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Evidence, dosing ranges, and a new Harvard clue on Alzheimer’s risk
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Curro Clavero — Nutritional EpigeneticsMethylene Blue
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Curro Clavero — Nutritional EpigeneticsMethylene Blue
Curro Clavero — Nutritional EpigeneticsAlpha-ketoglutarate (Calcium AKG)
A key molecule for energy, epigenetics, cancer, and the slowing of aging
Curro Clavero — Nutritional EpigeneticsEpigenetic Self-Test: What’s Your Methylation Status (and What to Do Next)
A practical, evidence-based guide to SAMe/SAH, homocysteine, and a safe action plan.
Curro Clavero — Nutritional EpigeneticsLithium and the Brain
Evidence, dosing ranges, and a new Harvard clue on Alzheimer’s risk
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(This article is for educational purposes only and does not constitute medical advice. Lithium can interact with medications and is not appropriate for everyone. Do not start, stop, or change any treatment without talking to your healthcare professional.)
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I’ve spent several years closely following research advances on this compound ever since, about six years ago, I heard University of Texas neuroscientist, biologist, and pharmacologist Francisco González-Lima talk about the benefits of methylene blue for Alzheimer’s disease.
Since several clients have already asked me about it—because it seems to be trending on social media—I think this is a good time to discuss its benefits, possible uses, and above all, the precautions.
Let’s get to it.
Methylene blue is a synthetic chemical compound, deep blue in color, created in 1876 by the chemist Heinrich Caro as a textile dye. Its medical potential, however, was discovered years later, when the Nobel Prize–winning physician and scientist Paul Ehrlich, in 1891, used it to stain cells and study their behavior under the microscope. That finding led him to explore its therapeutic properties, making it one of the first synthetic treatments for diseases such as malaria.
Since then, it has been used in various fields, including medicine, thanks to its unique chemical properties that allow it to cross cell membranes and act inside cells, especially in the function of mitochondria, the powerhouses of our cells.
These features give it the ability to enhance cellular functions, protect against oxidative damage, and optimize energy metabolism.
Next, I’ll explain what makes this compound so special.
Methylene blue can switch between two chemical forms depending on what the cell needs:
• Reduced form (colorless): can donate electrons.
• Oxidized form (blue): can accept electrons.
This shift acts like a switch that helps balance chemical reactions in the mitochondria—the redox processes (reduction–oxidation). Let’s take a look.
In the mitochondria, electrons flow through a system called the electron transport chain to generate energy (ATP). Sometimes this system fails. That’s where methylene blue comes in: if the system is blocked or damaged, methylene blue can serve as an electron “bridge” that facilitates flow. In this way, it helps produce more energy (ATP).
By stabilizing the process above, methylene blue also reduces the generation of “free radicals” (ROS: reactive oxygen species), oxidative molecules that damage cells and accelerate aging. In addition, thanks to its ability to alternate between oxidized and reduced forms, it neutralizes ROS without being chemically depleted, making it a highly efficient antioxidant under oxidative stress.
It has also been observed that methylene blue can help restore antioxidants such as glutathione, thereby strengthening the cell’s natural defenses.
Sometimes proteins inside cells fold incorrectly, which can cause serious problems, as in neurodegenerative diseases like Alzheimer’s or Parkinson’s. Methylene blue can prevent toxic aggregates from forming by inhibiting the buildup of harmful proteins such as beta-amyloid and tau in the brain. Even with aggregates that have already formed, it has shown the ability to dissolve these deposits and help cells function better.
Methylene blue is especially useful in situations where oxygen is scarce. It helps cells make better use of oxygen, optimizing each available molecule to produce energy.
This is its best-known, approved use. Methylene blue helps reverse this condition, in which hemoglobin loses its ability to carry oxygen, restoring it to its functional state.
Postmortem studies have found that the enzyme cytochrome c oxidase is inhibited in brains with Alzheimer’s, which prevents the brain from using oxygen to produce energy. Methylene blue acts as an alternative pathway that facilitates electron transport in the mitochondria, thereby restoring energy metabolism, which improves memory and cerebral blood flow.
In addition, as noted above, methylene blue is beneficial because it reduces the accumulation of harmful proteins (beta-amyloid and tau) and protects against cellular damage by decreasing oxidative stress.
