Health Benefits and Risks of Methylene Blue in Medicine
What Is Methylene Blue?
Methylene blue is a dark green powder with important medical and biological uses. When it’s dissolved in water, it forms a beautiful blue solution. It's a popular stain in biology labs because it makes the nucleus of a cell visible. It's also used as a dye in medical tests and during surgery because it colors body fluids and tissues, making them easy to see.
Methylene blue is a medicine as well as a dye. It was the first synthetic drug to be created and was originally used as a malaria treatment. Today it's used to treat a blood disorder called methemoglobinemia and neural problems resulting from treatment by ifosfamide, a chemotherapy drug. In addition, methylene blue is a weak antiseptic and helps to treat urinary tract infections. Research suggests that it may also be a useful medication for other health problems.
A Biological Stain
Methylene blue powder is green in color and is actually methylene blue chloride (or more technically, methylthioninium chloride). When this compound is added to water, it breaks up into the positive methylene blue ion, which has a blue color, and the negative chloride ion, which is colorless.
The positive methylene blue ions are attracted to negative particles, such as the nucleic acids (DNA and RNA) in the nuclei of cells. They bind to the nucleic acids and stain them blue, making them more visible than their background.
A Medical Dye
Methylene blue solutions range from light blue to dark blue in color, depending on their concentration. Concentration is an important topic when considering the chemical, not only with respect to its ability to act as a biological stain but also with respect to its safety as a medicine.
Methylene blue's ability to color parts of cells is helpful in certain medical tests. The dye gives doctors an improved view of body tissues. Fortunately, doctors are becoming more aware of the fact that when the chemical is placed in the body as a dye it may also have other effects.
New methylene blue and methyl blue are also biological stains. They are not the same chemical as methylene blue, despite their similar names.
Methylene blue treats health problems as well as acting as a dye. For example, it's very useful for clearing excess methemoglobin from a person's bloodstream. Methemoglobin is a chemically altered form of hemoglobin, the red pigment in our blood that transports oxygen from the lungs to our cells. An excessive amount of methemoglobin in the blood has serious consequences. Unlike normal hemoglobin, the altered form can't transport oxygen effectively. Our cells can't survive without the oxygen supplied by hemoglobin.
Methemoglobinemia is a potentially dangerous disorder in which the blood contains a higher amount of methemoglobin than normal. The condition may be inherited, but it's more often acquired during life. Taking certain medications and eating too many foods containing nitrates or nitrites can cause the disorder. In mild cases of methemoglobinemia, the body can heal itself if the trigger for the disorder is avoided. In more serious cases, medical help is needed.
Benzocaine in Teething Gel and Methemoglobinemia
One possible cause of acquired methemoglobinemia is giving a baby a teething gel containing benzocaine. Benzocaine is a local anesthetic that relieves gum and mouth pain. The benzocaine may trigger excess methemoglobin production. As the methemoglobin builds up in a baby's blood, the blood may turn brown and the skin, lips, and nail beds may become pale, grey, or blue (cyanosis). Additional symptoms may included shortness of breath and a rapid heartbeat. The condition is a medical emergency.
In May, 2018, the FDA (Food and Drug Administration) warned the public to stop buying teething products containing benzocaine due to the possibility of methemoglobinemia development. It also sent messages to the makers of the teething products to ask them to stop selling them. The FDA says that if the companies don't comply, they will take regulatory action. The agency says that in addition to being potentially dangerous, the teething products aren't very effective because they are quickly washed away by saliva.
A dilute solution of methylene blue is generally administered intravenously to a patient with methemoglobinemia. This decreases the amount of methemoglobin in the blood. It's important to get the patient to a hospital quickly so that they can receive the treatment.
According to the FDA, methemoglobinemia most often occurs in children younger than two years of age. It may occasionally affect people of other ages, including adults. Adults may report that they have a headache and feel light-headed in addition to having other symptoms.
Ifosfamide is a very helpful chemotherapy drug for a variety of cancer types. Unfortunately, like other powerful drugs it can cause side effects. Doctors can help to minimize or eliminate any side effects that develop.
One of the less common side effects of ifosfamide treatment is toxicity to the central nervous system, causing a brain dysfunction known as encephalopathy. This may result in problems such as confusion, blurred vision, hallucinations, and seizures. The administration of a methylene blue infusion may be a helpful treatment for the neurotoxicity.
Urinary Tract Infections (UTIs)
Methylene blue isn't sufficiently antimicrobial to fight a urinary tract infection on its own. It's helpful when combined with other drugs, such as an antibiotic or other antibacterial medications, however. Methylene blue is sometimes sold under the brand name of Urolene Blue when it's used as a medicine.
Methylene blue shouldn't be given to people with kidney problems because they may have trouble excreting it in the urine. This means that the chemical stays in their body for longer than normal.
Some Other Possible Uses for Methylene Blue
Other uses of methylene blue are being investigated. Some experiments have been done with isolated human cells or with mice. While the results of these experiments are intriguing, they may or may not apply to the human body.
- Malaria: Methylene blue was once used to fight malaria. It is an effective treatment, but it hasn't been popular as a preventative medicine due to its ability to color the urine and the whites of the eyes. Researchers are now testing medications that contain methylene blue combined with another drug.
- Cancer: When certain isolated cancer cells are treated with methylene blue and then exposed to light, the cells die. Methylene blue treatment followed by light treatment has also destroyed tumors transplanted into mice and placed under their skin. The observations are interesting, but they don't necessarily mean that the chemical can be used to treat human cancer. More research is needed.
