How Methylene Blue Can Help Promote Healthier Skin

Methylene blue may be one of the most important medicines people need to have in their homes. In fact, it’s on the World Health Organization’s “Model List of Essential Medicines.”1

First synthesized in 1876 by German chemist Heinrich Caro,2 methylene blue can help save lives. In fact, it’s found in every hospital in the world, and used in surgeries, treating methemoglobinemia and as a staining tool for experiments. But that’s not all — research suggests that it may help promote healthy skin and even overall wellness.

How Methylene Blue Works to Benefit Your Health

Before diving into how methylene blue can help promote skin health, it’s important to have a basic understanding of how it works. In my interview with Francisco Gonzalez-Lima, Ph.D., an expert on methylene blue, he mentions that this drug has several mechanisms of action, but the most notable one is its effect on the electron transfer chain, which can promote mitochondrial health. He explains:

“Our body uses electrons as part of the electron transport chain that happens inside mitochondria, and these electrons, moved along through the mitochondria, are generated from electron donors that we produce by the foods that we eat.

All the foods that we eat, the only way they contribute to energy is by producing electron donors. They donate these electrons to the electron transport inside the mitochondria. The ultimate electron acceptor in nature is oxygen. That’s why the process of removing electrons from a compound is referred to as oxidation.

In mitochondria, this process is called oxidative phosphorylation. The electron transport is coupled with the phosphorylation of adenosine to eventually produce the adenosine triphosphate molecule (ATP). Methylene blue is an electron cycler. It’s an auto-oxidizing compound.

So, methylene blue donates its electrons directly to the electron transport chain, it obtains electrons from surrounding compounds, and maintains oxygen consumption and energy production. By doing this, it helps oxygen to be fully reduced into water.

So, it becomes two things that are often not found together. It acts as an antioxidant, because oxygen is neutralized into water by donating electrons to the electron transport, and it produces energy, because when the electron transport pumps are moving along oxidative phosphorylation, you have an increase in ATP formation.”

Methylene Blue Can Help Promote Youthful Skin

In a study3 published in Scientific Reports, researchers sought to learn how methylene blue can help promote skin health. What prompted this line of thought was a prior study, wherein they discovered methylene blue “stimulated cell proliferation and delayed senescence in skin fibroblasts from patients with Hutchinson-Gilford progeria syndrome,” a rare genetic disorder that causes accelerated aging.

To test the hypothesis, the researchers applied methylene blue on 2D primary dermal fibroblasts, as well as reconstructed 3D human skin models. They also tested other well-known reactive oxygen species (ROS) scavengers — N-Acetyl-L-cysteine (NAC), MitoQ and MitoTEMPO — to serve as a baseline for the effectiveness of methylene blue.4

What they discovered about methylene blue’s potential was nothing short of striking. According to their findings, methylene blue was “the most effective in reducing mitochondrial ROS and promoting skin cell proliferation.”5

In addition, they found that methylene blue may help delay or reverse phenotypes from skin cells from elderly participants. Using a different test, they extracted two dermal fibroblast lines from participants over 80 years old and treated these with methylene blue for four weeks. They discovered that methylene blue helped suppress gene expression related to aging, as well as reduced mitochondrial superoxide (believed to be the original ROS6) levels similar to young cells.7

Aside from these findings, the researchers noted that methylene blue can help upregulate Nrf2 expression, an “essential regulator of antioxidant defense system,” which contributes to reduced overall ROS.

“In summary, MB at nanomolar concentration is potent to scavenge free radicals and stimulate cell proliferation in both young and old dermal fibroblasts.

MB treatment on 3D reconstructed skin models provides strong evidence of its potential for improving skin viability, increasing skin hydration and thickness, promoting skin elastin and collagen synthesis, and protecting the skin matrix through the inhibition of enzymatic degradation by MMP. Altogether, our study suggests that MB can be a promising agent for use in antiaging cosmetics,” they concluded.

Other published research support these findings. In one example, published in The FASEB Journal,8 methylene blue was found to help increase the lifespan of fibroblast samples and cell proliferation, all the while reducing aging markers.9

Methylene Blue May Also Help Facilitate Wound-Healing

Making you appear youthful is not the only application of methylene blue. In a 2020 study,10 researchers noted that it may be used as a photosensitizer to treat infected wounds via photodynamic therapy (PDT).

For the experiment, five patients of varying ages were selected, and all of them had infected wounds lasting between one and three months. Before PDT was administered, the wounds were cleaned, then methylene blue was applied to the affected area and covered with film before being exposed to light. After repeated sessions, researchers noted reduced wound secretions, suggesting that the process also helped eliminate antibiotic-resistant bacteria.11

For context, PDT is a two-stage treatment that uses light energy (typically a laser) to activate a photosensitizer, an inert drug that becomes toxic to cancerous tissue once exposed to light. But as noted by the Mayo Clinic, PDT can also be used to eliminate viruses, fungi and bacterial infections.12

Other Beneficial Applications of Methylene Blue

Methylene blue has also been shown to have several other health benefits, including:

Boosting brain health — Research13 suggests that methylene blue’s ability to cross the blood-brain barrier makes it a promising aid for Alzheimer’s disease, Parkinson’s disease and brain injuries.

