Methylene Blue research

What published studies found for Methylene Blue: 7 papers, 7 in humans, with sample sizes and key results, plus 128 registered clinical trials.

Reported side effects

• commonGastrointestinal effects [ref]
• commonUrinary effects [ref]
• commonDose-dependent decrease in hemoglobin [ref]
• uncommonHeadache [ref]
• uncommonDiarrhea [ref]
• reportedSerotonin syndrome when combined with serotonergic antidepressants [ref]

Registered clinical trials

128 trials of Methylene Blue on ClinicalTrials.gov: 22 active, 71 completed, 19 with posted results. Registered trials include ones that haven't published yet.

All 128 Methylene Blue trials, with countries and recruiting status

Meta-analyses & systematic reviews

Human studies

? Inconclusivehuman RCTJ Alzheimers Dis · 2018

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.

n = 800 humansNon-randomized cohort analyses as modified primary outcomes within an 18-month phase III trial of LMTM18 months

Revised, non-randomized cohort analysis of an 800-patient phase 3 LMTM trial suggested benefit for monotherapy users; authors state a new randomized trial is needed.

Studied

Patients with mild Alzheimer's disease

Compared with

LMTM 4 mg twice a day (randomized control, add-on or monotherapy)

Main outcome

ADAS-cog, ADCS-ADL, MRI atrophy, glucose uptake

Sample

800 mild AD patients randomized; monotherapy subgroups n = 79 and n = 76

Authors' conclusion

Results support the hypothesis that LMTM might be effective as monotherapy and that 4 mg twice a day may work as well as higher doses; a further randomized trial is required.

Limitations

Primary analysis revised before unblinding to non-randomized subgroup comparisons; monotherapy vs add-on is not randomized.

PubMed 29154277DOIFree full text

~ Mixedhuman RCTJ Prev Alzheimers Dis · 2026

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.

n = 598 humansPhase 3 trial with modified delayed-start design; hydromethylthionine mesylate (HMTM) 16 or 8 mg/day52 weeks controlled, followed to 104 weeks

Phase 3 trial of HMTM (598 patients, MCI or mild-moderate Alzheimer's): no separation on primary clinical endpoints at 52 weeks, with later cognitive and biomarker differences in the MCI subgroup.

Key resultNo significant co-primary difference at 52 weeks; in MCI, ADAS-cog13 differences at 78 weeks (p = 0·0291) and 104 weeks (p = 0·0308); NfL progression reduced at 52 weeks (p = 0·0291)

Studied

Participants with MCI or mild to moderate dementia due to Alzheimer's disease, 82 centres

Compared with

Methylthioninium chloride 4 mg twice weekly (urinary colourant for blinding)

Main outcome

ADAS-cog11 and ADCS-ADL23; NfL, pTau217 and grey matter atrophy biomarkers

Sample

598 amyloid β-PET positive participants (263 MCI, 335 mild to moderate dementia)

Authors' conclusion

Symptomatic activity in the control arm precluded separation on primary endpoints at 52 weeks; in MCI, clinical separation emerged only at 78 and 104 weeks. HMTM was well tolerated.

Limitations

Primary clinical endpoints not met at 52 weeks; control arm had symptomatic activity; later findings partly rely on external controls.

PubMed 41570392DOIFree full text

Verdicts are judged on each paper's own main outcome; grades run from A (strong human evidence) to D (little or none). Details are read from the abstracts, and figures are reproduced only from openly licensed full texts. Not medical advice.