Methylene blue – the perfect nootropic?

Methylene blue is a synthetic chemical compound, a dye with a characteristic blue color, which is currently used as nootropic support by fans of experimental supplementation. It was synthesized in 1876 by a German chemist looking for dyes for the textile industry, where it was widely used for dyeing fabrics. Today, we encounter the use of methylene blue in so-called biohacking as an element influencing cognitive functions or cellular mitochondrial work. Is using this type of "supplementation" safe? Does methylene blue actually have health-promoting potential? I decided to tackle this issue and present the facts regarding supplementation with this dye.

From dye to the first synthetic drug

The real breakthrough came at the end of the 19th century. The legendary Paul Ehrlich, a pioneer of hematology and immunology, noticed during his research on cell staining that methylene blue selectively stains certain microorganisms, including malaria parasites. In 1891, this discovery led him to the landmark use of methylene blue as the first fully synthetic drug in history – effective in treating malaria. It was a milestone that opened the door to the entire field of chemotherapy. Shortly thereafter, its antiseptic properties were discovered, and it began to be used for disinfecting wounds and treating urinary tract infections.

Evolution of methylene blue use in the 20th and 21st Centuries

In the 20th century, methylene blue solidified its position in medicine. It was recognized as a key antidote in the treatment of methemoglobinemia – a dangerous condition in which the blood loses its ability to transport oxygen. It also began to be used as a diagnostic dye in surgery, allowing for the precise visualization of specific tissues or ducts. Today, in the 21st century, methylene blue is experiencing a renaissance. It is being intensively researched for its neuroprotective, nootropic (improving cognitive functions), anti-aging properties, and even as support in anti-cancer therapies.

How does methylene blue work?

The secret of methylene blue's versatility lies in its unique mechanism of action at the cellular level. Its main stage is the mitochondria – small organelles inside our cells, often called "cellular power plants" because they are responsible for the production of energy (ATP), which drives almost all life processes.

Methylene blue improves mitochondria

Methylene blue acts as a versatile "electron acceptor and donor." In low doses, it can improve the functioning of the mitochondrial electron transport chain. Put simply, it acts as a kind of "bypass" for electrons, avoiding potential "traffic jams" or damaged parts of this chain. This increases the efficiency of ATP production, the primary energy currency of the cell. More energy means that cells, especially those with high energy demands like neurons in the brain or heart muscle cells, can function more efficiently and are more resistant to damage.

A dual role: antioxidant and pro-oxidant

One of the most fascinating features of methylene blue is its ability to act as both an antioxidant and a pro-oxidant, depending on the dose and the cellular environment.

• Antioxidant action: At low, therapeutic concentrations, methylene blue effectively neutralizes harmful free radicals, protecting cells from oxidative stress, which is one of the main factors accelerating aging and the development of many lifestyle diseases.
• Pro-oxidant action: In significantly higher doses or in the presence of light (as in photodynamic therapy), methylene blue can generate reactive oxygen species that are toxic to pathogens (bacteria, viruses, fungi) and cancer cells, leading to their destruction.

Effect on neurotransmitters

Methylene blue also demonstrates the ability to inhibit the activity of an enzyme called monoamine oxidase (MAO), specifically MAO-A. This enzyme is responsible for the breakdown of important neurotransmitters such as serotonin (the "happiness hormone") and norepinephrine. By inhibiting its action, methylene blue can contribute to an increase in the levels of these substances in the brain, which explains its potential antidepressant and mood-enhancing effects.

Advantages and benefits of methylene blue

The broad spectrum of methylene blue's action translates into an impressive list of potential health benefits that are the subject of numerous scientific studies.

Potential support for brain health and cognitive functions

This is one of the most exciting fields of research. Due to its ability to easily cross the blood-brain barrier and improve the energy metabolism of neurons, methylene blue is considered a powerful nootropic agent.

• Improvement of memory and concentration: Studies, including those using brain imaging (fMRI), have shown that low doses of methylene blue can improve short-term memory, memory consolidation (converting short-term memories into long-term ones), and the ability to maintain attention.
• Neuroprotection: By protecting neurons from oxidative stress and improving their energy "supply," methylene blue can slow down neurodegenerative processes. It is being researched as a potential supporting agent in the prevention and therapy of diseases such as Alzheimer's and Parkinson's. Preliminary studies suggest it may inhibit the aggregation of tau proteins, which form harmful tangles in the brains of people with Alzheimer's disease.

