The Curious Case Of Methylene Blue, A Dye That Might Slow Ageing

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Methylene blue is a blue dye that is used in laboratories all around the world, and is also used in some surgical procedures to identify different tissues. Yet in one of many cases of extraordinary medical effects coming from unexpected places, methyl blue might just slow down the ageing process.

What exactly is methylene blue?

It’s a salt, specifically methylthioninium chloride. It forms solid greenish crystals when dry and dissolves in water with a deep blue colour. However, things get interesting when looking at methylene blue’s biological effects.

What does it do?

The list of biological effects of methylene blue is long. It was first synthesised almost 150 years ago and was used to stain microorganisms. Scientists quickly noticed that microorganisms stained with methylene blue were inactivated, and started using it as an antiseptic and a treatment for malaria. In fact, methylene blue is thought to be the first synthetic medication ever used in this way, and was given to people with urinary tract infections. Methylene blue has mostly been superseded by newer drugs, but it is still used to treat methaemoglobinemia, a condition in which a form of haemoglobin is produced that is unable to release the oxygen it is carrying.

Methylene blue is also a potent antioxidant and anti-inflammatory compound. Our cells constantly produce damaging compounds called free radicals. These are a natural byproduct of cellular metabolism and are capable of damaging other important molecules like proteins and genetic material, which in turn leads to inflammation as a response to damage. It is thought that damage inflicted by free radicals (also known as oxidative stress) and inflammation slowly erodes our cells’ ability to function over time, contributing to the ageing process and the development of age-related diseases. Antioxidants like methylene blue can neutralise these free radicals, theoretically protecting against oxidative stress, inflammation and ageing. Methylene blue has also been shown to activate cells’ natural antioxidant capabilities and to suppress the production of inflammatory signalling molecules.

The properties of methylene blue may be particularly relevant when it comes to the mitochondria, the ‘power plants’ of the cell. Not only does methylene blue protect against oxidative stress, to which mitochondria are particularly vulnerable, but it may also enhance mitochondria’s ability to produce ATP, the cell’s universal fuel. This is because generating ATP involves stripping electrons from nutrients and delivering them to certain proteins within the mitochondria, which is carried out by an electron transporter. Methylene blue seems to be able to act as an alternative electron transporter, and also activates some genes involved in the synthesis of new mitochondria, resulting in healthier ATP production overall. This is relevant to the ageing process because mitochondrial function becomes increasingly poor as we age, and this is thought to be a major driver of ageing.

Does it really slow ageing?

This all sounds good on paper, but what is the evidence that methylene blue can actually slow ageing when administered?

Methylene blue has been shown to have a range of benefits in animals, particularly when it comes to the central nervous system. In rodents, injection of methylene blue has been found to increase the activity of mitochondrial proteins in the brain, reduce inflammation, improve cognitive function and increase lifespan. Much of this evidence comes from animals with genetically induced neurological diseases, against which methylene blue seems to protect. This makes it a promising candidate for slowing cognitive decline in humans. Scientists think that the decline in mitochondrial health and ATP production mentioned earlier is especially important in the brain, which uses more energy than any other organ. The brain is also especially vulnerable to inflammation and oxidative stress.

So, onto the big question: does this work in humans?

In Alzheimer’s disease:

If you search for the answer, you may come across some articles on the internet claiming the same statistic: that oral methylene blue reduced hallmarks of dementia by 85% in a phase III clinical trial. This is sometimes conveniently accompanied by links to products containing methylene blue. Unfortunately, these claims are misleading – the study they are referring to was for a compound called hydromethylthionine, which is a derivative of methylene blue, but not the same molecule. This study reanalysed data from two phase III clinical trials of hydromethylthionine in Alzheimer’s patients that both suggested it was ineffective. The reanalysis suggested that at the lowest dose, which was intended as a control, the levels of hydromethylthionine in the blood correlated with improved Alzheimer’s symptoms. This prompted further trials that appear to have been successful, as the company responsible is in the process of applying for regulatory approval in the UK.

The 85% reduction claim is also misleading. The study showed a significant improvement in a commonly used assessment of dementia severity (the ADAS-Cog score) which was predicted to be equivalent to an 85% reduced cognitive decline over 65 weeks had the study lasted that long, but again, this was not a trial for methylene blue. There was a phase II study prior to this that suggested some benefit to methylene blue in Alzheimer’s patients, but the graveyard for such drugs is large, so this isn’t really much to go on.

For skin ageing:

There is another area in which methylene blue has shown some promise: combatting skin ageing. As the physical barrier protecting the body from external sources of damage, the skin is exposed to higher levels of oxidative stress than most tissues, and research suggests that methylene blue is a more powerful antioxidant than many widely used products. Studies have found methylene blue to be effective in promoting wound healing, skin hydration and thickness in cultured 3D reconstructions of human skin tissue. However, we weren’t able to find any clinical trials investigating the effectiveness of methylene blue for supporting skin health.

General anti-ageing effects:

Some evidence for the potential of methylene blue comes from studies of progeroid cells. Progeria is a fatal genetic disease in which people rapidly accumulate age-related pathologies as children. This happens because of abnormalities in a protein that holds the cell nucleus together, resulting in accelerated DNA damage and dysfunctional mitochondria. Research shows that exposing progeroid cells to methylene blue can significantly improve mitochondrial function. While the problems that occur in progeria are not exactly the same as those that occur in normal ageing, this does lend some credence to the idea that methylene blue could have untapped potential for slowing ageing more generally. However, it is still entirely possible that methylene blue does absolutely nothing to combat ageing in healthy people.

The Take-Home Message

Methylene blue has several biological effects that make it potentially capable of slowing down some aspects of the ageing process. However, any claims that it actually works are premature, as there’s very little evidence to go on at the moment. Methylene blue is under investigation for the treatment of skin ageing, and a derivative of methylene blue might soon be available for the treatment of Alzheimer’s disease. While generally safe at appropriate doses, methylene blue can also have a range of rather unpleasant side effects and drug interactions when ingested. At present, it is only approved by the FDA for treatment of methemoglobinemia.