Methylene blue helps mitochondrial respiration and improves brain energy metabolism. By doing that, it can improve cognitive performance and prevent neurodegeneration. It is also a powerful strategy to improve your mitochondria, which generates the vast majority of the energy your cells produce from food.
What is Methylene Blue?
Methylene blue is the parent molecule for hydroxychloroquine and chloroquine, off-patent drugs commonly used to treat not only malaria but also COVID-19. Best known as a fish tank antiseptic and textile dye for blue jeans, it was actually the first synthetic drug in modern history, developed in 1876. Since then, we’ve discovered it has many really important medicinal benefits.
The first medical application of methylene blue was for malaria. In 1890, Paul Ehrlich, a scientist at the famous Charité Hospital in Berlin, Germany, discovered methylene blue inhibits an enzyme that weakens the malaria parasite.
One of the first antipsychotic medications was also made from methylene blue. Other drugs developed from or with it include antibiotics and antiseptics. In the past, it was commonly used to treat urinary tract infections. It’s also been used as an antiviral agent in blood used for transfusions.
To this day, methylene blue is found in every hospital in the world, as it’s the only known antidote for metabolic poisons (any poison that interferes with oxygen transport or displaces oxygen, either from the blood or from the mitochondria).
For example, if you’re admitted for carbon monoxide poisoning, they’ll give you methylene blue intravenously. Cyanide is another example. The only known antidote for cyanide poisoning is methylene blue. It’s also been speculated that methylene blue might be useful in the treatment of acute lung infections such as SARS-CoV-2.
Methylene Blue, an Antioxidant and Energy Producer
While it has several mechanisms of action, a unique feature is that it acts on the level of electrons. In this interview, Francisco Gonzalez-Lima, Ph.D. 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.
Oftentimes, we have things that improve energy metabolism, but then they lead to oxidative stress. In the case of methylene blue, that’s not the case.
You can increase oxygen consumption rates, increase ATP production for energy metabolism, and at the same time reduce oxidative stress which, of course, will lead to reduction in oxidative damage at the level of mitochondria, then at the level of the other parts of the cells, and eventually membranes of the cells, and reactions that are cascades of this oxidative damage.”
Basically, as an electron cycler, methylene blue acts like a battery, but unlike other compounds that do the same thing, it doesn’t cause damaging oxidation in the process. If anything interferes with oxygenation or cellular respiration, such as cyanide, methylene blue is able to bypass that point of interference through electron cycling, thus allowing mitochondrial respiration, oxygen consumption and energy production to function as it normally would.
Improved Mitochondrial Respiration Improves Health, Cognition
Methylene blue can also be helpful in instances where you have impaired blood flow that prevents the delivery of oxygenated hemoglobin to the tissues. In this case, methylene blue helps counteract the reduced blood flow by optimizing the efficiency of mitochondrial respiration.
Healthy blood flow is particularly important for brain function, and many older people have chronic hypo-perfusion that contributes to neurodegeneration and memory problems. These issues can be prevented by methylene blue.
In summary, inside the electron transport chain in your mitochondria are five complexes, the primary purpose of which is to conduct the electrons generated from food, primarily carbohydrates and fat, in the form of acetyl CoA. Sometimes the electron transport chain gets blocked or impaired, and methylene blue is able to bypass such blockages.
When you’re perfectly healthy, low doses of methylene blue will enhance oxygen consumption, mitochondrial respiration and ATP production above baseline, basically optimizing the whole system. So, it acts as a metabolic enhancer and not just an antidote for metabolic poisons and other inhibitory processes.
The most important complex, Cytochrome c Oxidase, which catalyzes the reaction of oxygen becoming water, is blocked by cyanide. But methylene blue can insert electrons wherever there is a blockage.
What’s more, when you’re perfectly healthy, low doses of methylene blue will enhance oxygen consumption, mitochondrial respiration and ATP production above baseline, basically optimizing the whole system. So, it acts as a metabolic enhancer and not just an antidote for metabolic poisons and other inhibitory processes.
Methylene blue’s action on mitochondrial respiration is also coupled with biochemical upregulation of your oxygen consumption machinery in general, and hemodynamic processes that increase local blood supply to tissues. This upregulation remains even after the methylene blue is expelled from your system (primarily through urination unchanged as your body minimally metabolizes it), and over time, it can actually increase the number of mitochondria. In your brain, this will benefit cognition, as your brain is the most energy-dependent organ in your body.
Methylene blue also activates the Nrf2 pathway. Nrf2 is a transcription factor that, when activated, goes into the cell’s nucleus and binds to the antioxidant response element (AREs) in the DNA. It then induces the transcription of further cytoprotective enzymes such as glutathione, superoxide dismutase catalase, glutathione peroxidase, phase II enzymes, heme-1 oxygenase and many others.
Methylene Blue for Brain Health
Perhaps one of the most revolutionary benefits of methylene blue is for the prevention and treatment of dementia, neurodegenerative diseases such as Alzheimer’s and Parkinson’s, and neural injuries caused by stroke and traumatic brain injuries (TBIs). This is particularly important as the COVID jabs have radically increased strokes.
“Any process where increasing oxygen-based energy production plays a major role, methylene blue will have a role to play. One of the first studies we did that was very impressive [was on] a model in the eye. The reason we used the eye was because the retina in animals is readily accessible so that we can inject into the retina.
Rotenone [a broad-spectrum pesticide and Complex 1 inhibitor] inhibits mitochondrial respiration, subsequently there is atrophy and degeneration of the retinal layer, which is very dramatic. If methylene blue is on board, we can prevent this process because the mitochondrial respiration can continue, so the tissue is not affected.
This was a model called an optic neuropathy due to mitochondrial defects. It’s the most common form of blindness in younger people, so we did this to verify in vivo that [methylene blue] could have this neuroprotective effect. Then it was performed in other things like brains. Similar phenomenon was discovered ...
Methylene blue can be protective in ischemic and hemorrhagic strokes and hypoxia. In other words, there was a reduced amount of oxygen delivered to the animals, and with the use an fMRI, noninvasively, in the animals to see that there was an increase in the amount of cerebral metabolic rate for oxygen consumption in the presence of methylene blue under hypoxic conditions.
With respect to dementia, by the time you see the tau protein inside neurons, those neurons are metabolically, essentially, dead, so it is too late. By acting on that, you cannot recover the metabolic machinery and the health of the neurons.
So, those neurons are not rescued in any way that is functionally meaningful. Generally speaking, biomarkers are not good therapeutic targets because they may or may not have any causal relationship with the disease.”
In biohacker circles, low-dose methylene blue is used as a nootropic, meaning a compound that helps improve cognitive function. However, while some promote sublingual or buccal application (under your tongue or on the inside of your cheek), the best way is to swallow it, as the acid in your stomach makes it more bioavailable.