Methylene Blue – Health benefits, side effects, how to use, and more!

Key Takeaways:
Methylene Blue has a host of benefits as a nootropic, including: improved mood, increased energy, and enhanced cognitive function.
Methylene Blue is also believed to improve memory formation and recall.
Methylene Blue has been shown to be safe and well-tolerated in both short- and long-term studies.
Methylene Blue is a potent antioxidant that can protect cells from damage.
Methylene Blue has also been shown to improve circulation and help fight fatigue.

Methylene Blue – Health benefits, side effects, how to use, and more!

Over the last few years, Methylene Blue’s popularity has exploded due to its promotion by popular biohackers and influential voices in the health and wellness space.

Methylene blue has been used as an antiseptic and medication for various diseases since the 1800s. It also happens to be one of the most potent brain boosters in existence. Methylene Blue has been shown to improve memory, focus, and mood while offering a high level of neuroprotection.

Methylene Blue’s high reward, low-risk profile makes it one of the most exciting supplements in the biohacking world. This article explores the rewards methylene blue delivers while also touching on proper dosing and potential risks.

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What Is Methylene Blue?

Methylene Blue
Methylene blue is a synthetic substance that was originally used as a dye. It’s also known by some other names, including methylthioninium chloride and methyl thionine chloride

Recently it has become popular with nootropic users because of its incredible benefits to the brain. Methylene blue can increase energy levels, boost memory, protect against neurodegenerative diseases like Alzheimer’s disease and dementia, slow down aging effects on the body, and even improve mood disorders such as depression. Not only does methylene blue serve all of these purposes for your mind and body – it usually comes in at less than $20 per dose!

How Methylene Blue Works In The Brain

Methylene blue works in the brain by crossing the blood-brain barrier. Once it’s in the brain, it can reversibly inhibit MAO-A. This means that methylene blue can prevent dopamine and serotonin from being broken down, leading to increased levels of these neurotransmitters.1R R Ramsay, C Dunford, and P K Gillman, Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction Br J Pharmacol. 2007 Nov

Dopamine and serotonin are essential for cognitive function since they play primary roles in memory, focus, learning, mood, and many other aspects of brain health. By increasing levels of these neurotransmitters, methylene blue can provide significant benefits to cognitive performance and overall well-being.

Methylene Blue

In the body, Methylene Blue can help you when there is a problem with how the body’s cells use energy. When the body does not work right, it can’t make enough ATP, which might cause issues like too many free radicals. But methylene blue helps the cells use energy more efficiently and lowers free-radical production.2T Komlódi , L Tretter, Methylene blue stimulates substrate-level phosphorylation catalysed by succinyl-CoA ligase in the citric acid cycle Neuropharmacology. 2017

Check out some of Methylene Blue’s Brain-Boosting benefits below!

Memory Enhancement

Methylene blue has been found to improve memory in many studies.3Penny D Riha , Aleksandra K Bruchey, David J Echevarria, F Gonzalez-Lima, Memory facilitation by methylene blue: dose-dependent effect on behavior and brain oxygen consumption Eur J Pharmacol. 2005

One paper showed that methylene blue can reverse forgetfulness and enhance cognitive function in people with early-stage Alzheimer’s disease.4Julio C. Rojas,a Aleksandra K. Bruchey,a and F. Gonzalez-Lima, Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue Prog Neurobiol. 2012

Methylene Blue

In another study, methylene blue was shown to be effective at preventing age-related memory decline. It was even able to restore some lost memories in aging rats!5Narriman Lee Callaway , Penny D Riha, Aleksandra K Bruchey, Zeenat Munshi, F Gonzalez-Lima, Methylene blue improves brain oxidative metabolism and memory retention in rats Pharmacol Biochem Behav. 2004

In fact, one study showed that methylene blue was even able to reduce plaque build-up in the brains of mice with Alzheimer’s disease. Plaque build-up is a hallmark sign of Alzheimer’s.6David X. Medina, Antonella Caccamo, and Salvatore Oddo, Methylene Blue Reduces Aβ Levels and Rescues Early Cognitive Deficit by Increasing Proteasome Activity Brain Pathol. 2011

If you’re looking for a way to improve your memory, methylene blue might be the answer.

