Methylene blue is a good mitochondrial and cognitive enhancer, with other nice effects. Read on to learn how methylene blue can benefit you and which variety is the best to use.
What is Methylene Blue?
Methylene blue, also known as methylthioninium chloride, is a medication and dye.
Methylene Blue Snapshot
- Acts as an antioxidant to mitochondria
- Improves memory consolidation.
- Protects the brain.
- Enhances mood
- is anti-cancer
- is anti-microbial
- Possible negative impact on the gut microbiome at large doses.
- Should be careful with MAOIs and taking it with lots of sun exposure
- Can cause higher blood pressure, so people with already high blood pressure should be wary.
- Doesn’t taste the best.
Benefits of Methylene Blue
1) Methylene Blue is an Anti-Depressant
Methylene Blue (MB) is a monoamine oxidase inhibitor (MAOI) (R).
2) Methylene Blue is Anti-Cancer
3) Methylene Can Help Alzheimer’s, Dementia and Parkinson’s and Huntington’s
It also partially repairs impairments in mitochondrial function and cellular metabolism (R).
Methylene blue can alleviate mitochondrial abnormalities in a cellular model of progeria (R).
4) Methylene Blue Increases Blood Pressure
In diseased states, blood pressure often drops too low.
Methylene blue, an inhibitor of nitric oxide synthase and guanylate cyclase has been found to improve the hypotension associated with various clinical states (R).
5) Methylene Blue Improves Cognitive Performance in Healthy People
A randomized, double-blinded, placebo-controlled clinical trial of twenty-six subjects (age range, 22–62 years) was conducted on low dose methylene blue (~280mg, which is actually a high dose in my book) (R).
In this randomized study, low-dose methylene blue increased functional MR imaging activity during sustained attention and short-term memory tasks and potentiated memory retrieval (R).
Compared with control subjects, oral administration of low-dose methylene blue increased functional MR imaging response during the encoding, maintenance, and retrieval components of a short-term memory task in multiple clusters in the prefrontal, parietal, and occipital cortex (R).
Administration of methylene blue increased response (more brain activity) in the bilateral insular cortex during a psychomotor vigilance task (Z = 2.9–3.4, P= .01–.008) and functional MR imaging response during a short-term memory task involving the prefrontal, parietal, and occipital cortex (Z = 2.9–4.2, P = .03–.0003). Methylene blue was also associated with a 7% increase in correct responses during memory retrieval (P = .01) (R).
The insular cortex is important for sustained attention (R).
The study concluded: “Low-dose methylene blue can increase functional MR imaging activity during sustained attention and short-term memory tasks and enhance memory retrieval” (R).
Methylene blue has been shown to support memory consolidation and is neuroprotective as well (R).
On the other hand, MB is known to enhance memory retention and other brain functions in which ionotropic glutamate receptors are involved. It is possible that MB benefits cognitive function by modulating AMPA/kainate and NMDA-type ionotropic glutamate receptors (R).
Part of the cognitive enhancing effects is mediated by improvements in mitochondrial function.
6) Methylene Blue Helps Mitochondrial Function
It also has been shown that in low doses methylene blue protects the brain from disease by acting as an antioxidant in the mitochondria. It also acts as an artificial electron donor to complex I-IV of the mitochondria.
This means that it can increase ATP production. ATP is the currency of life and the energy that powers humans. If our production of ATP declines, our physical and mental performance declines. Even healthy individuals can benefit from a boost in ATP production.
High concentrations of MB promote oxidative stress. Therefore, it is expected that low MB doses or concentrations will be, in general, more effective than large ones at facilitating physiological effects within mitochondria.
In fact, at high local concentrations, MB can potentially “steal” electrons away from the electron transport chain complexes, disrupting the redox balance and acting as a pro-oxidant (R).
At low concentrations, MB can interact with oxygen to form water, which would decrease the superoxide radicals produced during the process of oxidative phosphorylation. MB can also trap leaking electrons produced by mitochondrial inhibitors and preserve the metabolic rate by bypassing blocked points of electron flow, thus improving mitochondrial respiration (R, R2, R3).
