Printed from https://bottledhope.co/supplements/methylene-blue/. Last reviewed 2026-09-25. Check the site for the latest version.

Methylene blue

A blue dye approved in the US as a prescription injection for acquired methemoglobinemia. Its label warns of serotonin syndrome with opioids and serotonergic drugs, including many antidepressants.

Explained simply · Last reviewed 2026-09-25

What it is

Methylene blue is a blue dye that, in the US, is approved as a prescription injection. Its FDA label describes it as a water-soluble thiazine dye, and research papers also call it methylthioninium chloride. It is approved for acquired methemoglobinemia, given into a vein.

More about Methylene blue

Its FDA label describes it as a water-soluble thiazine dye, and research papers also call it methylthioninium chloride. It is approved for acquired methemoglobinemia, given into a vein.

The label adds that in the body it is first converted to a form called leucomethylene blue, and that it can turn the skin and body fluids blue. The safety section below reports its approved use and the warnings on its label. The human trials cited on this page gave methylene blue by mouth, as capsules, for uses other than its approved one.

Some Alzheimer’s disease research used LMTX, which the authors of the 2015 trial cited below describe as a stable reduced form of methylthioninium. The ratings below do not count results for LMTX as evidence about methylene blue.

Also known as: methylthioninium chloride

At a glance

Safety: known risks, 5 groups who should avoid it or take extra care and 1 documented interaction. See Safety ↓

Claims made about Methylene blue, and how strong the evidence is for each:

Improves memory or attention in healthy adultsEvidence rating: Insufficient
Improves thinking and memory in people with bipolar disorderEvidence rating: Insufficient
Eases lingering depression and anxiety in bipolar disorder, added to lamotrigineEvidence rating: Limited
Slows decline in Alzheimer’s diseaseEvidence rating: Insufficient

Longevity and aging claims

Claims made about Methylene blue and aging, and how strong the evidence is for each. A change in a marker is not the same as a longer life.

Helps people live longerEvidence rating: Insufficient

Each rating follows our published rules and the sources cited for it. We don’t add our own medical judgment. How we rate

Safety

Read this before the ratings below.

Risks

United States regulatory status: methylene blue is approved by the US Food and Drug Administration (FDA) as a prescription drug given by injection. The FDA-approved prescribing information for ProvayBlue (methylene blue) injection, for intravenous use, revised February 2024, gives its initial US approval as 2016 and states that it “is indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia”. That is its approved medical use, reported here as a regulatory fact, not rated as a claim. The label is for an injection given into a vein (“for intravenous use”), not for a product taken by mouth.
Prescription status: the US National Library of Medicine’s DailyMed listing of the current ProvayBlue label, updated 28 May 2025, classes it as a “HUMAN PRESCRIPTION DRUG LABEL”, gives the route of administration as “INTRAVENOUS”, and shows the vial and ampule labels marked “Rx only”. The label warnings below are taken from the February 2024 FDA label; the last two items report trials, not the label.
Serotonin syndrome: the label’s boxed warning states that the drug “may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids”. The label reports that serotonin syndrome “has been reported with the use of methylene blue class products”, mostly in people also taking serotonergic drugs such as SSRI, SNRI or MAOI antidepressants, and that “Some of the reported cases were fatal.” The signs it lists include agitation, hallucinations, delirium and coma; a fast heart rate, unstable blood pressure, sweating and a high temperature; tremor, rigidity and muscle jerks; seizures; and nausea, vomiting and diarrhea.
Breakdown of red blood cells (hemolysis): the label states that treating people who have glucose-6-phosphate dehydrogenase (G6PD) deficiency “may result in severe hemolysis and severe anemia”, and contraindicates the drug for them. It also states that hemolysis “can occur during treatment of methemoglobinemia” and that the onset of anemia may be delayed by a day or more.
Allergic reactions: the label states that “Anaphylactic reactions to methylene blue class products have been reported”, and contraindicates the drug in people with severe hypersensitivity reactions to methylene blue or any other thiazine dye.
Pregnancy: the label states that the drug “may cause fetal harm when administered to a pregnant woman”. It reports that injection of a methylene blue class product into the amniotic fluid during the second trimester “was associated with neonatal intestinal atresia and fetal death”, and that methylene blue given by mouth to pregnant rats and rabbits produced adverse developmental outcomes.
Breastfeeding: because of “the potential for serious adverse reactions, including genotoxicity”, the label advises to “discontinue breast-feeding during and for up to 8 days after treatment”.
Confusion and dizziness: the label states that treatment “may cause confusion, dizziness and disturbances in vision”, and advises against driving or operating machinery until these have resolved.
Other effects the label lists: it “may cause a blue discoloration of the skin and body fluids”; phototoxicity may occur, so it advises protection from light; and methylene blue in the blood “may result in an underestimation of the oxygen saturation reading by pulse oximetry”.
Animal and laboratory findings reported on the label: in a two-year study in which rats were given methylene blue by mouth, it caused pancreatic islet adenomas or carcinomas (tumors) in male rats; a two-year study in mice found no drug-related tumors. Methylene blue was genotoxic in several laboratory tests, and negative in a micronucleus test in mice.
Taken by mouth in the bipolar disorder trial: in the trial cited below, the authors report that the most common side effects were mild and transient; they included urinary tract burning, diarrhea, nausea and headaches. Among the reasons participants left that trial were blue urine, increased anxiety and fluid retention, one person each.
Taken by mouth in the Alzheimer’s disease trial: in the trial cited below, the most commonly reported adverse events in people taking methylene blue included digestive effects (mainly diarrhea), urinary effects (mainly painful or frequent urination) and falls; digestive and urinary effects were also the most common reason for stopping. The authors report that it caused dose-dependent decreases in red blood cell count and hemoglobin and rises in methemoglobin, and note that methylene blue “is known to be associated with dose-related anemia”; they report no cases of clinically significant anemia and write that the effects “generally were not clinically significant”.