Neuroprotection

One of methylene blue’s most important benefits is its ability to protect the brain from damage.

It does this by increasing energy production in cells and preventing them from dying prematurely.

This can help prevent or slow down neurodegenerative diseases like Alzheimer’s, dementia, and Parkinson’s disease.7Shao-Hua Yang, Wenjun Li, Nathalie Sumien , Michael Forster , James W Simpkins, Ran Liu, Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots Prog Neurobiol. 2017

Multiple studies demonstrate methylene blue’s protective effects on the brain. One study found that methylene blue can in fact protect cells from free radicals.8M J Kelner, R Bagnell, B Hale, N M Alexander, Potential of methylene blue to block oxygen radical generation in reperfusion injury Basic Life Sci. 1988

Methylene Blue

Another study, carried out by researchers at the Max-Planck Institute for Experimental Medicine, showed methylene blue to be effective against neuroinflammation caused by microglia. Microglia are immune cells located in the brain whose job is similar to white blood cells – they attack threats like infections. But when there is nothing to fight off, their presence can cause inflammation leading to problems like Alzheimer’s disease or Parkinson’s disease (Parkinson’s Disease Treatment & Management). This means methylene blue might serve as an effective treatment for conditions involving harmful levels.9Payam Dibaj , Jana Zschüntzsch, Heinz Steffens, Jörg Scheffel, Bettina Göricke, Jochen H Weishaupt, Karim Le Meur, Frank Kirchhoff, Uwe-Karsten Hanisch, Eike D Schomburg, Clemens Neusch, Influence of methylene blue on microglia-induced inflammation and motor neuron degeneration in the SOD1(G93A) model for ALS nPLoS One. 2012

As an antioxidant, it has been shown to reduce tau protein aggregation while improving energy metabolism. These actions are of particular interest for treating neurodegenerative diseases with tau protein aggregates known as tauopathies.10Claude Michel Wischik,Damon Wischik, Peter Bentham, Kwang Meng Seng Tau aggregation inhibitor (TAI) therapy with rember™ arrests disease progression in mild and moderate Alzheimer’s disease over 50 weeks Alzheimer’s & dementia: the journal of the Alzheimer’s Association . 2008

MB improved the behavioral abnormalities in one study and reduced tau pathology, inflammation, and oxidative damage in mice by upregulating Nrf2/ARE genes.11Artem P.GureevaMikhail Yu.SyromyatnikovaTatyana M.GorbachevaaAnatoly A.StarkovbVasily N.Popov, Methylene blue improves sensorimotor phenotype and decreases anxiety in parallel with activating brain mitochondria biogenesis in mid-age mice Neuroscience Research. 2016

This is exciting considering all the benefits Nrf2 activation can elicit.12Artem P. Gureev, Ekaterina A. Shaforostova, Vasily N. Popov, Regulation of Mitochondrial Biogenesis as a Way for Active Longevity: Interaction Between the Nrf2 and PGC-1α Signaling Pathways Front. Genet., 14 May 2019

Mood- Enhancement

Methylene Blue
Methylene blue can also help improve mood disorders like depression, bipolar disorder, and schizophrenia.

One study found that methylene blue could even effectively improve symptoms of bipolar disorder.13Martin Alda,Margaret McKinnon,Ryan Blagdon,Julie Garnham,Susan MacLellan,Claire O’Donovan,Tomas Hajek,Cynthia Nair,Serdar Dursun and Glenda MacQueen, Methylene blue treatment for residual symptoms of bipolar disorder: Randomised crossover study Cambridge University Press:2018

Anxiety and Depression

Methylene blue shows promise in combatting anxiety and depression precisely due to its effectiveness at preventing oxidative stress-related cell damage.14Martin Alda , Margaret McKinnon , Ryan Blagdon , Julie Garnham , Susan MacLellan , Claire O’Donovan , Tomas Hajek , Cynthia Nair , Serdar Dursun , Glenda MacQueen, Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study Br J Psychiatry. 2017

This can avoid the harmful effects of chronic stress, which increases anxiety and other harmful physical changes like increased risk for heart disease or obesity.

