What are the benefits of methylene blue? A medical review

Methylene blue is a common dye that is known to have antioxidant, antidepressant, antimalarial, neuroprotective, and cardioprotective properties. It is FDA approved for the treatment of methemoglobinemia, a blood condition that leads to tissues not getting enough oxygen.

Methylene blue has other non-approved (off-label) uses, such as use as a dye during certain procedures and for ifosfamide-induced encephalopathy. It is typically given intravenously by a healthcare professional. Below, we’ll review potential benefits and risks of methylene blue.

Cognitive Benefits

Several studies in animals and humans have demonstrated methylene blue's potential to enhance cognitive function, particularly memory, attention, and executive function. These cognitive benefits may be partially attributed to:

• Increasing brain-derived neurotrophic factor (BDNF) levels, a protein involved in learning and memory.
• Improving mitochondrial function in neurons, enhancing oxygen consumption in the brain.

These improvements in brain metabolism provide neurons with greater energy resources for optimal functioning, potentially explaining the observed cognitive benefits. It is important to note that studies in this area have been small, and more research is needed in humans to fully understand the effects of methylene blue on cognition.

Human Studies

• Functional magnetic resonance imaging study: A study of 26 adults found a low dose of methylene blue improved memory retrieval by 7% 1 hour after administration. Researchers observed increased activity in areas of the brain associated with memory and attention (i.e., prefrontal, parietal, and occipital cortex).
• Functional connectivity study: Another MRI study of 28 adults showed that a low dose of methylene blue can increase functional connectivity between areas in the brain associated with memory and coordination.

Animal Studies

• Memory in rats: A study in rats showed that methylene blue improves spatial memory retention and brain oxidative metabolism.

Neuroprotective Effects

Beyond enhancing normal cognitive function, methylene blue demonstrates neuroprotective effects. Research suggests it helps protect neurons from oxidative stress and neuroinflammation, both implicated in neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. By reducing oxidative damage and inflammation, methylene blue may help preserve cognitive function and delay the onset of age-related cognitive decline.

Animal and In-Vitro Studies

• In Alzheimer's disease models, methylene blue has shown promising results in preventing the aggregation of amyloid-β (Aβ) and tau proteins in rats, two pathological hallmarks of the disease.
• Studies of methylene blue in rats have shown restoration in mitochondrial function.
• In vitro studies have shown that methylene blue prevents dopaminergic loss.
• A study in mice showed methylene blue improved motor coordination, suggesting a potential role in Parkinson’s disease treatment.

While these studies suggest that methylene blue may have potential benefits for neurodegenerative diseases, more studies (especially large-scale human trials) are needed to confirm these benefits in humans and determine a proper treatment dosage.

Anti-Aging Properties

In addition to brain health, methylene blue shows potential in addressing skin aging. Like brain tissue, skin undergoes mitochondrial dysfunction during aging, which contributes to decreased skin elasticity, increased wrinkle formation, and impaired wound healing. Environmental factors like UV radiation also play a role in skin aging. Methylene blue's antioxidant properties may help counter these effects, potentially offering a novel approach to skin rejuvenation.

While methylene blue is found in some anti-aging products sold over the counter, there is currently not enough research to know how effective it is and the optimal dose to prevent or treat wrinkles.

Antimicrobial Properties

Methylene blue is known to have disinfectant properties, and has historically been used to treat gonorrhea, bladder infections, Candida infections, and Lyme disease. It is also being studied as an antiviral against SARS-CoV-2 for COVID-19 treatment. Its antimicrobial effects are primarily mediated through DNA damage. It has also been shown to block RNA translation and replication of viral RNA in COVID-19 studies. Currently, methylene blue is not FDA approved to treat any infection.

Antidepressant Effects

Because methylene blue has a similar chemical structure to tricyclic antidepressants, it has some antidepressant properties. However, it can interact with antidepressant medications and cause a life-threatening condition called serotonin syndrome.

