The Shocking Well being Advantages of Methylene Blue


On this interview, Francisco Gonzalez-Lima, Ph.D., discusses a very highly effective technique to enhance your mitochondria, which generate the overwhelming majority of the power your cells produce from meals.

Gonzalez-Lima is an knowledgeable on methylene blue, which helps mitochondrial respiration and improves mind power metabolism. By doing that, it might enhance cognitive efficiency and forestall neurodegeneration.

“With methylene blue, we now have been capable of present all of these [benefits],” Gonzalez-Lima says. “Our group was the primary to map the consequences of methylene blue within the mind of people and present its results on enhancing mind metabolism, blood circulate and reminiscence operate.”

What Is Methylene Blue?

Methylene blue is the mother or father molecule for hydroxychloroquine and chloroquine, off-patent medication generally used to deal with not solely malaria but additionally COVID-19. Finest often known as a fish tank antiseptic and textile dye for blue denims, it was really the primary artificial drug in trendy historical past, developed in 1876. Since then, we’ve found it has many truly vital medicinal advantages.

The primary medical utility of methylene blue was for malaria. In 1890, Paul Ehrlich, a scientist on the well-known Charité Hospital in Berlin, Germany, found methylene blue inhibits an enzyme that weakens the malaria parasite.

One of many first antipsychotic drugs was additionally created from methylene blue. Different medication developed from or with it embrace antibiotics and antiseptics. Prior to now, it was generally used to deal with urinary tract infections. It’s additionally been used as an antiviral agent in blood used for transfusions.

To this present day, methylene blue is present in each hospital on the earth, because it’s the one identified antidote for metabolic poisons (any poison that interferes with oxygen transport or displaces oxygen, both from the blood or from the mitochondria).

For instance, should you’re admitted for carbon monoxide poisoning, they’ll offer you methylene blue intravenously. Cyanide is one other instance. The one identified antidote for cyanide poisoning is methylene blue. It’s additionally been speculated that methylene blue is perhaps helpful within the remedy of acute lung infections resembling SARS-CoV-2.

Importantly, methylene blue is a hormetic drug, which implies that low doses have the alternative impact as excessive doses. For instance, it’s primarily utilized in emergency rooms on the higher dosage restrict (3 milligrams to 4 mg per kilo of body weight) for methemoglobinemia, which is when a metabolic poison interferes with the transport of oxygen in hemoglobin, by the iron in hemoglobin being oxidized to +3 reasonably than its regular decreased +2 state.

Nonetheless, should you take too excessive a dose, you produce methemoglobinemia. At dosages in between, there’s no impact. Likewise, whereas low dosages have an antioxidant impact, excessive doses are pro-oxidative and may kill micro organism and tumor cells.

Methylene Blue, an Antioxidant and Vitality Producer

Gonzalez-Lima’s analysis has primarily targeted on low-dose advantages for nonacute functions over the long term — resembling neuroprotective advantages and cognitive enhancement. Whereas it has a number of mechanisms of motion, a singular function is that it acts on the extent of electrons. He explains:

“Our physique makes use of electrons as a part of the electron transport chain that occurs inside mitochondria, and these electrons, moved alongside by the mitochondria, are generated from electron donors that we produce by the meals that we eat.

All of the meals that we eat, the one approach they contribute to power is by producing electron donors. They donate these electrons to the electron transport contained in the mitochondria. The last word electron acceptor in nature is oxygen. That is why the method of eradicating electrons from a compound is known as oxidation.

In mitochondria, this course of is known as oxidative phosphorylation. The electron transport is coupled with the phosphorylation of adenosine to ultimately produce the adenosine triphosphate molecule (ATP). Methylene blue is an electron cycler. It is an autooxidizing compound.

So, methylene blue donates its electrons on to the electron transport chain, it obtains electrons from surrounding compounds, and maintains oxygen consumption and power manufacturing. By doing this, it helps oxygen to be totally decreased into water.

