Transcription
Methylene blue is a compound that's intrigued me for a long time, but I've never talked about it on this channel before. The reason for that is because my understanding of how it worked just wasn't all that solid. Well, I feel like I've remedied that, and so today's video is going to be all about methylene blue.
Okay, it's been a while now since I talked about any supplements or any strategies that could actually make a difference in how well we all age. So for the first video of the new year, I thought it was time to get back to a discussion about something that could actually move the needle, and it appears that methylene blue could do just that.
Now, I want to state right here that I'm not a medical professional, I'm not a scientist or a researcher, and you probably shouldn't listen to anything I say without doing your own due diligence. I'm just a guy who's been trying to defeat the aging process for about six or seven years now, and you know I've met with a certain degree of success. I thought I'd share what I learned with you guys. I'm definitely not making any recommendations. That said, I decided to add methylene blue to my supplement stack, and I'm going to tell you why. But before we get into that, let's take a look at what methylene blue is and how it works.
So, methylene blue is a salt with the official name of methylthioninium chloride. Methylene blue has been used historically as both a dye and as a medication. It was first prepared in 1876 as a dye used in textile manufacturing. Now, interestingly enough, it was the oral dye used to stain blue jeans. In 1891, it was discovered to be effective in the treatment of malaria, and it became the first-ever fully synthetic medication.
So, methylene blue has a long history of safety; in fact, it's on the World Health Organization's list of essential medicines. Later, it was used as an antibacterial, antiviral, and antifungal. In fact, it's still in use today as an antifungal to treat fish tanks. It was also discovered to be effective in treating carbon monoxide and cyanide poisoning. More recently, it's been discovered to possess neuroprotective properties. It's been shown to increase cognition, improving memory and learning. It also has anti-depressive properties, improving mood, and all of these benefits can be traced back to methylene blue's impressive ability to shuffle electrons around. It's what's called an electron cycler, and another example of an electron cycler would be NAD. Both of these molecules cycle back and forth between what's known as an oxidized and reduced state.
Now, more on that in just a minute. So, in understanding how methylene blue does its magic, we have to lay a little groundwork. We need to talk for a minute about a process that goes on within each of our cells, within the mitochondria, and this process is called cellular respiration. We need to talk about a particular aspect of cellular respiration.
Okay, so cellular respiration is a process of breaking down molecules of glucose, which comes from the food that we eat, and molecules of oxygen that come from the air that we breathe, and recombining them into molecules of water and carbon dioxide. Now, this process is really pretty complicated, and the purpose of cellular respiration is not to obtain water and CO2. Water and CO2 are just waste products. The real purpose of cellular respiration is to create molecules of ATP, adenosine triphosphate. ATP is the fuel that drives all of our cellular processes.
So, the process of cellular respiration can be broken down into three subprocesses. Let's call them the first two: glycolysis and the Krebs cycle, or the citric acid cycle. We're not going to talk about them because they're not really relevant to the discussion about methylene blue. But the third process, called oxidative phosphorylation, is because of something called the electron transport chain, which is part of that process. There are five protein complexes embedded into the inner mitochondrial membrane, and the first four, known as complexes 1 through 4, are what make up the ETC, or the electron transport chain. The ETC passes electrons from one complex to the next down the chain.
Now, when electrons move or are passed along, that's a definition of electricity. So, passing electrons along this chain creates energy, and that energy is used to pump hydrogen ions into the intermembrane space, or IMS, which is the space between the inner and outer mitochondrial membranes. So, here's how that works: the reduced form of NAD, which is called NADH, comes along and donates or gives up an electron to the first complex in the electron transport chain. That complex then passes that electron onto a molecule of CoQ10. The complex uses the energy gained from that passing to pump a hydrogen ion from the matrix across the inner membrane into the inner membrane space.
Since a molecule of NADH has given up an electron, it becomes the oxidized form of NAD, called NAD+. The molecule of CoQ10 picks up another electron from complex 2 and passes both of these electrons on to complex 3. Complex 3 passes those electrons onto a molecule called the cytochrome complex and uses the energy from that passing to pump more hydrogen ions into the IMS. The cytochrome complex then passes the electrons on to complex 4, and here's where the electron transport chain ends. Complex 4 uses the electrons to bond atoms of hydrogen and oxygen together, creating molecules of H2O, or water, and complex 4 uses the energy from this to pump still more hydrogen ions into the IMS.
Now, all these hydrogen ions getting pumped from the matrix into the IMS, or the inner membrane space, creates an imbalance. There's a lot more hydrogen ions in the IMS than there are in the matrix. This imbalance is known as an electrical gradient, and ions naturally flow from an area of high concentration to an area of low concentration, and they do that through the fifth complex embedded in the inner mitochondrial membrane, the complex known as ATP synthase.
