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 vitality your cells produce from meals.
Gonzalez-Lima is an professional on methylene blue, which helps mitochondrial respiration and improves mind vitality metabolism. By doing that, it will probably enhance cognitive efficiency and stop neurodegeneration.
“With methylene blue, we’ve been in a position to 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 move and reminiscence perform.”
What Is Methylene Blue?
Methylene blue is the guardian molecule for hydroxychloroquine and chloroquine, off-patent medication generally used to deal with not solely malaria but additionally COVID-19. Greatest often called 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 actually vital medicinal advantages.
The primary medical software 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 medicines was additionally made out of methylene blue. Different medication developed from or with it embody 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 today, methylene blue is present in each hospital on this planet, 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, in the event 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 therapy of acute lung infections reminiscent of SARS-CoV-2.
Importantly, methylene blue is a hormetic drug, which signifies 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 moderately than its regular decreased +2 state.
Nevertheless, in the event 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 might kill micro organism and tumor cells.
Methylene Blue, an Antioxidant and Vitality Producer
Gonzalez-Lima’s analysis has primarily centered on low-dose advantages for nonacute functions over the long run — reminiscent of neuroprotective advantages and cognitive enhancement. Whereas it has a number of mechanisms of motion, a novel 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 means they contribute to vitality 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 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 vitality manufacturing. By doing this, it helps oxygen to be absolutely decreased into water.
So, it turns into two issues which are typically 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 vitality, as a result of when the electron transport pumps are shifting alongside oxidative phosphorylation, you’ve a rise in ATP formation.
Oftentimes, we’ve issues that enhance vitality metabolism, however then they result in oxidative stress. Within the case of methylene blue, that is not the case.
You may enhance oxygen consumption charges, enhance ATP manufacturing for vitality metabolism, and on the identical time scale 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 components of the cells, and ultimately membranes of the cells, and reactions which are 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, reminiscent of cyanide, methylene blue is ready to bypass that time of interference by electron biking, thus permitting mitochondrial respiration, oxygen consumption and vitality manufacturing to perform because it usually would.
Improved Mitochondrial Respiration Improves Well being, Cognition
Methylene blue may also be useful in cases the place you’ve impaired blood move that stops the supply of oxygenated hemoglobin to the tissues. On this case, methylene blue helps counteract the decreased blood move by optimizing the effectivity of mitochondrial respiration.
Wholesome blood move is especially vital for mind perform, and lots of older folks have continual 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 function of which is to conduct the electrons generated from meals, primarily carbohydrates and fats, within the type of acetyl CoA. Generally the electron transport chain will get blocked or impaired, and methylene blue is ready to bypass such blockages.
A very powerful advanced, Cytochrome c Oxidase, which catalyzes the response of oxygen changing 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 be coupled with biochemical upregulation of your oxygen consumption equipment normally, 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 will probably really enhance the variety of mitochondria. In your mind, this can profit cognition, as your mind is essentially 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 factor (AREs) within the DNA. It then induces the transcription of additional cytoprotective enzymes reminiscent of glutathione, superoxide dismutase catalase, glutathione peroxidase, section II enzymes, heme-1 oxygenase and lots of others.
Methylene Blue for Mind Well being
Maybe some of the revolutionary advantages of methylene blue is for the prevention and therapy of dementia, neurodegenerative illnesses reminiscent of 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 rising oxygen-based vitality manufacturing performs a serious position, methylene blue could 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 instantly accessible in order that we are able to inject into the retina.
Rotenone [a broad-spectrum pesticide and Complex 1 inhibitor] inhibits mitochondrial respiration, subsequently there may be atrophy and degeneration of the retinal layer, which could be very dramatic. If methylene blue is on board, we are able to forestall this course of as a result of the mitochondrial respiration can proceed, so the tissue will not be affected.
This was a mannequin referred to as an optic neuropathy on account of mitochondrial defects. It’s the commonest type of blindness in youthful folks, so we did this to confirm in vivo that [methylene blue] might have this neuroprotective impact. Then we did it in different issues like brains. We discovered the same phenomenon …
Methylene blue will be protecting in ischemic and hemorrhagic strokes. We’ve additionally printed a examine with a hypoxia. In different phrases, we decreased the quantity of oxygen delivered to the animals, and we might use an fMRI, noninvasively, within the animals to see that we have been in a position to enhance the quantity of cerebral metabolic price for oxygen consumption within the presence of methylene blue beneath hypoxic circumstances.
