On this interview, Francisco Gonzalez-Lima, Ph.D., discusses a extremely highly effective technique to enhance your mitochondria, which generate the overwhelming majority of the vitality your cells produce from meals.
Gonzalez-Lima is an knowledgeable on methylene blue, which helps mitochondrial respiration and improves mind vitality metabolism. By doing that, it could actually enhance cognitive efficiency and forestall neurodegeneration.
“With methylene blue, we have now 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 circulation and reminiscence perform.”
What Is Methylene Blue?
Methylene blue is the mother or father molecule for hydroxychloroquine and chloroquine, off-patent medicine generally used to deal with not solely malaria but in addition COVID-19. Finest referred to as a fish tank antiseptic and textile dye for blue denims, it was really the primary artificial drug in fashionable historical past, developed in 1876. Since then, we’ve found it has many actually essential 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 drugs was additionally constituted of methylene blue. Different medicine developed from or with it embrace antibiotics and antiseptics. Up 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 this planet, because it’s the one recognized 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 provide you with methylene blue intravenously. Cyanide is one other instance. The one recognized antidote for cyanide poisoning is methylene blue. It’s additionally been speculated that methylene blue is likely to be helpful within the therapy of acute lung infections akin to SARS-CoV-2.
Importantly, methylene blue is a hormetic drug, which signifies that low doses have the other 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 somewhat than its regular decreased +2 state.
Nonetheless, 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 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 — akin to neuroprotective advantages and cognitive enhancement. Whereas it has a number of mechanisms of motion, a novel characteristic 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 via 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 vitality is by producing electron donors. They donate these electrons to the electron transport contained in the mitochondria. The final 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 finally 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 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 vitality, as a result of when the electron transport pumps are transferring alongside oxidative phosphorylation, you might have a rise in ATP formation.
Oftentimes, we have now 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 injury on the degree of mitochondria, then on the degree of the opposite components of the cells, and finally membranes of the cells, and reactions which might be cascades of this oxidative injury.”
Principally, as an electron cycler, methylene blue acts like a battery, however not like 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, akin to cyanide, methylene blue is ready to bypass that time of interference via 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 situations the place you might have impaired blood circulation that stops the supply of oxygenated hemoglobin to the tissues. On this case, methylene blue helps counteract the decreased blood circulation by optimizing the effectivity of mitochondrial respiration.
Wholesome blood circulation is especially essential for mind perform, and lots of older individuals have persistent hypoperfusion that contributes to neurodegeneration and reminiscence issues. These points, Gonzalez-Lima says, could 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. 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 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, principally 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 typically, 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 via urination unchanged as your physique minimally metabolizes it), and over time, it could actually really enhance the variety of mitochondria. In your mind, this can 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 aspect (AREs) within the DNA. It then induces the transcription of additional cytoprotective enzymes akin to 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 crucial revolutionary advantages of methylene blue is for the prevention and therapy of dementia, neurodegenerative ailments akin to Alzheimer’s and Parkinson’s, and neural accidents brought on by stroke and traumatic mind accidents (TBIs). That is notably essential 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 significant function, methylene blue can have a task to play. One of many first research we did that was very spectacular [was on] a mannequin within the eye. The explanation 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 stop this course of as a result of the mitochondrial respiration can proceed, so the tissue shouldn’t be affected.
This was a mannequin referred to as an optic neuropathy as a consequence of mitochondrial defects. It’s the most typical type of blindness in youthful individuals, 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 could 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 may use an fMRI, noninvasively, within the animals to see that we had been capable of enhance the quantity of cerebral metabolic charge for oxygen consumption within the presence of methylene blue below 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 better the metabolic equipment and the well being of the neurons.
So, these neurons aren’t rescued in any approach 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, that means a compound that helps enhance cognitive perform. Nonetheless, whereas some promote sublingual or buccal software (below 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 essential makes use of: It’s a extremely efficient agent in opposition to 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 bought 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 “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 best drug of selection.
Whereas methylene blue could be very secure, there are some contraindications. One is G6PD deficiency, which can also be a contraindication for high-dose ascorbic acid remedies, which could possibly 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 doubtlessly result in serotonin syndrome, which isn’t good. The chance of this, nevertheless, could be very small. Gonzalez-Lima explains:
“With respect to the warning in regards to the SSRIs, the issue shouldn’t 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 data, there’s by no means been greater than 5 circumstances, 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 have now 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 below these particular [surgical] circumstances.
Canada limits the warning to that specific software, however our FDA went past that to any type of serotonergic drug. I believe there may be completely no proof for oral methylene blue having interactions on this low-dose vary with any SSRIs.
And after they speak 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 remedies — could be as a consequence of any type of a MAO inhibitor function.
As well as, it is because of its metabolic enhancing perform, so it antagonizes among the despair signs just like the low vitality that’s skilled with despair. So sure, it’s efficient to scale back signs of despair. Sadly, this warning goes to make some physicians frightened of utilizing it together with SSRIs.”
As talked about, methylene blue is a hormetic, so low dosages have the other impact of excessive dosages. Whereas each potential 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 therapy, 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 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 offers the next instance of how methylene blue has been used within the therapy of fears and phobias:
“One of many processes wherein a reminiscence formation can be utilized therapeutically is whenever you type 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 simply 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 training is the method of consolidation, which requires vitality.
So, by facilitating the vitality availability in the course of the consolidation part, which occurs over numerous hours, then the subsequent time [you’re exposed to fear-evoking stimuli, you’ve] consolidated that extinction reminiscence extra successfully.
We’ve achieved this additionally with post-traumatic stress dysfunction (PTSD), the place you utilize extended publicity remedy. In that state of affairs, you may give 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 via publicity to scale back their worry ranges, that’s whenever you need 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.
Find out how to Choose a Excessive-High quality Product
Final however not least, deciding on the proper product is of essential significance, along with getting the dosing proper. There are three fundamental varieties of methylene blue: industrial, chemical and pharmaceutical-grade.
The one model you’ll need 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 numerous 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 larger purity, nevertheless 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 can be marked USP, which stands for United States Pharmacopeia.
In line with Gonzalez-Lima, USP is best 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 get hold of the pharmaceutical grade.
“Ascorbic acid is a technique 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 perform.