{ "checked": "2026-10-25", "page": "https://jabbitapp.com/research/methylene-blue-nootropic-longevity-mitochondria-evidence-teardown.html", "fda_label": { "name": "PROVAYBLUE (methylene blue) injection", "setid": "4f6848e5-35ed-4046-b13c-3032b5ba3232", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4f6848e5-35ed-4046-b13c-3032b5ba3232", "quotes": [ "PROVAYBLUE is indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia.", "PROVAYBLUE may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids.", "Avoid concomitant use of PROVAYBLUE with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs) and opioids.", "Patients with glucose-6-phosphate dehydrogenase deficiency (G6PD) due to the risk of hemolytic anemia", "The presence of methylene blue in the blood may result in an underestimation of the oxygen saturation reading by pulse oximetry.", "PROVAYBLUE may cause fetal harm when administered to a pregnant woman.", "Treatment with PROVAYBLUE may cause confusion, dizziness and disturbances in vision", "Advise patients that PROVAYBLUE may cause a blue discoloration of the skin and body fluids", "Initial U.S. Approval: 2016", "PROVAYBLUE (methylene blue) injection, USP" ], "boxed_warning": "Serotonin syndrome with concomitant use of serotonergic drugs" }, "drugsfda": { "applications": 8, "nda": "NDA204630", "nda_original_approval": "2016-04-08", "anda": 7, "routes": { "INTRAVENOUS": 12 } }, "faers": { "reports_naming_methylene_blue": 1605, "reports_with_serotonin_syndrome": 518, "last_updated": "2026-07-30", "top_reactions": [ { "term": "SEROTONIN SYNDROME", "count": 518 }, { "term": "DRUG INTERACTION", "count": 401 }, { "term": "DRUG INEFFECTIVE", "count": 301 }, { "term": "HYPOTENSION", "count": 212 }, { "term": "OFF LABEL USE", "count": 194 } ] }, "tga_alert": { "url": "https://www.tga.gov.au/safety/safety-monitoring-and-information/safety-alerts/imported-unregistered-methylene-blue-products", "published": "2025-09-25", "quotes": [ "increasing importation and use of unregistered oral methylene blue (methylthioninium chloride) products in Australia", "These products are being promoted for unapproved (off-label) uses, such as cognitive enhancement, mood improvement, and anti-ageing effects.", "They have not been assessed by us for quality, safety or efficacy", "may contain incorrect or undisclosed and harmful ingredients", "Methylene blue should not be used during pregnancy.", "Do not use oral methylene blue products unless advised or prescribed by a healthcare professional.", "We will notify the Australian Border Force (ABF) to seize and destroy", "Most methylene blue products imported from online stores do not include clear instructions or warnings.", "Medicines that affect serotonin levels such as some painkillers and selective serotonin reuptake inhibitors (SSRIs), a common type of antidepressant, can cause serotonin syndrome when taken with methylene blue.", "may experience red blood cell damage (haemolysis) if they take methylene blue." ] }, "taurx_company_statements": { "faq": { "url": "https://taurx.com/medical-professionals/frequently-asked-questions", "quotes": [ "It is not approved or licensed by any medicines regulator and is not available to be prescribed.", "HMTM was granted an Innovation Passport by the MHRA in 2022", "a final decision on our Marketing Authorisation Application (MAA) expected in 2026" ] }, "mhra_response_2025_10_01": { "url": "https://taurx.com/insights/industry-news/mhra-response-to-hmtm-marketing-authorisation-application", "quote": "it requires some further information before a final determination on the suitability of hydromethylthionine mesylate (HMTM), as a potential oral treatment for Alzheimer’s disease, can be reached." }, "rfi_2025_06_04": { "url": "https://taurx.com/insights/industry-news/taurx-finalises-responses-to-mhra-request-for-information", "quote": "TauRx can confirm it has completed the request for information (RFI) received from the Medicines and Healthcare products Regulatory Agency (MHRA)" } }, "registry": { "clinicaltrials_gov_methylene_blue_records": 343, "hmtm_lmtm_records": { "NCT04370288": [ "UNKNOWN", "PHASE1", 20 ], "NCT02245568": [ "TERMINATED", "PHASE3", 913 ], "NCT01626378": [ "COMPLETED", "PHASE3", 220 ], "NCT01689233": [ "COMPLETED", "PHASE3", 800 ], "NCT01689246": [ "COMPLETED", "PHASE3", 891 ], "NCT03539380": [ "AVAILABLE", "NA", null ], "NCT03446001": [ "COMPLETED", "PHASE3", 598 ], "NCT01626391": [ "TERMINATED", "PHASE2", 9 ] } }, "pubmed": { "rct_methylene_blue_cognition_memory": 