In a rat model of cerebral ischemia, MB was able to speed up the removal of damaged mitochondria from a cell prior to cell death (mitophagy) (R).
Thus, MB is a potential target for mitochondrial dysfunction (R).
7) Methylene Blue is Antimicrobial
Methylene blue was first used in 1891 to treat malaria.
Photodynamic therapy using the light-activated antimicrobial agent, MB kills methicillin-resistant Staphylococcus aureus (MRSA) in superficial and deep excisional wounds (R).
8) Methylene Blue Can Extinguish Fear
Preclinical studies have shown that low-dose methylene blue increases memory retention after learning tasks, including fear extinction (R).
Adult participants displaying marked claustrophobic fear were randomly assigned to double-blind administration of 260 mg of methylene blue (N=23) or administration of placebo (N=19) immediately following six 5-minute extinction trials in an enclosed chamber (R).
The study concluded that Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session but may have a deleterious effect on extinction when administered after an unsuccessful exposure session (R).
9) Methylene Blue Can Slow Skin Aging
A very recent study showed MB to be an effective antioxidant in connective tissue cells. This was true whether the cells were taken from healthy donors or from patients with a premature aging disease (R).
MB was more effective at building connective tissue and delaying cell death than other common mitochondrial-targeting antioxidants (R).
MB treatment changed the expression of some of the proteins in the skin. For example, the expression of elastin and collagen, essential elements of healthy skin, was increased (R).
Dosage for Different Effects
MB has wildly different effects depending on the dose. In the milligram doses, it shows some MAO-I properties and can kill certain infections.
In the microgram doses, however, it acts via hormetic mechanisms and likely won’t kill an infection or have MAO-I properties.
Methylene blue definitely has an effect and I’ve subjectively noticed that it does so by increasing mitochondrial function, as it’s supposed to.
After lots of experimentation with mitochondrial enhancers, you begin to know what mitochondrial enhancement feels like. Anyway, I find it’s a great antidepressant and a nice tool for enhancement over the long term.
I take it once a day and I cycle with other mitochondrial enhancers. I end up taking it about 3-4X a week because I have many other mitochondrial enhancers in my toolkit.
Instructions for Prepare a Solution
Safe Dosage of Methylene Blue
The recommended safe dose appears to be between 1 and 4 mg/kg, depending on the source (R).
Most side effects of MB appear to be dose-dependent and do not occur with doses <2 mg/ kg, a dose range that is widely used in the clinical applications of MB (R).
In in vitro studies, MB demonstrates biological actions at a wide range of concentrations, from 0.1 nM to 10 mM, and toxic effects have only been reported at concentrations higher than 100 mM. (R)
I personally take much lower dosages of methylene blue – about 90 mcg.
Contraindications of Methylene Blue
Methylene blue is contraindicated in patients who have developed hypersensitivity reactions to it and in severe renal insufficiency. It is relatively contraindicated in G6PD deficient patients as it can cause severe hemolysis and also in patients with Heinz body anemia (R).
As mentioned, it should not be taken with an SSRI or serotonin increasing drug, if you’re taking a high dosage (R).
Babies are particularly prone to adverse effects of Methylene blue. It causes hyperbilirubinemia, meth-Hemoglobin formation, hemolytic anemia, respiratory distress, pulmonary edema, phototoxicity and bluish discoloration of tracheal secretions and urine (R).
Methylene Blue also interferes with the pulse oximeter’s light emission resulting in falsely depressed oxygen saturation reading (R).
Caution When Buying
It is important to note that even pharmaceutical (USP) grade Methylene Blue contains impurities, such as arsenic, aluminum, cadmium, mercury, and lead (R).
At low doses, the presence of contaminants is not of great concern, but at higher doses, non-specific effects due to the accumulation of various toxic and bioactive substances are possible (R).
Industrial-grade and chemical-grade MB sold as a dye or stain can consist of more than 8% or 11% of various contaminants (NTP, 2008, Sigma Chemical Co, St. Louis, MO) and should not be administered to humans or animals (R).
For example, commercial chemical suppliers routinely warn that their non-USP MB products are of a chemical grade not suitable for use in living applications (R).