Who should avoid it or take extra care

Anyone taking an antidepressant or another serotonergic medicine, or an opioid: see the interaction below.
People with G6PD deficiency: the label contraindicates the drug because of the risk of hemolytic anemia.
Anyone who has had a severe allergic reaction to methylene blue or another thiazine dye: the label contraindicates the drug.
Pregnant or breastfeeding women: see the label warnings above.
People with kidney or liver problems: the label reports that methylene blue levels in the blood rose significantly in people with kidney impairment, and advises monitoring people with any liver impairment for toxicity and drug interactions for longer, because methylene blue is extensively metabolized in the liver.

Documented interactions

Serotonergic medicines, including SSRI, SNRI and MAOI antidepressants, bupropion, buspirone, clomipramine, mirtazapine, linezolid, opioids and dextromethorphan: The FDA label for the injection advises avoiding these together with methylene blue “because of the potential for serious CNS reactions, including potentially fatal serotonin syndrome”, and reports serotonin syndrome with “methylene blue class products” (see the risks above). It states that literature reports suggest methylene blue “is a potent reversible inhibitor of monoamine oxidase”, and advises telling patients “not to take serotonergic drugs within 72 hours after the last dose”. Source [1]

Safety sources: Source [1]Source [2]Source [3]Source [4]

What the evidence says

Each claim is rated on its own evidence. Ratings follow the scale on our methodology page.

Improves memory or attention in healthy adults Evidence rating: Insufficient
People take it hoping it will sharpen their memory and focus.
One small 2016 trial of a single dose in 26 healthy adults found a memory gain within the methylene blue group, but the difference from placebo was not significant.
Too little research to say. No systematic review of methylene blue for memory or attention in healthy people was found, and this page cites one small trial. In that 2016 randomized, double-blind trial, 26 healthy adults aged 22 to 62 took a single dose of methylene blue or a placebo capsule. Only six of them were older than 30. The placebo capsule contained a food coloring. Everyone was tested before and one hour after, and the trial’s main measures were brain-activity scans.

On a short-term memory task, correct answers rose by about 7% from before to after in the methylene blue group. That was a statistically significant change within the group, and there was no change in the placebo group. When the two groups were compared, the authors write that the difference “trended but was not significant”. Reaction times on an attention task did not differ between the groups.

The authors conclude that “Low-dose methylene blue can increase functional MR imaging activity during sustained attention and short-term memory tasks and enhance memory retrieval”. They describe the study as a proof of concept with a relatively small sample. They say future studies will include a larger sample and repeated dosing.

Under this site’s rules, an insufficient rating means the evidence is too limited to show whether there is an effect. It does not mean the trial found none.

Sources: Source [1]
Improves thinking and memory in people with bipolar disorder Evidence rating: Insufficient
People with bipolar disorder take it hoping it will help their thinking and memory.
A 2022 systematic review found one small trial and reports no significant findings for it; the trial found practically no differences between a higher and a very low dose.
Too little research to say. A 2022 systematic review by a task force of the International Society for Bipolar Disorders covered cognition trials published between 2015 and 2021. It found one randomized trial of methylene blue, and reports “No significant findings” for it on cognition. The review did not pool results or grade the certainty of the evidence.

In that 2017 crossover trial, 37 adults with bipolar disorder who were taking lamotrigine took a higher dose and a very low dose of methylene blue. They took each dose for three months, in random order, and cognition was a secondary outcome. The trial’s authors found “practically no differences” between the two doses on any of the cognitive tests.

