Exploring Low-Dose Oral Methylene Blue for Mitochondrial Support

About 95 percent of people have some level of mitochondrial dysfunction, and methylene blue has the potential to help most of them, according to Scott Sherr, MD.

“It could be used across the board for a variety of patients to help them feel better and faster while you're doing the hard work of trying to figure out why their mitochondria aren't working,” said Dr. Sherr, Chief Operating Officer of Transcriptions TX, a methylene blue retailer.

Nicknamed the "magic bullet," methylene blue’s ability to target specific bacteria without causing serious harm to the rest of the body was revolutionary for its time. It was the first drug registered with the U.S. Food and Drug Administration in 1897, originally used as an antimicrobial to treat diseases like malaria. Later, it would be among the earliest drugs used for psychosis. However, after the advent of antibiotics and antipsychotics, it came out of favor due in part to its alarming side effect of turning urine blue.

Recently, there’s been a renewed interest in the drug. Methylene blue, a liquid dye, reemerged largely after the COVID-19 pandemic because of its antiviral, antifungal, and antibacterial properties, in addition to its purported ability to improve mitochondrial function. Now, practitioners like Dr. Sherr are using it to help treat a variety of conditions.

“There's a huge breadth of how we can use this from the severe chronic complex medical illness side all the way to the performance side,” said Dr. Sherr. “And the key is that dosing matters.”

Due to its affordable cost and accessibility, methylene blue is still used to treat malaria in parts of Africa. However, in traditional medical settings, it's mainly used for the blood disorder methemoglobinemia. In addition, the dye is sometimes used in surgical settings to mark certain areas of the body.

Today, hospitals also use methylene blue for emergency treatment of poisoning by cyanide, nitrate, and carbon monoxide, as well as septic shock. In these contexts, it’s usually administered intravenously in relatively large amounts. But, according to Dr. Sherr, the drug can have significant beneficial effects even in small, oral doses.

The Resurgence of Methylene Blue

Claims that methylene blue, a drug studied since the 1800s, can treat modern complex health issues have been met with criticism. During the early days of the pandemic, social media influencers promoted methylene blue not only as a performance enhancer but also as a possible cure for COVID-19, which was thus seized upon by untrustworthy online distributors.

Dr. Sherr’s company was among the first to start selling methylene blue commercially, but since then, many manufacturers that use questionable ingredients have followed suit. “Now, there's a ton of companies that have it, but the quality is a challenge across the board,” he explained.

The proposed indications for methylene blue are far-reaching; ongoing research explores its use for neurodegenerative diseases, cancer, COVID-19, and cardiovascular disease. However, human clinical trials to substantiate these applications are limited.

“Most of the studies that have been done, except for a few small human trials, have been done in animals,” said Dr. Sherr. “So, when we're talking about Alzheimer's, traumatic brain injury, and acute ischemic stroke, most of that's been done in animals.”

Methylene Blue for Mitochondrial Support

Methylene blue not only enhances energy production but also acts as a strong antioxidant, classifying it as a redox cycler. In addition, it has high bioavailability— almost all an administered dose reaches the bloodstream quickly, whether it’s taken intravenously, orally, or in other forms.

Dr. Sherr said he believes that patients with chronic conditions like Lyme disease, post-mold exposure, or post-COVID, who continue to experience symptoms due to poor mitochondrial function, may benefit from low-dose methylene blue. However, he said, that’s not to say it will cure them.

“During my presentations on methylene blue, I've been very clear that it should really only be used as a synergistic treatment right now, not as a standalone, and that most of the data is still not in humans,” he explained.

Dr. Sherr said treatments should involve starting with a small dose and gradually increasing it until an effective dose is reached, then maintaining or adjusting as needed based on the patient's response. For enhanced mitochondrial function, he suggests 60 milligrams. He recommends slightly higher doses for acute infections or trauma, approximately 50 to 70 milligrams.