So, it turns into two issues which might be usually not discovered collectively. It acts as an antioxidant, as a result of oxygen is neutralized into water by donating electrons to the electron transport, and it produces power, as a result of when the electron transport pumps are transferring alongside oxidative phosphorylation, you might have a rise in ATP formation.

Oftentimes, we now have issues that enhance power metabolism, however then they result in oxidative stress. Within the case of methylene blue, that is not the case.

You’ll be able to enhance oxygen consumption charges, enhance ATP manufacturing for power metabolism, and on the identical time cut back oxidative stress which, in fact, will result in discount in oxidative harm on the stage of mitochondria, then on the stage of the opposite elements of the cells, and ultimately membranes of the cells, and reactions which might be cascades of this oxidative harm.”

Mainly, as an electron cycler, methylene blue acts like a battery, however in contrast to different compounds that do the identical factor, it doesn’t trigger damaging oxidation within the course of. If something interferes with oxygenation or mobile respiration, resembling cyanide, methylene blue is ready to bypass that time of interference by electron biking, thus permitting mitochondrial respiration, oxygen consumption and power manufacturing to operate because it usually would.

Improved Mitochondrial Respiration Improves Well being, Cognition

Methylene blue can be useful in situations the place you might have impaired blood circulate that stops the supply of oxygenated hemoglobin to the tissues. On this case, methylene blue helps counteract the decreased blood circulate by optimizing the effectivity of mitochondrial respiration.

Wholesome blood circulate is especially vital for mind operate, and lots of older folks have persistent hypoperfusion that contributes to neurodegeneration and reminiscence issues. These points, Gonzalez-Lima says, will be prevented by methylene blue.

In abstract, contained in the electron transport chain in your mitochondria are 5 complexes, the first objective of which is to conduct the electrons generated from meals, primarily carbohydrates and fats, within the type of acetyl CoA. Typically the electron transport chain will get blocked or impaired, and methylene blue is ready to bypass such blockages.

An important advanced, Cytochrome c Oxidase, which catalyzes the response of oxygen turning into water, is blocked by cyanide. However methylene blue can insert electrons wherever there’s a blockage.

What’s extra, whenever you’re completely wholesome, low doses of methylene blue will improve oxygen consumption, mitochondrial respiration and ATP manufacturing above baseline, mainly optimizing the entire system. So, it acts as a metabolic enhancer and never simply an antidote for metabolic poisons and different inhibitory processes.

Methylene blue’s motion on mitochondrial respiration can also be coupled with biochemical upregulation of your oxygen consumption equipment generally, and hemodynamic processes that enhance native blood provide to tissues.

And, as detailed by Gonzalez-Lima within the interview, this upregulation stays even after the methylene blue is expelled out of your system (primarily by urination unchanged as your physique minimally metabolizes it), and over time, it might really enhance the variety of mitochondria. In your mind, it will profit cognition, as your mind is probably the most energy-dependent organ in your physique.

Methylene blue additionally prompts the Nrf2 pathway. Nrf2 is a transcription issue that, when activated, goes into the cell’s nucleus and binds to the antioxidant response ingredient (AREs) within the DNA. It then induces the transcription of additional cytoprotective enzymes resembling glutathione, superoxide dismutase catalase, glutathione peroxidase, part II enzymes, heme-1 oxygenase and lots of others.

Methylene Blue for Mind Well being

Maybe one of the revolutionary advantages of methylene blue is for the prevention and remedy of dementia, neurodegenerative ailments resembling Alzheimer’s and Parkinson’s, and neural accidents attributable to stroke and traumatic mind accidents (TBIs). That is significantly vital because the COVID jabs have radically elevated strokes. As defined by Gonzalez-Lima:

“Any course of the place growing oxygen-based power manufacturing performs a serious position, methylene blue may have a task to play. One of many first research we did that was very spectacular [was on] a mannequin within the eye. The rationale we used the attention was as a result of the retina in animals is quickly accessible in order that we will inject into the retina.