The authors suggest their participants’ cognitive functioning may have been relatively preserved at the start, leaving little room to improve. They also suggest the very low comparison dose may have had some benefit of its own, which they consider unlikely. One small trial that found no effect is too little evidence to show an effect, and it is not evidence that there is none.

Several of the review’s authors disclose consulting or other fees from drug companies. The review states that the work was not funded.

Sources: Source [1]Source [2]
Eases lingering depression and anxiety in bipolar disorder, added to lamotrigine Evidence rating: Limited
People with bipolar disorder take it hoping it will ease lingering low mood and anxiety.
One small 2017 trial in people taking lamotrigine found lower depression scores, and some improvement in anxiety, on a higher dose than on a very low dose.
This rating rests on one small trial, in people taking lamotrigine. The trial tested methylene blue taken by mouth for a use that is not its FDA-approved one. The approved product is an injection for acquired methemoglobinemia (see the safety section).

In the 2017 double-blind crossover trial, 37 adults with bipolar disorder took methylene blue by mouth alongside their usual medicines. Their mood symptoms had only partly responded to long-term treatment. Every participant had to be taking lamotrigine as their main mood stabilizer. Each took a higher dose and a very low dose for three months each, in random order. The authors used the very low dose in place of a placebo because methylene blue discolours urine. Of the 37, 27 completed the six months.

Depression scores on two rating scales were significantly lower on the higher dose, and anxiety scores also improved. The authors note that the anxiety result appeared to come mainly from a lasting improvement in people who took the higher dose first. Mania scores stayed low throughout.

The authors describe the severity of mood symptoms in the trial as relatively low. They say the findings cannot necessarily be generalized to people on mood stabilizers other than lamotrigine. They conclude that methylene blue “used as an adjunctive medication improved residual symptoms of depression and anxiety in patients with bipolar disorder”. The trial was funded by a grant from the Stanley Foundation. The authors thank Star Pharmaceuticals for supplying both the active medication and the comparison capsules, without saying whether they were donated. They declare no conflicts of interest.

Sources: Source [1]
Slows decline in Alzheimer’s disease Evidence rating: Insufficient
People with Alzheimer’s disease take it hoping it will slow their decline.
One exploratory, company-funded 2015 trial found a benefit on a cognitive scale at one dose in moderate disease, but that result rested on 17 people.
Too little research to say, and no systematic review of methylene blue itself for Alzheimer’s disease is cited. The one trial cited, published in 2015, was an exploratory, placebo-controlled phase 2 study. It compared three doses of methylene blue (methylthioninium chloride) with placebo in 321 people with mild or moderate Alzheimer’s disease.

At 24 weeks, its prespecified primary analysis found a significant benefit on a cognitive scale at the middle dose in people with moderate disease. The authors note this rested on 17 people. They also report a benefit on a brain blood-flow scan measure at that dose in people with mild disease. On the cognitive scale, the lowest dose did not differ from placebo. The authors write that no benefit could be seen in people with mild disease, because those on placebo did not decline over 24 weeks. They add that formulation and absorption factors affecting the highest-strength capsules confound that dose’s results.

The authors report that “With continued treatment for 50 weeks, benefit was seen on the ADAS-cog scale in both mild and moderate subjects”. They also write that the 50-week data, “being as they are exploratory and post hoc, cannot support an inferential claim in the same way that the 24 week data can”. They write that their results support further trials, but that these “cannot be conducted” with methylene blue itself, because of absorption and longer-term tolerability limitations. They add that phase 3 trials were instead using a stable reduced form called LMTX. Those later trials are about that compound, not methylene blue, and this page does not rate them.

The study was financed entirely by TauRx Therapeutics. Three authors are officers of, and hold beneficial interests in, the company, and four are paid consultants to it.

Sources: Source [1]

Longevity and aging

What the cited sources report about lifespan, death from any cause, and markers studied in connection with aging. A change in a marker is not the same as a longer life. Each outcome is rated on its own evidence, on the same scale as the claims above.

Helps people live longer Evidence rating: Insufficient
People take it hoping it will slow aging and help them live longer.
No cited study measured lifespan in people; in a 2014 mouse study, methylene blue in the diet did not significantly change survival in male or female mice.
No cited study has measured lifespan or death from any cause in people taking methylene blue. The only lifespan evidence cited is in mice.

The mouse study is a 2014 report from the Interventions Testing Program, funded in part by the US National Institute on Aging. Methylene blue was added to the diet from 4 months of age. It did not significantly change survival in male or female mice of a genetically mixed strain, with results pooled across three test sites.

In females, the authors report a significant 6% increase in maximum lifespan, pooled across the sites. The test behind that result compares the proportion of mice still alive in each group at the age by which 90% of the mice had died, not the ages themselves. Median lifespan in females was 12% higher at one of the three sites. The authors do not consider that biologically significant, because pooled across all three sites the increase was a non-significant 1%. At another site there was a non-significant suggestion of shorter survival in males.