With respect to dementia, by the point you see the tau protein inside neurons, these neurons are metabolically, primarily, useless, 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 aren’t rescued in any means that’s functionally significant. Typically talking, biomarkers aren’t good therapeutic targets as a result of they could or might not have any causal relationship with the illness.”
In biohacker circles, low-dose methylene blue is used as a nootropic, which means a compound that helps enhance cognitive perform. Nevertheless, whereas some promote sublingual or buccal software (beneath your tongue or on the within of your cheek), one of the simplest 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 without doubt one of 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 a long time 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 nearly any pathogen within the bladder. Plus, it has the extra “facet 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 handiest drug of alternative.
Contraindications
Whereas methylene blue could be very protected, there are some contraindications. One is G6PD deficiency, which can be a contraindication for high-dose ascorbic acid therapies, which might be lethal. Methylene blue can be a gentle monoamine oxidase (MAO) inhibitor, so taking excessive doses with a selective serotonin reuptake inhibitor (SSRI) antidepressant might probably result in serotonin syndrome, which isn’t good. The chance of this, nonetheless, could be very small. Gonzalez-Lima explains:
“With respect to the warning in regards to the SSRIs, the issue will not be methylene blue however the quantity of SSRI. The issue was in a selected software 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 have 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’ve 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 isn’t 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 beneath these particular [surgical] circumstances.
Canada limits the warning to that individual software, however our FDA went past that to any form of serotonergic drug. I feel there may be completely no proof for oral methylene blue having interactions on this low-dose vary with any SSRIs.
And after they discuss in regards to the MAO inhibitor perform, it actually solely works as an MAO inhibitor within the larger 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, in the event you repeat it cumulative therapies — will be on account of any form of a MAO inhibitor position.
As well as, it is because of its metabolic enhancing perform, so it antagonizes a number of the melancholy signs just like the low vitality that’s skilled with melancholy. So sure, it’s efficient to cut back signs of melancholy. Sadly, this warning goes to make some physicians petrified of utilizing it together with SSRIs.”
Dosing Ideas
As talked about, methylene blue is a hormetic, so low dosages have the alternative impact of excessive dosages. Whereas each doable dose response has not been examined, as a basic guideline, the advantages Gonzalez-Lima discusses on this interview are based mostly 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 therapy, the higher restrict is between 3 mg to 4 mg per kg, which is often the vary given as an IV antidote for methemoglobinemia. For nonacute, extra long-term therapy, 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 okay. He provides the next instance of how methylene blue has been used within the therapy 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 worry. People who’ve a phobia, you may expose them to the precise state of affairs that’s concerned within the phobia, and there’s a studying referred to as extinction studying that occurs that you just extinguish your response.
In that state of affairs, 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 vitality.
So, by facilitating the vitality availability in the course of the consolidation section, which occurs over quite a few hours, then the following time [you’re exposed to fear-evoking stimuli, you’ve] consolidated that extinction reminiscence extra successfully.
We’ve executed this additionally with post-traumatic stress dysfunction (PTSD), the place you employ extended publicity remedy. In that state of affairs, you can provide the methylene blue after totally different classes the place you see that there’s a good extinction studying.
In different phrases, the place persons are studying by publicity to cut back their worry 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 therapy 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.
The best way to Choose a Excessive-High quality Product
Final however not least, choosing the right product is of essential significance, along with getting the dosing proper. There are three primary sorts 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 a number of impurities, and sometimes comprise solely 10% to 25% methylene blue.
Chemical or laboratory grade, which is used for staining functions on laboratories, has a a lot larger 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 sort used when injected intravenously for antidote functions, or used orally. These merchandise will likely be marked USP, which stands for United States Pharmacopeia.
Based on Gonzalez-Lima, USP is best when it comes to 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 get hold of the pharmaceutical grade.
“Ascorbic acid is a method 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 means to enhance your general well being and cognitive perform.
