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 skilled on methylene blue, which helps mitochondrial respiration and improves mind vitality metabolism. By doing that, it will possibly enhance cognitive efficiency and forestall 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 bettering mind metabolism, blood circulate and reminiscence operate.”
What Is Methylene Blue?
Methylene blue is the dad or mum molecule for hydroxychloroquine and chloroquine, off-patent medicine 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 fashionable 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 drugs was additionally constituted of methylene blue. Different medicine developed from or with it embody 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 today, methylene blue is present in each hospital on the 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, when you’re admitted for carbon monoxide poisoning, they’ll offer you 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 corresponding to SARS-CoV-2.
Importantly, methylene blue is a hormetic drug, which implies 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 moderately than its regular diminished +2 state.
Nevertheless, when 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 run — corresponding to 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 manner 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 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 totally diminished 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 possibly can enhance oxygen consumption charges, enhance ATP manufacturing for vitality metabolism, and on the similar time scale back oxidative stress which, after all, will result in discount in oxidative injury on the stage of mitochondria, then on the stage of the opposite components of the cells, and finally membranes of the cells, and reactions which are cascades of this oxidative injury.”
Mainly, 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, corresponding to cyanide, methylene blue is ready to bypass that time of interference by electron biking, thus permitting mitochondrial respiration, oxygen consumption and vitality manufacturing to operate because it usually would.
Improved Mitochondrial Respiration Improves Well being, Cognition
Methylene blue will also be useful in cases the place you’ve impaired blood circulate that forestalls the supply of oxygenated hemoglobin to the tissues. On this case, methylene blue helps counteract the diminished 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, 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.
A very powerful 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, once 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 be coupled with biochemical upregulation of your oxygen consumption equipment on the whole, 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 possibly really enhance the variety of mitochondria. In your mind, this may 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 corresponding to glutathione, superoxide dismutase catalase, glutathione peroxidase, section II enzymes, heme-1 oxygenase and lots of others.
Methylene Blue for Mind Well being
Maybe one of the vital revolutionary advantages of methylene blue is for the prevention and therapy of dementia, neurodegenerative ailments corresponding to Alzheimer’s and Parkinson’s, and neural accidents brought on by 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 vitality manufacturing performs a significant function, methylene blue may have a job 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 may 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 is just not affected.
This was a mannequin referred to as an optic neuropathy resulting from mitochondrial defects. It’s the most typical 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 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 diminished the quantity of oxygen delivered to the animals, and we might use an fMRI, noninvasively, within the animals to see that we had been in a position to enhance the quantity of cerebral metabolic charge 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 manner that’s functionally significant. Usually talking, biomarkers aren’t 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. Nevertheless, whereas some promote sublingual or buccal software (beneath your tongue or on the within of your cheek), the easiest way 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 likely 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 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 nearly any pathogen within the bladder. Plus, it has the extra “aspect impact” of bettering 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 alternative.
Whereas methylene blue may be very secure, there are some contraindications. One is G6PD deficiency, which can be a contraindication for high-dose ascorbic acid remedies, which may very well 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 danger of this, nonetheless, may be very small. Gonzalez-Lima explains:
“With respect to the warning concerning the SSRIs, the issue is just not 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 had been anesthetized, they usually nonetheless had SSRIs [in their system], they usually 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, they usually wrote a rebuttal paper the place they point out that there isn’t any proof to recommend 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 sort 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 once they speak 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, when you repeat it cumulative remedies — could be resulting from any sort of a MAO inhibitor function.
As well as, it is because of its metabolic enhancing operate, so it antagonizes among the despair signs just like the low vitality that’s skilled with despair. So sure, it’s efficient to cut back signs of despair. Sadly, this warning goes to make some physicians fearful 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 doable dose response has not been examined, as a basic 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 ok. He provides 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 once you type a reminiscence to extinguish worry. People who’ve a phobia, you may expose them to the precise scenario 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 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 training is the method of consolidation, which requires vitality.
So, by facilitating the vitality availability throughout the consolidation section, which occurs over a lot of hours, then the subsequent time [you’re exposed to fear-evoking stimuli, you’ve] consolidated that extinction reminiscence extra successfully.
We’ve performed 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 totally 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 worry ranges, that’s once 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, deciding on the proper product is of essential significance, along with getting the dosing proper. There are three fundamental forms 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 lot 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, nevertheless it’s nonetheless not appropriate for medicinal functions because it sometimes has heavy metallic contaminants like lead, cadmium and arsenic. Over time, the impurities can accumulate in your physique, leading to toxicity. You should purchase a stainless-steel spoon that measures 8-10 mg. With out the spoon it will likely be very tough to measure.
Pharmaceutical grade is 99%+ pure. That is the sort used when injected intravenously for antidote functions, or used orally. These merchandise shall be marked USP, which stands for United States Pharmacopeia.
In line 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 gained’t discover methylene blue at your native pharmacy however many compounding pharmacies can receive the pharmaceutical grade.
“Ascorbic acid is a strategy 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 manner to enhance your total well being and cognitive operate.