Methylene blue reduces the production of inflammatory mediators such as nitric oxide (NO) by inhibiting the enzyme nitric oxide synthase (NOS), helping to control excessive tissue inflammation.
It protects cells from damage that could lead to apoptosis (programmed cell death), especially under conditions of oxidative stress or mitochondrial damage.
MAO is an enzyme that breaks down neurotransmitters such as serotonin and dopamine. By inhibiting it, methylene blue can increase the levels of these neurotransmitters in the brain, which could have applications in treating neurological and depressive disorders.
Methylene blue activates processes such as mitochondrial biogenesis (creation of new mitochondria) and autophagy (removal of damaged cellular components), helping to maintain cellular health.
It enhances cell proliferation in fibroblasts (the cells responsible for collagen and elastin) and helps protect the skin against oxidative damage and UV radiation.
It is used in combination with light to treat certain types of cancer, such as skin, lung, and prostate cancers. Methylene blue generates reactive oxygen species (ROS) when activated by light, and these ROS attack and eliminate tumor cells.
Methylene blue has antiviral, antibacterial, and antifungal effects: E. coli, Candida, hepatitis, HIV…
Methylene blue is a compound that is not present in foods or in nature, so we are not evolutionarily accustomed to ingesting it. Those who already know me and have read my books—especially the latest, Nutritional Epigenetics—know that, while this is not a decisive reason to rule out taking a molecule as a supplement, it does make me “open my eyes wider” and apply the “precautionary principle” more rigorously.
In addition, we do not have long-term studies on its continuous use, and although there are some studies in humans, most have been conducted in animals.
That said, everything suggests that at low doses (which we’ll see in the next section) it is safe, but at moderate or high doses it can cause side effects such as headaches, dizziness, disorientation, confusion, nausea, or vomiting. It can also tint the urine blue-green—an innocuous effect that disappears as the compound is cleared.
At high doses (>7 mg/kg [>~3.2 mg/lb]) the risks of serious side effects rise significantly, including hypertension, hemolysis, and neurotoxicity.
Let’s move on now to the special precautions.
G6PD deficiency is a genetic condition that affects the body’s ability to protect cells—especially red blood cells—from damage caused by certain medications, foods, or infections.
In people with this condition, methylene blue is not metabolized properly, which can trigger a serious problem called hemolytic anemia, in which red blood cells are destroyed faster than the body can replace them. This can cause fatigue, weakness, yellowing of the skin (jaundice), and other symptoms related to a lack of oxygen in tissues.
Methylene blue is contraindicated during pregnancy, as it can harm the fetus, including intestinal malformations and fetal death.
Its use is not recommended during breastfeeding, as it can pass to the infant through breast milk and cause adverse effects.
In people with kidney problems, methylene blue can accumulate in the body, increasing the risk of toxicity.
It should be avoided in people taking antidepressants or medications that increase serotonin, due to the risk of serotonin syndrome.
The most common format is a 1% solution (which equals 10 mg/mL) with a dropper. As with any supplement, it’s very important to ensure quality (purity) and use a pharmaceutical-grade product—especially in this case.
Each drop contains 0.05 mL (0.5 mg of methylene blue).
As noted above, it’s essential to keep the dose low to avoid potential adverse effects. A low dose would be approximately 0.5 mg per kilogram of body weight (≈0.227 mg per pound). Using a 1% product, that works out to 1 drop per kilogram of body weight (≈1 drop per 2.2 lb). For example, if you weigh 60 kg (about 132 lb), you would need 30 mg of methylene blue, which equals 60 drops per day.
There are now 5% products, so you would need to account for that and divide the above dose by 5.
The ideal approach is to mix it with water. Given its 12–14-hour half-life, I recommend not taking the entire daily dose at once, but splitting it into two doses every 12 hours (or three doses every 8 hours).
Until we have broader studies on its long-term use in humans, I do not recommend taking it continuously, except in the following two situations:
Intermittently: during periods of stress, fatigue, or in the face of a significant physical or cognitive challenge.
Continuously: in people with Alzheimer’s disease, where the risk/benefit ratio is favorable. In these cases, the long-term risk is very low, given the patients’ advanced age, while the potential benefit can be considerably high.
***
Get "Nutritional Epigenetics" on Amazon
***
Enjoyed this? Collect this post on Paragraph to support more research like this.
