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Methylene Blue

Methylthioninium chloride

Old dye, hyped as a brain booster — human data are thin.

Preliminary evidence 🧠Nootropic⏳Longevity

✚ Updated · How we grade evidence

Evidence tier
Preliminary
Research weight
Citations
7 verified / 7
Classification
Nootropic
❝
What the evidence says. Graded preliminary: a single fMRI RCT showed a 7% memory-retrieval gain and two small psychiatry RCTs supported fear-extinction learning, but the large phase-3 Alzheimer's trial of the derivative LMTM failed its primary endpoints. The mechanism is real but durable cognitive benefit in healthy people is unproven. (Preliminary evidence: Early or small human trials; promising but not yet conclusive.)

What is Methylene Blue?

Methylene Blue (Methylthioninium chloride) is a nootropic used for possible short-term memory boost. NutriDex grades the human evidence as Preliminary. Methylene blue is a century-old synthetic dye used medically to treat methemoglobinemia and now marketed as a nootropic and 'longevity' aid. The strongest human signal is a randomized fMRI study in 26 healthy adults where a single low oral dose raised brain activity during attention and memory tasks and produced a 7% increase in correct memory-retrieval responses. Two small psychiatry RCTs found it can enhance retention of fear-extinction (exposure therapy) when learning succeeds. However, the large 891-patient phase-3 trial of its reduced derivative LMTM in Alzheimer's disease failed both primary cognitive and functional endpoints, with benefit seen only in an unplanned monotherapy subgroup. At low doses it supports mitochondrial electron transport, but evidence for lasting cognitive enhancement or extended lifespan in humans is absent. Effects are acute and dose-dependent — higher doses impair, not help.

Purported Benefits

✓Possible short-term memory boost
✓Mitochondrial energy support
✓Aids fear-extinction learning
✓Treats methemoglobinemia (medical use)

Evidence by outcome

The same supplement can be well-proven for one use and unproven for another — here is the human evidence graded outcome by outcome.

OutcomeEvidenceEffectStudies
Acute short-term memory boostSingle low-dose fMRI RCT (n=26) gave a 7% rise in correct memory retrieval; acute, one small trial. Preliminary ↑ benefit · small 1
Enhance fear-extinction / exposure therapyTwo small RCTs improved extinction retention only when post-session fear was low; can worsen it when high. Preliminary ↔ mixed · small 2
Alzheimer's cognition (LMTM derivative)Phase-3 trial (n=891) of the MB derivative failed both co-primary endpoints; benefit only in unplanned subgroup. Moderate — no effect · negligible 1
Treat methemoglobinemia (medical use)Established medical indication at 1 mg/kg IV; not a supplement use and carries serotonin-syndrome/G6PD warnings. Strong ↑ benefit · large 1

Dosing & Compounds

Typical Dose
Nootropic research uses single low oral doses (~0.5–4 mg/kg, often ~280 mg); there is no established supplement regimen, and high doses are toxic.
Active Compounds
Methylthioninium chloride (oxidized)Leucomethylthioninium (reduced)

Safety & Cautions

Methylene blue is a potent reversible MAO-A inhibitor and carries an FDA boxed warning for potentially fatal serotonin syndrome when combined with SSRIs, SNRIs, MAOIs, bupropion, triptans, tramadol or other serotonergic drugs — avoid these for at least 2 weeks before and 24–72 hours after. It is contraindicated in G6PD deficiency (causes hemolytic anemia) and should be avoided in pregnancy. High doses paradoxically cause methemoglobinemia, blue-green urine/skin, nausea, headache and can raise blood pressure; it may also interact with other MAO-affecting drugs. It is a prescription drug, not a dietary supplement, and unregulated 'pharma-grade' products vary in purity. Educational only — always check with your doctor or pharmacist before combining Methylene Blue with any medicine.

