August 15, 2023

The color blue often evokes feelings of calm, depth, and mystery.

But did you know there's a particular shade of blue with a rich history that can impact your health in profound ways? Meet methylene blue, the 19th-century dye turned trove of modern-day health benefits.

Introduced in the 19th century by German chemist Heinrich Caro as a textile dye, methylene blue quickly captured the attention of pioneering scientists like Robert Koch and Paul Ehrlich. Recognizing its unique antimicrobial properties, they helped transition it from textile labs to medical clinics. By the onset of the 20th century, methylene blue was hailed as a groundbreaking treatment for malaria, a position it still maintains today.

Now, you might wonder why malaria treatment is relevant to you. It's not about the threat of the disease or any of your upcoming travel plans. Rather, it's because the mechanism by which methylene blue acts on malaria has incredible implications for your health.

Methylene blue is, in essence, a redox agent. Don't let the jargon spook you; all that means is that methylene blue is a supercharger for your biology at the cellular level.

When combined with other biohacking modalities such as infrared light therapy and hyperbaric oxygen (see featured image for this article: that's me combining a Lumetol Blue methylene blue troche with a Vielight Neuro intracranial and intranasal red light headset) methylene blue becomes something akin to a cuppa coffee for your brain. Indeed, one physician cites research here and says: “Methylene blue, in conjunction with red light therapy, is so effective at remedying hallmarks of dementia that some might even call it a cure.” Another of my friends, Dr. Scott Sherr, discussed the marriage of methylene blue and hyperbaric oxygen in our podcast discussion here.

So why does this stuff work so well? Basically, methylene blue donates and accepts electrons based on the needs of the biological process at hand. This ability to shuffle electrons makes methylene blue an integral part of several biochemical reactions, especially those involving cellular energy production. All you really need to know, though, is that methylene blue is one of the most broadly beneficial tools for improving your health with very few side effects. 

Now, you may have heard me talk about methylene blue in the past. John Lieurance, DC, and I delved into methylene blue among other topics on a podcast late last year and during a keynote presentation John and I gave in Sarasota Florida. In those episodes and other mentions (including this popular Instagram post), I’ve detailed some of the benefits of methylene blue or provided resources for further personal learning, but I’ve never before laid out a true guide to using methylene blue. 

In this article, that's precisely what I've set out to provide: a comprehensive guide or ‘map' to understanding this compound, from what it does and how it’s currently used in medicine, how you will feel when you use it, and in what scenarios you wouldn’t want to try it. Here, at long last, is your personal guide to methylene blue. 

The Many Uses of Methylene Blue

Since its creation in the late 1800s, methylene blue has experienced a storied history of use ranging from veterinary medicine to textile dye.

Understanding the far-reaching benefits of this compound can be more fully appreciated by knowing a bit about the breadth and depth of its application over the years.

Today, methylene blue is used in a number of ways:

Antiseptics: Over time, the medical community started utilizing methylene blue as a potent antiseptic, preventing infections and assisting in treating minor wounds.

Medical diagnostics: In medical procedures, methylene blue has served as a valuable diagnostic tool, used to literally highlight leaks in the gastrointestinal tract or the urinary system.

Treatment for methemoglobinemia: In more severe medical scenarios, methylene blue has been a game-changer in the treatment of methemoglobinemia, a condition that impairs blood oxygen-carrying capabilities. 

Alzheimer's disease research: As scientific understanding evolves, new potential uses for methylene blue are emerging. Among the most promising of these is Alzheimer's disease research, where methylene blue may inhibit protein clump formation in the brain.

Malaria treatment: Methylene blue remained the chief anti-malaria compound until the creation of the drug Chloroquine. Methylene blue acts by inhibiting the parasite's survival and reproduction within red blood cells.

Biological and microbiological applications: Methylene blue's usefulness extends to biological and microbiological studies, including:

• Cell staining: Methylene blue is used to highlight certain structures inside the cell. 

• Microorganism culture: Methylene blue can be used to track micro-organism growth.

• Indicator dye: Methylene blue is used as an indicator in a number of tests.

Veterinary medicine: In veterinary medicine, methylene blue is a multi-use tool. It treats fungal or bacterial infections in fish and other aquatic animals and is used as a diagnostic tool to assess kidney function or detect urinary tract abnormalities.

Industrial applications: Methylene blue is still employed as a dye, as well as for other uses in the industrial world, like identifying the oxidization potential of certain chemicals. 