Now, these ions passing through ATP synthase actually spin a part of that complex like water spinning a turbine. This is mechanical energy, and it's used to bind an atom of phosphorus to a molecule of ADP, or adenosine diphosphate, creating a molecule of adenosine triphosphate, or ATP. For every molecule of glucose that is broken down, up to 32 molecules of ATP are generated by ATP synthase. That ATP then circulates throughout the cell, driving cellular processes before getting converted back to ADP. And that's cellular respiration.
But our story doesn't end there because cellular respiration just isn't all that efficient. As electrons move down the electron transport chain, some of them slide off through a process called electron slippage. Once these electrons are set free, they wander about the matrix, interacting with other molecules, particularly molecules of O2, or oxygen. When molecules of oxygen react to the free electrons, they form a molecule called ROS, or reactive oxygen species, and ROS is a free radical.
Now, free radicals are unstable molecules, and they can interact with other molecules, damaging them in the process. Over time, this damage accumulates and eventually interferes with the functioning of the cell. Cellular function breaks down, and the cell itself becomes damaged. Now, an accumulation of damaged cells produces damaged dysfunctional tissue, otherwise known as aging—intrinsic aging, to be specific, because this damage is internal to the cell. This whole process of free radicals starting a cascade of damage resulting in intrinsic aging is known as the free radical theory of aging, and antioxidants are kind of the hero to offset the villainy of free radicals.
But the whole free radical theory of aging and the ability of antioxidants to prevent intrinsic aging have sort of fallen out of fashion. In fact, David Sinclair has come right out and stated that the path of investigation was a dead end, that it proved not to lead to any meaningful prevention or reduction in aging. But I kind of feel that antioxidants have made a bit of a comeback. While some antioxidants, like vitamins C and E, have proved to be a little disappointing, others have much more promise, like glutathione, which can be naturally produced in the body by precursors like glycine and N-acetylcysteine, or NAC.
Now, click on the link right up here if you're interested in watching a video that I did on those two supplements. As it turns out, glutathione is the most powerful antioxidant in the body, and taking glutathione seems to improve mitochondrial efficiency.
Okay, this is where methylene blue enters the picture. Methylene blue improves mitochondrial efficiency in several different ways. First, it acts as an antioxidant, absorbing those free electrons that are floating around the matrix, binding with oxygen to become a superoxide, the first step on a path to becoming a free radical. Now, this is really not that different from other antioxidants like vitamins C and E and curcumin, but methylene blue can also bind that superoxide to hydrogen atoms that are also floating around the matrix, creating water and perhaps strengthening the electrical gradient across the inner membrane, making cellular respiration more efficient.
But that's not all it does. Remember, methylene blue is an electron cycler, like NAD. While NADH can feed electrons to complex 1, methylene blue can accept electrons from NADH as well as scavenge free electrons that have slid off the ETC and then pass them directly to the cytochrome complex, which then passes them to complex 4. So, it bypasses the first three complexes, relieving them of some of their electron burden.
So, when methylene blue is present in the mitochondria, ATP production becomes much more efficient. And like other electron cyclers, methylene blue has an oxidized state and a reduced state. The oxidized state is called MB+ for methylene blue plus, and it's in this state that methylene blue is blue. The reduced state is called LMBb, and when methylene blue is in this state, it's colorless.
So, on the one hand, methylene blue enhances the function of complex 4 by making it work faster and more efficiently, increasing both oxygen consumption and ATP production, but boosting the production of ROS at the same time. However, that boost is offset by the fact that methylene blue binds superoxide to hydrogen atoms, cutting off the production of ROS before it even starts.
Now, as cool as all that is, methylene blue boosts mitochondrial function in yet another way that has nothing to do with the mitochondria. Methylene blue can also enter red blood cells, where it changes the configuration of iron in hemoglobin, which is the molecule in red blood cells that carries oxygen. This change improves the oxygen-carrying capacity of hemoglobin, leading to an increase in ATP production from the electron transport chain. This explains why methylene blue is used in the treatment of carbon monoxide poisoning. Carbon monoxide binds to hemoglobin, preventing it from binding with oxygen. Methylene blue restores that oxygen-binding capacity. In fact, the only FDA-approved use of methylene blue is in treating methemoglobinemia, a condition where the capacity of hemoglobin to carry oxygen is severely diminished.
All right, so there's one more aspect of methylene blue that I want to tell you about. In order for methylene blue to be effective and work its magic, it has to penetrate several different membranes and get into the matrix of the mitochondria, right? Well, it turns out that methylene blue is both hydrophilic and lipophilic, meaning that it's very permeable through almost any biomembrane, including the blood-brain barrier. This means that it can get into the neurons, which are one of the cells that require the highest amounts of energy, or ATP. This is where methylene blue gets its neuroprotective and neurotropic capabilities; it boosts energy production in brain cells.