One animal model suggests that methylene blue may also be helpful as an alternative treatment for schizophrenia.15S I Deutsch , R B Rosse, B L Schwartz, M Fay-McCarthy, P B Rosenberg, K Fearing, Methylene blue adjuvant therapy of schizophrenia Clin Neuropharmacol. 1997

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Anti-Aging Effects

Methylene Blue

Methylene blue works by helping your mitochondria produce more energy. This extra energy helps protect cells from damage – including the kind of damage that leads to aging.16Oana M Duicu , Andreea Privistirescu , Adrian Wolf , Alexandra Petruş , Maria D Dănilă , Corina D Raţiu , Danina M Muntean , Adrian Sturza, Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts Can J Physiol Pharmacol. 2017

Because methylene blue boosts this anti-aging effect, it’s been shown to slow down some signs of aging in animal models.

One study published in the journal Cell showed that methylene blue could extend the lifespan of worms by up to 20%.17Alexandra Vaccaro,Shunmoogum A. Patten,Sorana Ciura,Claudia Maios,Martine Therrien,Pierre Drapeau,Edor Kabashi ,J. Alex Parker, Methylene Blue Protects against TDP-43 and FUS Neuronal Toxicity in C. elegans and D. rerio pLos One. 2012

Another study on fruit flies showed that methylene blue could extend their lifespan by up to 15%.

And finally, a study published in The Journals of Gerontology showed that methylene blue can increase the lifespan of mice by up to 14%.

While more research is needed, these studies suggest that methylene blue might be able to help you live a longer and healthier life.

Several studies suggest methylene blue could have an anti-aging effect on humans too! And unlike many longevity treatments, methylene blue’s low price tag makes it a cost-effective way to fight the signs of aging.

Mitochondrial Energy

Methylene blue is a mitochondrial booster. This means that it helps mitochondria produce more energy. Mitochondria are the powerhouses of our cells, and when they have more energy, they can do a better job protecting us from damage

This extra energy methylene blue produces can help protect cells from damage. Even better, methylene blue can help protect mitochondria themselves from harm. One study published in the journal Redox Biology showed that methylene blue could protect cells and increase energy production even when exposed to a toxin.

Methylene Blue

Methylene blue has been shown to induce mitochondrial biogenesis, which increases the number of mitochondria inside cells through Nrf2 by stimulating H2O2 production and changing the relation NAD+/NADH, leading to PGC-1α activation through phosphorylation by AMPK.18Artem P. Gureev, Ekaterina A. Shaforostova and Vasily N. Popov, Regulation of Mitochondrial Biogenesis as a Way for Active Longevity: Interaction Between the Nrf2 and PGC-1α Signaling Pathways Front. Genet., 14 May 2019

Methylene Blue and Traumatic Brain Injury

Multiple studies show that MB is a potential candidate for TBI treatment.

One study showed methylene blue could reduce swelling and inflammation in rats after a TBI.19Ashley M. Fenn, John P. Skendelas, Daniel N. Moussa,Megan M. Muccigrosso, Phillip G. Popovich, Jonathan Lifshitz,Daniel S. Eiferman,corresponding and Jonathan P. Godbout, Methylene Blue Attenuates Traumatic Brain Injury-Associated Neuroinflammation and Acute Depressive-Like Behavior in Mice J Neurotrauma. 2015

Methylene Blue

Another found that methylene blue could improve memory, learning, and coordination when administered shortly after a traumatic brain injury.20Lora Talley Watts, Justin Alexander Long, Jonathan Chemello, Samantha Van Koughnet, Angelica Fernandez, Shiliang Huang,1 Qiang Shen,and Timothy Q. Duong, Methylene Blue Is Neuroprotective against Mild Traumatic Brain Injury J Neurotrauma. 2014

Methylene blue even has potential as a preventative measure as this same study showed that it blue could protect rats from TBI-induced damage when given before the injury occurred.