I highlight methylene blue’s history of use to make a point. Methylene blue is a highly versatile compound with many applications. 

This is equally true regarding your health. Methylene blue, as you’ll learn shortly, has a long list of potential benefits with few side effects.

As long as you’re willing to deal with some blue urine (because yes, that will happen), read on.

The Health Benefits of Methylene Blue

Methylene blue has profound benefits for health due to its action as a redox agent.

In essence, methylene blue acts as an electron donor, improving the electron transport chain at the cellular level. 

The electron transport chain is critical to your body’s ability to create energy at the cellular level. This means more ATP production by your mitochondria, which is how your body creates energy at the most foundational level. 

Methods that support mitochondrial health often have far-reaching benefits and fewer side effects, and in the case of methylene blue, this looks like:

Cognitive enhancement: Research indicates methylene blue can bolster memory, attention, and overall mental performance. This cognitive benefit arises from the compound's ability to elevate energy production in brain cells and enhance mitochondrial activity. These actions underpin neurotransmitter function and facilitate smoother communication between neurons, paving the way for heightened cognitive prowess.

Neuroprotective effects: Methylene blue offers potent neuroprotective properties. It helps inhibit the buildup of harmful proteins, such as beta-amyloid plaques and tau tangles, infamous for their association with neurodegenerative disorders like Alzheimer's. This protective feature may slow down the progression of such diseases and help maintain brain health. It has also shown promise in preventing neurodegeneration in the cases of traumatic brain injury and Parkinson's via its mitochondrial effects. 

Mood elevation: For individuals wrestling with mood disorders, methylene blue surfaces as a promising aid. By amplifying the activity of neurotransmitters like serotonin and norepinephrine, it may play a pivotal role in mood regulation. This suggests that methylene blue could help alleviate symptoms associated with depression and anxiety. 

Pain-reduction and anti-inflammatory effects: Methylene blue is stepping into the limelight as a potent antioxidant and anti-inflammatory agent. As an antioxidant, it neutralizes harmful free radicals that can damage cells and contribute to disease development. Simultaneously, its anti-inflammatory properties may help modulate the body's inflammatory response, potentially mitigating the risk of chronic diseases associated with inflammation.

Anti-aging benefits: Methylene blue shows great promise as an anti-aging modality. Mitochondrial dysfunction has been linked to aging across various tissues in the body. Methylene blue can mitigate this dysfunction to some degree. It also promotes autophagy, which removes dysfunctional “senescent” cells, allowing healthy new cells to form instead. 

When taking methylene blue, you’re most likely to experience improvements in focus and mood, reductions in aches and pains, and increases in energy.

Methylene blue may also aid in reducing symptoms of chronic infections such as Borrelia or Lyme, but you should work with a doctor or a functional medicine practitioner if using methylene blue or any other modality to treat a disease or condition.

Now that you understand the benefits of methylene blue, here’s the answer to the question you’ve been waiting for: How do you use it?

How To Use Methylene Blue

Thankfully, using methylene blue is pretty straightforward. 

The key elements to keep in mind are quality, dosage, and delivery.

Beyond that, side effects are uncommon and usually both temporary and harmless at low levels. 

In terms of quality, you always want pharmaceutical-grade methylene blue. Being that this compound is used so often in lab research and as a dye in industrial applications, it is especially important you know your source is made for human consumption. Many methylene blue products are available that have harmful fillers in them and are not fit for human consumption.

Dosing: My friend Dr. John Lieurance suggests 0.5-1 mg per kilogram of body weight per day, 2 to 4 days per week. In his book, Methylene Blue & Metabolic Medicine (which you can download for free), he mentions that 20 to 60mg per day is a good therapeutic dose for most people.  With his patients, Dr. John will often pulse methylene blue 2 to 4 days per week, using a mix of sustained release methods and oral supplementation. 

Oral delivery: As with most supplements, you probably lean first towards oral delivery. Methylene blue appears to have high bioavailability when consumed orally, so this isn’t a bad route to go by any means. However, this method can stain your tongue blue, and other “sustained release” options have the advantage of delivering methylene blue over the course of the day, which may be superior for easing side effects yet maximizing benefits. 

