methylene blue nootropic

Methylene Blue

David Tomen
Author:
David Tomen
Jill Corleone, RD
Fact Checked:
Jill Corleone, RD
18 minute read
Methylene Blue boosts mitochondrial energy, is anti-aging, and improves mood and memory

 

Key Takeaways

  1. Methylene Blue, a synthetic compound, is used as a nootropic to enhance memory, mood, and longevity.
  2. It improves mitochondrial function and respiration in the brain, positively impacting memory and mood.
  3. Methylene Blue shows promise in treating neurological disorders such as mild cognitive impairment, Alzheimer’s, and Parkinson’s disease.
  4. It acts as an antioxidant, increases brain cell lifespan, and positively affects neurotransmitters.
  5. Methylene Blue dosage recommendation is 0.5 – 4 mg/kg of body weight per day.

 

Methylene Blue (methylthioninium chloride) is a synthetic compound used as a nootropic to increase memory, mood and longevity.

Soon after Methylene Blue was synthesized a blue dye for textiles in the late 1800’s, it became the first synthetic drug to be used in humans. It was used for the treatment of malaria.

In the early 20th century, psychiatrists were using Methylene Blue in the experimental treatment of schizophrenia.[i]

Methylene Blue is currently being studied as potential therapy for mild cognitive impairment, Alzheimer’s and Parkinson’s disease, and other neurodegenerative disorders. All sharing a common problem with mitochondrial function.

Your brain’s neurons rely almost entirely on mitochondria-derived energy. Failure of mitochondrial function can affect the rest of your body. But it’s particularly detrimental to your brain.

This is where Methylene Blue steps in as possibly one of the most important anti-aging and neurological disease preventing nootropics we have available today.

As a nootropic, Methylene Blue quickly crosses the blood-brain barrier. It improves mitochondrial efficiency and respiration, acts as an antioxidant, and increases brain cell lifespan. Resulting in improved memory and mood.

Here we’ll dive into over 140 years of research on how Methylene Blue helps your brain.

Methylene Blue helps:

  • Neurotransmitters: Methylene Blue inhibits monoamine oxidase and acetylcholinesterase activity which increases levels of catecholamines and acetylcholine. And boosts serotonin and norepinephrine affecting anxiety, depression and memory.
  • Mitochondrial Energy: Methylene Blue assists brain cell respiration by increasing oxygen. And donating electrons to the electron transport chain within mitochondria. This same process is used to create ATP within mitochondria from the food you eat. So MB contributes to this energy-production process in place of the nutrients you get from your food. Increasing cellular energy positively effects mood and memory.
  • Neuroprotectant: Methylene Blue is a potent antioxidant. Reactive oxygen species are produced inside mitochondria. The first free radical that is formed inside a cell is superoxide. MB will bind to superoxide and reduce it to water. It stops the oxidative cascade at its very beginning. Before it gets a chance to do damage.

Overview

Methylene Blue (methylthioninium chloride) was first synthesized in 1876 by German chemist Heinrich Caro at BASF as an aniline-based dye for cotton staining.

The chemical structure of Methylene Blue
Methylene Blue

In 1891, German physician and Noble Prize recipient Paul Ehrlich pioneered the use of Methylene Blue for the treatment of malaria.[ii]

Ehrlich discovered that when MB was injected into animals in the lab, it would quickly concentrate in the brain. And had an uncanny ability to selectively target diseased tissues in the body.

It was Ehrlich who coined the term “Magic Bullet” for this unique action displayed by Methylene Blue. A term still in use today.

Methylene Blue has since been used to treat dementia, in cancer chemotherapy, malaria, methemoglobinemia, urinary tract infections, cyanide and carbon monoxide poisoning.[iii]

As a nootropic, Methylene Blue is used to enhance mitochondrial function, increase cerebral blood flow, and acts as an antidepressant.

What does Methylene Blue to the brain?

How does Methylene Blue work in the brain?

Methylene Blue boosts brain health and function in several ways. But two in particular stand out.

  1. Methylene Blue improves memory. Unlike other nootropics which often work by increasing neurotransmitter synthesis and neural signaling, MB improves memory by increasing brain cell respiration. Or how the brain cell utilizes oxygen.

Studies show dramatic increases of cellular oxygen consumption and glucose uptake when using Methylene Blue. MB increases CMRO2 (cerebral metabolic rate) through increased activity in the mitochondrial electron transport chain.

