A related compound, leuco-methylthioninium (LMTM), did not slow decline in 891 people with mild to moderate Alzheimer's disease over 15 months. A later trial of the same compound in 598 people also missed its main goals at 52 weeks.
Mild to moderate Alzheimer's disease; later trial MCI or mild-moderate AD (amyloid-positive) · Outcome: ADAS-Cog and ADCS-ADL (co-primary)
Confidence applies to this claim and context.
AttentionNot assessedNo current independent attention assessment
EvidenceNo mapped studiesNo reviewed experiment families currently mapped
ConfidenceNot assessedFor: A related compound, leuco-methylthioninium (LMTM), did not slow decline in 891 people with mild to moderate Alzheimer's disease over 15 months. A later trial of the same compound in 598 people also missed its main goals at 52 weeks.. No current reviewed confidence assessment for this claim.
The GapAttention not measured
Attention describes reviewed public attention, evidence shows study types, and confidence applies only to the stated claim. There is no overall score.
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We haven't called this yet. Watch it and we'll tell you when there's enough to say something useful.
Why we checked it
Attention is high but mixed. English Wikipedia's Methylene blue article had 27,929 views in September 2026. PubMed added 125 records in the 30 days to Oct 11 2026, but most concern its use as a dye in surgery, imaging or chemistry, not brain health.
Here's where it actually stands
Methylene blue is a blue dye that is also a prescription drug. Given into a vein, it treats acquired methemoglobinemia, a blood problem in which blood cannot carry oxygen well. The FDA first approved the brand ProvayBlue for this in 2016 under its accelerated-approval pathway, and generic injections since 2023. Its label carries a boxed warning: combined with many antidepressants or opioids, it can cause serotonin syndrome, which can be fatal. It can also make pulse-oximeter readings wrong. Its label says people with G6PD deficiency, an inherited enzyme condition, should not receive it. In them, it can break down red blood cells. Online, it is promoted for memory, energy and aging. Human evidence for those uses is limited to small, short studies. A related drug was tested in large Alzheimer's trials, which missed their main goals.
What we know
A related compound, leuco-methylthioninium (LMTM), did not slow decline in 891 people with mild to moderate Alzheimer's disease over 15 months. A later trial of the same compound in 598 people also missed its main goals at 52 weeks.
What we don't know
Does methylene blue improve memory, energy or healthy aging in people?
Claims
A related compound, leuco-methylthioninium (LMTM), did not slow decline in 891 people with mild to moderate Alzheimer's disease over 15 months. A later trial of the same compound in 598 people also missed its main goals at 52 weeks. · headlineMild to moderate Alzheimer's disease; later trial MCI or mild-moderate AD (amyloid-positive) · Outcome: ADAS-Cog and ADCS-ADL (co-primary)Confidence: Not assessed · source checked
Would change this claim: If a registered randomized trial lasting months shows a meaningful cognitive benefit in healthy or older adults, we would add it to the opening and re-grade the "not shown" line.
Source: 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. · PMID 27863809 · Lancet · 27863809 Findings: no treatment benefit on co-primary outcomes; 41570392 Results: not possible to show differences on co-primary endpoints at 52 weeks; later MCI subgroup differences reported by the authors · Verify ↗Source: 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. · PMID 41570392 · J Prev Alzheimers Dis · 27863809 Findings: no treatment benefit on co-primary outcomes; 41570392 Results: not possible to show differences on co-primary endpoints at 52 weeks; later MCI subgroup differences reported by the authors · Verify ↗
In a randomized trial of 26 healthy adults, one low oral dose of methylene blue changed brain activity on MRI during attention and memory tasks and was linked to 7% more correct memory answers one hour later.Healthy adults aged 22-62 · Outcome: fMRI task response; memory retrieval accuracyConfidence: Not assessed · source checkedSource: Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain. · PMID 27351678 · Radiology · Abstract, Results: increased insular and prefrontal/parietal/occipital response; 7% increase in correct responses during memory retrieval (P=.01) · Verify ↗
In septic shock, a single-center trial of 91 patients found that intravenous methylene blue shortened time on blood-pressure drugs (69 vs 94 hours). A meta-analysis of six small trials found possible lower short-term mortality, rated low certainty.Adults with septic shock (ICU) · Outcome: Time to vasopressor discontinuation; short-term mortalityConfidence: Not assessed · source checkedSource: Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial. · PMID 36915146 · Crit Care · 36915146 Results: 69 h vs 94 h (p<0.001), mortality similar; 38904978: six RCTs (302 patients), RR 0.66 (0.47-0.94), low certainty · Verify ↗Source: Methylene Blue in Septic Shock: A Systematic Review and Meta-Analysis. · PMID 38904978 · Crit Care Explor · 36915146 Results: 69 h vs 94 h (p<0.001), mortality similar; 38904978: six RCTs (302 patients), RR 0.66 (0.47-0.94), low certainty · Verify ↗Source: Methylene Blue in Early Septic Shock · NCT NCT04446871 · Hospital Civil de Guadalajara · 36915146 Results: 69 h vs 94 h (p<0.001), mortality similar; 38904978: six RCTs (302 patients), RR 0.66 (0.47-0.94), low certainty · Verify ↗
Mapped studies / experiment families
One experiment counts once, even with several registrations or publications. Counts above describe the headline claim.