***
https://pmc.ncbi.nlm.nih.gov/articles/PMC8699482/
https://www.ncbi.nlm.nih.gov/books/NBK557593/
https://link.springer.com/article/10.1134/S0006297922090073
https://pmc.ncbi.nlm.nih.gov/articles/PMC9618115/
https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-020-00197-z
(This article is for educational purposes only and does not constitute medical advice. Lithium can interact with medications and is not appropriate for everyone. Do not start, stop, or change any treatment without talking to your healthcare professional.)
***
If this helped you, collect this post on Paragraph to support my work. Thank you!
***
I’ve spent several years closely following research advances on this compound ever since, about six years ago, I heard University of Texas neuroscientist, biologist, and pharmacologist Francisco González-Lima talk about the benefits of methylene blue for Alzheimer’s disease.
Since several clients have already asked me about it—because it seems to be trending on social media—I think this is a good time to discuss its benefits, possible uses, and above all, the precautions.
Let’s get to it.
Methylene blue is a synthetic chemical compound, deep blue in color, created in 1876 by the chemist Heinrich Caro as a textile dye. Its medical potential, however, was discovered years later, when the Nobel Prize–winning physician and scientist Paul Ehrlich, in 1891, used it to stain cells and study their behavior under the microscope. That finding led him to explore its therapeutic properties, making it one of the first synthetic treatments for diseases such as malaria.
Since then, it has been used in various fields, including medicine, thanks to its unique chemical properties that allow it to cross cell membranes and act inside cells, especially in the function of mitochondria, the powerhouses of our cells.
These features give it the ability to enhance cellular functions, protect against oxidative damage, and optimize energy metabolism.
Next, I’ll explain what makes this compound so special.
Methylene blue can switch between two chemical forms depending on what the cell needs:
• Reduced form (colorless): can donate electrons.
• Oxidized form (blue): can accept electrons.
This shift acts like a switch that helps balance chemical reactions in the mitochondria—the redox processes (reduction–oxidation). Let’s take a look.
In the mitochondria, electrons flow through a system called the electron transport chain to generate energy (ATP). Sometimes this system fails. That’s where methylene blue comes in: if the system is blocked or damaged, methylene blue can serve as an electron “bridge” that facilitates flow. In this way, it helps produce more energy (ATP).
By stabilizing the process above, methylene blue also reduces the generation of “free radicals” (ROS: reactive oxygen species), oxidative molecules that damage cells and accelerate aging. In addition, thanks to its ability to alternate between oxidized and reduced forms, it neutralizes ROS without being chemically depleted, making it a highly efficient antioxidant under oxidative stress.
It has also been observed that methylene blue can help restore antioxidants such as glutathione, thereby strengthening the cell’s natural defenses.
Sometimes proteins inside cells fold incorrectly, which can cause serious problems, as in neurodegenerative diseases like Alzheimer’s or Parkinson’s. Methylene blue can prevent toxic aggregates from forming by inhibiting the buildup of harmful proteins such as beta-amyloid and tau in the brain. Even with aggregates that have already formed, it has shown the ability to dissolve these deposits and help cells function better.
Methylene blue is especially useful in situations where oxygen is scarce. It helps cells make better use of oxygen, optimizing each available molecule to produce energy.
This is its best-known, approved use. Methylene blue helps reverse this condition, in which hemoglobin loses its ability to carry oxygen, restoring it to its functional state.
Postmortem studies have found that the enzyme cytochrome c oxidase is inhibited in brains with Alzheimer’s, which prevents the brain from using oxygen to produce energy. Methylene blue acts as an alternative pathway that facilitates electron transport in the mitochondria, thereby restoring energy metabolism, which improves memory and cerebral blood flow.
In addition, as noted above, methylene blue is beneficial because it reduces the accumulation of harmful proteins (beta-amyloid and tau) and protects against cellular damage by decreasing oxidative stress.
Methylene blue reduces the production of inflammatory mediators such as nitric oxide (NO) by inhibiting the enzyme nitric oxide synthase (NOS), helping to control excessive tissue inflammation.
It protects cells from damage that could lead to apoptosis (programmed cell death), especially under conditions of oxidative stress or mitochondrial damage.