Key Studies

Safety Ostrovsky 2026 ✓ Full text
StatPearls: FDA boxed warning for fatal serotonin syndrome with serotonergic drugs; contraindicated in G6PD deficiency; methemoglobinemia dose 1 mg/kg IV.
RCT Rodriguez 2016 ✓ PubMed
Single low-dose oral MB raised fMRI response in attention/memory regions and gave a 7% increase in correct memory-retrieval responses (n=26).
RCT Zoellner 2017 ✓ PubMed
MB-augmented imaginal exposure for PTSD improved evaluator-rated response and quality of life vs placebo (NNT 7.5) at 3-month follow-up.
RCT Gauthier 2016 ✓ PubMed
Phase-3 trial of LMTM (MB derivative) in 891 mild-moderate Alzheimer's patients failed both co-primary endpoints; effect only in an unplanned monotherapy subgroup.
RCT Telch 2014 ✓ PubMed
260 mg MB after exposure improved 1-month retention of fear extinction and contextual memory when post-session fear was low (n=42); worsened it when fear was high.
Review Saeed 2023 ✓ PubMed
Review of 6 RCTs of MB and derivatives in Alzheimer's: signals of benefit but inconsistent; calls for larger trials before clinical use.
Review Pelgrims 2000 ✓ PubMed
Case series of 12 patients: IV MB resolved or prevented ifosfamide-induced encephalopathy, though some untreated cases also resolved spontaneously.
7 sources cited · 7 verified Search all studies on PubMed ↗

Common questions about Methylene Blue

What is Methylene Blue used for?

Methylene Blue is most often taken for Possible short-term memory boost, Mitochondrial energy support, Aids fear-extinction learning, Treats methemoglobinemia (medical use). Old dye, hyped as a brain booster — human data are thin.

Does Methylene Blue work — what does the evidence say?

Preliminary evidence. Early or small human trials; promising but not yet conclusive. Methylene blue is a century-old synthetic dye used medically to treat methemoglobinemia and now marketed as a nootropic and 'longevity' aid. The strongest human signal is a randomized fMRI study in 26 healthy adults where a single low oral dose raised brain activity during attention and memory tasks and produced a 7% increase in correct memory-retrieval responses. Two small psychiatry RCTs found it can enhance retention of fear-extinction (exposure therapy) when learning succeeds. However, the large 891-patient phase-3 trial of its reduced derivative LMTM in Alzheimer's disease failed both primary cognitive and functional endpoints, with benefit seen only in an unplanned monotherapy subgroup. At low doses it supports mitochondrial electron transport, but evidence for lasting cognitive enhancement or extended lifespan in humans is absent. Effects are acute and dose-dependent — higher doses impair, not help.

What is the typical dose of Methylene Blue?

Nootropic research uses single low oral doses (~0.5–4 mg/kg, often ~280 mg); there is no established supplement regimen, and high doses are toxic.

Is Methylene Blue safe? Any cautions or side effects?

Methylene blue is a potent reversible MAO-A inhibitor and carries an FDA boxed warning for potentially fatal serotonin syndrome when combined with SSRIs, SNRIs, MAOIs, bupropion, triptans, tramadol or other serotonergic drugs — avoid these for at least 2 weeks before and 24–72 hours after. It is contraindicated in G6PD deficiency (causes hemolytic anemia) and should be avoided in pregnancy. High doses paradoxically cause methemoglobinemia, blue-green urine/skin, nausea, headache and can raise blood pressure; it may also interact with other MAO-affecting drugs. It is a prescription drug, not a dietary supplement, and unregulated 'pharma-grade' products vary in purity.

How many studies support Methylene Blue?

NutriDex cites 7 sources for Methylene Blue, graded "Preliminary".

Cite this page
APA

Peh, D. (2026). Methylene Blue (Methylthioninium chloride): Benefits, Dosage, Side Effects & Evidence. NutriDex — The Supplement Research Compendium. Retrieved 26 Jun 2026, from https://nutridex.info/s/methylene-blue

BibTeX
@misc{nutridex_methylene_blue,
  author       = {Peh, Daryl},
  title        = {Methylene Blue (Methylthioninium chloride): Benefits, Dosage, Side Effects \& Evidence},
  year         = {2026},
  howpublished = {NutriDex --- The Supplement Research Compendium},
  url          = {https://nutridex.info/s/methylene-blue},
  note         = {Reviewed by Dr Daryl Peh, MBBS Singapore, MMed FM. Accessed 2026-06-26}
}

For medical claims, citing the underlying primary studies linked above is preferred. NutriDex is an educational reference, not medical advice.

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