Medical Applications of Methylene Blue

Methylene blue is FDA approved for the treatment of methemoglobinemia, a condition in which the oxygen-carrying capacity of red blood cells is reduced. This condition can result from exposure to certain drugs like dapsone and local anesthetics, foods that contain high levels of nitrates, or it may be passed down through families.

Beyond its approved use, methylene blue has numerous off-label applications in clinical medicine:

• Vasoplegic syndrome treatment: Methylene blue is used during coronary procedures, particularly coronary artery bypass grafting, to increase systemic vascular resistance when epinephrine is not working well.
• Surgical mapping: During lumpectomy/mastectomy with sentinel lymph node biopsy, methylene blue serves as a dye to map lymph nodes for signs of malignancy.
• Pain reduction: Applied 45 seconds before propofol administration, methylene blue can reduce post-injection pain.
• Antimalarial agent: Methylene blue can treat Plasmodium falciparum in regions showing resistance to traditional antimalarials like chloroquine and pyrimethamine-sulfadoxine.
• Encephalopathy treatment: For ifosfamide-induced encephalopathy, methylene blue prevents the formation of neurotoxic metabolites causing the condition.
• Parathyroid identification: During parathyroidectomy procedures, methylene blue helps identify the parathyroid glands.
• Chromoendoscopy-targeted biopsies: Methylene blues serves as a dye to highlight abnormalities in the digestive tract lining.

What Are the Risks of Methylene Blue?

Like most medications, there are potential risks and side effects from taking methylene blue. Side effects may occur at recommended doses, but high doses of methylene blue are particularly dangerous and can be life-threatening. The most common side effect is a blue-green discoloration of the skin and bodily fluids such as urine. Other risks associated with use of methylene blue include:

• Serotonin syndrome: Methylene blue blocks a protein that breaks down serotonin called monoamine oxidase A (MAO-A). Taking it with other medications that can increase serotonin (e.g., SSRIs, SNRIs, opioids, triptans) can put you at risk for a life-threatening condition called serotonin syndrome. Symptoms include fever, stiff muscles, fast heartbeat, confusion, and agitation.
• Allergic reactions: Serious allergic reactions, such as anaphylaxis, have been reported by patients who have taken methylene blue. Symptoms may include hives, swelling, tightening of the airways, and difficulty breathing.
• Cardiovascular effects: Particularly in high doses, methylene blue can cause a rise in blood pressure and heart rate. It can also cause EKG changes.
• Hemolytic anemia: Methylene blue can trigger a breakdown of red blood cells, which may require blood transfusion. This effect can be delayed 1 or more days after starting methylene blue. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at a higher risk. Symptoms may include feeling tired, dark urine, and jaundice.
• Neurological side effects: Methylene blue can cause dizziness, confusion, and vision changes. It is not recommended to drive or operate heavy machinery until these side effects have resolved.
• Phototoxicity: Methylene blue can cause the skin to become more sensitive to sunlight, which can lead to a higher risk of sunburn. Avoid sun exposure and wear protective clothing when going outside after taking methylene blue.
• Harm to babies: Due to the potential risk to unborn babies, pregnant women are not recommended to take methylene blue. It is also recommended to stop breastfeeding for up to 8 days after treatment.

Conclusion

Methylene blue has diverse therapeutic potential spanning cognitive enhancement, anti-aging effects, and various medical applications. From improving memory and protecting against neurodegenerative diseases to fighting skin aging and treating rare conditions like methemoglobinemia, methylene blue's versatility makes it a compound that continues to be researched. While research into its potential for neuroprotection, cognitive enhancement, and other benefits is ongoing, these applications are not yet proven or approved.

Due to significant risks and potential drug interactions, particularly serotonin syndrome, methylene blue should never be self-administered and should only be used under the strict supervision of a healthcare provider who is aware of all other medications and health conditions.

See also:

Drug information

• Methylene Blue Information for Consumers
• Methylene Blue prescribing info & package insert (for Health Professionals)
• Side Effects of Methylene Blue (detailed)
• Methylene Blue user reviews (2)

Related support groups

• Methylene Blue (2 questions, 10 members)

Medical Disclaimer