Do you love methylene blue? Well, here at Troscriptions, blueing ourselves is the best thing since sliced (gluten free, dairy free, soy free, non-GMO, and no-bees-were-harmed to make this) bread.

In previous blogs, we’ve covered many methylene blue topics including its history, many potential uses (especially as a Health Optimization Nootropic), and we have implored you to never drink actual fish tank cleaner (please!).

But what we haven’t dialed in yet is dosing.

So, in this article that’s exactly what we are going to do!

We’ll discuss the why behind Troscriptions dosing and also take a deep dive into the potential dangers of taking higher dose methylene blue, especially for longer periods of time. 

Are you ready to come dance (and blue yourself) in the nuance of dosing as we explore the Blueniverse once again?

Let’s go! 

Oh, wait! But first…

A Quick (but detailed) Refresher on Methylene Blue's Mechanisms 

Methylene blue is called an electron cycler. At doses up to 3 mg/kg, it acts both as an electron donor to the electron transport chain in your mitochondria and as an electron acceptor of free electrons from reactive oxygen and nitrogen species (i.e., works like an antioxidant, an antioxidant as powerful or possibly even more powerful than glutathione).

There are very few compounds that cycle electrons as effectively as methylene blue.

In addition, methylene blue also increases cytochrome oxidase (complex IV) function in your mitochondria and drives increased glucose consumption. The latter occurs because the mitochondria are making more energy and need more substrate to supply electrons to the electron chain. Lest you forget that the major reason we need to eat is to supply our mitochondria with electrons!

While increasing glucose consumption and energy production, methylene blue also increases the supply of NAD+ whether there is oxygen around or not. At <2 mg/kg, it also causes the release of nitric oxide and the dilation of blood vessels to get more oxygen-rich blood to the area of increased glucose consumption. 

For those nerds amongst us (we are guilty), because methylene blue can enhance complex IV function and NAD+ supply, it can bypass potentially dysfunctional mitochondrial complexes I and II. This is a big deal, and a major reason why methylene blue works to reverse or compensate for mitochondrial damage. 

And there’s more! 

Methylene blue also changes the conformation of hemoglobin in RBCs to help it carry oxygen more efficiently, promotes oxygen dumping into tissues so it can be utilized easier, helps clear senescent cells, increases mitochondrial biogenesis, and works as a monoamine oxidase inhibitor (MAO-I) which leads to neurotransmitter release (including dopamine and serotonin). 

Phew! Are you keeping up? This compound is doing a lot and has a large therapeutic range… from 8 to 210 mg (<0.5 to 3 mg/kg). 

Even at doses >3 mg/kg, when methylene blue is no longer an electron cycler and becomes purely oxidative, there may be a role for it in cancer and sepsis,. 

But that’s a huge therapeutic range. How do you know what dose is best for you?

Methylene Blue Dosing 

The key point is to distinguish what kind of dosing helps acutely (i.e., for a disease or condition) vs. what dosing will help optimize health. And also to be aware of the significant dangers of taking too much methylene blue at high doses for a long period of time. 

Here at Troscriptions, we are focused on optimizing health rather than treating disease. After all, this is the ethos of our company. And to this end, we provide financial support to Health Optimization Medicine and Practice (HOMe/HOPe), a nonprofit organization that is training doctors and practitioners on how to optimize health rather than treat disease.

Let’s chat about the risks of higher dose methylene blue and why we use lower dosing at Troscriptions. 

Methylene Blue and the disruption of GI Biofilms

Our concern with higher dose methylene blue is that it may disrupt natural and healthy gastrointestinal biofilms, leading to issues with your gut lining and gut microbiota. We’ll get back to what we mean by higher dose in a minute. First, let’s talk about biofilms.

Biofilms are a collective of one or more types of microorganisms that can grow on many different surfaces. They produce extracellular polymeric substance (EPS), which gives the surface a film-like/sticky consistency. A fully functioning biofilm structure is comprised of microbial cells and EPS, has a defined architecture, and provides an optimal environment for the exchange of genetic material between cells of the same and different phyla, otherwise known as trans-kingdom interactions. 