Methylene Blue increases activity in the mitochondrial electron transport chain.Methylene Blue functions as an alternative electron carrier in the electron transport chain in mitochondria. It accepts electrons from NADH and transfers them to cytochrome c.[iv]

Cytochrome complex (cytochrome c) is a component of the electron transport chain in mitochondria. Playing a role in apoptosis and as an antioxidant.

Methylene Blue also stimulates glucose metabolism. Taken together, increases in CMRO2 and glucose uptake means that MB elevates oxygen consumption which helps glucose increase ATP production.

Increases in ATP production provides more cellular energy for better overall brain function including cognition, mood and memory.

  1. Methylene Blue is an antioxidant. MB has a unique mechanism of action that is fundamentally different from traditional antioxidants. During cellular respiration, the first free radical formed inside a cell is superoxide (O2).

Methylene Blue binds to superoxide and reduces it to water. It stops the oxidative cascade at its very beginning. Before it gets a chance to do damage.[v]

So think of Methylene Blue as having a unique dual property. First, it increases cellular energy production which normally leads to oxidative stress. And second, it eliminates this oxidative stress. Making it a metabolic enhancer and an antioxidant.

Researchers tested Methylene Blue in animal models of neurological disease. First, researchers used rotenone (a potent pesticide) which causes severe dopamine depletion in the part of the brain associated with Parkinson’s.

Methylene Blue rescued brain cell mitochondria from the damaging effects of this toxin. By donating electrons in the electron transport chain broken by rotenone. Essentially bypassing the broken transport chain with donated electrons as an alternative electron carrier.

Methylene Blue also countered cerebral ischemia reperfusion damage. The tissue damage caused when blood supply returns to tissue after a lack of oxygen from a stroke. And can occur with Traumatic Brain Injury. MB accomplished this by rerouting mitochondrial electron transfer.

And Methylene Blue dramatically countered the behavioral, neurochemical, and neuropathological impairment found in Parkinson’s disease.[vi]

How things go bad

As we live life, our brain chemistry and metabolism changes.

↓ Mitochondrial energy levels decline

↓ Attention, memory and mental agility decline

↓ Tau proteins and amyloid plaques clog the brain

Free radicals damage brain cell mitochondria

Cerebral blood flow declines

All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more.

So Methylene Blue can help for age-related cognitive decline, as well as a student looking to do better in school. By boosting brain cell mitochondria energy production levels. And improving cerebral blood flow.

What to expect when taking Methylene Blue

Methylene Blue benefits

Low dose Methylene Blue supplementation provides memory enhancing effects in animals and humans. It works as an antidepressant, is anti-aging, helps dementia, Huntington’s and Alzheimer’s.

Methylene Blue increases low blood pressure, improves cognition in healthy people, boosts mitochondrial function, is anti-microbial, can help eliminate fear and even slow skin aging.

Methylene Blue boosts acetylcholine

Research shows that Methylene Blue is an acetylcholinesterase inhibitor with a preference for muscarinic acetylcholine receptors. Meaning MB prevents the breakdown of acetylcholine and making more available in your brain.[vii]

Methylene Blue is an antidepressant

Methylene Blue is a monoamine oxidase inhibitor (MAOI). It inhibits MAO-A more than MAO-B, but inhibits both at large doses.[viii]

One study in 1987 showed that 15 mg per day of Methylene Blue was a potent antidepressant in those with severe depression.[ix]

Another study with 31 Bipolar Disorder patients compared 300 mg per day of Methylene Blue with 15 mg per day. The patients were also on lithium treatment. The study showed that the 300 mg dose of Methylene Blue was a “useful addition to lithium in the long-term treatment of manic-depressive psychosis”. And patients were significantly less depressed.[x]

Methylene Blue resists Alzheimer’s Disease

Alzheimer’s disease and other forms of dementia are associated with a buildup of the protein Tau. Clinical trials show that Methylene Blue inhibits Tau formation. And is under consideration as a treatment for Alzheimer’s.[xi]

Methylene Blue has an inhibitory action on the cGMP pathway, and affects other molecular events closely related to the progression of Alzheimer’s.

Methylene Blue boosts neuron resistance to the formation of amyloid plaques and neurofibrillary tangles. And helps repair impairments in mitochondrial function and cellular metabolism.