Antidepressant action of methylene blue

Its historical use in psychiatry (though rarer today) and its mechanism of MAO-A inhibition mean that methylene blue is being studied for the treatment of mood disorders. It may alleviate symptoms of depression and anxiety, especially in individuals for whom standard therapies do not yield the expected results. However, its action in this regard is complex and requires strict specialist supervision.

Anti-Aging properties

In vitro studies on human skin cells (fibroblasts) have yielded extremely promising results. It has been shown that methylene blue:

• Increases collagen and elastin production: These are key proteins responsible for skin firmness and elasticity.
• Improves skin hydration: It makes the skin thicker and better at retaining water.
• Protects against damage: As a strong antioxidant, it protects skin cells from the harmful effects of free radicals generated by, among others, UV radiation and environmental pollution.

Medical applications of the product

• Treatment of methemoglobinemia: This is its main, FDA-approved use. Methylene blue administered intravenously effectively restores normal hemoglobin function, saving lives in cases of poisoning, e.g., with nitrates.
• Photodynamic therapy: Used as a photosensitizer in the treatment of certain skin cancers (e.g., melanoma) and infections. After activation by light of the appropriate wavelength, it selectively destroys pathological cells.
• Antimicrobial action: Effectively combats a wide spectrum of bacteria, viruses (including, as research suggests, viruses from the Herpes family and the Zika virus), and fungi. Research also indicates its potential effectiveness against resistant forms of Borrelia bacteria, which cause Lyme disease.

Disadvantages of methylene blue

Despite the impressive list of advantages, methylene blue is not a substance without flaws and potential risks. Its use, especially without supervision, can lead to serious health consequences.

Potential side effects and adverse reactions

Side effects depend largely on the dose, route of administration, and individual sensitivity.

• Very common and typical: The most well-known and harmless effect is the blue or green coloration of urine and feces. It can also temporarily stain the skin and mucous membranes.
• Common: Nausea, vomiting, abdominal pain, dizziness, and headaches may occur.
• Rare but serious: At higher doses, hemolytic anemia (breakdown of red blood cells) may occur, especially in individuals with a genetic deficiency of the G6PD enzyme. Allergic reactions are also possible, as well as neurological symptoms such as anxiety, tremors, or confusion.

Risk of serotonin syndrome

This is the most serious risk associated with oral intake of methylene blue. As an MAO-A inhibitor, it must absolutely not be combined with drugs that increase serotonin levels, such as:

• Antidepressants from the SSRI group (e.g., fluoxetine, sertraline, citalopram)
• Antidepressants from the SNRI group (e.g., venlafaxine, duloxetine)
• Other MAO inhibitors
• Triptans (migraine medications)
• Certain strong painkillers (e.g., tramadol, pethidine)
• Dietary supplements such as L-tryptophan or 5-HTP.

Such a combination can lead to serotonin syndrome – a life-threatening condition manifested by high fever, agitation, seizures, muscle rigidity, and consciousness disorders.

Contraindications for using the nootropic

The use of methylene blue is contraindicated in:

• Pregnant and breastfeeding women (it can be harmful to the fetus).
• Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Individuals with severe kidney or liver failure.
• Infants.

Summary: versatile, but demanding respect

Methylene blue is undoubtedly one of the most extraordinary and versatile substances in the arsenal of modern science. Its journey from denim dye, through a malaria drug, to a potential elixir for the brain and skin, is a testament to the unlimited possibilities of human discovery. It offers a wide spectrum of benefits, from improving cellular energy and cognitive functions to fighting pathogens and slowing down aging processes.

However, its power goes hand in hand with responsibility. This is not an ordinary supplement. Its improper use, ignoring contraindications and dangerous drug interactions, can lead to serious or even fatal consequences. Before anyone decides to explore its properties, consultation with a qualified physician is absolutely crucial to assess the potential risks and benefits in each individual case. Methylene blue, treated with knowledge and respect, remains a fascinating tool with enormous potential.

Scientific sources:

1. Bistas E, Sanghavi DK. Methylene Blue. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available at: https://www.ncbi.nlm.nih.gov/books/NBK557593/
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3. Xiong Z-M, O’Donovan M, Sun L, Choi J Y, Ren M, Cao K. Anti-Aging Potentials of Methylene Blue for Human Skin Longevity. Scientific Reports. 2017; vol 7, article number: 2475. Published: May 30, 2017. DOI: https://www.nature.com/articles/s41598-017-02419-3
4. Xue H, Thaivalappil A, Cao K. The Potentials of Methylene Blue as an Anti-Aging Drug. Cells. 2021 Dec 1;10(12):3379. doi: 10.3390/cells10123379. PMID: 34943887; PMCID: PMC8699482.