Methylene blue is a synthetic phenothiazine dye, not a peptide. It is FDA-approved (as ProvayBlue) for acquired methemoglobinemia and is used off-label at low doses for mitochondrial and cognitive support. Its defining pharmacological feature is a hormetic dose-response: low doses act as an electron cycler that improves mitochondrial respiration, while high doses reverse this and become pro-oxidant. It is also a potent MAO-A inhibitor, which creates a serious and frequently overlooked serotonin syndrome risk.
Category: Cognitive / Neuroprotection. Evidence rating: C (early/mixed human evidence).
Clinical status: FDA-approved (ProvayBlue) for acquired methemoglobinemia. Cognitive, mitochondrial and neuroprotective uses are off-label and supported mainly by preclinical and small early-phase human work.
Methylene blue acts as an alternative electron carrier in the mitochondrial electron transport chain. It accepts electrons from NADH and donates them directly to cytochrome c, bypassing Complex I and Complex III — the two principal sites of superoxide generation. This "electron shunting" sustains…
Safety considerations: Serotonin syndrome is the most serious risk. Methylene blue is a potent MAO-A inhibitor and the FDA has issued a specific warning about combining it with serotonergic drugs (SSRIs, SNRIs, MAOIs, triptans, tramadol). This has caused serious and fatal reactions; G6PD deficiency is a hard contraindication — methylene blue can cause severe hemolytic anemia in G6PD-deficient individuals, and can paradoxically worsen methemoglobinemia; Blue-green discoloration of urine is universal and harmless; skin and sclera staining occurs at higher doses.
Reviewed by the PeptideAtlas Editorial Team.
| Molecular formula | C16H18ClN3S |
|---|---|
| Molecular weight | ~319.85 g/mol |
| CAS number | 61-73-4 |
| Half-life | ~5-6 hours |
| Bioavailability | ~70% oral |
| Production method | synthetic |
| Anti-doping status | not-listed |
| US regulatory status | FDA-approved prescription drug (ProvayBlue) for methemoglobinemia. Off-label cognitive/mitochondrial use is common but unapproved. Sold widely as a non-pharmaceutical grade chemical, which is unsafe for ingestion. |
Related peptides: Neuroxelin.
No. It is a synthetic phenothiazine dye (a small molecule). It is listed here because it appears frequently in mitochondrial and nootropic protocols alongside peptides such as SS-31 and MOTS-c.
The dose-response is hormetic and genuinely biphasic. At low concentrations methylene blue cycles as an electron carrier and antioxidant; at high concentrations that same redox cycling generates superoxide, so it becomes pro-oxidant. Above roughly 7 mg/kg it can induce the very methemoglobinemia it is approved to treat.
Serotonergic drugs. Methylene blue is a potent MAO-A inhibitor and the FDA has warned specifically about serotonin syndrome when it is combined with SSRIs, SNRIs, MAOIs, triptans or tramadol. Anyone on an antidepressant should not take methylene blue without medical guidance.
No. Blue-green urine is expected and harmless. Skin and eye staining can occur at higher doses and is also reversible, but it is a signal you are dosing above the low-dose range.
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