Rotenone [a broad-spectrum pesticide and Complex 1 inhibitor] inhibits mitochondrial respiration, subsequently there’s atrophy and degeneration of the retinal layer, which may be very dramatic. If methylene blue is on board, we will stop this course of as a result of the mitochondrial respiration can proceed, so the tissue isn’t affected.

This was a mannequin known as an optic neuropathy on account of mitochondrial defects. It’s the most typical type of blindness in youthful folks, so we did this to confirm in vivo that [methylene blue] may have this neuroprotective impact. Then we did it in different issues like brains. We discovered an identical phenomenon …

Methylene blue will be protecting in ischemic and hemorrhagic strokes. We’ve additionally revealed a examine with a hypoxia. In different phrases, we decreased the quantity of oxygen delivered to the animals, and we may use an fMRI, noninvasively, within the animals to see that we had been capable of enhance the quantity of cerebral metabolic fee for oxygen consumption within the presence of methylene blue underneath hypoxic circumstances.

With respect to dementia, by the point you see the tau protein inside neurons, these neurons are metabolically, primarily, lifeless, so it’s too late. By performing on that, you can’t get well the metabolic equipment and the well being of the neurons.

So, these neurons usually are not rescued in any approach that’s functionally significant. Typically talking, biomarkers usually are not good therapeutic targets as a result of they could or could not have any causal relationship with the illness.”

In biohacker circles, low-dose methylene blue is used as a nootropic, that means a compound that helps enhance cognitive operate. Nonetheless, whereas some promote sublingual or buccal utility (underneath your tongue or on the within of your cheek), one of the best ways is to swallow it, because the acid in your abdomen makes it extra bioavailable.

Urinary Tract Infections within the Aged

In my thoughts, this is among the most vital makes use of: It’s a extremely efficient agent towards urinary tract infections (UTIs). Many aged are placed on antibiotics, which disrupts their microbiome. Methylene blue was used for a lot of many years at a dose of 65 mg per day and was even offered in pharmacies as Urolene Blue.

Since your physique doesn’t actually metabolize it, it’s excreted by your kidneys into your bladder the place it reaches very excessive concentrations over time and turns into a potent oxidant stress that kills just about any pathogen within the bladder. Plus, it has the extra “aspect impact” of enhancing mind well being and decreasing dementia. In my thoughts, it’s reprehensible medical malpractice to not use methylene blue in UTIs within the aged. It clearly is the most secure and simplest drug of alternative.

Contraindications

Whereas methylene blue may be very secure, there are some contraindications. One is G6PD deficiency, which can also be a contraindication for high-dose ascorbic acid therapies, which may very well be lethal. Methylene blue can also be a light monoamine oxidase (MAO) inhibitor, so taking excessive doses with a selective serotonin reuptake inhibitor (SSRI) antidepressant may probably result in serotonin syndrome, which isn’t good. The danger of this, nevertheless, may be very small. Gonzalez-Lima explains:

“With respect to the warning concerning the SSRIs, the issue isn’t methylene blue however the quantity of SSRI. The issue was in a particular utility of methylene blue the place they use it for parathyroid surgical procedure as a stain …

To my information, there’s by no means been greater than 5 instances, the place the sufferers had been anesthetized, and so they nonetheless had SSRIs [in their system], and so they did repeated flushing within the open neck with methylene blue, which exceeded these doses that we now have been speaking about.

The U.S. FDA reacted with this warning. However this has been reviewed by each surgeons and pharmacologists on the Mayo Clinic, and so they wrote a rebuttal paper the place they point out that there is no such thing as a proof to counsel oral methylene blue has any interplay with the therapeutic dosing of serotonergic compounds, particularly SSRIs, and that this was one thing that occurred underneath these particular [surgical] circumstances.

Canada limits the warning to that exact utility, however our FDA went past that to any sort of serotonergic drug. I feel there’s completely no proof for oral methylene blue having interactions on this low-dose vary with any SSRIs.

