Methylene Blue
A synthetic dye first made in 1876 that has remarkable medicinal properties. At low doses (0.5-4 mg/kg), methylene blue acts as a mitochondrial electron carrier, enhancing cellular respiration and ATP production. It is the only known compound that can donate and accept electrons in the mitochondrial electron transport chain, essentially serving as a backup energy pathway when mitochondria are stressed.
Dosage
Nootropic dose: 0.5-2 mg/kg body weight (typically 30-60 mg for most adults). Pharmaceutical grade USP only — never use industrial or aquarium-grade. Start at the lowest dose. Turns urine blue/green (harmless).
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Half-Life
5-6 hours
Administration
Oral (solution, capsules). Must be pharmaceutical/USP grade. Sublingual for faster absorption.
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Mechanism of Action
Methylene blue has a unique property: it acts as an alternative electron carrier in the mitochondrial electron transport chain, cycling between oxidized (blue) and reduced (leuco) forms. It can accept electrons from Complex I (NADH) and donate them directly to cytochrome c, bypassing dysfunctional Complex II and III—maintaining ATP production when mitochondria are damaged or in hypoxic conditions. Methylene blue inhibits nitric oxide synthase (NOS), reducing NO production and the formation of peroxynitrite (ONOO-), a potent oxidant that damages mitochondria. It acts as a redox cycler with antioxidant properties and may enhance cytochrome c oxidase (Complex IV) activity. At low doses, it inhibits tau protein aggregation and tau-tau interactions (relevant to Alzheimer's pathology) and may improve mitochondrial respiration through multiple mechanisms.
Regulatory Status
FDA-approved for methemoglobinemia (ProvayBlue). Available as a supplement at lower doses. Being studied for Alzheimer's disease (TauRx Therapeutics).
Risks & Safety
Common
Blue/green discoloration of urine and potentially skin at higher doses, nausea, headache.
Serious
Serotonin syndrome risk when combined with SSRIs, SNRIs, or MAOIs — DO NOT combine. Contraindicated in G6PD deficiency (can cause hemolytic anemia).
Rare
Confusion, shortness of breath, chest pain.
Compare Methylene Blue With
Research Papers
10Published: July 7, 2003
AI Summary
Methylene blue finds its major utilization in toxicology in the treatment of methemoglobinemia at a dose of 1 to 2 mg/kg intravenously. People with G-6-PD deficiency, along with patients exposed to aniline dyes and dapsone, may present with special risks in the treatment of methemoglobinemia.
Published: August 31, 2021
AI Summary
Methylene blue's mechanism of action is somewhat complex and based partly on its oxidizing capabilities, ironically the same mechanism that causes MetHB. Methylene blue's pharmacologic actions, dosing, and adverse effects will also be discussed.
Published: July 24, 2019
AI Summary
Abstract too short to summarize.
Published: February 2, 2006
AI Summary
To evaluate the use of methylene blue for the treatment of ifosfamide-induced encephalopathy.
Published: February 28, 1994
AI Summary
To describe the manifestations of methylene blue toxicity, with a review of the literature.
Published: August 31, 2021
AI Summary
Abstract too short to summarize.
Published: October 10, 2012
AI Summary
The availability of preoperative and other intraoperative localization methods, and the reported adverse effects of methylene blue make its routine use debatable. The aim of this study was to perform a systematic review of the use of methylene blue in parathyroidectomy.
Published: February 9, 2026
AI Summary
Studies suggest that methylene blue decreases vasopressor requirements for critically ill patients with minimal safety risks. This clinical review aims to review the pharmacology, efficacy, and safety surrounding methylene blue use in patients with septic shock.
Published: June 26, 2025
AI Summary
First, methylene blue does not specifically bind DNA, and thus, in complex samples, it is a poor reporter for assays that use the binding properties of methylene blue to drive the assay specificity. Third, despite a voltage potential peak close to that of oxygen reduction, methylene blue is one of the more favorable redox reporters currently des...
Frequently Asked Questions
What is Methylene Blue used for?
A synthetic dye first made in 1876 that has remarkable medicinal properties. At low doses (0.5-4 mg/kg), methylene blue acts as a mitochondrial electron carrier, enhancing cellular respiration and ATP production. It is the only known compound that can donate and accept electrons in the mitochondrial electron transport chain, essentially serving as a backup energy pathway when mitochondria are stressed.
What are the side effects of Methylene Blue?
Common: Blue/green discoloration of urine and potentially skin at higher doses, nausea, headache. Serious: Serotonin syndrome risk when combined with SSRIs, SNRIs, or MAOIs — DO NOT combine. Contraindicated in G6PD deficiency (can cause hemolytic anemia). Rare: Confusion, shortness of breath, chest pain.
How is Methylene Blue administered?
Methylene Blue is administered via oral (solution, capsules). must be pharmaceutical/usp grade. sublingual for faster absorption..
What is the half-life of Methylene Blue?
The half-life of Methylene Blue is 5-6 hours.
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