- Psoriasis: Methylene blue has been successfully used as a photosensitizer in the treatment of psoriasis. The process of sensitizing cells to light exposure with a chemical and then shining light on the cells to treat a health problem is known as photodynamic therapy, or PDT.
- Alzheimer's Disease: In this disease, plaques made of a protein called beta amyloid build up between nerve cells and tangles of a protein called tau build up within the nerve cells. Preliminary research indicates that at certain doses methylene blue can prevent tau aggregations in mice. Methylene blue has also improved memory in mice and seems to improve the functioning of the mitochondria. Mitochondria are the cell organelles that produce energy.
- Cyanide Poisoning and Carbon Monoxide Poisoning: In the past methylene blue has been used to treat both of these problems, but newer treatments are generally used today.
A Potent MAO Inhibitor
An excitatory neurotransmitter is a chemical that transmits signals between nerve cells, or neurons. When a nerve impulse reaches the end of a neuron, neurotransmitter molecules are released from storage sacs (synaptic vehicles), travel across the gap between the neuron and a second neuron, and then bind to receptors on the second neuron. This causes the appearance of a nerve impulse in the second neuron.
Neurotransmitters are normally broken down or recycled when they've done their job. Monoamine oxidase enzymes break down specific neurotransmitters in the body, including a neurotransmitter called serotonin.
A monoamine oxidase inhibitor (MAO inhibitor) is a medication that inhibits monoamine oxidase enzymes, allowing neurotransmitters such as serotonin to work for longer and raising their level in the body. MAO inhibitors are used to treat some cases of depression and sometimes other disorders too, such as Parkinson's disease and migraines. The FDA (Food and Drug Administration) says that methylene blue is a "potent" MAO inhibitor.
Serotonin is involved in mood, appetite, sleep, memory, and learning. Its exact functions are still being investigated. A low level of serotonin is often said to be linked to depression, but some researchers dispute this idea.
Methylene Blue and Serotonin Reuptake Inhibitors
Although methylene blue can certainly be helpful in some situations, in others it can be harmful. For example, when methylene blue is taken with a type of medication called a serotonin reuptake inhibitor, or SRI, serotonin may rise to a dangerous level.
What is an SRI?
Some serotonin is reabsorbed into nerve cells after it has performed its function instead of being broken down. A protein called a serotonin transporter moves the chemical back into the nerve cells. A serotonin reuptake inhibitor is a medication that blocks the activity of the transporter. The serotonin therefore continues to act as a neurotransmitter in the tiny space between nerve cells. This can be helpful in diseases that may be caused by a lack of serotonin, including (possibly) some types of depression. A larger quantity of the chemical is beneficial—but only up to a point.
The Combination of Methylene Blue and an SRI
Methylene blue or any other MAO inhibitor increases the level of serotonin to a dangerous level in people who are also taking certain SRIs. The resulting condition is known as serotonin syndrome. Some of the symptoms of the syndrome include a rapid heartbeat, high blood pressure, sweating, diarrhea, agitation, confusion, and lack of muscle coordination. Serotonin syndrome may sometimes be life threatening.
G6PD Enzyme Deficiency
Glucose-6-phosphate-dehydrogenase, or G6PD, is an important enzyme in the life of a red blood cell. Some people have a genetic problem that prevents them from making enough of this enzyme. As a result, the red blood cells burst when the person ingests certain chemicals or becomes ill with certain infections. The disorder caused by the destruction of the red blood cells is known as hemolytic anemia. Methylene blue is one of the triggers of hemolytic anemia in people with a G6PD deficiency.
G6PD deficiency is sometimes known as favism, but the two conditions aren't quite the same. Favism is a condition in which a person experiences hemolytic anemia in response to eating fava beans (which are also called broad beans). People with favism have a G6PD deficiency. However, not everyone with a G6PD deficiency has a problem when they eat fava beans.
Methylene blue is a medical dye and a powerful medication that under some conditions is harmful. It should never be administered as a prank.
The Methylene Blue Prank
If methylene blue is ingested in sufficient quantities, it turns the urine and the sclera (the white part of the eyes) blue. It's used in pranks to color an unsuspecting person's urine. However, this can be dangerous for people taking an SRI medication and for people with a G6PD deficiency.
The Royal Society of Chemistry has condemned the use of methylene blue in pranks designed to turn urine blue, not only because this use invades someone's personal space but also because of its potential danger. While a small dose of methylene blue may be safe, someone slipping the powder into food as a joke is unaware of the toxic dose or of hidden medical problems or medications in their victim.
Methylene blue is widely used as a biological stain in schools as well as professional laboratories and is a familiar substance for many science students. They may not realize that it can have potent effects in the body.
A Versatile Chemical
Methylene blue is very useful in certain medical settings and has important health benefits. It's a powerful chemical that has far more profound effects on our body than simply coloring tissues. It may have even more benefits in the future as scientists learn more about its behavior and discover additional ways to manage methylene blue as a medication. More research is needed, however, especially as methylene blue seems to affect many different molecules and systems in our bodies.
- Methemoglobinemia and benzocaine from the FDA
- FDA warning about benzocaine teething products from CNN
- Ifosfamide neurotoxicity from the British Columbia Cancer Agency
- Urinary tract infection from the Mayo Clinic
- Malaria from the Journal of Antimicrobial Chemotherapy (Oxford Academic)
- Tumor destruction in mice from the NIH (National Institutes of Health)
- Psoriasis from the NIH
- Tau proteins from Human Molecular Genetics (Oxford Academic)
- Serotonin syndrome from the Anesthesia Patient Safety Foundation
- Methylene blue prank warning from the Royal Society of Chemistry
Questions & Answers
© 2013 Linda Crampton