No reviewed experiment families mapped yet.
Studies & active trials
US regulatory timeline
Apr 8, 2016ProvayBlue injection approved under accelerated approval (21 CFR 314.500) for acquired methemoglobinemia in children and adults (NDA 204630).U.S. FDA (Drugs@FDA) ↗
Dec 5, 2023First of seven generic intravenous methylene blue approvals listed in openFDA (through 2025-12-23).U.S. FDA (openFDA Drugs@FDA) ↗
Only papers and registered trials an editor reviewed for this page. Being listed is not a finding; the claims above say what they show.
Methylene Blue in Septic Shock: A Systematic Review and Meta-Analysis.PMID 38904978 · DOI 10.1097/CCE.0000000000001110Study · Published · Jul 1, 2024 · Crit Care ExplorOpen source ↗
Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial.PMID 36915146 · DOI 10.1186/s13054-023-04397-7Study · Published · Mar 13, 2023 · Crit CareOpen source ↗
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.PMID 27863809 · DOI 10.1016/S0140-6736(16)31275-2Study · Published · Dec 10, 2016 · LancetOpen source ↗
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.PMID 41570392 · DOI 10.1016/j.tjpad.2026.100480Study · Published · J Prev Alzheimers DisOpen source ↗
Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain.PMID 27351678 · DOI 10.1148/radiol.2016152893Study · Published · RadiologyOpen source ↗
Early Methylene Blue in the Microhemodynamics of Septic PatientsNCT NCT07264543Trial · Recruiting · Mar 27, 2026 · Centro de Estudos e Pesquisa em Emergencias Medicas e Terapia IntensivaOpen registry record ↗
Intravenous Methylene Blue for Treating Refractory Neonatal Septic ShockNCT NCT06306001Trial · Not yet recruiting · Mar 12, 2024 · Post Graduate Institute of Medical Education and Research, ChandigarhOpen registry record ↗
Methylene Blue in Early Septic ShockNCT NCT04446871Trial · Completed · Hospital Civil de GuadalajaraOpen registry record ↗
What would change our mind
If a registered randomized trial lasting months shows a meaningful cognitive benefit in healthy or older adults, we would add it to the opening and re-grade the "not shown" line.
If FDA issues a new safety communication on non-prescription methylene blue products, we would add it to the safety sentence.
Early Methylene Blue in the Microhemodynamics of Septic PatientsCentro de Estudos e Pesquisa em Emergencias Medicas e Terapia Intensiva · checked Oct 11, 2026 · NCT NCT07264543; status:RECRUITING; primary completion 2026-11-30 (estimated)
Intravenous Methylene Blue for Treating Refractory Neonatal Septic ShockPost Graduate Institute of Medical Education and Research, Chandigarh · checked Oct 11, 2026 · NCT NCT06306001; status:NOT_YET_RECRUITING; primary completion 2026-03-14 (estimated)
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.J Prev Alzheimers Dis · checked Oct 11, 2026 · PMID 41570392; DOI 10.1016/j.tjpad.2026.100480
Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial.Crit Care · checked Oct 11, 2026 · PMID 36915146; DOI 10.1186/s13054-023-04397-7
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.Lancet · checked Oct 11, 2026 · PMID 27863809; DOI 10.1016/S0140-6736(16)31275-2
Methylene Blue in Septic Shock: A Systematic Review and Meta-Analysis.Crit Care Explor · checked Oct 11, 2026 · PMID 38904978; DOI 10.1097/CCE.0000000000001110
Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain.Radiology · checked Oct 11, 2026 · PMID 27351678; DOI 10.1148/radiol.2016152893
Does methylene blue improve memory, energy or healthy aging in people?
Human data are limited to small, single-dose imaging studies. A related compound did not slow Alzheimer's decline in large trials. A ClinicalTrials.gov search on 2026-10-11 found no active trial of methylene blue for cognition, memory or dementia.
What would answer it: A registered, randomized, placebo-controlled trial of at least several months measuring cognition or function, with safety monitoring for serotonin syndrome.
Established: intravenous methylene blue is an FDA-approved treatment for acquired methemoglobinemia, and it can cause serotonin syndrome with serotonergic drugs and opioids. Not shown: that methylene blue improves memory, energy or aging in people. Only small, short studies exist.
Does methylene blue improve survival in septic shock?Trials so far are small and single-center; the pooled mortality benefit is low certainty.What would answer it: A large multicenter randomized trial with mortality as a primary or key outcome; current registered trials are small (e.g. NCT07264543, 50 participants, est. 2026-11).