What Is Methylene Blue?

Methylene blue (ProvayBlue) is a medication doctors use to treat a rare blood condition called methemoglobinemia. Naturally, methylene blue is a solid. But as a medical treatment, it’s dissolved in water to make a blue liquid solution you get as an injection. 

Methylene blue has been around since it was invented in the 19th century by a German chemist. The textile industry first used it for dyeing purposes. Later, bacteriology, microscopy, and chemistry labs used its color-changing properties in experiments and tests.

About 125 years ago, a German physician began using methylene blue as a medical treatment for malaria. Since then, its uses have evolved. Currently, it’s FDA-approved only for treating methemoglobinemia, although doctors also use it off-label for other conditions. 

The FDA approved methylene blue as a treatment for methemoglobinemia in 2016. Methemoglobinemia is a blood disorder that keeps your red blood cells from delivering oxygen to your tissues. 

Sometimes methemoglobinemia is called “blue baby syndrome” because the lack of oxygen to the body’s tissues turns your lips, skin, tongue, and nail beds blue. This is also called cyanosis. Some people inherit this condition through genes they get from their parents, but many people get it when they take certain medications or recreational drugs or are exposed to certain chemicals. 

Methemoglobinemia can be life-threatening. Methylene blue is a cure for the disorder. It works by causing a chemical reaction in your blood. Methylene blue donates electrons to (reduces) methemoglobin molecules and converts them to hemoglobin. This increases the amount of oxygen they can deliver to your tissues. 

Methylene blue was originally designed to treat methemoglobinemia. It may also have some off-label uses, but they're still being studied. (Photo Credit: Creatas Video+/Getty Images)

A doctor or nurse will give you this medication in a clinic as an IV infusion into a vein. The infusion takes about 5 to 30 minutes. Usually it takes only one dose to work as a treatment for methemoglobinemia, but if you’re still having symptoms an hour after your first dose, your doctor may give you a second one.  

Before your health care team gives you methylene blue, they’ll review your medical history to see if you have any conditions that could affect how the medication works in your body. The main contraindication (a specific situation in which you shouldn’t use it because it may be harmful) for methylene blue is having a glucose-6-phosphate dehydrogenase (G6PD) deficiency.

“We worry about the drug causing hemolysis [the breakdown of red blood cells] in people who have congenital deficiency of G6PD,” says Charles Abrams, MD, director of the Penn-CHOP Blood Center in Philadelphia. This is a genetic disorder you’re born with that also affects red blood cells. Using methylene blue can make this worse. 

Your doctor will also ask if you:

Could have cyanide poisoning, which you can get from too much of certain foods, medications, or chemicals

Have a genetic disorder called glucose-6-phosphate dehydrogenase (G6PD) deficiency

Have kidney or liver disease

Are allergic to methylene blue, phenothiazines, thiazide diuretics, other medicines, foods, dyes, or preservatives

Are pregnant, trying to get pregnant, or breastfeeding. 

Taking methylene blue can cause some side effects, including:

These side effects aren’t serious and should go away without medical care. 

You could have more serious side effects, such as:

Chest pain

Confusion

Dizziness

Headache

Increased sweating

Stomach pain

Tell your doctor right away if you have these side effects. 

Interactions

Some medications don’t work well with methylene blue, either because they affect how methylene blue works or methylene blue affects how they work. Some medicines that should not be taken with methylene blue include:

Antidepressant medications are a concern because of a complication called serotonin syndrome. Serotonin syndrome is a drug reaction that happens when medication combinations create high levels of serotonin in your body. You can have mild symptoms like shivering and diarrhea or severe symptoms like muscle rigidity, fever, and seizures. It can even cause death if you don't treat it. 

Be sure your doctor knows all the medications you take so they can discuss how methylene blue may interact with them. 

Other Claims and Uses

Methylene blue has a long history of off-label and experimental use. Studies are still ongoing for these claims. 

“Hematologists only use methylene blue for methemoglobinemia, but it is sometimes used by ICU physicians as adjunctive therapy for shock,” says Abrams.

One study showed treating shock with methylene blue significantly shortened the time it took to reverse the effects of shock and shortened the length of stay in the intensive care unit.

Some of the other off-label and experimental uses include:

Poison antidote. Doctors use methylene blue as a cure for nitrite or aniline poisoning. You may come into contact with these chemicals in a factory, farm, or lab setting. 

Memory improvement. One theory behind methylene blue’s cognitive boosting abilities has to do with the high concentration of mitochondria in your brain and how the solution affects it. Studies show that several cognitive diseases that happen with age, such as Alzheimer’s and dementia, happen when mitochondria start to dysfunction. Since methylene blue can cross the blood-brain barrier (the protective layer that controls the passage of substances between the bloodstream and the brain), some researchers are studying whether it can help reduce oxidative stress on mitochondria and improve memory. 

Cancer detection. Methylene blue can be used in both cancer detection and in some cases, treatment. It acts as a dye to highlight abnormal cells, including cancer cells, and can also be used in photodynamic therapy (PDT) to destroy cancer cells.

Treating brain ifosfamide-induced encephalopathy. This brain disorder is caused by a certain chemotherapy medication.

Disinfectant. Emerging research shows that treating surfaces and personal protective equipment (PPE) with methylene blue and light can kill SARS-CoV-2, Ebola virus, norovirus, and other highly contagious pathogens.  

Anti-aging agent. Some studies have looked at methylene blue’s ability to improve cognitive function and slow aging.  

It’s rare for someone to have methylene blue toxicity, or an overdose of methylene in their system. But if this does happen, there isn’t an antidote. If you’re allergic to methylene blue, you should stop taking it immediately, followed by supportive care by your doctor. It’s not common for methylene blue to cause a serious allergic reaction. 

Serotonin syndrome can be fatal, which is why doctors don’t use methylene blue along with medications that include or increase serotonin, such as certain antidepressants. 

Is Methylene Blue Safe?

Methylene blue is safe for people who don’t have certain medical conditions or take medications that interfere with it. It’s only FDA approved for treating methemoglobinemia, but your doctor may prescribe it for off-label use if you have a condition it could help. You should always take methylene blue under the supervision of a doctor.  

Methylene blue is a blue liquid solution that’s FDA-approved to treat a rare blood problem called methemoglobinemia, where red blood cells can’t carry oxygen the right way. You get it as an IV infusion in your vein, and it often works after just one dose. Doctors sometimes use it for other things too, like treating certain types of shock, poisonings, or during cancer surgery to help find lymph nodes. Some early research also suggests it might help fight infections like COVID-19 or even have benefits for aging and brain health, but those uses are still being studied.

Can methylene blue be used with Lugol's iodine solution?

Yes, this technique is called double staining. Lugol’s iodine is a solution of potassium iodide with iodine in water. Your doctor may use both Lugol’s iodine and methylene blue together to diagnose a problem during an endoscopy. Typically doctors use this particular double staining method to find squamous cell carcinoma or other precancerous cells in the esophagus.

Does vitamin C interact with methylene blue?

If you take vitamin C with methylene blue, it can boost its effects. When you combine the two, their antioxidant power increases. You should only ever take methylene blue under the care of a doctor. Discuss any other medicines or vitamins that you are taking with them.

How long does it take for methylene blue to work in humans​?

The IV infusion of methylene blue takes less than 30 minutes in a clinic. Usually this one dose is enough to stop symptoms and treat the problem. If you still have symptoms of methemoglobinemia after one hour, your doctor may give you a second dose.