The authors conclude that methylene blue “did not lead to strong or consistent effects on lifespan” in these mice at the dose used.

Sources: Source [1]

Which form the evidence used

Supplements are sold in several forms. This is what the sources on this page say about them — which form the research used, and any comparison those sources themselves made. Where they made none, this page does not rank the forms.

Capsules swallowed by mouth, Details
All three human trials this page cites used capsules taken by mouth: a single dose, in capsules, in the memory trial in healthy adults, and capsules taken every day for months in the bipolar disorder and Alzheimer’s disease trials. None of them compared capsules with another form. The sources cited on this page do not address whether methylene blue capsules or drops sold to the public are approved, or how they are regulated. Source [1]Source [2]Source [3]
Drops or another liquid taken by mouth, Details
No study cited here tested methylene blue drops or any other liquid taken by mouth. The human trials cited here all used capsules, and the mouse lifespan study mixed methylene blue into the mice’s food. The FDA label reports animal studies in which methylene blue was “administered orally” to pregnant rats and rabbits, and two-year studies in which rats and mice were given “oral doses”, but does not say what form those doses took. So the cited evidence cannot say whether drops and capsules differ in absorption, effects or side effects. The sources cited here do not address whether capsules or drops sold to the public are approved, or how they are regulated. Source [1]Source [2]Source [3]Source [4]Source [5]
Injection into a vein, Details
The FDA-approved prescribing information cited on this page is for ProvayBlue injection, “for intravenous use”, for acquired methemoglobinemia. The DailyMed listing of its label gives the route as “INTRAVENOUS” and shows the vial and ampule labels marked “Rx only”. It is not a product taken by mouth, and none of the trials cited for the claims on this page used it. Most of the warnings in the safety section come from its label, which reports several of them, including serotonin syndrome and allergic reactions, for “methylene blue class products”, not only for this injection. The safety section also reports side effects from the trials that gave methylene blue by mouth. Source [1]Source [2]Source [3]Source [4]Source [5]

Sources

Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain
Radiology, 2016 · Randomized controlled trial · Supporting source
Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force
Bipolar Disorders, 2022 · Systematic review · Primary source
Some of its authors disclose ties to industry.
Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study
The British Journal of Psychiatry, 2017 · Trial without a placebo group · Supporting source
Tau Aggregation Inhibitor Therapy: An Exploratory Phase 2 Study in Mild or Moderate Alzheimer’s Disease
Journal of Alzheimer’s Disease, 2015 · Randomized controlled trial · Supporting source
This source discloses industry funding.
Some of its authors disclose ties to industry.
Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males
Aging Cell, 2014 · Animal or laboratory study · Supporting source
PROVAYBLUE (methylene blue) injection, USP, for intravenous use: prescribing information
U.S. Food and Drug Administration (Drugs@FDA, NDA 204630), 2024 · Health authority summary · Primary source
PROVAYBLUE- methylene blue injection (DailyMed label listing)
U.S. National Library of Medicine (DailyMed), 2025 · Health authority summary · Primary source

Page history

Show all 6 changes to this page

2026-09-28 — Rewritten to the content style guideline; ratings and sources unchanged.
2026-09-26 — Corrected the source type of the 2017 bipolar disorder trial from a randomized controlled trial to a trial without a placebo group: it compared a higher dose of methylene blue with a very low dose, with no placebo arm. The trial was already counted as supporting evidence only, so no rating changed.
2026-09-26 — Added a section on forms, at the owner’s request. It reports that the human trials cited here all used capsules taken by mouth, that none tested drops or another liquid taken by mouth, so the cited evidence cannot say whether drops and capsules differ, and that the FDA-approved product cited here is an injection into a vein. It notes that the sources cited on this page do not address how capsules or drops sold to the public are regulated. No new source was added, and no rating changed.
2026-09-26 — Published. The claims, the FDA label warnings and every source passed the site's source and wording reviews over two revision rounds. The summary follows ADR 0027; the owner's decisions are recorded in docs/08-open-decisions.md.
2026-09-25 — Revised after source review. The summary now says the approved product is a prescription injection given into a vein, and no longer describes its supplement or market status, which no cited source states. The prescription status is now cited to the DailyMed label listing. The bipolar mood claim is scoped to people taking lamotrigine, and the Alzheimer’s summary adds the authors’ 50-week result with their caveat. No rating changed.
2026-09-25 — First drafted, under ADR 0017. Memory and attention in healthy adults, cognition in bipolar disorder, and Alzheimer’s disease rated insufficient; lingering depression and anxiety in bipolar disorder rated limited; lifespan rated insufficient.