Research also shows that cholinergic, serotonergic and glutamatergic systems all play important roles in the development of Alzheimer’s and other cognitive disorders. Methylene Blue provides beneficial effects in mediating these pathways.[xii]

This is particularly significant because most existing treatments for Alzheimer’s can only prevent the disease before it is diagnosed. But Methylene Blue shows promise in delaying the effects of Alzheimer’s and dementia after it is diagnosed.

Methylene Blue is anti-aging

Does methylene blue increase dopamine?Research shows that Methylene Blue is an effective anti-aging nootropic. MB increases mitochondrial complex IV by 30%, enhances cellular oxygen consumption by 37-70%, increases heme synthesis, and reverses premature senescence caused by H2O2 or cadmium.

Methylene Blue is considered a redox agent. Meaning it cycles between oxidized and reduced forms. This cycling by MB helps block oxidant production in brain cell mitochondria.[xiii]

Mitochondrial complex IV is the last enzyme in the respiratory electron transport chain in mitochondria. The last step in synthesizing ATP. Your cellular source of energy.

Iron (heme) is an essential element and participates in oxygen transport, DNA synthesis and electron transport. Heme synthesis begins in mitochondria. Every cell requires heme to function properly.[xiv]

Senescence or biological aging is the gradual deterioration of cellular function. And is caused by telomere shortening that triggers DNA damage in response to reactive oxygen species, hydrogen peroxide (H2O2), cadmium and other toxins. Methylene Blue helps prevent premature senescence or premature cell death.

Methylene Blue improves memory

Animal studies have shown that a single low dose of Methylene Blue enhances long-term contextual memory. This type of memory is the conscious recall of the source and circumstances of a specific memory.

Other studies show that Methylene Blue in low doses taken after the event helps memory retention of the event. A study done with rats revealed why this works.

In this study, rats received 1 mg/kg of MB post-training for 3 days. The researchers then measured cytochrome c oxidation in participants brains. The idea was to determine if an increase in metabolic energy was behind the memory enhancing qualities of MB.

The study found that in the Methylene Blue treated group, brain cytochrome oxidase activity was 70% higher than in the placebo-treated group.

The findings suggest that repeated post-training supplementation of Methylene Blue improves memory consolidation. And this memory boost is due to the increased metabolic capacity in brain regions that require more energy during discrimination learning.[xv]

 How does Methylene Blue feel?

Is Methylene Blue safe to ingest?Many who use Methylene Blue say if you try this nootropic that you will likely feel different than any other supplement you’ve ever tried.

Neurohackers report when reading or studying, once you’re done, you should feel like you fully understand the subject material. And you’ll be able to use what you learned in the future.

Methylene Blue seems to facilitate a full understanding of something on the first try.

Many neurohackers report the biggest nootropic effect they experience with Methylene Blue is “after the fact learning”. You take in the information. And it’s like your brain sorts through the material. Then stores it in a form you can easily access later.

Methylene Blue has this uncanny ability to rewire your brain to forget about any negative associations you have of a situation. And only retains the positive aspects of that memory.

Some report that Methylene Blue makes you “feel young again”. It eliminates social anxiety. You’ll feel focused and more confident.

Some say that workouts seem easier because you have more energy. Your mitochondria are energized. And you may find that recovery from workouts is easier.

Some users love its anxiolytic benefits because Methylene Blue helps eliminate stress. So you have more energy in any situation with a relaxed state of mind.

And one recurring theme from many is improved sleep while using Methylene Blue.

Studies show Methylene Blue can prevent or slow the decline of mitochondrial function.

Methylene Blue Clinical Research

Research into Methylene Blue for its therapeutic value goes back to the late 1800’s. But it’s only in the last couple of decades that scientists have been able to decode exactly how Methylene Blue works in the brain. All the way down to the molecular level in mitochondria.

A study in 2017 found that Alzheimer’s Disease could be caused by more than the accumulation of amyloid beta in the brain. The scientists looked into the two main components that produce energy in cells.

  1. Glycolysis is the mechanism used to convert glucose into fuel within mitochondria.
  2. Creating this fuel in mitochondria uses oxygen in a process called mitochondrial respiration.

The researchers found that as the brain ages, mitochondrial metabolism deteriorates. Resulting in a reduction in the molecules needed for energy production. And possibly the main culprit behind many neurological diseases including Alzheimer’s and Parkinson’s.[xvi]

A study conducted at Children’s Hospital Oakland Research Institute may have found the solution to this mitochondrial energy problem in brain cells.