Methylene blue has been found to bypass the Complex I/III activity in the electron transfer chain and directly reducing the production of free radicals rather than scavenging them. Animal tests also suggest that it can partially restore the membrane in Complex III-inhibited mitochondria.14

Managing osteoarthritis — In a 2021 study,15 researchers recommended methylene blue for treating osteoarthritis. Using animal test models, they discovered that it helped reduce pain and joint deterioration. The test group that received methylene blue also had a lower number of osteophytes (bone spurs), which form when bone is damaged by arthritis.16

In another study,17 osteoarthritic test animals injected with methylene blue experienced better weight distribution between each knee, as well as reduced swelling. Methylene blue also helped suppress biomarkers related to the progression of osteoarthritis, such as tumor necrosis factor alpha and interleukin 6. Pain was also reduced.

Relieving pain — In connection with the benefit mentioned above, research suggests that methylene blue may generally alleviate pain. According to a study18 published in Frontiers in Neuroscience, methylene blue inhibits suppresses nitric oxide (NO) production (since NO is a proinflammatory mediator) that can lead to pain relief.

Reducing risk of vasoplegia — A complication that can occur after heart surgery, vasoplegia is characterized by low blood pressure despite a normal heartbeat,19 and methylene blue seems to help in this regard.

In a 2010 review,20 researchers noted that intravenous administration of methylene blue before cardiac surgery can help lower the risk of vasoplegic syndrome in high-risk patients.

If complications do occur, severity is lessened. Methylene blue was also shown to be used for post-cardiac operations, helping decrease mortality. It’s believed that methylene blue applies these benefits by inhibiting guanylate cyclase, a class of enzymes that control bacteria in humans,21 thus lowering vascular smooth muscle relaxation.

Promoting mitochondrial health — Methylene blue may help boost your body’s antioxidant capabilities, according to a study22 published in the International Journal of Molecular Sciences.

Researchers noted that upon administration, methylene blue helped boost hydrogen peroxide production and subsequent activation of the Nrf2/ARE signaling pathway. This resulted in the activation of antioxidant genes that helped decrease mitochondrial DNA damage in the context of cisplatin administration, a drug used for cancer treatment that can damage kidney function.23

Preventing further environmental damage of sunscreens — I generally don’t recommend using sunscreen, as it will hamper vitamin D production. Instead, it’s far better to cover up your skin with clothing once you’ve reached your ideal sun exposure time.

However, if you absolutely want to use a sunscreen, such as if you’re going to be outdoors for long periods of time, your safest bet is to use a product containing zinc oxide and/or titanium dioxide that doesn’t contain nanosized particles.

In addition to these ingredients, consider a sunscreen that has methylene blue, as it has been shown to be safe for coral reefs. Most sunscreens sold today contain oxybenzone, a chemical that can damage aquatic ecosystems.24

Methylene Blue May Help After a Heart Attack

While heart attack can cause sudden death, survivors face the serious threat of reperfusion injury, where cellular dysfunction and decay may worsen following the restoration of blood flow. Administering methylene blue can help mitigate this tissue damage, but it’s important to avoid overdose.

For nonacute, longer-term treatments, including managing dementia and post-stroke, as well as cognitive enhancement and overall health optimization, low doses of 0.5 milligrams (mg) to 1 mg per kilogram of body weight are recommended.

Additionally, keep 10 mg of sublingual melatonin on hand. Like methylene blue, it can minimize reperfusion injury when taken immediately after a heart attack or stroke. According to a report from The Conversation:25

“Laboratory studies of heart attack … have shown that melatonin does indeed protect the heart from damage after a heart attack. Similar studies have shown that when rats’ hearts are deprived of oxygen, as occurs in a heart attack, providing the heart with melatonin had a protective effect.”

The Correct Methylene Blue Matters

Based on what’s been published about methylene blue, it’s a compound well worth having in your medicine cabinet. But, don’t just go out and get any methylene blue you can find. Selecting the right product is important, and there are three types typically sold — industrial-grade, chemical-grade (laboratory-grade) and pharmaceutical-grade.

The only one you should use is the pharmaceutical-grade variety. Other types of methylene blue, such as the one found in pet stores, are meant for keeping aquariums clean. Industrial-grade methylene blue contains impurities, and only 10% to 25% is real methylene blue.

Chemical-grade methylene blue is used for staining experiments by laboratories. While it has higher purity, it’s still not suitable for health applications, as it can contain lead, cadmium and arsenic. When ingested, these impurities can accumulate in your body over time, causing toxicity.

Pharmaceutical-grade methylene blue is 99% pure, and is the one used for intravenous administration and oral ingestion. They are marked USP, or United States Pharmacopeia. However, you may need a prescription to purchase it. Once you have this type, I recommend buying a stainless-steel spoon that measures 8 to 10 mg for accurate measurements.

Generally, dosing is between 0.5 mg and 1 mg per kilogram of body weight, with an upper limit of 4 mg for acute treatment of things like cyanide poisoning, for which methylene blue is the only antidote. It has a half-life of 12 to 13 hours, so taking it once a day is sufficient.

According to Gonzalez-Lima, USP methylene blue has better purity than the European pharmaceutical-grade one. Moreover, taking it with ascorbic acid can improve absorption. You probably won’t find pharmaceutical-grade methylene blue at your local pharmacy, but many compounding pharmacies carry them. If you have trouble finding a reliable source, simply ask your physician to write you a prescription to a compounding pharmacy.

With regard to cosmetic use, a small number of companies have started manufacturing topical creams and lotions that contain methylene blue.