Methylene Blue: From an 1876 Cloth Dye to Brain Science

In 1876, a chemist at a German dye company made a bright new blue for cotton cloth. It was called methylene blue. As a cloth dye, it never became a star.

As a science tool, it was a hit. In the 150 years since, it has stained nerve cells, treated malaria and become an FDA-approved medicine. Now brain scientists are curious about it.

What it is

Methylene blue is not a peptide. It is a small dye molecule. It belongs here because of what it does inside cells.

A peptide is a short chain of amino acids, like a short bead bracelet. New to this? Start with what a peptide is.

In 1886, a German scientist gave it to a living animal. Its nerve cells soaked up the dye and turned blue.

In 1891, he used it to treat malaria. That made it one of the first lab-made medicines.

Today it is a medicine for methemoglobinemia, a blood problem. Hemoglobin is the protein in red blood cells that carries oxygen. In this problem, too much of it gets changed into a form that can't drop oxygen off well.

Methylene blue turns it back into the normal kind.

What it does in the body

Methylene blue has a neat trick. It can grab electrons, tiny bits of charge, and pass them on.

When it holds them, it loses its color. When it hands them off, it turns blue again.

This trick matters in mitochondria, the cell's power plants. Inside them, electrons get passed down a line of helpers.

It works like passing a baton in a relay race. That race is how cells make energy from food and oxygen.

If one runner gets stuck, the race slows down. In lab studies, methylene blue can grab the baton and run it past the stuck runner.

In rodents, it gets into the brain with ease. Levels there were 10 to 20 times higher than in the blood an hour later.

Scientists have spotted something curious, too. In lab studies, low and high amounts can have opposite effects.

What scientists have found

In cells: In lab tests, methylene blue acted as a spare carrier for electrons. It got around a jam in the power-plant line. A copy with its electron trick turned off could not do this.

In nerve cells in a dish, it raised oxygen use. It also shielded them from several kinds of harm.

In animals: In a 2004 study, rats learned where food was hidden on a board full of holes. Rats given a low dose after each lesson remembered better a day later.

Of their visits, 66% went to the right holes. For rats without it, it was 31%. The same low dose also made a key power-plant protein in rat brains more active.

In another study, rats got a toxin that jams the power-plant line. Methylene blue protected their brain cells that make dopamine, a chemical messenger.

In people: In a 2016 study, 26 healthy adults got one low dose or a placebo, a dummy look-alike. An hour later, brain scans lit up more during tasks of focus and short-term memory. The methylene blue group got about 7% more answers right on a memory test.

A close cousin of methylene blue was tested in 891 people with Alzheimer's disease. They took it for 15 months. It did not beat the other group on the main tests.

For the blood problem, its FDA label sums up studies in adults. In 26 of 28 checked, the changed form fell by at least half.