The researchers found that Methylene Blue can prevent or slow the decline of mitochondrial function.

One of the key aspects of Alzheimer’s is mitochondrial dysfunction. Specifically complex IV dysfunction. And this is where Methylene Blue steps in.

The study found that Methylene Blue enhances complex IV in mitochondria. It increases oxygen consumption. And it reverses premature cell death.

The researchers concluded that Methylene Blue may be useful to delay mitochondrial dysfunction with aging and the decrease in complex IV in Alzheimer’s disease.[xvii]

Methylene Blue Improves Memory

26 healthy volunteers aged 22 – 62 participated in a double-blind, randomized, placebo-controlled clinical trial. Purpose of the study was to measure the effects of Methylene Blue on working memory and sustained attention.

Study results showed that a single low-dose of Methylene Blue resulted in an increase in short-term memory ability. In an area of the brain associated with the senses and visual processing.

Timothy Duong, Ph.D., the study author concluded Methylene Blue showed promise “in healthy aging, cognitive impairment, dementia and other conditions that might benefit from drug-induced memory enhancement”.[xviii]

Another study published in the American Journal of Psychiatry tested fear extinction (elimination of fear) and contextual memory. Both are forms of long-term memory.

In this study, participants received either Methylene Blue or a placebo after being placed in a small dark chamber for a couple of minutes to address their fear.

One month later, participants that had used Methylene Blue had less retained fear than those given a placebo. The study authors concluded, “Methylene Blue enhances memory and the retention of fear extinction”.[xix]

Methylene Blue helps Bipolar Disorder

Animal studies have demonstrated that Methylene Blue can provide antidepressant and anxiolytic benefits. Possibly because it can increase serotonin and dopamine levels.

Canadian researchers noted that Methylene Blue also improved mitochondrial function and decreased oxidative damage. So, they hypothesized that Methylene Blue may be effective for bipolar disorder symptoms if combined with lamotrigine which is used as a mood stabilizer.

This study at Dalhousie University in Halifax compared the effectiveness of lamotrigine (Lamictal®) along with daily supplementation of either 195 mg or 15 mg of Methylene Blue in patients with Bipolar Disorder.

Patients took a dose (Lamictal and either 195 mg or 15 mg of Methylene Blue) for three months. Then proceeded to reduce Methylene Blue dosage for an extended period of 3 months. The team found that bipolar participants had reduced depression and anxiety when taking the higher dose of Methylene Blue compared to when they were on the lower dose.

Several Bipolar Disorder patients in the study chose to continue using Methylene Blue after the study concluded.[xx]

Methylene Blue Dosage Recommendations

Recommended safe doses based on clinical studies with animals and humans ranges from 0.5 – 4 mg/kg. So a 90 kg (200 lb.) body weight translates to 45 – 360 mg of Methylene Blue.

How much oral methylene blue should I take?45 mg of a Methylene Blue dose is a safe. But 360 mg of MB is much too high in my opinion even if you’re 200 lbs.

The bottom line is there is no true recommended dose for Methylene Blue. My recommendation is start with the lowest dose of 0.5 mg/kg and see how you react. A repeat dose may be taken if no effects occur.

Methylene Blue is water-soluble so you don’t need to take it with a meal, or healthy fat like some nootropics.

Methylene Blue has a half-life of about 5 hours. So you can dose twice a day.

Methylene Blue is famous for turning urine blue. But for most neurohackers, your urine will only stain blue at doses roughly exceeding 500 mcg. Some recommend preventing blue urine by mixing Methylene Blue with ascorbic acid for 3 hours before taking it.

Methylene Blue is also available as a doctor-administered injection for therapeutic use. IV Methylene Blue is typically used to treat diseases like malaria or with anti-cancer therapy.

Methylene Blue Potential Drug Interactions & Side Effects

Methylene Blue shows a hermetic dose-response, with opposite effects at low and high doses.

In other words, lower doses of Methylene Blue work well as a nootropic. But high doses do not because MB can potentially “steal” electrons away from the electron transport chain. Disrupting the redox balance and acting as a pro-oxidant (instead of an antioxidant).[xxi]

Methylene Blue Potential Drug Interactions & Side EffectsAdverse effects of Methylene Blue also come from chemical impurity. Even pharmaceutical (USP) grade Methylene Blue can contain impurities like arsenic, aluminum, cadmium, mercury and lead which puts you at increased risk for heavy metal toxicity.

