Methylene blue and Alzheimer's disease
The relationship between methylene blue (MB) and Alzheimer's disease (AD) has recently attracted increasing scientific attention since it has been suggested that MB may slow down the progression of this disease. In fact, MB, in addition to its well characterized inhibitory actions on the cGMP pathway, affects numerous cellular and molecular events closely related to the progression of AD. Currently, MB has been shown to attenuate the formations of amyloid plaques and neurofibrillary tangles, and to partially repair impairments in mitochondrial function and cellular metabolism. Furthermore, various neurotransmitter systems (cholinergic, serotonergic and glutamatergic), believed to play important roles in the pathogenesis of AD and other cognitive disorders, are also influenced by MB. Recent studies suggest that the combination of diverse actions of MB on these cellular functions is likely to mediate potential beneficial effects of MB. This has lead to attempts to develop novel MB-based treatment modalities for AD. In this review article, actions of MB on neurotransmitter systems and multiple cellular and molecular targets are summarized with regard to their relevance to AD.
https://pubmed.ncbi.nlm.nih.gov/19433072/
Protective role of methylene blue in Alzheimer's disease via mitochondria and cytochrome c oxidase
The key cytopathologies in the brains of Alzheimer's disease (AD) patients include mitochondrial dysfunction and energy hypometabolism, which are likely caused by the accumulation of toxic species of amyloid-beta (Abeta) peptides. This review discusses two potential approaches to delay the onset of AD. The first approach is use of diaminophenothiazines (e.g., methylene blue; MB) to prevent mitochondrial dysfunction and to attenuate energy hypometabolism. We have shown that MB increases heme synthesis, cytochrome c oxidase (complex IV), and mitochondrial respiration, which are impaired in AD brains. Consistently, MB is one of the most effective agents to delay senescence in normal human cells. A key action of MB appears to be enhancing mitochondrial function, which is achieved at nM concentrations. We propose that the cycling of MB between the reduced leucomethylene blue (MBH2) and the oxidized (MB) forms may explain, in part, the mitochondria-protecting activities of MB. The second approach is use of naturally occurring osmolytes to prevent the formation of toxic forms of Abeta. Osmolytes (e.g., taurine, carnosine) are brain metabolites typically accumulated in tissues at relatively high concentrations following stress conditions. Osmolytes enhance thermodynamic stability of proteins by stabilizing natively-folded protein conformation, thus preventing aggregation, without perturbing other cellular processes. Experimental evidence suggests that the level of carnosine is significantly lower in AD patients. Osmolytes may inhibit the formation of Abeta species in vivo, thus preventing the formation of soluble oligomers. Osmolytes are efficient antioxidants that may also increase neural resistance to Abeta. The potential significance of combining MB and osmolytes to treat AD are discussed.
https://pubmed.ncbi.nlm.nih.gov/20463399/
Methylene Blue for Alzheimer's, Dementia, Parkinson's and UTIs?
methylene blue
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.
Importantly, methylene blue is a hormetic drug, which means that low doses have the opposite effect as high doses. For example, it’s primarily used in emergency rooms at the upper dosage limit (3 milligrams to 4 mg per kilo of bodyweight) 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 rather than its normal reduced +2 state.
However, if you take too high a dose, you produce methemoglobinemia. At dosages in between, there’s no effect. Likewise, while low dosages have an antioxidant effect, high doses are pro-oxidative and can kill bacteria and tumor cells.
Methylene Blue, an Antioxidant and Energy Producer
Gonzalez-Lima’s research has primarily focused on low-dose benefits for nonacute purposes over the longer term — such as neuroprotective benefits and cognitive enhancement. While it has several mechanisms of action, a unique feature is that it acts on the level of electrons. He 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 autooxidizing 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 hypoperfusion that contributes to neurodegeneration and memory problems. These issues, Gonzalez-Lima says, 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.
And, as detailed by Gonzalez-Lima in the interview, 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. As explained by Gonzalez-Lima:
“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 we did it in other things like brains. We found a similar phenomenon ...
Methylene blue can be protective in ischemic and hemorrhagic strokes. We’ve also published a study with a hypoxia. In other words, we reduced the amount of oxygen delivered to the animals, and we could use an fMRI, noninvasively, in the animals to see that we were able to increase 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.
Continued here
https://www.onedaymd.com/2022/04/methyl ... entia.html
Methylene blue for Alzheimer’s disease
How does Methylene Blue cure Alzheimer’s
According to experts at the University of Texas Health Science Center, an oral dosage of Methylene Blue can improve the reaction of brain areas that govern concentration and short-term memory.
Major cytopathology in the patients’ brains includes the failure of mitochondria and energy rate, which are presumably caused by the buildup of harmful amyloid-beta peptides. Methylene Blue boosts heme production and mitochondrial respiration, which is deficient in Alzheimer’s disease brains.
