Methylene blue studies and research data

Methylene blue (methylthioninium chloride, 3,7-bis(dimethylamino)phenothiazin-5-ium chloride) is a small cationic thiazine dye with the formula C16H18ClN3S (anhydrous chloride, 319.86 g/mol on the US label). The US label calls it an oxidation-reduction agent. In the body it is first reduced to leucomethylene blue by an NADPH reductase, and the leuco form reduces the ferric iron of methemoglobin back to normal hemoglobin. FDA approved ProvayBlue (NDA 204630, Provepharm; label distributed by American Regent) on 2016-04-08 for acquired methemoglobinemia. The 2025 label text (DailyMed version 28, 2025-06-12) says: 1 mg/kg intravenously over 5 to 30 minutes, with one repeat dose of 1 mg/kg after one hour if methemoglobin stays above 30 percent or symptoms persist, and a single dose in moderate or severe renal impairment. It carries a boxed warning: serious or fatal serotonin syndrome with serotonergic drugs and opioids. The label also lists G6PD deficiency (hemolytic anemia) and severe hypersensitivity as contraindications, a possible pulse oximeter error, and says the half-life is about 24 hours. In the EU, Methylthioninium chloride Proveblue (Provepharm) is authorised since 2011-05-06 for acute symptomatic treatment of drug- or chemical-induced methemoglobinemia. The EMA summary gives 1 to 2 mg/kg over five minutes for adults and for children above three months. Seven FDA generic applications (ANDA, approved 2023 to 2025) now exist. FDA lists no methylene blue on its 503A or 503B nominated bulk-substance lists under that spelling. WADA names no methylene blue in the 2026 or 2027 Prohibited List. The only general clause that could touch an infusion is M2.2 (more than 100 mL per 12 hours, with a hospital-treatment exception). ChEMBL records one mechanism: inhibition of soluble guanylate cyclase. The US label says literature reports suggest it is a potent reversible inhibitor of monoamine oxidase, which is the label's explanation for serotonin syndrome. The reduced leuco form is a different substance (hydromethylthionine, LMTM) that TauRx develops for Alzheimer disease. Most of the roughly 29,000 Europe PMC records that name methylene blue treat it as a lab dye or reagent, not as a drug. In wellness and biohacker communities people take low oral or mouth-held doses (reports of 2 to 50 mg a day) for energy, focus and mitochondrial support. I read no trial of that use. NPR reported in December 2025 that it is not clear whether methylene blue meets the legal definition of a dietary supplement.

Kind

Small molecule

Formula

C₁₆H₁₈ClN₃S

Identifiers

ChEMBLCHEMBL405110 (opens in a new tab)CHEMBL191083 (opens in a new tab)CHEMBL550495 (opens in a new tab)PubChem CID6099 (opens in a new tab)4139 (opens in a new tab)104827 (opens in a new tab)UNII8NAP7826UB (opens in a new tab)ZMZ79891ZH (opens in a new tab)T42P99266K (opens in a new tab)DrugBankDB09241 (opens in a new tab)DB08167 (opens in a new tab)CAS61-73-47220-79-37060-82-4KEGGD02312 (opens in a new tab)D10537 (opens in a new tab)

Development

Approved in the US and EU (Methylthioninium chloride Proveblue, 2011)Provepharm SAS (France) holds ProvayBlue (US) and Proveblue (EU); American Regent distributes the US label. Cosmo Technologies holds Lumeblue (oral, EU). TauRx develops the leuco form hydromethylthionine (LMTM) for Alzheimer disease (a different substance).Approved: ProvayBlue injection for acquired methemoglobinemia in the US (2016) and Proveblue in the EU (2011); generic injections in the US since late 2023. ClinicalTrials.gov API v2 on 2026-10-13: 411 studies for the term 'methylene blue OR methylthioninium OR ProvayBlue' (404 for the exact phrase 'methylene blue'; 349 when the same words are searched as interventions only). Titles seen in Europe PMC (not read): a 2026 paper on atypical population pharmacokinetics of hydromethylthionine in Alzheimer disease that is said to explain unexpected phase 3 results (PMID 41917677), a phase 3 trial of hydromethylthionine mesylate (PMID 41570392), and methylene blue trials in septic shock and perioperative delirium. The highest phase 'approved' refers to the injection for methemoglobinemia only. No approval exists for oral use, for cognition or for aging. Source (opens in a new tab)

• NAD+ (nicotinamide adenine dinucleotide) evidence
• MOTS-c evidence
• Epitalon evidence
• Glutathione evidence