Methylene Blue

Background

Methylene blue is used as a powerful nootropic but is also known to have a number of useful medical purposes over the last 100 years, and is considered one of the top essential medicines by the World Health Organization. Also known as methylthioninium chloride, Methylene Blue is an an FDA-approved drug has been used for the treatment of various diseases like malaria and some psychiatric disorder for more than 100 years. Methylene blue (MB) is used as medicine and a commonly used dye that exhibits antioxidant, antimalarial, antidepressant and cardioprotective properties. As a medication, it is mainly used to relieve of methemoglobinemia, specifically to relieve of methemoglobin levels that are greater than 30% or in which there are symptoms despite oxygen therapy. The neuroprotective effect of methylene blue (MB) has been identified against various brain disorders, including ischemic stroke.[1][2]

Benefits

Methylene blue is a good mitochondrial enhancer and has some cognitive enhancing properties. The health benefits of microdosing methylene blue are numerous and it comes with many nice effects on the brain and body.
It improves the oxygen consumption of cells, increasing cellular energy, which in turn enhances memory (both long- and short-term), is neuroprotective, and is an antioxidant. Methylene blue accumulates in areas of cells with a high concentration of mitochondria, it stops free radicals as they are formed, hindering any oxidant damage or stress. The following are that Methylene blue can benefit you:

  • Acts as an antioxidant to mitochondria [5]
  • Improves cognitive performance [6]
  • Improves memory consolidation [7]
  • Protects the brain [8]
  • Enhances mood [9]
  • Helps people fight cancer [10][6]
  • Reduces depression [11]
  • Hinders skin aging [12]
  • Can help with Alzheimer’s, Dementia and Parkinson’s and Huntington’s Diseases [13]
  • Improves the hypotension associated with various clinical states [14]

Methylene blue is proposed to affect neurodegeneration in Alzheimer’s disease via inhibition of tau protein aggregation and amyloids. It also may help Alzheimer’s by increasing acetylcholine (via acetylcholinesterase inhibition). It also partially repairs impairments in mitochondrial function and cellular metabolism. By acting as an electron carrier and mitochondrial enhancer, it has promise in Parkinson’s disease.

How it works

Main mechanism of action of Methylene blue involves inhibition of nitric oxide synthase and guanylate cyclase.
In Alzheimer: a mechanistic study found that methylene blue oxidizes cysteine sulfhydryl groups on tau to keep tau monomeric. One preclinical treatment study in tauopathy mice reported anti-inflammatory or neuroprotective effects mediated by the Nrf2/antioxidant response element (ARE); another reported insoluble tau reduction and a learning and memory benefit when given early.
In Methemoglobinemia: Methylene Blue acts by reacting within RBC to form leukomethylene blue, which is a reducing agent of oxidized hemoglobin converting the ferric ion (fe+++) back to its oxygen carrying ferrous state(fe++).
As antimalarial agent: Methylene Blue, a specific inhibitor of P.falciparum glutathione reductase has the potential to reverse CQ resistance and it hinders the polymerization of haem into haemozoin similar to 4-amino-quinoline antimalarials.
For ifofosamide induced neurotoxicity: Methylene blue acts as an alternative electron acceptor, and reverses the NADH inhibition of hepatic gluconeogenesis while also inhibiting the transformation of chloroethylamine into Chloroacetaldehyde, and also inhibits multiple amine oxidase activities, hindering the formation of Chloroacetaldehyde.[3]
Methylene blue (MB) is readily absorbed in blood and quickly distributed to various organs. Other functions of MB include cognition enhancing properties and increase oxygen consumption efficacy in isolated mitochondria. MB (1 mg/kg) has also reported to increase COX activity and thereby improving energy functions in AD brains. MB acts as both mitochondrial restorer as well as antioxidant.[4]

Considerations

Though Methylene blue has numerous cognitive benefits, it has some common side effects which include headache, vomiting, confusion, shortness of breath, and high blood pressure. Other side effects may include serotonin syndrome, red blood cell breakdown, and allergic reactions. It often turns the urine, sweat, and stool blue to green in color. Using during pregnancy may harm the baby. Consult your doctor before using Methylene blue.

Recommendations

Methylene blue has a hormetic dose response meaning that low doses are beneficial, while high doses are harmful. So, you are recommended not to take more than 5mg per kilogram of body weight (and take less if you are obese).  Anywhere from 0.5mg – 5mg per kilogram may be safe and effective.
But at high doses, watch out!  It interferes with the ability of red blood cells to carry oxygen and can be fatal.

Sources