At low doses, these contaminants are not that big of a problem. But higher doses will result in the accumulation of these toxins in your cells. Doctors should monitor patients with any hepatic impairment due to toxins related to high doses of serotonergic drugs like Methylene Blue.

Side effects with Methylene Blue are rare when doses are under 2 mg/kg. But can include stomach pain, chest pain, dizziness, headache, sweating, confusion, high blood pressure, shortness of breath, accelerated heartbeat, tremor, skin turning blue, urine turning blue or green, reduction of red blood cells, or jaundice (only reported in infants).

Reduce the Risk of Serotonin Syndrome

Monoamine Oxidase (MAOI) inhibition becomes a big problem at around 2 mg/kg of Methylene Blue. So if you are using antidepressants or antianxiety medications that affect dopamine or serotonin, you should NOT use Methylene Blue.

Because using Methylene Blue with one of these medications could cause possible interactions resulting in a hypertensive crisis or Serotonin Syndrome. Which can be deadly.

This includes not using Methylene Blue if you are using any selective serotonin reuptake inhibitors (SSRI’s) and monoamine oxidase inhibitors (MAOI’s) including 5-HTP, bupropion, buspirone, citalopram, clomipramine, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, MAOIs like Marplan, Nardil, and Parnate, milnacipran, mirtazapine, paroxetine, rasagiline, sertraline, selegiline, St. John’s wort, trazodone, tryptophan, Zimelidine, and venlafaxine.

The above list is my no means complete nor does it include all of the drugs that may be contraindicated with Methylene Blue. Check with your health care provider if a drug or supplement you are using may also be contraindicated with this nootropic.

Do not use Methylene Blue if you are pregnant or breast-feeding. Or if you are dealing with any type of renal impairment.

Where to buy Methylene Blue

Methylene Blue is sold as a liquid, and in crystalline powder form.

Industrial-grade and chemical-grade Methylene Blue is sold as a dye or stain. And can consist of more than 8% – 11% of various contaminants. And should NOT be used as a nootropic.

Only pharmaceutical (USP) grade Methylene Blue should be used as a nootropic. Ask for a Certificate of Analysis which should include the amount of contaminants such as arsenic, aluminum, cadmium, mercury and lead.

I recommend CZTL Methylene Blue due to their robust testing program. They ship in 1 gram containers of powder with dosage and mixing instructions in each shipment. Along with a Certificate of Analysis (CofA) verifying the purity of the Methylene Blue you get from them.

Another option in liquid form is Science.bio – Methylene Blue which is pre-mixed. And use the coupon code: davidtomen10 for a 10% discount when you check out.

Nootropics Expert Recommendation

Nootropics Expert Tested and ApprovedMethylene Blue 0.5 – 4 mg/kg of body weight per day

I recommend using Methylene Blue as a nootropic supplement.

Your body does not make Methylene Blue on its own. So to get its benefits you must take it as a supplement.

Methylene Blue is especially helpful for those dealing with anxiety and depression.

Methylene Blue is also particularly useful to students and executives who want to boost cognition, learning and memory.

Methylene Blue is a fast-acting nootropic that can also help prevent brain mitochondrial degeneration. Providing potential as an anti-aging nootropic.

Methylene Blue donates electrons in the electron transport chain in your mitochondria. So experienced neurohackers suggest avoiding CoQ-10 or idebenone when using MB because it seems to make Methylene Blue much less effective. Remember earlier in this review when I said the too much Methylene Blue can be counter-productive. The same applies here.

Idebenone is an Alzheimer’s drug that has some nootropic benefit. But it works similar to Methylene Blue because it acts as a transporter in the electron transport chain in mitochondria. Possibly potentiating Methylene Blue.

I recommend CZTL Methylene Blue

Or Science.bio – Methylene Blue which is pre-mixed. And use the coupon code: davidtomen10 for a 10% discount when you check out.

As an Amazon Associate I earn from qualifying purchases. This post may also contain other affiliate links and I will be compensated if you make a purchase after clicking on my links.

[i] Allexsaht W.J. “The use of methylene blue in the treatment of catatonic dementia praecox patients.” Psychiatric Quarterly. 1938;12:245–252.