My favorite way to take methylene blue orally is using troches, which are hard cube-shaped supplements meant to be dissolved under your tongue for 30 minutes. Dr. John has a methylene blue troche called Lumetol Blue, which contains approximately 40mg per full-sized troche, which may be split down into four 10mg sections. The Lumetol Blue bars are combined with polyphenols like quercetin and curcumin, but if you want pure methylene blue, Troscriptions also offers a pure methylene blue troche which contains 48mg per cube and can be split into 12mg pieces. Troscriptions also have their own blends that contain methylene blue alongside synergistic compounds like a bit of caffeine or hemp extract for added benefits. (For 10% off Lumetol Blue, enter code BEN10 at checkout once you join the Mitozen Club for $10 for lifetime access; for 10% off Troscriptions, enter code BEN at checkout.)

IV delivery: The first and most common sustained release delivery method of methylene blue is with an IV. This method is often used in hospital settings to get methylene blue into the blood quickly and also to directly control the rate of dosing. However, IVs require access to a clinic that provides methylene blue as a therapy and may be restrictive if you don’t like needles.

Suppositories (the “magic bullet”): You’ve likely heard the phrase “magic bullet.” Did you know the term was initially coined to describe methylene blue? German Nobel Laureate Paul Ehrlich had come up with the term based on the effects of methylene blue, to describe a compound that could kill bacteria and other pathogens without harming the human body. 

Another way “magic bullet” is used is to describe suppositories, aka supplements you stick up your butt. Now before you go all squeamish on me, suppository delivery has some distinct advantages to oral supplementation without the many restrictive qualities of taking an IV. In the case of methylene blue, suppository delivery allows for sustained release, spreading your dosage throughout the day like an IV. 

It mimics a long IV drip in many ways, without requiring you to strap in for hours at a clinic. I use the Lumetol Blue Bullet+ version by my friend Dr. John over at MitoZen Scientific (use code BEN at checkout for 5% off), which contains 60mg of methylene blue. 

To use a suppository, lay on your right side and bend your right leg while leaving your left leg straight. Take the bullet, and do the deed, inserting it into your rectal cavity via the pointy side. 

You may want to try coconut oil or KY jelly when taking suppositories, but I’ve found most “bullet” suppository supplements are plenty slippery on their own. 

Once the suppository is in there, either wait 30 minutes to an hour, or, for fast “retention” you can do what I do and perform a 30-second to 1-minute handstand using your wall. I’ve found that after the handstand, I don’t have issues with “losing” the suppository. 

You may feel an urge to use the bathroom after inserting a suppository, even if you don’t actually have to poop. Simply wait and push through it. Once the suppository dissolves (approximately 10 to 30 minutes), the urge will usually go away.

Potential Side Effects of Methylene Blue

The individual effects of methylene blue can vary. 

Though you’re likely to experience increased mental clarity, improved memory, enhanced mood, and a sense of well-being, it’s possible to have other reactions. 

Possible side effects of methylene blue include:

• Blue urine and stool: Methylene blue can cause your urine and stool to turn blue temporarily. This discoloration is harmless and will usually resolve on its own.

• Gastrointestinal disturbances: It's possible you will experience mild gastrointestinal symptoms such as nausea, vomiting, or diarrhea. These side effects are usually temporary and resolve on their own.

• Allergic reactions: Although rare, some individuals may have an allergic reaction to methylene blue. If you experience symptoms such as rash, itching, swelling, or difficulty breathing, seek medical attention immediately.

It is important to note that these side effects are generally mild and transient. However, if you experience any concerning or persistent side effects, discontinue use and consult a healthcare professional.

By conducting bloodwork before starting methylene blue, your doctor can ensure that it is safe for you to take, monitor any changes during the treatment, and make informed decisions about your overall health. One company called MinuteMD.com exists as an online telemedicine service that specializes in the utilization of methylene blue.

On the flip side, there are plenty of supplements that can work synergistically with methylene blue to give you a power combo of mitochondria-boosting pizzazz, antioxidant-increasing armor, or brain-protecting shielding.

Supplement Combinations With Methylene Blue

To truly harness and optimize the benefits of methylene blue, you may want to dig into the intricate world of synergistic supplementation.

It's not just about taking a combination of supplements, but about understanding how certain substances can enhance each other's properties. When you combine supplements with intention and knowledge, you can amplify the advantages of methylene blue, offering enhanced support to your body's diverse systems.

Antioxidants

Methylene blue inherently offers antioxidant properties that help neutralize free radicals, combatting oxidative stress. To further bolster the body's defense mechanisms, consider layering it with other antioxidants such as the following.

