Methylene Blue

Article written by Jeremy Mikolai, ND

Methylene Blue has seen a resurgence in interest over the last several years and is featured in many social media posts and conversations.  People ask me what I think about methylene blue and whether I recommend it for them.

Methylene Blue has been used in chemistry and investigated in research for decades. It was developed started life as a textile dye in 1876. It’s actually the first fully man-made medicine. Methylene blue is used in chemistry as a red-ox indicator because it changes color when certain types of chemical reactions take place.(1) It has also been researched as a medical treatment for many conditions including depression, bipolar, schizophrenia, Alzheimer’s disease, neurodegeneration, septic shock, skin aging, premature aging, mitochondrial dysfunction, and malaria. (2-5)

Methylene Blue has at least one approved routine medical application for use in emergency cases of acquired methemoglobinemia – a disruption of oxygen carrying in the blood. The medication form of Methylene Blue comes with a black box warning about the potential for serious or fatal serotonin syndrome, especially when used during the same times as other mood, behavioral, and pain meds like SSRIs, SNRIs, MAOIs, and opioids. (6)

Most people who ask me about it are interested in what they’ve heard about potential cognitive and mood benefits from taking it. They’ve heard it can improve concentration and memory, mood and energy levels. Most likely that is because it can increase neurotransmitter levels including serotonin, dopamine, epinephrine, and norepinephrine. It is true that it has this effect, and the effect is strong enough to make it potentially dangerous. It’s notorious for leading to serotonin overload, which can be life- threatening.

Methylene Blue works by decreasing the enzyme that breaks down many neurotransmitters (MAOI). (2) That makes it easy for the amount of neurotransmitters like serotonin to overload and that can be a medical emergency. (6) Frequently taking Methylene Blue can cause pain in the extremities, change in taste, feeling hot, dizziness, sweating, nausea and skin discolorations. Less commonly it may cause headache, musculoskeletal pain, tingling and numbness, fainting, itching, anxiety, chest discomfort and other symptoms. In people with some enzyme deficiencies (G6PD), it can cause massive red blood cell breakdown. (6)

When I am asked about methylene blue, I ask a few more questions; I want to learn more about why the person is interested in it or what benefit they are seeking. Most recently, the person who was asking sought an improvement in mood and attention. I told them a bit about the history and how it works and the risks associated with taking it.

Another person who asked me about Methylene Blue revealed they had been taking Methylene Blue regularly in the past, but they had stopped. I asked why they stopped and they said it felt like they were having a serotonin overload. I thought that was very interesting and insightful that a person would describe it that way and I don’t doubt them for a second.

I don’t recommend that anyone use Methylene Blue for any reason on their own. It can raise neurotransmitters to dangerous levels and can do so quickly. There are a lot of potential side effects including serious and life-threatening ones. There are also questions and concerns about the quality, manufacture, and appropriateness of internal use of available products that are accessed without prescription.

In natural medicine we have so many ways to increase neurotransmitters and improve neurotransmitter balance safely and reliably. There are numerous treatments for balancing mood, improving attention, reducing stress, improving energy and reducing fatigue that are safe and effective. So, I recommend that folks do what these people did: avoid Methylene Blue and consult a trusted health professional to help you meet your goals.

1. Schirmer RH, Adler H, Pickhardt M, Mandelkow E. "Lest we forget you--methylene blue...". Neurobiol Aging. 2011

Dec;32(12):2325.e7-16. doi: 10.1016/j.neurobiolaging.2010.12.012. Epub 2011 Feb 12. PMID: 21316815.

2. Delport A, Harvey BH, Petzer A, Petzer JP. Methylene blue and its analogues as antidepressant compounds.

Metab Brain Dis. 2017 Oct;32(5):1357-1382. doi: 10.1007/s11011-017-0081-6. Epub 2017 Jul 31. PMID: 28762173.

3. Tucker D, Lu Y, Zhang Q. From Mitochondrial Function to Neuroprotection-an Emerging Role for Methylene Blue.

Mol Neurobiol. 2018 Jun;55(6):5137-5153. doi: 10.1007/s12035-017-0712- Epub 2017 Aug 24. PMID: 28840449;

PMCID: PMC58267813.

4. Ibarra-Estrada M, Kattan E, Aguilera-González P, Sandoval-Plascencia L, Rico-Jauregui U, Gómez-Partida CA,

Ortiz-Macías IX, López-Pulgarín JA, Chávez-Peña Q, Mijangos-Méndez JC, Aguirre-Avalos G, Hernández G. Early

adjunctive methylene blue in patients with septic shock: a randomized controlled trial. Crit Care. 2023 Mar

13;27(1):110. doi: 10.1186/s13054-023-04397-7. PMID: 36915146; PMCID: PMC10010212.

5. Xue H, Thaivalappil A, Cao K. The Potentials of Methylene Blue as an Anti-Aging Drug. Cells. 2021 Dec

1;10(12):3379. doi: 10.3390/cells10123379. PMID: 34943887; PMCID: PMC8699482.

6. Methylene blue. Epocrates. Retrieved July 11, 2025 from www.epocrates.com