[ii] Schirmer R.H., Coulibaly B., Stich A., Scheiwein M., Merkle H., Eubel J., Becker K., Becher H., Müller O., Zich T., Schiek W., Kouyaté B. “Methylene blue as an antimalarial agent.” Redox Report. 2003;8(5):272-5. (source)

[iii] Wainwright M., Crossley K.B. “Methylene Blue–a therapeutic dye for all seasons?” Journal of Chemotherapy 2002 Oct;14(5):431-43. (source)

[iv] Wen Y., Li W., Poteet E.C., Xie L., Tan C., Yan L.J., Ju X., Liu R., Qian H., Marvin M.A., Goldberg M.S., She H., Mao Z., Simpkins J.W., Yang S.H. “Alternative mitochondrial electron transfer as a novel strategy for neuroprotection.” Journal of Biological Chemistry. 2011 May 6; 286(18):16504-15. (source)

[v] Poteet E. et. Al. “Neuroprotective Actions of Methylene Blue and Its Derivatives” PLOS One 2012; 7(10): e48279. (source)

[vi] Wen Y., Li W., Poteet E.C., Xie L., Tan C., Yan L.J., Ju X., Liu R., Qian H., Marvin M.A., Goldberg M.S., She H., Mao Z., Simpkins J.W., Yang S.H. “Alternative mitochondrial electron transfer as a novel strategy for neuroprotection.” Journal of Biological Chemistry. 2011 May 6; 286(18):16504-15. (source)

[vii] Pfaffendorf M., Bruning T.A., Batnik H.D., van Zwieten P.A. “The interaction between methylene blue and the cholinergic system.” British Journal of Pharmacology. 1997 Sep;122(1):95-8. (source)

[viii] Ramsay R.R., Dunford C., Gillman P.K. “Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction.” British Journal of Pharmacology. 2007 Nov;152(6):946-51 (source)

[ix] Naylor G.J., Smith A.H., Connelly P. “A controlled trial of methylene blue in severe depressive illness.” Biological Psychiatry. 1987 May;22(5):657-9. (source)

[x] Naylor G.J., Martin B., Hopwood S.E., Watson Y. “A two-year double-blind crossover trial of the prophylactic effect of methylene blue in manic-depressive psychosis.” Biological Psychiatry. 1986 Aug;21(10):915-20. (source)

[xi] Crowe A., James M.J., Lee V.M., Smith A.B. 3rd, Trojanowski J.Q., Ballatore C., Brunden K.R. “Aminothienopyridazines and methylene blue affect Tau fibrillization via cysteine oxidation.” Journal of Biological Chemistry. 2013 Apr 19;288(16):11024-37 (source)

[xii] Oz M., Lorke D.E., Petroianu G.A. “Methylene blue and Alzheimer’s disease.” Biochemical Pharmacology. 2009 Oct 15;78(8):927-32. (source)

[xiii] Atamna H., Nguyen A., Schultz C., Boyle K., Newberry J., Kato H., Ames B.N. “Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways.” FASEB Journal. 2008 Mar;22(3):703-12. (source)

[xiv] Abbaspour N., Hurrell R., Kelishadi R. “Review on iron and its importance for human health” Journal of Research in Medical Sciences 2014 Feb; 19(2): 164–174. (source)

[xv] Wrubel K.M. et. El. “The Brain Metabolic Enhancer Methylene Blue Improves Discrimination Learning in Rats” Pharmacological and Biochemical Behavior. 2007 Apr; 86(4): 712–717. (source)

[xvi] Sonntag K.C., Ryu W., Amirault K.M., Healy R.A., Siegel A.J., McPhie D.L., Forester B., Cohen B.M. “Late-onset Alzheimer’s disease is associated with inherent changes in bioenergetics profiles” Scientific Reports 2017; 7 (source)

[xvii] Atamna H., Nguyen A., Schultz C., Boyle K., Newberry J., Kato H., Ames B.N. “Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways.” FASEB Journal. 2008 Mar;22(3):703-12 (source)

[xviii] Rodriguez P., Zhou W., Barrett D.W., Altmeyer W., Gutierrez J.E., Li J., Lancaster J.L., Gonzalez-Lima F., Duong T.Q. “Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain.” Radiology. 2016 Nov;281(2):516-526. (source)

[xix] Telch M.J., BRuchey A.K., Rosenfield D., Cobb A.R., Smits J., Pahl S., Gonzalez-Lima F. “Effects of Post-Session Administration of Methylene Blue on Fear Extinction and Contextual Memory in Adults With Claustrophobia” American Journal of Psychiatry Volume 171, Issue 10, October 2014, pp. 1091-1098 (source)