• Vitamin C: This water-soluble vitamin can enhance the immune system and is renowned for supporting skin health.

• Vitamin E: Vitamin E is a fat-soluble vitamin crucial for protecting cells from oxidative damage.

• Glutathione: Often referred to as the body's “master antioxidant,” glutathione plays an indispensable role in detoxification.

• Coenzyme Q10: Beyond its antioxidant functions, coenzyme Q10 is fundamental in supporting cellular energy production. 

Mitochondrial support

Methylene blue improves mitochondrial function, and combining it with supplements that also promote mitochondrial health can enhance its effects. Here are a few you could try.

• Alpha-lipoic acid: Alpha-lipoic acid aids in energy metabolism and also boasts antioxidant properties.

• Acetyl-L-carnitine: This compound plays a role in energy production by assisting in transporting fatty acids into the mitochondria.

• Pyrroloquinoline quinone (PQQ): PQQ is believed to aid in generating new mitochondria and enhance cellular energy production (get 10% off a combination Liposomal Glutathione + COQ10, and PQQ supplement here with code bengreenfield10).

Nootropics

When the goal is cognitive enhancement, combining methylene blue with certain nootropics may have synergistic effects.

• Alpha-GPC: Alpha-GPC is known to support cholinergic brain functions, potentially enhancing memory and learning.

• Bacopa monnieri: A staple in Ayurvedic medicine, Bacon monnieri is associated with cognitive enhancement and stress reduction.

• Lion's mane: Studies suggest Lion's mane may support the production of nerve growth factor, which could be beneficial for brain health.

• Omega-3 fatty acids (DHA and EPA): Essential components for brain health, DHA and EPA have been linked to better memory and cognitive function.

Navigating the vast world of supplements can be overwhelming. However, methylene blue, with its diverse benefits, presents a compelling cornerstone to build a holistic health regimen. As a reminder, it's important to consult with a healthcare professional before making any significant changes to your supplement intake.

When You Shouldn’t Take Methylene Blue

While methylene blue use is unlikely to cause major side effects, there are scenarios where you’d want to avoid use. 

Certain conditions may make you a poor candidate for methylene blue use, or certain medications you might be using.

Selective Serotonin Reuptake Inhibitors (SSRIs), for example, contraindicate with methylene blue. Because methylene blue can increase serotonin, you would not want to use it alongside these anti-depressant medications as the combination could lead to a dangerous condition known as serotonin syndrome. 

Here are some scenarios where you would not want to use methylene blue:

• G6PD deficiency: G6PD (glucose-6-phosphate dehydrogenase) deficiency is a genetic condition that affects red blood cells. If you have this condition, taking methylene blue can cause the red blood cells to break down, leading to a potentially serious condition called hemolysis. Therefore, if you have G6PD deficiency, it is generally recommended to avoid methylene blue.

• Kidney problems: If you have significant kidney problems or impaired kidney function, taking methylene blue may not be suitable. This is because methylene blue is primarily eliminated from the body through the kidneys. If your kidneys are not functioning properly, it can affect the way the medication is processed and potentially lead to an accumulation of the drug in your body.

• Liver problems: Similarly, if you have liver disease or liver problems, it may impact the metabolism and clearance of methylene blue from your body. The liver plays a crucial role in processing medications, and if it is not functioning optimally, it can affect how your body handles methylene blue.

• Low blood pressure: Methylene blue can lower blood pressure in some individuals. If you already have low blood pressure or are taking medications to lower your blood pressure, combining it with methylene blue may lead to excessively low blood pressure, causing dizziness, lightheadedness, or fainting.

• Certain medications: Methylene blue can increase serotonin in moderate and high doses. Taking methylene blue alongside serotonin-increasing drugs or compounds could put you at risk of serotonin syndrome, a dangerous condition that can cause heart problems and requires hospitalization. This condition is rare, but it is worth checking with your doctor if you are unsure if any of your medications would put you at risk for serotonin syndrome. 

• Monoamine Oxidase Inhibitors (MAOIs): Combining methylene blue with MAOIs can increase the risk of serotonin syndrome, a potentially life-threatening condition. It is essential to consult a healthcare professional before using methylene blue if you are taking MAOIs or have recently discontinued their use.