8, "rct_methylene_blue_aging_longevity": 2, "rct_aging_note": "Both hits are dental/photodynamic studies, not trials of taking methylene blue for aging." }, "key_trials": [ { "trial": "Lancet 2016, mild-moderate Alzheimer's", "n": 891, "result": "Main goals not met", "pmid": "27863809" }, { "trial": "2018 mild Alzheimer's trial", "n": 800, "result": "Plan revised; non-randomized comparison", "pmid": "29154277" }, { "trial": "LUCIDITY 2026, Alzheimer's/MCI", "n": 598, "result": "Main goals not met at 52 weeks", "pmid": "41570392" }, { "trial": "Phase 2 2015, Alzheimer's", "n": 321, "result": "Mixed, dose-finding", "pmid": "25550228" }, { "trial": "Surgery 2021, IV, open-label", "n": 248, "result": "Less delirium after surgery", "pmid": "33091706" }, { "trial": "PTSD 2017, with exposure therapy", "n": 42, "result": "Some gains; mixed at 3 months", "pmid": "28686823" }, { "trial": "Claustrophobia 2014", "n": 42, "result": "Helped or hurt, depending", "pmid": "25018057" }, { "trial": "Bipolar 2017, add-on", "n": 37, "result": "Mood better; cognition not", "pmid": "27284082" }, { "trial": "Healthy adults 2016, one dose", "n": 26, "result": "7% more correct memory answers", "pmid": "27351678" } ], "key_trials_total_n": 3005, "abstract_quotes": { "27863809": { "title": "Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial", "journal": "Lancet", "year": "2016", "quotes": [ "we recruited and randomly assigned 891 participants", "The prespecified primary analyses did not show any treatment benefit at either of the doses tested for the coprimary outcomes", "the results do not suggest benefit of LMTM as an add-on treatment for patients with mild to moderate Alzheimer's disease.", "Gastrointestinal and urinary effects were the most common adverse events" ] }, "29154277": { "title": "Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer's Disease: Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial", "journal": "J Alzheimers Dis", "year": "2018", "quotes": [ "Mild AD patients (n = 800)", "Prior to unblinding, the Statistical Analysis Plan was revised", "non-randomized cohort analyses", "A further suitably randomized trial is required to test this hypothesis." ] }, "41570392": { "title": "Clinical, imaging and blood biomarker outcomes in a Phase 3 clinical trial of tau aggregation inhibitor hydromethylthionine mesylate in mild cognitive impairment and mild to moderate dementia due to Alzheimer's disease", "journal": "J Prev Alzheimers Dis", "year": "2026", "quotes": [ "A total of 598 amyloid β-PET positive participants were included", "intended as an inactive urinary colourant", "It was not possible to demonstrate significant differences on the co-primary clinical endpoints (ADAS-cog11 and ADCS-ADL23) at 52 weeks due to symptomatic activity in the control arm.", "In participants with MCI, significant clinical separation was seen only at 78 and 104 weeks.", "Headache (1·5%) and diarrhoea (1·2%) were the most frequent adverse effects." ] }, "36281683": { "title": "Oral Tau Aggregation Inhibitor for Alzheimer's Disease: Design, Progress and Basis for Selection of the 16 mg/day Dose in a Phase 3, Randomized, Placebo-Controlled Trial of Hydromethylthionine Mesylate", "journal": "J Prev Alzheimers Dis", "year": "2022", "quotes": [ "The trial comprises a 12-month double-blind, placebo-controlled phase" ] }, "42000569": { "title": "Assessment of clinical and neuroimaging efficacy of treatment targeting tau pathology in mild cognitive impairment and mild to moderate Alzheimer's disease with hydromethylthionine mesylate using external control data", "journal": "J Prev Alzheimers Dis", "year": "2026", "quotes": [ "A traditional randomised placebo-controlled trial (RCT) was precluded by loss of blinding due to urinary colouration and therapeutic activity", "Propensity score matching yielded 127 pairs" ] }, "41917677": { "title": "Atypical population pharmacokinetics of hydromethylthionine in patients with Alzheimer's disease explains unexpected phase 3 trial results", "journal": "Br J Clin Pharmacol", "year": "2026", "quotes": [ "The data suggest it is not possible to maintain comparable urinary discolouration without therapeutic activity in a standard placebo-controlled trial design." ] }, "25550228": { "title": "Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer's disease", "journal": "J Alzheimers Dis", "year": "2015", "quotes": [ "An exploratory double-blind, randomized, placebo-controlled, dose-finding trial", "conducted in 321 mild/moderate AD