Now, other nootropics increase neurotransmitter synthesis and neural signaling, but methylene blue increases brain cell respiration. Studies have shown an increase in the cerebral metabolic rate of oxygen, also known as CMRO2, with methylene blue supplementation. As a result, they've also shown increased activity during sustained attention and during short-term memory tasks. Methylene blue can also enhance memory retrieval and is associated with a 7% boost in correct responses during memory retrieval tasks. It's also been shown to improve fan oxidation in the brain, which is a sign of good health.
Methylene blue also has anti-depressant effects. It functions as an MAO, or monoamine oxidase inhibitor. So, monoamines are things like dopamine, melatonin, and serotonin, and they are neurotransmitters. Inhibiting MAO prevents monoamine transmitter breakdown, which leads directly to increases in these neurotransmitters. Methylene blue also functions as a cholinesterase inhibitor, increasing the amount of acetylcholine that's available. Acetylcholine is a neurotransmitter in the brain responsible for arousal, attention, memory, and motivation, and it's also considered to be a nootropic.
Finally, methylene blue can also inhibit skin aging. Some studies show that it has better results than either vitamin C or vitamin A, which is what retinol is. It actually serves as a buffer between the DNA in the skin and the UV rays in sunlight, so it reduces the DNA damage to skin, which is a form of extrinsic aging. It can also boost the production of fibroblasts and promote wound healing.
All right, let's talk about how to take it. First off, don't drink fish tank cleaner. Yeah, it's got methylene blue in it, but it's also got a lot of other stuff that you don't want to take, like a lot of impurities, including heavy metals like arsenic, aluminum, cadmium, and lead. Same for industrial-grade methylene blue. Your safest choice is to get USP or pharmaceutical-grade methylene blue from a source that posts their third-party testing for purity and potency.
So, the typical way that you would take methylene blue is to use an eye dropper and a 1% solution of methylene blue. A single drop of the 1% solution is about a half a milligram. Ten drops is 5 mg, and 20 drops is 10 mg. So, now there are a couple of ways that you can purchase methylene blue. The most common way is to buy a 50 ml bottle of the 1% solution. Now, a 50 ml bottle contains about 1,000 drops and costs about $25. Just to put that into perspective, as a 200 lb man, I would take about 45 mg per day at a minimum. That's about 90 drops, but I could go up to 360 mg a day. That's about 720 drops. So, a 50 ml bottle could last me between 11 days and about a day and a half.
But there's another way that you can purchase methylene blue in bulk and in powdered form. You can get 10 g of powdered methylene blue for about $135. Now, to make a 1% solution, add 1 g of methylene blue to 100 ml of distilled water. That 10 g of methylene blue will make about a liter of 1% solution, so that's the equivalent of 20 50 ml bottles. That comes out to about $6.75 per 50 ml bottle compared to $25 a bottle for the pre-prepared version.
So, methylene blue has a half-life of somewhere around 5 to 6.5 hours, which means that you'll have to take it two or three times a day. You should be taking a relatively low dose of methylene blue. A low dose is defined as between half a milligram and 4 mg per kilogram of body weight. So, for me, since I weigh about 200 lb right now, that would be between 45 and 360 milligrams a day, spread out over three doses. A moderate dose of methylene blue is between 4 and 10 mg per kilogram. At this dose, methylene blue actually starts to turn from an antioxidant into being pro-oxidant. At this dose, methylene blue becomes an electron donor and starts to facilitate the generation of singlet oxygen and peroxide radicals. A high dose of methylene blue is anything over 10 milligrams per kilogram a day, and at this dose, methylene blue can have harmful oxidative effects. So, keep your dose of methylene blue below 4 milligrams per kilogram of body weight a day.
So, another thing to be mindful of is the potential risk of serotonin syndrome, which is when high levels of serotonin build up in the body. Now, it's usually caused by medications or drug interactions, so don't take methylene blue with any SSRIs, SNRIs, or any drug that increases serotonin levels. Now, for all your psychonauts out there, certain psychedelic substances like MDMA and psilocybin increase serotonin levels. The vine used in ayahuasca ceremonies has MAO-like properties, like methylene blue, so just be careful about what you're stacking.
All right, that about wraps up this video on methylene blue. In summary, because of its rather dramatic impact on the mitochondrial production of ATP, it has a lot of benefits for anyone trying to defeat aging. It boosts energy levels overall; it boosts energy within the cells, providing for improved cellular function. It might be especially useful in defeating mitochondrial dysfunction, one of the hallmarks of aging. It has several different antioxidant effects, boosts the ability of red blood cells to carry oxygen, is both neuroprotective and a nootropic, improves memory, can act as an anti-depressant, and preserve neurotransmitters, and it can improve the aging of skin. Methylene blue is a compound that I'll definitely be adding to my supplement stack.
Okay, I'm out of here. Check this playlist if you're curious about the hallmarks of aging, or click on the link down here if you'd like to learn more about my online course, The Longevity Guide. And that's it! I'll see you guys next week.