• Selective Serotonin Reuptake Inhibitors (SSRIs): Combining methylene blue with SSRIs can also increase the risk of serotonin syndrome. If you are taking SSRIs, it is important to inform your healthcare professional before considering methylene blue.

Conclusion

Methylene blue is one of the oldest man-made compounds used in medicine. 

Though originally developed as a dye, it didn’t take long for methylene blue’s health applications to be discovered. It became one of the first effective malaria treatments and has gone on to become a highly effective tool for a number of infections, medical conditions, and health benefits. 

Due to its action as a redox agent, methylene blue has a number of positive benefits. By acting as an electron donor, methylene blue supercharges your mitochondria, and via this method of action has potent effects on cognitive enhancement, energy, anti-inflammatory effects, and anti-aging implications.

Here's a summary of the most important points in this article:

• Methylene blue, since its inception in the 1800s, has had a diverse range of applications from medical diagnostics and treatments, to industrial dyeing processes.
• In modern research and medicine, it plays roles in Alzheimer's disease research, treatment of methemoglobinemia, and was historically a chief anti-malaria compound. Methylene blue supports cellular energy production by improving the electron transport chain, leading to enhanced ATP creation by mitochondria.
• It offers cognitive enhancement, neuroprotection against disorders like Alzheimer's, mood elevation, pain reduction, anti-inflammatory effects, and potential anti-aging benefits due to its mitochondrial support and autophagy promotion.
• Beyond its inherent health benefits, methylene blue might assist in treating chronic infections like Lyme disease, but medical consultation is essential.
• Ensure you obtain pharmaceutical-grade methylene blue made for human consumption to avoid harmful fillers and non-consumable forms.
• Dosage recommendation varies; Dr. John Lieurance suggests 0.5-1mg/kg of body weight 2 to 4 days a week, with 20 to 60mg daily being therapeutic for many.
• Oral delivery, particularly via troches (like Lumetol Blue or Troscriptions), is common and practical but can result in a blue-stained tongue (use code BEN10 for 10% off Lumetol Blue after you join the Mitozen Club and 10% off Trosciptions).
• BioBlue is a methylene blue dropper bottle that doesn't stain your mouth (as you can place it near the back of the throat) and uses a unique blend of ingredients that have been incorporated with the pharmaceutical grade (USP >99.5%) methylene blue at 1% solution — including NMN, gold, silver, and fulvic acid (use code BEN for 10% off).
• IV delivery provides quick and controlled dosing but requires clinical access and may be problematic for those averse to needles.
• Suppositories, like the Lumetol Blue Bullet+  (use code BEN for 5% off) by MitoZen Scientific, offer sustained release similar to IVs without the need for clinic visits. The application involves inserting the suppository rectally, and turning your body upside down can help with retention.
• While methylene blue typically enhances mental clarity, mood, and well-being, potential side effects include temporary blue discoloration of urine and stool, mild gastrointestinal disturbances, and rare allergic reactions.
• Enhance the inherent antioxidant properties of methylene blue by layering it with others like Vitamin C, Vitamin E, Glutathione, and Coenzyme Q10 for a comprehensive defense against oxidative stress.
• Pair methylene blue with supplements like Alpha-lipoic acid, Acetyl-L-carnitine, and PQQ for amplified mitochondrial health; for cognitive enhancement, consider nootropics like Alpha-GPC, Bacopa monnieri, Lion's mane, and Omega-3 fatty acids.
• Refrain from using methylene blue if you have G6PD deficiency, kidney or liver issues, or low blood pressure. Additionally, be cautious and consult with a healthcare professional if you are on medications that increase serotonin levels, like MAOIs and SSRIs, as combining them with methylene blue can lead to a potentially fatal condition called serotonin syndrome.
• Combine methylene blue with hyperbaric oxygen and/or red light therapy for enhanced effects.

Throughout its long history, methylene blue has consistently demonstrated diverse and impactful health benefits, from treating malaria to enhancing cognitive functions. Its unique mechanism of action, primarily through supporting mitochondrial function and acting as a redox agent, positions it as a valuable asset in both medical treatments and holistic health regimens. As a final reminder, as with any supplement or treatment, it's crucial to ensure its quality, use it appropriately, and be aware of potential interactions and contraindications to harness its benefits safely.

Let me know your experience with methylene blue in the comments. I read every single one of your replies, and I can't wait to hear what you've gained from this biohack. And if you haven't tried it yet, and you have questions, leave those too!