subjects", "The delivery of the highest dose was impaired due to dose-dependent dissolution and absorption limitations.", "further study of MT is warranted in AD." ] }, "42702342": { "title": "From target engagement to translational disconnect: A systematic review and narrative synthesis of direct tau-targeted clinical trials in Alzheimer's disease and primary tauopathies", "journal": "Pharmacol Res", "year": "2026", "quotes": [ "the small-molecule aggregation inhibitor LMTM did not demonstrate consistent clinical benefit in phase 3 trials." ] }, "32037892": { "title": "An evaluation of hydromethylthionine as a treatment option for Alzheimer's disease", "journal": "Expert Opin Pharmacother", "year": "2020", "quotes": [ "Derived from methylene blue, hydromethylthionine is a tau aggregation inhibitor", "Randomized clinical trials with hydromethylthionine failed to show any impact of the doses used on the disease course." ] }, "27351678": { "title": "Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain", "journal": "Radiology", "year": "2016", "quotes": [ "Twenty-six subjects (age range, 22-62 years) were enrolled.", "Methylene blue was also associated with a 7% increase in correct responses during memory retrieval (P = .01)." ] }, "27284082": { "title": "Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study", "journal": "Br J Psychiatry", "year": "2017", "quotes": [ "Thirty-seven participants were enrolled", "The effects of methylene blue on cognitive symptoms were not significant." ] }, "28686823": { "title": "Enhancing Extinction Learning in Posttraumatic Stress Disorder With Brief Daily Imaginal Exposure and Methylene Blue: A Randomized Controlled Trial", "journal": "J Clin Psychiatry", "year": "2017", "quotes": [ "Patients with chronic PTSD (DSM-IV-TR; N = 42)", "Both IE + MB and IE + PBO showed strong clinical gains that did not differ from standard PE at 3-month follow-up.", "The findings provide preliminary efficacy for a brief IE treatment for PTSD" ] }, "25018057": { "title": "Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia", "journal": "Am J Psychiatry", "year": "2014", "quotes": [ "(N=23)", "(N=19)", "participants displaying moderate to high levels of posttraining fear tended to fare worse at the follow-up if they received methylene blue posttraining.", "may have a deleterious effect on extinction when administered after an unsuccessful exposure session." ] }, "33091706": { "title": "Methylene blue reduces incidence of early postoperative cognitive disorders in elderly patients undergoing major non-cardiac surgery: An open-label randomized controlled clinical trial", "journal": "J Clin Anesth", "year": "2021", "quotes": [ "Prospective, randomized, open-label clinical trial.", "Two hundred and forty-eight elderly patients", "(7.3% vs. 24.2%, OR = 0.24" ] }, "17721552": { "title": "Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction", "journal": "Br J Pharmacol", "year": "2007", "quotes": [ "MB was a potent (tight binding) inhibitor for MAO A.", "MB is a potent reversible inhibitor of MAO A with implications for gut uptake of amines when administered orally.", "This inhibition of MAO A would be expected to lead to perturbations of 5-hydroxytryptamine metabolism and hence account for ST occurring when administered to patients on SSRI treatment." ] }, "28840449": { "title": "From Mitochondrial Function to Neuroprotection-an Emerging Role for Methylene Blue", "journal": "Mol Neurobiol", "year": "2018", "quotes": [ "MB can reroute electrons in the mitochondrial electron transfer chain directly from NADH to cytochrome c", "In both in vitro and in vivo studies, MB has shown impressive efficacy in mitigating neurodegeneration" ] } }, "title_only": { "37828274": { "title": "Methylene Blue-Induced Serotonin Toxicity: Case Files of the Medical Toxicology Fellowship at the New York City Poison Control Center", "journal": "J Med Toxicol", "year": "2024" }, "41725094": { "title": "Methylene blue and the social media phenomenon: Key information for nurses", "journal": "Nursing", "year": "2026" } }, "analysis": { "note": "Jabbit analysis. Methylene blue is an FDA-approved intravenous drug for acquired methemoglobinemia with a boxed warning for serotonin syndrome. Its nootropic and longevity claims rest on lab and animal work and a handful of small human studies; the derivative drug tested in three phase 3 Alzheimer's trials missed its main goals as designed and is not approved anywhere, with a UK decision pending per the company." } }