Methylene Blue has repeatedly been shown to be one of the most effective treatments for delaying maturity in human cells. One of Methylene Blue’s primary actions seems to be to improve mitochondrial activity. Methylene blue as a medication is approved by FDA for the treatment of methemoglobinemia, the control of UTIs in the aged, and as a surgical tissue dye
Usually, Methylene Blue is utilized in its original form as methylthioninium chloride; however, clinical testing in Alzheimer’s used both forms- reduced and oxidized Methylene Blue.
Oxidative stress is reduced in the accumulation of Alzheimer’s-like tau and -amyloid. Methylene blue decreases mitochondrial oxidant generation and free radical creation in vitro. It can also alter mitochondrial respiration downstream activities such as lipid oxidation, ATP synthesis, and ECM formation, contributing to improved neuronal oxidative metabolic capacity. Methylene blue may easily transition between oxidized and reduced states, acting as an electron carrier in the electron transport chain of the mitochondrial matrix. Additionally, methylene blue therapy increases cellular Oxygen consumption, ATP generation, and glucose absorption.
Mechanism of Methylene Blue on Alzheimer’s
The connection between Methylene Blue and Alzheimer’s disease has lately received more research interest because it has been proposed that Methylene Blue might halt the course of progress in Alzheimer’s. In fact, in addition to its well-known inhibitory effects on the cGMP pathway, Methylene Blue can influence a wide range of cellular and molecular processes associated with the course of Alzheimer’s disease. Currently, Methylene Blue has been proven to reduce the production of neurofibrillary tangles and plaques, as well as to partly restore the function of Mitochondria and cellular metabolic deficits.
https://www.macsenlab.com/blog/methylen ... lzheimers/
The blockbuster drug methylene blue is experimentally proven to restore brain function in people with Alzheimer’s, Parkinson’s and other forms of dementia – but big pharma says you can’t have it!
Existing ‘approved’ drugs for dementia obviously don’t work or they would be curing people and the disease would vanish. But that doesn’t mean effective treatment’s don’t exist.
In this article you’re going to learn what’s happening in the brain of a person with dementia, and how the inexpensive drug methylene blue can help rejuvenate the aging brain. Methylene blue is so effective for dementia that some might even call it a cure.
Methylene Blue and The Hallmarks of Alzheimer’s Disease
Scientists studying the brains of Alzheimer’s patients have noticed commonalities among patients, including abnormally shaped tau proteins, or “neurofibrillary tangles” within brain cells called neurons. Let’s look at the impact of methylene blue on these hallmarks and determine if it can help resolve them.
Hallmark 1: Neurofibrillary “Tangles”
The brains of mice that’ve been genetically engineered to lack tau protein do not function properly, leading researchers to conclude the misshapen tau proteins found in brain cells of Alzheimer’s patients play a role in the disease.
A group of scientists from Gakushuin University and Keio University School of Medicine in Japan published a study in 2019 that reports methylene blue can repair the problem by inhibiting the formation of tau neurofibrillary tangles in the brain.[xii]
Hallmark 2: Beta Amyloid Plaques
Another hallmark of the Alzheimer’s-diseased brain is the appearance of beta amyloid plaque surrounding brain cells. Remarkably, methylene blue has been shown to prevent beta amyloid plaques from forming on the outside of neurons.[xiii]
Evidence suggests that methylene blue can help resolve both of the primary hallmarks of Alzheimer’s disease. Not bad for a fabric dye!
But what about on actual Alzheimer’s patients outside the laboratory? Can methylene blue help actual patients with dementia?
Clinical Trial: Methylene Blue Boosts Brain of Dementia Patients
In a study on Alzheimer’s patients in 2019, scientists administered 8mg-16mg of methylene blue daily while monitoring their brain function. The methylene blue stopped Alzheimer’s disease dead in its tracks![x] [xi]
“Treatment with 8mg-16mg MB daily reduced cognitive decline by more than 85%! That is the perverted medical profession’s way of saying that MB effectively stopped AD in its tracks, or at least its cognitive symptoms, which is what this disease is all about. It is a type of dementia after all. Perhaps just as importantly, it found that drugs currently approved for managing symptoms of AD interfere with the therapeutic benefit of MB when administered together with it!”
– Georgi Dinkov
Treatment Dose for Dementia
For those interested in using methylene blue for Alzheimer’s, an important finding from the study was that a dose of 200mg of methylene blue had no greater benefit than a much smaller dose of 8mg.
The study concluded that methylene blue is expected to be therapeutic in doses up to 16mg, and patients would see no additional benefit from taking higher doses.
“Treatment benefit is predicted to be maximal at 16 mg/day as monotherapy,” the scientists reported.
https://www.endalldisease.com/methylene ... -dementia/
This is why while I might forget my AMEX when I travel, I will never forget to take a supply of MB. It's the Grand Mother of all power agents.
