become problematic if MB is combined with certain medications, such as:
SSRIs (e.g., Zoloft, Prozac, Lexapro)
SNRIs (e.g., Cymbalta, Effexor)
Tricyclic antidepressants
MAO inhibitors
Certain opioids (like Demerol or tramadol)
If you are currently taking any of these medications, you should not take methylene blue without discontinuation and supervision from a qualified provider. A washout period of 2–4 weeks may be necessary before it is safe to use MB.
Bottom line: If you are taking an antidepressant or serotonergic medication, MB can lead to a potentially life-threatening condition known as serotonin syndrome. Symptoms include confusion, agitation, muscle rigidity, and dangerously high fevers.
2. G6PD Deficiency
Methylene blue is contraindicated in patients with G6PD deficiency, a common genetic enzyme disorder affecting red blood cells. This deficiency can hinder the cells' ability to manage oxidative stress. Because MB has mild pro-oxidant effects, it can trigger hemolytic anemia in those with G6PD deficiency. This condition is more prevalent in individuals of African, Mediterranean, or Southeast Asian descent.
Bottom line: Anyone considering MB should screen for G6PD deficiency beforehand, especially if there is a family history or ethnic background suggesting increased risk.
3. Pregnancy and Breastfeeding
Methylene blue is not recommended during pregnancy, particularly in the second and third trimesters. It has been linked to fetal abnormalities, such as intestinal atresia, when used in diagnostic procedures during pregnancy. There is limited data on MB in breastfeeding, so it is generally advised to avoid it during lactation unless absolutely necessary.
4. Overdose Risks
More is not better when it comes to MB. At therapeutic doses, MB acts as an antioxidant and mitochondrial enhancer. However, at very high doses, it can become a pro-oxidant, potentially causing:
Nausea and vomiting
Dizziness or confusion
Elevated blood pressure
Paradoxical methemoglobinemia (the very condition it’s used to treat)
Safe dose ranges for functional medicine typically fall between 0.5 to 4 mg/kg/day, depending on the purpose and form used.
Common and Harmless Side Effects
These effects are usually not a cause for concern, but it’s good to be prepared for them:
| Symptom | Cause | Notes |
|-----------------------------|-----------------------------------|--------------------------------------------|
| Blue or green urine | Renal excretion of MB | Completely benign; resolves after discontinuation |
| Green-tinged stool | GI elimination | Harmless but can stain toilet bowls |
| Taste disturbances | Oral MB | Some find it metallic or bitter |
| Mild nausea or GI upset | Especially with oral forms | Take with food to reduce symptoms |
| Headache or dizziness | Transient vasoconstriction | Usually resolves quickly |
Routes of Administration and Dosing
Most patients do well starting at low doses (1–10 mg/day) for cognitive support or chronic illness support, then titrating slowly if needed.
| Route | Use Case | Notes |
|------------------------------|------------------------------------|--------------------------------------------|
| IV | Emergency use (e.g., methemoglobinemia, septic shock) | Must be medical-grade; only in clinical settings |
| Oral (capsule/tablet) | Cognitive, fatigue, chronic infection support | Moderate bioavailability; common in functional medicine |
| Sublingual or buccal | Nootropic uses; improved absorption | Faster onset; may stain mouth temporarily |
| Topical | Photodynamic therapy (skin/mucosal infections) | Stains skin; not systemically absorbed in meaningful amounts |
| Inhalation or intrathecal| Highly experimental | Not advised without research protocol |
Pharmaceutical vs. Aquarium Grade
NEVER use aquarium or textile-grade methylene blue for human consumption. These grades are not tested for:
Heavy metals (e.g., lead, mercury)
Sterility
Dosage accuracy
Always source USP pharmaceutical-grade MB from a reputable compounding pharmacy or supplier.
Summary Safety Checklist
G6PD screening completed
No serotonergic medications or recent discontinuation
Not pregnant or breastfeeding
Using pharmaceutical-grade MB
Starting at low dose (with food or sublingual form)
Urine discoloration explained to patient
Final Thoughts
Methylene blue is a powerful compound. Like any powerful tool, it must be used wisely. With the right precautions, MB can be a safe, affordable, and versatile therapy for brain health, mitochondrial support, and chronic infections. However, it’s not a DIY supplement. Functional medicine providers should supervise its use, especially when multiple conditions or medications are involved.
Want to Know if Methylene Blue is Safe For You?
Harmony Health Clinic offers guided methylene blue protocols for fatigue, brain fog, mold illness, and more — using only pharmaceutical-grade formulations.
References
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Schirmer RH, et al. Rejuvenation of methylene blue. Antioxid Redox Signal. 2011;14(2):1957–1967. doi:10.1089/ars.2010.3628
FDA Drug Safety Communication. Methylene blue may cause serious CNS reactions when given to patients taking certain psychiatric medications. U.S. Food and Drug Administration. https://www.fda.gov
ProvayBlue (methylene blue injection) Prescribing Information. American Regent, Inc. Revised 2016.
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Mayo Clinic. Methylene blue (oral route, injection route) – description and side effects. https://www.mayoclinic.org
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Alam M, et al. A randomized split-face clinical trial of methylene blue 0.5% cream in skin aging. J Invest Dermatol. 2017;137(1):207–210. doi:10.1016/j.jid.2016.07.036
10. Yasuda H, et al. Methylene blue induces hemolysis in patients with G6PD deficiency. Blood. 2003;101(5):1971–1972. doi:10.1182/blood-2002-05-1443
11. Jansen EC, et al. Risk of birth defects from methylene blue use during pregnancy. Obstet Gynecol. 2003;101(5 Pt 2):1125–1129. doi:10.1016/S0029-7844(02)02699-6
12. International Programme on Chemical Safety. Methylene blue – Environmental Health Criteria. World Health Organization.



