Methylene Blue Benefits: What the Human Trials Show, and Who Should Never Take It

Methylene blue is an old hospital drug that, at low doses, helps mitochondria move electrons. In small human trials it improved memory retrieval and leftover depression.

It also has two hard limits. It is dangerous with antidepressants, and it is dangerous for people with G6PD deficiency. Read that part before anything else.

What is methylene blue?

It is a blue dye that doctors have used for a long time. Its main hospital use is methemoglobinemia, a blood problem where hemoglobin cannot carry oxygen. The dose there is 1 to 2 mg per kg, given into a vein. (Clifton 2003)

The reason people take it as a supplement is different. A review of the brain research describes low-dose methylene blue as an electron cycler in the mitochondrial electron transport chain. It supports the respiratory enzyme cytochrome oxidase. The same review says the dose response is hormetic: low and high doses have opposite effects. (Rojas 2012)

That last sentence matters. More is not better with this compound.

Methylene blue benefits: what the studies show

• Memory in healthy adults. 26 people aged 22 to 62 took a single low oral dose or a placebo and had brain scans before and one hour after. Methylene blue raised brain activity during attention and short-term memory tasks. Correct answers during memory retrieval went up by 7%. (Rodriguez 2016)
• Fear memory. 42 adults with claustrophobia did exposure training in a small chamber. Right after, 23 got 260 mg of methylene blue and 19 got a placebo. A month later, the people whose fear was already low at the end of training had less fear if they had taken methylene blue. (Telch 2014)
• Leftover depression in bipolar disorder. 37 patients on lamotrigine took 195 mg a day or a 15 mg comparison dose in a 6-month crossover trial. The active dose improved depression and anxiety scores. The effect on cognition was not significant. (Alda 2017)
• PTSD therapy. 42 patients got 260 mg or a placebo after each of 5 daily exposure sessions. Methylene blue improved the rated treatment response, with a number needed to treat of 7.5. (Zoellner 2017)
• Skin, in the lab. In cultured human skin cells and a 3D skin model it lowered reactive oxygen species and raised elastin and collagen. That is a dish, not a face. (Xiong 2017)

Methylene blue and red light therapy

The two get paired because they aim at the same target. A review describes near-infrared light as having similar neurometabolic mechanisms of action as low-dose methylene blue. Both are meant to improve mitochondrial respiration. (Gonzalez-Lima 2014)

The direct test is in mice. 55 mice were put under chronic stress for 4 weeks. Light through the skull, methylene blue, and the two together all reversed the learning and memory damage. The abstract does not say the combination beat either one alone. (Meynaghizadeh-Zargar 2020)

I found no human trial of the combination. For light itself, see Ray Peat on red light.

Methylene blue dosage: what the studies used

• Hospital use for methemoglobinemia: 1 to 2 mg per kg, into a vein.
• Fear and PTSD studies: 260 mg by mouth, once after a session.
• Bipolar trial: 195 mg a day. The 15 mg dose was used as the comparison.
• Brain scan study: described only as a single low oral dose. The abstract gives no number.
• Absorption: in 16 healthy people, 500 mg in water by mouth had an absolute bioavailability of 72.3%. It is well absorbed. (Walter-Sack 2009)

These are study doses. They are not a recommendation. I have never posted a personal dose, so I am not going to invent one here.

Methylene blue side effects, and is methylene blue safe?

This is the honest part, and it is the most important section of this page.

• Serotonin syndrome with SSRIs and MAOIs. Methylene blue is a potent reversible inhibitor of the enzyme MAO-A, which breaks down serotonin. That makes it an MAO inhibitor itself. (Ramsay 2007) A systematic review found 26 patients who became acutely confused after a methylene blue infusion. 24 of them were taking a serotonin reuptake inhibitor and 1 was taking clomipramine. (Ng 2010)
• G6PD deficiency. An evidence review found solid evidence to prohibit only seven drugs in people with this enzyme defect. Methylene blue is one of them, because it can destroy red blood cells. An estimated 400 million people carry a G6PD mutation. (Youngster 2010)
• High doses. In a large trial of a related form of the molecule, the most common side effects were gut and urinary, hemoglobin fell slightly with dose (not to a clinically significant degree), and the control pill had to contain a little of the drug because it colours urine and stool. (Gauthier 2016)
• It does not help everyone. In the claustrophobia study, people who finished training still afraid tended to do worse on methylene blue than on placebo.
• The biggest trial was negative. That same large trial gave the related compound to 891 people with Alzheimer's disease for 15 months. It showed no benefit at either dose.

So is it safe? At hospital doses a toxicology review calls it generally safe, with dose-related effects on red blood cells. I found no long trial in healthy people taking it every day.

If you take an SSRI, an SNRI, an MAOI or any other antidepressant, do not take methylene blue. Do not stop your medication to try it either. That is a talk with your doctor.

Methylene blue supplements

The brain researchers specify low-dose USP methylene blue, which is the pharmaceutical grade. What is sold as a supplement, a lab stain or an aquarium product is not checked the same way. In my view that is a real risk with a compound you take by the drop.

What I think

I list methylene blue among the compounds that support oxidative metabolism. In my view it belongs to a family of molecules that handle reactive oxygen and lower lactate. I have also written about using it on the scalp together with caffeine. Those are my ideas, not trial results.

It comes after the basics. Sugar, salt, sunlight, sleep and gelatin do more than any dye.

If serotonin is the thing you are trying to fix, start with how to lower serotonin.

Quick answers

What are the benefits of methylene blue?

In small human trials a low dose improved memory retrieval by 7% in 26 healthy adults, helped the retention of fear extinction after a successful exposure session, and improved residual depression and anxiety in 37 people with bipolar disorder. A large Alzheimer's trial of a related compound found no benefit.

What are the side effects of methylene blue?

The serious ones are serotonin syndrome when it is combined with serotonergic antidepressants, and destruction of red blood cells in people with G6PD deficiency. In a large trial of a related form, gut and urinary effects were the most common. It also colours urine.

What methylene blue dosage was used in studies?

Hospitals use 1 to 2 mg per kg into a vein for methemoglobinemia. Fear and PTSD studies used a single 260 mg oral dose, and a bipolar trial used 195 mg a day. These are research doses, not advice.

Is methylene blue safe?

It is an established hospital drug, but it is not safe for everyone. It must not be combined with SSRIs, MAOIs or similar antidepressants, and people with G6PD deficiency should avoid it. There is no long-term trial of daily use in healthy people.

Do methylene blue and red light therapy work together?

Both are proposed to improve mitochondrial respiration. In a study of 55 stressed mice, each one reversed memory problems, alone and together. No human trial has tested the combination.

Is a methylene blue supplement the same as the drug?

Not necessarily. The brain research specifies pharmaceutical USP-grade methylene blue. Supplements and dye products are not held to that standard.