“The dosing can be very low to see a significant impact,” said Dr. Sherr. “Most of the research published [on Alzheimer's disease] is seeing benefit from even six, four, eight, 12, 16, or 25 milligrams, which are really, really low doses.”

At these low doses, Dr. Sherr explained that methylene blue is safe and inexpensive, making it accessible to a variety of patients. Although, he did note that patients should not use methylene blue if they are pregnant, breastfeeding, or have a G6PD deficiency. In addition, for practitioners who lack expertise in methylene blue, he warned against giving it to patients taking serotonergic drugs and psychedelics.

Methylene Blue in Clinical Practice

While the research may show promise, for many physicians, that’s not enough. Robert Rountree, MD, a core faculty member for the Institute of Functional Medicine who has been practicing integrative medicine in Boulder, Colorado since 1983, said there’s too little evidence for him to recommend the drug to patients.

“It seems to have some therapeutic potential beyond the accepted indications, but the human data is too limited for me to say whether it is effective and safe for mitochondrial support and the wide range of related clinical conditions for which it is being recommended by some practitioners,” said Dr. Rountree. “In other words, there are still lots of unknown issues to be resolved before it will be acceptable for more widespread use.”

According to David Brady, ND, Chief Medical Officer for Designs for Health, Inc. and Diagnostic Solutions Labs, LLC, the mechanisms of methylene blue are strange and somewhat unclear. But, he said, its potential mitochondrial effects made it an attractive option for his patients struggling with symptoms of persistent and post-exertional fatigue.

Dr. Brady said he tried using oral methylene blue on several of his long-COVID patients, including his wife, and saw no remarkable changes. He explained that the improvements he did see were hard to attribute to methylene blue directly, as the patients were all undergoing other treatments simultaneously.

“Believe me, I wanted it to work,” said Dr. Brady. “My wife has [long-COVID], and I don't care what fixes her fatigue. I don't care if it's a drug. I don't care if it's a supplement. I don't care if it's a rain dance in the driveway. I don't care. I just really wanted it to work as well as they said.” He also tried methylene blue for his patients with chronic fatigue, even pushing the dose a bit, to no avail. “I just honestly haven't seen the dramatic clinical effect that they're saying.”

While some practitioners are skeptical, others swear by it. In fact, Dr. Sherr’s father, Alan Sherr, D.C., who is the founder and director of the Northport Wellness Center in Northport, New York, is a strong proponent of methylene blue products. He said he recommends them to a variety of his patients, from those struggling with anxiety to those with acute viral infections. 

“A patient will report within a day or two that they're getting better faster from their symptoms, along with more vitality, less fatigue, and getting up in the morning with a little bit more of an oomph rather than needing a cup of coffee,” said Dr. Alan Sherr. “Those are things we hear regularly.”

The Bottom Line

Whether low-dose methylene blue improves mitochondrial function is up for debate, mostly because there is not enough clinical research to draw meaningful conclusions. However, if integrative practitioners are interested in trying it for their patients, Dr. Brady suggests keeping a few things in mind:

• Know the source: While methylene blue is a prescription drug when used intravenously, oral doses are over the counter. It’s important to research safe and reliable methylene blue retailers because non-pharmaceutical-grade products can be filled with toxins.
• Drug interactions: Although lose-dose methylene blue is generally safe, high amounts can have serious interactions with antidepressants and anti-anxiety medications. In addition, methylene blue is a nitric oxide inhibitor. If patients are taking nitric oxide supplements to improve blood circulation, methylene blue may make them less effective.
• Control expectations: Patients with complex illnesses like long COVID are often desperate for solutions. If you decide to put them on methylene blue, it should be with the explicit caveat that it’s an experimental treatment and may not work.

Dr. Brady’s parting advice for practitioners: Do your homework. “Take the time to learn about methylene blue and how to use it correctly,” he explained. “Using the right dosage according to body weight is crucial if you want to give it a proper trial; don't buy some random liquid off Amazon, and if your patients are on antidepressants or anxiolytic drugs, they should either not take it or be monitored by a practitioner who understands the interactions.”