|By Jonathan Roseland||Connect|
Full disclosure: this review was written by BlueBrainBoost.
There's a lot of compelling evidence for the nootropic effects of methylene blue.
Methylene blue is currently under clinical development for the treatment of Alzheimer's disease by TauRx.
Unlike other drugs, methylene blue is relatively "clean." This means that methylene blue doesn't really perturb any neurotransmitter systems. Instead, methylene blue enhances the efficiency of mitochondrial bioenergetics.
The mitochondria are the energetic powerhouses of the cell. They produce all the ATP. Improving ATP production in the brain is a viable cognitive enhancement strategy. For example, thyroid hormone (which regulates ATP production and cell metabolism at the basic level) has nootropic effects if you're slightly hypothyroid. Hypothyroidism is linked to slowed cognitive tempo, depression, and anergy.
Head Strong by Dave Asprey makes the case that optimizing your Mitochondria is the ultimate performance enhancing Biohack because your Mitochondria are the fundamental energy generation mechanism that underlie everything else. From the book:
Animal studies also show that methylene blue is a powerful nootropic. Rats that were treated with methylene blue showed improvements in cognition and memory retention. So did humans in another study, where methylene blue was shown to help short-term memory. Methylene blue definitely helps mitochondrial respiration, and you can feel the difference if you try it.
Mechanism of Action
From the book:
It can cross the blood-brain barrier and acts as an antioxidant in the brain. It also improves the efficiency of your mitochondria by carrying more electrons into the electron transport chain and increasing your mitochondria’s oxygen consumption. (p. 286)
Usage and Dosage
Dave advise that you keep the dosage very low:
The problem is that as doses get higher, methylene blue becomes a pro-oxidant and can do the opposite of what you’d expect— cause oxidative stress. Larger doses may also harm your gut bacteria, and if you have high blood pressure, it’s not a good idea to try this one. It’s also really harmful for babies. (p. 287)
I'm introduction this example about thyroid hormone because it demonstrates how important ATP production and mitochondrial fucntion is the in the brain.
Methylene blue does a few different things. It's a blood brain barrier-permeable antioxidant. One difficulty with many antioxidants is that they never make it into the brain. For example, many people supplement with GABA, but it's clear that GABA is too water soluble to ever get into the brain.
In addition to being a potent antioxidant with good brain penetration, methylene blue behaves like an aritifical electron donor and electron acceptor. If you've taken biochemistry, you'll know that REDOX (reduction-oxidation) reactions are vital to the electron transport chain (ETC). The ETC is what allows mitochondria to pump protons out of the mitochondrial matrix and generate ATP.
So in a way, behaves methylene blue can accept and donote electrons, it makes REDOX reactions more efficient and snappy. The net effect is reduced oxidative stress in the brain and increased oxidative phosphorylation and ATP production.
All this theortical information is nice, but what evidence is there that this actually works in humans? Well, there are a couple of studies dating back to the 1970's that demonstrate improvements in memory formation following methylene blue adminstration.
These effects were subsequently replicated in different animal models and experimental paradigms. In clinical trials, methylene blue has shown to slow the rate of cognitive decline, but more research is needed to confirm the benefits. I think going forward, we'll see some more translational research on the benefits and risks of methylene blue in humans.