Methylene blue is an old dye with approved intravenous uses. Its research in people is recent and the trials are small, and the strongest human results come from intravenous doses given during surgery. Oral capsules have been tested much less.
What is approved, and what is not
Methylene blue is FDA-approved for treating methemoglobinemia, a blood disorder, given intravenously. Its use for memory, mood or healthy ageing is not approved.
Doses matter. Trials in people have used single doses of about 2 mg/kg intravenously, or about 4 mg/kg by mouth, which is far above the 25 and 50 mg capsules sold here.
Healthy adults: a single dose and brain imaging
Rodriguez and colleagues randomized 26 adults aged 22 to 62 to one oral 280 mg dose (about 4 mg/kg) or placebo. Brain scans were taken during attention and short-term memory tasks, about one hour after the dose.
The drug group had about 7% more correct responses in memory retrieval than placebo. The authors describe this as a single low dose and a short study, not a measure of lasting memory change.
Claustrophobia: fear extinction
Telch and colleagues gave 42 adults with marked claustrophobic fear either 260 mg of methylene blue (23 people) or placebo (19 people) immediately after six exposure sessions.
Fear was measured again one month later. People who had lowered their fear well during training showed less fear in the methylene blue group. Those who had not may have done worse on the drug, so the result depends on how training went.
Surgery: delirium in older patients
Deng and colleagues randomized 248 older patients having non-cardiac surgery to 2 mg/kg of intravenous methylene blue within an hour of anaesthesia induction, or to saline. The study was open-label, so the staff knew who had which treatment.
Delirium occurred in 7.3% of the methylene blue group against 24.2% of the control group. Early cognitive dysfunction on day 7 was 16.1% against 40.2%. Adverse events were similar in both groups.
Dementia: the large trials
Several trials have tested methylene blue or its derivatives in Alzheimer's and mild cognitive impairment. Summaries of the large trials find no clear overall benefit, and blinding has been hard because the drug turns urine blue.
The Alzheimer's Drug Discovery Foundation summary calls the human evidence for dementia mixed and criticises the statistical analysis of some trials.
Safety and interactions
- Low doses are linked to stomach and urinary side effects.
- Higher doses can cause anaemia and serotonin toxicity.
- It should not be taken with serotonergic medicines such as SSRIs or MAOIs.
What this does not say
- It does not show that the capsules sold here improve memory, mood or cognition.
- The healthy-adult trial is one study of 26 people with brain imaging and short tasks.
- The fear-extinction and surgical trials used different routes, doses and populations from the capsules.
- No large trial has shown a clear cognitive benefit in people with dementia.
How we use this
Our physicians read these trials as early and mostly small studies. They do not treat the healthy-adult result as proof of a memory benefit.
Before any prescription, our physicians check serotonergic medicines and other interactions, and they set the dose on the label schedule rather than on the dose used in a trial.
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- 1.Rodriguez et al., Multimodal randomized functional MR imaging of the effects of methylene blue in the human brain, 2016 Radiology (RSNA)
- 2.Telch et al., Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia, 2014 American Journal of Psychiatry
- 3.Deng et al., Methylene blue reduces incidence of early postoperative cognitive disorders in elderly patients undergoing major non-cardiac surgery: an open-label randomized trial, 2021 Journal of Clinical Anesthesia
- 4.Alzheimer's Drug Discovery Foundation, Cognitive Vitality Report: Methylene blue (and TRx0237), last updated September 27, 2024 Alzheimer's Drug Discovery Foundation