Methylene Blue Side Effects and Toxicity

Methylene blue is generally safe and well-tolerated.

That said, there are some potential side effects to be aware of before you start taking methylene blue. These include nausea, vomiting, dizziness, headache, anxiety, and confusion.

Most of these side effects are mild and go away after a few days or weeks. However, it’s essential to consult with your doctor before starting methylene blue if you have any preexisting conditions that could worsen these side effects.

Methylene blue is also toxic in high doses. It’s essential not to take more than the recommended dose – doing so could lead to serious health problems.

Serotonin Syndrome

Methylene blue can also cause serotonin syndrome.21Kailash Kapadia, Felix Cheung, Wai Lee, Richard Thalappillil, F. Barry Florence,and Jason Kim, Methylene Blue Causing Serotonin Syndrome Following Cystocele RepairUrol Case Rep. 2016

This is a rare but potentially dangerous health condition caused by excess levels of the neurotransmitter serotonin.

Methylene blue causes this because it inhibits an enzyme called monoamine oxidase (MAO).

By inhibiting MAO, methylene blue increases our body’s level of serotonin, norepinephrine, and dopamine – three neurotransmitters that play essential roles in regulating mood.

Too much of one or more of these neurotransmitters can lead to symptoms like rapid heart rate, high blood pressure, sweating, shivering/shaking, nausea and vomiting, confusion and disorientation, agitation, and anxiety.

This is why you should avoid Methylene Blue when taking selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or other MAOIs.

It’s also recommended to avoid while Pregnant or Breastfeeding.

Methylene Blue Dosage

Methylene Blue

Methylene Blue dosage depends on your reason for taking it. The preponderance of scientific evidence shows that low dose use hits the sweet spot for effectiveness while avoiding issues like serotonin syndrome. 0.5–4 mg/kg taken orally is an acceptable amount used in both human and animal studies.22F. Gonzalez-Lima and Allison Auchter, Protection against neurodegeneration with low-dose methylene blue and near-infrared light Front. Cell. Neurosci., 12 May 2015

By IV 0.1 to 0.2 mL per kilogram of body weight.23RxList, METHYLENE BLUE RxList.2021

Contraindications

Avoid Methylene Blue in combination with the following drugs and supplements:

  • 5-HTP
  • Vyvanse (lisdexamfetamine)
  • Wellbutrin XL (bupropion)
  • Norco (acetaminophen / hydrocodone)

Drugs.com also recommends checking with your doctor about using Methylene Blue if you are using the following medications:

  • alfentanil, fentanyl;
  • buspirone;
  • digoxin, digitalis;
  • dihydroergotamine, ergotamine;
  • phenytoin;
  • pimozide;
  • quinidine;
  • warfarin (Coumadin, Jantoven);
  • an MAO inhibitor–isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, tranylcypromine, and others;
  • an “SSRI” antidepressant–citalopram, escitalopram, fluoxetine, paroxetine, sertraline, Prozac, Paxil, Zoloft, and others;
  • an “SNRI” antidepressant–desvenlafaxine, duloxetine, levomilnacipran, milnacipran, venlafaxine, Effexor, Cymbalta, Pristiq, and others;
  • other antidepressants–bupropion, clomipramine, mirtazapine; or
  • medicine to prevent organ transplant rejection–cyclosporine, sirolimus, tacrolimus.
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Author

Erik Abramowitz is a certified Nutritional Therapy Practitioner (NTP), Naturopathic Doctoral student, health coach, and father. He is the primary content creator for HolisticNootropics.com and the host of the Holistic Nootropics Podcast.