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Methylene Blue

for research purposes only.

Methylthioninium chloride ([7-(Dimethyl-amino) phenothiazin-3-ylidene]-dimethyla-zanium chloride,) commonly known as Methylene Blue (MB,) is an Analine based salt/ phenothiazine dye. It is the first fully synthetic compound to be used in medicine, first prepared in 1876 by German chemist Heinrich Caro. Methylene blue was the first such compound to be administered to humans, and was shown to be effective in the treatment of malaria (Guttmann& Ehrlich, 1891; Oz et al., 2011). It is usually used under doctor recommendations (usually administered via IV solution.)

 

Chemically speaking, Methylene Blue is prepared by oxidation of dimethyl-4-phenylenediamine in the presence of sodium thiosulfate:

 

Dimethyl-4-phenylenediamine is made by the nitrosylation of dimethylaniline followed by reduction. Dimethylaniline is derived from Analine. Aniline was first obtained in 1826 through the destructive distillation of a plant known as Indigo (Indigofera genus.) Its name is taken from the specific name of the indigo-yielding plant Indigofera anil (Indigofera suffruticosa.)

Methylene blue was also the first synthetic compound ever used as an antiseptic in clinical therapy, and the first antiseptic dye to be used therapeutically. In fact, the use of methylene blue and its derivatives was widespread before the advent of sulfonamides and penicillin. It is on the World Health Organization's List of Essential Medicines. It was used as a treatment for malaria in WWII, and for psychiatric disorders such as schizophrenia, later it was realized that it has a seriously broad spectrum of action and benefit. 

Methylene Blue has a wide array of benefits, so I'll do my best to narrow it down to some of the most impactful benefits (I'll include more info you can dive into on your own in the links below.)

 

MB is shown to promote autophagy, optimizing cellular respiration & energy production in the mitochondria (see studies below.) It activates the metabolic pathways of cell defense and energy metabolism, as well as repairs damaged mitochondria, DNA, cells & tissue.

Methylene Blue has been observed to decrease oxidant production and telomere erosion in MB-treated cells. (This one is major.)  It's also been shown to transiently increase the ratios NAD/NADH and pAMPK/AMPK (it cranks up your mitochondria, supports autophagy, and reduces chronic inflammation.) MB induces PGC1α, SURF1, and complex IV biogenesis. In other words, it's shows lots of promise in antiaging research because it suppresses the processes of biological aging.


Methylene Blue reduces or oxidizes itself wherever necessary, specifically during 
oxidative phosphorylation. MB increases NADH levels which in turn donate electrons into the electron transport chain where they are needed, or receive electrons when there's an excess. This, in turn helps to generate ATP.

There are currently over 23,000 studies on Methylene Blue published on The National Library of Medicine/Pubmed, and studies are still ongoing! The FDA currently only recognizes the use of Methylene Blue for treatment of: methemoglobinemia, cyanide poisoning, septic shock, urinary tract infection (prevention,) and carbon monoxide poisoning. This is available to purchase for research purposes only. All information provided here is solely for educational purpose.

Scroll down to see the various studies are linked below.

More info:

 

"Methylene blue has Neuroprotective effects"

- Lars Wiklund, Hari Shanker Sharma, in Progress in Brain Research, 2021

https://www.sciencedirect.com/science/article/abs/pii/S0079612321001552

"Combined activation of the energy and cellular-defense pathways may explain the potent anti-senescence activity of methylene blue"

- Redox Biology Vol 6, pages 426-435, December 2015

https://www.sciencedirect.com/science/article/pii/S2213231715001159

"Methylene blue induces macroautophagy through 5′ adenosine monophosphate-activated protein kinase (AMPK) pathway to protect neurons from serum deprivation"

- Front Cell Neurosci., 2013

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642497/

Methylene blue exerts a neuroprotective effect against traumatic brain injury by promoting autophagy and inhibiting microglial activation

https://pubmed.ncbi.nlm.nih.gov/26572258/

"Methylene Blue Reduces Neuronal Apoptosis and Improves Blood-Brain Barrier Integrity After Traumatic Brain Injury"

- Front. Neurol., 2019

https://www.frontiersin.org/articles/10.3389/fneur.2019.01133/full

"Methylene Blue: The Little-Known Disinfectant"

- American Society for Microbiology, 2022

https://asm.org/Articles/2022/March/Methylene-Blue-The-Little-Known-Disinfectant

"Methylene blue protects dopaminergic neurons against MPTP-induced neurotoxicity by upregulating brain-derived neurotrophic factor"

- Annals of the New York Academy of Sciences, 2018

https://pubmed.ncbi.nlm.nih.gov/29882218/

Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dotshttps://pubmed.ncbi.nlm.nih.gov/26603930/

"Methylene blue directly oxidizes glutathione without the intermediate formation of hydrogen peroxide"

- J Biol Chem, Dec 5 1985; 260(28):1568-71

https://pubmed.ncbi.nlm.nih.gov/4066667/

"Methylene blue is used in the treatment of some psychiatric disorders because of the anxio-lytic and antidepressant properties attributed to its ability to block activation of guanyl cyclase by nitric oxide"

- Naylor et al., 1986; Eroğlu & Cağlayan, 1997

https://pubmed.ncbi.nlm.nih.gov/9441729/

Recent studies suggested that methylene blue may have beneficial effects in the treatment of Alzheimer disease and memory improvement

- Oz et al., 2011

https://www.researchgate.net/publication/24418608_Methylene_blue_and_Alzheimer%27s_disease

"Common antioxidant could slow symptoms of aging in human skin"

- University of Maryland, 2017

https://www.sciencedaily.com/releases/2017/05/170530140701.htm

Methylene blue used as antidepressant compound

- Anzelle Delport, 2017
https://pubmed.ncbi.nlm.nih.gov/28762173/

Neuroprotective actions of methylene blue and its derivatives

https://pubmed.ncbi.nlm.nih.gov/23118969/

Methylene blue. A possible treatment for manic depressive psychosis 

https://pubmed.ncbi.nlm.nih.gov/6222095/

A two-year double-blind crossover trial of the prophylactic effect of methylene blue in manic-depressive psychosis
https://pubmed.ncbi.nlm.nih.gov/3091097/

"Methylene blue is more toxic to erythroleukemic cells than to normal peripheral blood mononuclear cells: a possible use in chemotherapy"

- C Kirszberg  1 , V M Rumjanek, M A M Capella, 2005
https://pubmed.ncbi.nlm.nih.gov/16052340/ 

 

The measurement of bioreductive capacity of tumor cells using methylene blue
https://pubmed.ncbi.nlm.nih.gov/26603930/

"Methylene Blue for treatment of hospitalized Covid-19 patients: A randomized, controlled, open-label clinical trial, phase 2"

- Rev Invest Clin, 2021

https://pubmed.ncbi.nlm.nih.gov/34019535/

"Methylene Blue Inhibits the SARS-CoV-2 Spike–ACE2 Protein-Protein Interaction–a Mechanism that can Contribute to its Antiviral Activity Against COVID-19"

- Front. Pharmacol., 2021

https://www.frontiersin.org/articles/10.3389/fphar.2020.600372/full
 

Inactivation of dengue virus by methylene blue/narrow bandwidth light system

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129913/


Methylene blue photodynamic therapy induces selective and massive cell death in human breast cancer cells
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3179-7


 

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