MAO is an enzyme that breaks down neurotransmitters such as serotonin and dopamine. By inhibiting it, methylene blue can increase the levels of these neurotransmitters in the brain, which could have applications in treating neurological and depressive disorders.
Methylene blue activates processes such as mitochondrial biogenesis (creation of new mitochondria) and autophagy (removal of damaged cellular components), helping to maintain cellular health.
It enhances cell proliferation in fibroblasts (the cells responsible for collagen and elastin) and helps protect the skin against oxidative damage and UV radiation.
It is used in combination with light to treat certain types of cancer, such as skin, lung, and prostate cancers. Methylene blue generates reactive oxygen species (ROS) when activated by light, and these ROS attack and eliminate tumor cells.
Methylene blue has antiviral, antibacterial, and antifungal effects: E. coli, Candida, hepatitis, HIV…
Methylene blue is a compound that is not present in foods or in nature, so we are not evolutionarily accustomed to ingesting it. Those who already know me and have read my books—especially the latest, Nutritional Epigenetics—know that, while this is not a decisive reason to rule out taking a molecule as a supplement, it does make me “open my eyes wider” and apply the “precautionary principle” more rigorously.
In addition, we do not have long-term studies on its continuous use, and although there are some studies in humans, most have been conducted in animals.
That said, everything suggests that at low doses (which we’ll see in the next section) it is safe, but at moderate or high doses it can cause side effects such as headaches, dizziness, disorientation, confusion, nausea, or vomiting. It can also tint the urine blue-green—an innocuous effect that disappears as the compound is cleared.
At high doses (>7 mg/kg [>~3.2 mg/lb]) the risks of serious side effects rise significantly, including hypertension, hemolysis, and neurotoxicity.
Let’s move on now to the special precautions.
G6PD deficiency is a genetic condition that affects the body’s ability to protect cells—especially red blood cells—from damage caused by certain medications, foods, or infections.
In people with this condition, methylene blue is not metabolized properly, which can trigger a serious problem called hemolytic anemia, in which red blood cells are destroyed faster than the body can replace them. This can cause fatigue, weakness, yellowing of the skin (jaundice), and other symptoms related to a lack of oxygen in tissues.
Methylene blue is contraindicated during pregnancy, as it can harm the fetus, including intestinal malformations and fetal death.
Its use is not recommended during breastfeeding, as it can pass to the infant through breast milk and cause adverse effects.
In people with kidney problems, methylene blue can accumulate in the body, increasing the risk of toxicity.
It should be avoided in people taking antidepressants or medications that increase serotonin, due to the risk of serotonin syndrome.
The most common format is a 1% solution (which equals 10 mg/mL) with a dropper. As with any supplement, it’s very important to ensure quality (purity) and use a pharmaceutical-grade product—especially in this case.
Each drop contains 0.05 mL (0.5 mg of methylene blue).
As noted above, it’s essential to keep the dose low to avoid potential adverse effects. A low dose would be approximately 0.5 mg per kilogram of body weight (≈0.227 mg per pound). Using a 1% product, that works out to 1 drop per kilogram of body weight (≈1 drop per 2.2 lb). For example, if you weigh 60 kg (about 132 lb), you would need 30 mg of methylene blue, which equals 60 drops per day.
There are now 5% products, so you would need to account for that and divide the above dose by 5.
The ideal approach is to mix it with water. Given its 12–14-hour half-life, I recommend not taking the entire daily dose at once, but splitting it into two doses every 12 hours (or three doses every 8 hours).
Until we have broader studies on its long-term use in humans, I do not recommend taking it continuously, except in the following two situations:
Intermittently: during periods of stress, fatigue, or in the face of a significant physical or cognitive challenge.
Continuously: in people with Alzheimer’s disease, where the risk/benefit ratio is favorable. In these cases, the long-term risk is very low, given the patients’ advanced age, while the potential benefit can be considerably high.
***
Get "Nutritional Epigenetics" on Amazon
***
Enjoyed this? Collect this post on Paragraph to support more research like this.
***
https://pmc.ncbi.nlm.nih.gov/articles/PMC8699482/
https://www.ncbi.nlm.nih.gov/books/NBK557593/
https://link.springer.com/article/10.1134/S0006297922090073
https://pmc.ncbi.nlm.nih.gov/articles/PMC9618115/
https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-020-00197-z
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