The Long, Strange Trip of Little Blue

I want to write to you, friends, about a molecule whose natural ability to shuttle electrons around has earned it quite a name and many uses. It’s a textile dye, a cancer drug, a staining agent (in medicine and chemistry), a supplement, a potential treatment for Alzheimer’s, and finally, an impressive skincare ingredient. A lot of hats for such a small molecule. I am, of course, talking about methylene blue (MB).

MB is the first fully man-made molecule, known to us since 1876. Due to the intense blue color of its oxidized form, it has been used as a textile dye. It is soluble in both water and oils, which means that it can penetrate the skin easily. In skin models, it has been shown to reverse the signs of ageing through multiple routes, making it a very interesting ingredient on which to build a skincare formulation.

Before we dive into what MB does in skin, let’s look at skin ageing itself. Aged skin has less elasticity, it is thinner and more wrinkled. Hyper-pigmentation and age spots are common. When injured, its wounds heal more slowly. We recognize two types of skin ageing, intrinsic and extrinsic.

Intrinsic ageing is what happens with the inevitable passage of time-collagen production diminishes, skin cells slow down proliferation, and become senescent (senescent cells are alive, but are not dividing any more, not creating new cells from old ones). Senescent cells are not innocent bystanders. They are not dividing any more, but they create a mixture of molecules that damage the neighboring cells and reduce the regenerative potential of tissue as a whole. Quite a turn of events, you may say.

Extrinsic ageing happens due to environmental factors - UV, pollution, the effects of alcohol, smoking, etc. For example, smoking causes the skin to appear lifeless and yellow. UVA rays penetrate deep into the skin and damage DNA and proteins. The cumulative effects of those over the years are visible in lines, sagging, or hyperpigmentation of the skin. The damage is brought through free radical species (ROS, short for radical oxygen species)-UV rays generate those in the skin, for example. They are high energy entities that react indiscriminately with many components of the skin, damaging them all. Air pollution can also cause ROS.

Free radicals don’t come just from outside. Our own cells make them, in organelles called mitochondria. Mitochondria function as little engines-they produce ATP, the fuel that our bodies use for many processes, but, as byproducts, they also produce ROS. One of the hallmarks of ageing is mitochondrial disfunction. As we age, mitochondrial function decreases, and it does so in a way that ATP synthesis decreases, whereas ROS formation increases, creating a vicious cycle of disfunction.

So what does little MB do to combat all of this?^{1, 2}

MB is a strong antioxidant, stronger than vitamin C or retinol, so it quenches free radical damage. It is a broad UV absorber, so it can act (in part) as a sunscreen. It helps wounds heal more quickly. It finds its way to mitochondria within skin cells where it can boost the production of ATP while reducing the production of ROS. It does so by providing electrons for ATP synthesis while avoiding one of the pathways that form free radicals. It is this ability to reduce the production of radicals that makes it a very attractive skincare ingredient. It effectively rejuvenates the mitochondrial function, making it produce more ATP per radical generated, akin to what young cells do. In yet another feat, it reverses cell senescence, literally keeping the cells dividing longer, making them function and appear younger.

Dosage of MB is cosmetics is important. Even if you don’t understand biochemistry, I’m sure you realize that a molecule that goes into skin easily, can penetrate cells and impact a variety of reaction cascades is a molecule that should be used carefully. Indeed, as always, the dose makes the poison. In cosmetics, we use very low concentrations of MB, sub-micromolar, which is regarded as safe. Higher doses turn out not to be better, and can either become toxic, or, comically, make your skin blue. So, beware of the makers that boast of high concentration MB in their products.

Finally, it needs pointing out that all of the impressive results come from studies on skin cells and skin models, not on real, live people. We are sure that clinical studies are being conducted already, but as of now, we are not aware of any published ones done on people. There is a good chance that the findings on cells will be replicated on humans, but sometimes, studies have a way of surprising us. That said, there are already products on the market -including our own- that feature MB on their ingredients lists.

If you are looking for something new in your skincare routine, methylene blue might just hit the spot.

Disclaimer: None of this is medical advice.

References

1. Kan Cao et al. The Potentials of Methylene Blue as an Anti-Aging Drug, Cells, 2021, 10, 3379-3389

2. Kan Cao et al. Anti-Aging Potentials of Methylene Blue for Human Skin Longevity 2017, 7, 2475-2487.