Microorganisms that form biofilms include bacteria, fungi, and protists. In the gut, biofilms naturally grow, both at the epithelial surface and in the lumen as mucin-attached and food particle-attached colonies. Communities of microbes that form biofilms are usually more resilient to stress and are well-known to keep surfaces like your mouth and gut healthy. This includes enhancing immune system function. They also function as a physical barrier to the intestinal lining. 

There are, however, times when these biofilms can become pathologic such as in dental plaques or with certain bacterial infections. When this occurs, biofilms can actually protect pathogenic bacteria and can be difficult for the host defense system to identify. 

Methylene blue is especially effective at disrupting biofilms of multiple organisms when combined with other synergistic therapies, such as photodynamic therapy. For example, it is often used at doses of 50 mg daily for infections with biofilms like Bartonella. 

High Doses May Be Dangerous due to methylene blue's half-life. Here’s why…

Methylene blue — whether IV, oral, or in troche form — is almost 100% bioavailable, meaning that almost all the methylene blue that you take in gets into your bloodstream. What’s the catch? Let us explain…

How long methylene blue stays in your body depends on its half-life. This is defined as the time it takes for one half the amount of methylene blue that you ingested to leave your body. 

The half-life of IV methylene blue is 24 hours 

The half-life of oral methylene blue is 4 to 6 hours. 

Let’s take the example of 100 mg oral methylene blue dose with a half-life of 6 hours:

Imagine you took your dose at 8 am in the morning…

half-life #1: 50 mg left in your body at 2 pm (i.e., 6 hours later) 

half-life #2: 25 mg left in your body at 8 pm (i.e., another 6 hours later)

half-life #3: 12.5 mg left in your body at 2 am

half-life #4: 6.25 mg left in your body at 8 am

This means that if you take 100 mg methylene blue at 8 am, you'll still have 6.25 mg of methylene blue in your body 24 hours later. 

As an alternative example: if we assume that the half-life is 4 hours, then there would be 3.125 mg of methylene blue left in your body at 8 am the next day.

Either way, if you take 100 mg on a daily basis, there will be a high chance for potential toxicity because methylene blue will continue to build up in your system.

And high dose methylene blue (especially >3 mg/kg) leads to mitochondrial dysfunction and inflammation, not to mention more issues with GI biofilms and your microbiota. 

High doses of Methylene Blue and Risk of Gastric Ulceration + Gastric Acid, Really? 

While higher doses of methylene blue may help treat disease, over the long term, it may cause gastric ulceration.

And there is no indication that methylene blue requires gastric acid to be activated. After all, IV methylene blue is 100% bioavailable and completely bypasses the GI system. This is an important counter for some of the arguments that are floating around the internet. :)

Methylene Blue and G6PD Deficiency

Although rare, higher doses of methylene blue may also cause hemolysis (the destruction of red blood cells) in those with G6PD deficiency, an inherited blood disorder. At low doses, this would be rare, but higher doses, especially for prolonged periods of time,may be dangerous. 

Conclusion

At Troscriptions, our products optimize health rather than treat disease. In this context, our methylene blue dosing was designed to leverage this magical blue compound for its energy enhancing and antioxidant properties while at the same time minimizing the risks of potential GI biofilm disruption, of methylene blue building up in the body, the potential for gastric ulceration, and other potential side effects. 

Our dosing also happens to be the dosing being studied in patients with neurocognitive conditions such as Alzheimer's disease (but we make no claims). 

Of course, our troches (or another methylene blue product) can be used at higher doses when needed to treat certain diseases or conditions. But if this is the case, titration and less regular dosing are key to decrease risk of toxicity. 

And a few words of advice to leave you with…

Make sure your methylene blue company is going the extra mile to give you a pure product. Many on the market, even USP designated products, may be contaminated with heavy metals. Industrial and chemical grade methylene blue should be avoided at all costs as well (cue the Darwin Awards, folks!). 

At Troscriptions, our methylene blue is: 

• Third-party tested from our manufacturer to ensure purity/potency
• USP grade 
• Tested AGAIN for purity/potency with each troche batch we make

Does your methylene blue company do all this? We doubt it!

Plus, there are 4 doctors on the Tro Team + practitioners around the world that use our products in clinical practice. 

No go forth and Blue Yourself… safely and effectively. 

To Health, Optimized. 

—Dr. Scott and the Troscriptions team