[xx] Alda M., McKinnon M., Blagdon R., Garnham J., MacLellan S., O’Donovan C., Hajek T., Nair C., Dursun S., MacQueen G. “Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study.” British Journal of Psychiatry. 2017 Jan;210(1):54-60 (source)

[xxi] Rojas J.C., Bruchey A.K., Gonzalez-Lima F. “Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue” Progress in Neurobiology. 2012 Jan; 96(1): 32–45. (source)

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Join The Discussion - 741 comments

Rebekah Higgins
June 16, 2018

This is so very interesting. As it is an MAOI do you have to watch carefully what you eat to avoid dietary interactions, like fermented foods etc?
also, I take a small amount of Trazodone 50-100mg per night and Ativan 1mg 2 x per day.

I know Ativan does not affect serotonin, but trazodone while not being an SSRI, does affect it but I do not know to what degree. At this dose do you think there is a potential for interaction or the syndrome?

PS. I would like to get off of these drugs eventually and have tried a plethora of options, L- Theanine etc, but my life circumstances and other things are chronically stressful without a definitive end in sight (an elder care situation and other things) and I have repeatedly found out that I am much better on these drugs than off. They keep me functional but the Ativan affects my memory. When I am ready to wean I will have more questions 🙂

    David Tomen
    June 16, 2018

    Rebekah, I would not recommend using any kind of nootropic that may affect serotonin and/or dopamine while on prescription antidepressants of any kind. It’s far too dangerous and not worth the chance of causing either Serotonin Syndrome or heart problems from hypertension.

    I get why you want to get off the prescription antidepressants. And nootropics are certainly a great alternative. But until you get off the meds, please be very, very careful.

      Rebekah Higgins
      June 16, 2018

      Thanks David. I appreciate it. I know of only one person who had the syndrome and it was caused by a mix of PRESCRIBED medication. Dr’s are largely not as on top of these interactions as they should be and we have to be vigilant ourselves. I do take NAC which affects dopamine, but I have had no adverse reactions for 6 months so I will keep it at 1200 as opposed to 1800mg. I will be super careful. Thanks.

Chris
February 7, 2018

Thanks so much for your thorough review here. I started w/ the .5mg/kg yesterday, and felt like various portions of my mental processing were a little more turned as a result.

Q: I’d love to see what the ceiling is w/ 4mg/kg, but the taste is a bit difficult for me. I’ve been diluting it in coffee, but even that isn’t enough to mask the taste. Any thoughts? Thanks!

    David Tomen
    February 7, 2018

    Chris, Methylene Blue was one of the more pleasant surprises I discovered and started using last year. Can’t help you on the taste however. I put mine in a small glass of cold water.

    Marcus
    October 2, 2018

    For both liquid and powder varieties of MB, I just encapsulate them in a large size gelatin capsule. Obviously for the liquid version, you need to encapsulate it each time just before you take it. But at least your tongue and teeth don’t turn blue!

    Janine Fuller
    November 3, 2023

    Chris I use gelatine capsules. You have to take the capsule immediately as MB starts breaking the capsule down in a short time. No taste and no staining.

Juliano
January 10, 2018

Is there any interaction between methylene blue and melatonin?

    David Tomen
    January 10, 2018

    Juliano, I’m not aware of a direct interaction between methylene blue and melatonin. But MB does affect serotonin levels and some of this neurotransmitter is converted into melatonin.

experimental² chris²
November 30, 2017

Thanks for your advice, David !

experimental² chris²
November 22, 2017

Hi David, very good article !
Cant wait to pee blue !
I found high pure grade 99,9% Methylene Blue on ebay. But im not sure what that exactly means. Can this 99,9% of MB still be impure with heavy metal and stuff. Meaning, is MB impure in itself? Hope you understand what i mean.
greetings, chris

    David Tomen
    November 23, 2017

    Chris, as far as I can tell from all my research, all Methylene Blue contains impurities. Even USP grade. But it’s “USP Grade” I’ve found to be safest to use and with the lower levels of heavy metals.

    That said, always ask for a Certificate of Analysis for this stuff. Especially for a vendor that you’re not familiar with like the one you found in eBay. Send them an email and ask for the CofA for that batch or lot number. If they can’t produce one that’s trustworthy, find another seller.

