METHYLENE BLUE

What to know about methylene blue

Once used to dye cotton and treat malaria, methylene blue is gaining attention for a variety of off-label uses. Learn where it started, how it works, and what the evidence says about its safety and health benefits.

By Leslie Goldman, MPH, Health Writer

Reviewed by Robert H. Shmerling, MD, Senior Faculty Editor, Harvard Health Publishing; Editorial Advisory Board Member, Harvard Health Publishing

A vibrantly colored cobalt-blue synthetic dye with a long history of concrete medical applications — treating malaria or a rare blood disorder called methemoglobinemia, for instance — methylene blue has some recognized medical uses. However, despite recent reports of off-label uses that have popped up in the news over the past few months, the only FDA-approved use for methylene blue is for the treatment of methemoglobinemia. This rare condition restricts the ability of red blood cells to deliver oxygen throughout the body.

Methemoglobinemia is typically caused by exposure to certain medications, chemicals, or recreational drugs; methylene blue primarily treats it by increasing hemoglobin’s oxygen-binding capacity. (Blue-tinged skin, resulting from inadequate oxygen levels in the blood, is a hallmark symptom of methemoglobinemia, so it’s somewhat ironic that the treatment itself is a shocking blue color.)

But the short-term use of a pharmaceutical-grade product in a controlled setting under the supervision of a skilled medical provider is different than buying an unregulated supplement off the internet and taking it every day because you’ve heard that it will give you loads of energy by “enhancing mitochondrial efficiency.”

In light of the increased attention being paid to the inky liquid, it makes sense to learn a bit about methylene blue’s history, how it works, and whether its various health claims stand up to closer scrutiny.

What is methylene blue, and how does it work?

As one of the world’s oldest organic dyes, methylene blue was first used in 1876 as a textile dye. Within a few years, scientists were using it to stain microorganisms to help diagnose certain infections. In 1891, it was found to be helpful to treat malaria, thus making methylene blue “the first synthetic compound ever used as an antiseptic in clinical therapy and the first antiseptic dye to be used therapeutically,” according to the authors of a Medicinal Research Reviews paper on the compound.

Methylene blue is used off-label for several medical conditions, including

• vasodilatory shock (also called distributive shock), a medical emergency in which the body can’t distribute sufficient blood to the heart, brain, and kidneys.

• as an antidote to cyanide poisoning

• in photodynamic therapy for disorders such as psoriasis and chronic wounds

• to help diagnose, manage, or improve the treatment of various types of cancer, including cancers of the breast, mouth and skin (for instance, methylene blue may be used to identify cancer that has spread to a nearby lymph node by staining the lymph node blue, according to Anna N. Yaroslavsky, Director of the Advanced Biophotonics Laboratory at the University of Massachusetts, Lowell, and a visiting scientist at Massachusetts General Hospital)

• to ease the pain of oral mucositis, inflammation of the oral mucous membranes that often occurs with either radiation therapy to the head and neck or with chemotherapy.

Methylene blue and the detection of cancer

Dr. Joseph D. Feuerstein, an associate professor of medicine at Harvard Medical School and clinical chief of gastroenterology at Beth Israel Deaconess Medical Center, says that applying methylene blue to the colon epithelium during a colonoscopy creates a “great contrast, where you can actually see it enhance the detection of polyps, and precancerous growths in the colon in general.” He uses it mostly in patients with longstanding inflammatory bowel disease (IBD) because of their increased risk for colorectal cancer

Besides aiding in the detection of multiple types of cancerous and precancerous lesions, methylene blue is sometimes combined with light therapy (such as that from a laser) to help treat lung cancer, breast cancer, and others.

Methylene blue for the masses?

As the public grows hungrier for anti-aging products with the potential to increase not just lifespan but health span, the popularity of supplements like vitamins, herbs, and nootropics  (and ” smart drugs”) has surged. In recent years, methylene blue has been added to this list. Although evidence of some proposed health benefits is inconclusive, advocates of methylene blue suggest that it can:

• slow aging

• enhance memory

• improve mood and focus

• prevent cancer

• reduce the risk of incurable neurological disorders like Alzheimer’s disease.

Because it’s shown promise in protecting mitochondria — the tiny structures that serve as the energy-producing powerhouses of cells that weaken as the decades tick by — people have started to promote methylene blue as a way to slow cellular aging, including in the brain.

Beware unverified health claims and unregulated off-label use.

As with any drug, it’s important to remember that there are no magic bullets, and any study suggesting that the newest hot product clears brain fog or fights cancer requires confirmation by other independent researchers. In fact, a 2023 paper published in the Journal of Cerebral Blood Flow & Metabolism reported that methylene blue (in similar doses studied by researchers at The University of Texas at Austin who claimed the compound had memory-enhancing properties) led to a ∼8% decrease in human brain blood flow.

Other researchers have pointed out that even pharmaceutical-grade methylene blue contains impurities, and that industrial-grade or chemical-grade methylene blue, like that sold as a stain or dye, should not be used in humans or animals. If someone ordered the wrong type of methylene blue off the internet, they could end up quite ill. (If you search for “methylene blue” on Amazon, for instance, you could end up inadvertently purchasing fish tank cleaner, as methylene blue is also used as an antifungal aquarium disinfectant.)

The blue tonic on so many people’s lips has other significant risks. For instance, methylene blue is a monoamine oxidase (MAO) inhibitor, a type of drug used to treat depression. It’s also structurally similar to tricyclic antidepressants. This is likely why it’s been touted as a nonprescription alternative to fight depression. But suppose a person is already taking certain antidepressants such as fluoxetine (Prozac) or duloxetine (Cymbalta) and adds methylene blue to their routine. In that case, it can result in a dangerous and sometimes fatal interaction.

The bottom line

In the race to see who can live the longest and healthiest, OTC compounds like methylene blue often gain intense attention. But they should also engender intense scrutiny. It’s critical to keep in mind that just because a particular drug or supplement works in a precise clinical setting (like breast cancer detection), that doesn’t necessarily mean that it can or should be used by the general population.

About the Author

Leslie Goldman, MPH, Health Writer

Leslie Goldman is a Chicago-based journalist specializing in women’s health. Her writing regularly appears in Prevention, AARP, Good Housekeeping, Real Simple, and more. View all posts by Leslie Goldman, MPH

About the Reviewer

Robert H. Shmerling, MD, Senior Faculty Editor, Harvard Health Publishing; Editorial Advisory Board Member, Harvard Health Publishing

Dr. Robert H. Shmerling is the former clinical chief of the division of rheumatology at Beth Israel Deaconess Medical Center (BIDMC). He is a current member of the corresponding faculty in medicine at Harvard Medical School.