And once they discuss concerning the MAO inhibitor operate, it actually solely works as an MAO inhibitor within the greater focus of the upper dose vary, not the low-dose vary. So, the consequences of methylene blue as an antidepressant — solely to a really restricted extent, should you repeat it cumulative therapies — will be on account of any sort of a MAO inhibitor position.

As well as, it is because of its metabolic enhancing operate, so it antagonizes a few of the despair signs just like the low power that’s skilled with despair. So sure, it’s efficient to cut back signs of despair. Sadly, this warning goes to make some physicians afraid of utilizing it together with SSRIs.”

Dosing Options

As talked about, methylene blue is a hormetic, so low dosages have the alternative impact of excessive dosages. Whereas each attainable dose response has not been examined, as a normal guideline, the advantages Gonzalez-Lima discusses on this interview are primarily based on dosages between 0.5 milligram per kilogram of body weight to 4 mg per kg. He admits decrease doses may match however he hasn’t examined them.

For an acute remedy, the higher restrict is between 3 mg to 4 mg per kg, which is usually the vary given as an IV antidote for methemoglobinemia. For nonacute, extra long-term remedy, 0.5 mg to 1 mg per kg per day works higher. It has a half-life of 12 to 13 hours, so once-a-day dosing is ok. He offers the next instance of how methylene blue has been used within the remedy of fears and phobias:

“One of many processes during which a reminiscence formation can be utilized therapeutically is whenever you kind a reminiscence to extinguish concern. People who’ve a phobia, you’ll be able to expose them to the particular scenario that’s concerned within the phobia, and there’s a studying known as extinction studying that occurs that you just extinguish your response.

In that scenario, we solely give methylene blue as soon as after this extinction studying to facilitate the method of reminiscence consolidation. What occurs after you undergo the educational is the method of consolidation, which requires power.

So, by facilitating the power availability throughout the consolidation part, which occurs over numerous hours, then the following time [you’re exposed to fear-evoking stimuli, you’ve] consolidated that extinction reminiscence extra successfully.

We’ve accomplished this additionally with post-traumatic stress dysfunction (PTSD), the place you utilize extended publicity remedy. In that scenario, you can provide the methylene blue after completely different periods the place you see that there’s a good extinction studying.

In different phrases, the place individuals are studying by publicity to cut back their concern ranges, that’s whenever you wish to reinforce that therapeutic studying by giving them the methylene blue proper after the session.”

For mind well being, nootropic results and the prevention or remedy of dementia, 0.5 mg to 1 mg per kg per day (or when wanted) is the dose Gonzalez-Lima recommends and makes use of.

Choose a Excessive-High quality Product

Final however not least, choosing the proper product is of essential significance, along with getting the dosing proper. There are three primary kinds of methylene blue: industrial, chemical and pharmaceutical-grade.

The one model you’ll wish to use medicinally is pharmaceutical-grade. Don’t ingest methylene blue from the pet retailer that’s meant for fish tanks. Industrial-grade methylene blue has plenty of impurities, and sometimes include solely 10% to 25% methylene blue.

Chemical or laboratory grade, which is used for staining functions on laboratories, has a a lot greater purity, however it’s nonetheless not appropriate for medicinal functions because it sometimes has heavy steel contaminants like lead, cadmium and arsenic. Over time, the impurities can accumulate in your physique, leading to toxicity.

Pharmaceutical grade is 99%+ pure. That is the type used when injected intravenously for antidote functions, or used orally. These merchandise can be marked USP, which stands for United States Pharmacopeia.

In keeping with Gonzalez-Lima, USP is healthier by way of purity than the European pharmaceutical grade, which has fewer necessities. Taking the methylene blue with some ascorbic acid (vitamin C) facilitates absorption. You received’t discover methylene blue at your native pharmacy however many compounding pharmacies can acquire the pharmaceutical grade.

“Ascorbic acid is a solution to facilitate the biking of methylene blue by selling its discount,” he explains. Contemplating the significance of mitochondrial well being, methylene blue seems to be a easy and remarkably efficient approach to enhance your total well being and cognitive operate.



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