Christian
November 3, 2017

Just wondering if I am understand right….a safe starting dose would be 45mg for a 200lb person and it goes on to say that turning urine blue “your urine will only stain blue at doses roughly exceeding 500 mcg”…so isn’t 45 mg about 90 times more than 500mcg (micrograms vs milligrams)….to me it looks like even the lowest safe dose will turn urine blue.
Maybe it’s not a big deal but I was just wondering if 500mcg was meant to be 500mg.
Having said that I am looking forward to getting my powder and making a solution to try.

    David Tomen
    November 3, 2017

    Christian, you are correct. This stuff has amazing staining power. Likely the reason why its first use was to dye textiles (i.e. blue jeans).

      Christian
      November 3, 2017

      Thank you David for your reply….I am still unclear though…you say I am correct…does that mean that 500mcg mentioned in the article was supposed to say 500MG?
      If 500 mcg micrograms causes blue urine then a dose of 45mg will be very colorful indeed.
      Thanks again for your time

        David Tomen
        November 4, 2017

        Christian, 500 mcg is 0.5 mg of Methylene Blue. And that wasn’t a mistake. MB is processed for excretion by your kidneys. And like everything else it’ll vary from person to person. Just think of the look you’ll get from the guy in the next urinal. He’ll think you just teleported in from Avatar.

        Christian
        November 4, 2017

        Thank you again David for the clarification 🙂

Philip Higson
November 2, 2017

Regarding Adverse effects,
If we put in a small amount of activated charcoal with the Methylene Blue drops would that reduce the effects that the chemical impurities?

Adverse effects of Methylene Blue also come from chemical impurity. Even pharmaceutical (USP) grade Methylene Blue can contain impurities like arsenic, aluminum, cadmium, mercury and lead.

Regards

    David Tomen
    November 2, 2017

    Philip, you are correct in that all Methylene Blue contains impurities. USP Grade MB available by prescription-only may be an exception. But some suppliers also mark their Methylene Blue as USP Grade or ‘pure’. Look for the Certificate of Analysis on their website (which is sometimes available by ‘lot number’). Or ask them for it.

    Levels of impurities varies greatly from USP Grade to ‘industrial grade’and other grades. I’m rather paranoid about limiting the toxins that I consume. But I think you may do more damage to your brain by stressing about it than the actual amount of contaminants in USP Grade Methylene Blue. Especially given the very small doses used.

    Activated Charcoal is an excellent detox supplement. But I don’t know if that would effect the bioavailability of Methylene Blue. It may. There are a couple of ‘heavy metal chelators’ here on Nootropics Expert. Do a search using the search bar top right. One of those may be a better option for detoxing heavy metals than Activated Charcoal when using Methylene Blue. But honestly that’s purely a guess on my part.

Larry Trowbridge
November 1, 2017

Do you have any recommendations on reliable places to purchase methylene blue, in either powder or liquid form? Many places I’ve found aren’t actually selling it for nootropic uses and it’s nearly impossible to figure out how to get a proper dose.

    David Tomen
    November 2, 2017

    Larry, synthetic nootropics including the racetams cannot legally be sold as dietary supplements in the USA. (Not sure about the legality in other countries). Methylene Blue as a nootropic is included in this category. They are often called “research compounds” and “not for human consumption” for that reason.

    The only ‘legal’ USP-grade pharmaceutical Methylene Blue is available as a prescription drug in the USA. This is not a well know nootropic. So most suppliers will not refer to it as a nootropic, dietary supplement or any other term normally associated with a supplement.

    In the USA I’m aware of Blue Brain Boost and Ceretropic who offer it in their store. I believe you can also get it from Acros Organics but need to search for the “pure” version. In Europe I’m aware of MitoBlue.

    If you dig deep into the supply chain you’ll find that all Methylene Blue ‘originates’ in China. Not necessarily a bad thing. But you need to get a Certificate of Analysis to find out the level of contaminants. Sometimes it is available (by lot number) on their website. Or you need to ask for it.

    And you’re right about figuring out the ‘proper dosage’. I can’t go into specifics because it entirely depends on the concentration of Methylene Blue which varies from manufacturer to manufacturer. There are a few excellent threads on Longecity and reddit which talk about dosing this nootropic.

    Stefan
    July 11, 2019

    Bruce Ames says 40mg to 100mg is sweet spot
    I use a4% USP grade
    Yielding 2mg per drop

      Chuck
      October 12, 2019

      Where do you buy yours Stefan?

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