Methylene Blue on the Airplane

or underwater.

I talked to someone last night who said he uses methylene blue under two circumstances:

• On airplanes that don’t have sufficient maintenance of oxygen concentrations in the cabin, he is unable to work effectively due to fatigue and haze, but methylene blue resolves this.

• When holding his breath to swim under water, he can swim twice as a long if he has taken methylene blue earlier in the day.

Here’s what’s NOT going on:

• Methylene blue is “turbo charging” his ATP production.

• Methylene blue is “healing” and “energizing” his mitochondria.

These statements are total nonsensical pseudoscience.

Methylene blue rewires the respiratory chain, which can help you if your respiratory chain is situationally limited by hypoxia, toxicity, genetics, or nutrition, but otherwise hurts you because there is no wiring of the respiratory chain better than the one nature endowed you with.

Using methylene blue indiscriminately to cover up problems with genetics and nutrition is not wise at all, but using it situationally because you understand what it is doing and know it works for you can be strategically sound.

Ordinarily, most ATP is made by ATP synthase in the mitochondrial respiratory chain, but small amounts are made during glycolysis (2 ATP per round) and the citric acid cycle (one ATP per round).

Glycolysis and the citric acid cycle load electrons onto NAD+ — a derivative of niacin or vitamin B3 — to form NADH, and NADH delivers them to the respiratory chain, reverting back to NAD+. As the electrons flow through the respiratory chain from complex I to coenzyme Q10 (Q) to complex III to cytochrome C, to complex IV, their energy is harvested by the three complexes to pump hydrogen ions. The conversion of oxygen to water at complex IV draws the electrons through the chain. The pumped hydrogen ions (H+) backflow through ATP synthase to drive the synthesis of ATP. The harvesting of the electron energy for H+ pumping is responsible for most of the ATP produced.

Some electrons from the citric acid cycle are derived from the oxidation of succinate to fumarate, which delivers the electrons to FAD — a derivative of riboflavin or vitamin B2 — held within the succinate dehydrogenase/complex II system:

After a string of reactions they are delivered to CoQ10 and then proceed similarly through the chain to complex III, cytochrome C, and complex IV.

If oxygen is not present, the chain will not oxidize NADH or FADH2, and this will shut down glycolysis and the citric acid cycle.

Methylene blue can oxidize both NADH and FADH2:

This will allow glycolysis and the citric acid cycle to keep running, generating small amounts of additional ATP.

However, there are two major limitations to this:

• This does not allow any pumping of H+ by the respiratory chain, so the additional ATP it can yield is produced very inefficiently.

• At some point all of the methylene blue (MB+) has been loaded with electrons, forming methylene white (MBH), and it can’t help anymore unless they are unloaded somewhere.

Most likely, some of these electrons are unloaded onto complex III:

Then others are unloaded onto oxygen to form hydrogen peroxide:

The hydrogen peroxide then oxidizes cytochrome C:

This then may allow some H+ pumping by complex III during the flow of electrons from NADH to methylene blue to complex III to cytochrome C, while the flow of electrons from NADH to methylene blue to oxygen to form hydrogen peroxide, which oxidizes cytochrome C, allows the electrons to continue flowing.

Complex III pumps 40% of the H+ in the respiratory chain, so this method of using the chain generates 60% less ATP than the normal route.

However, if the cell is able to expand oxygen-utilizing capacity by adding this to what is being used by complex IV instead of using it in place of the oxygen used by complex IV, then this will provide marginal expansion of ATP production.

The most reliable benefit would be to keep glycolysis and the citric acid cycle going despite less oxygen available.

If you imagine this lengthening your underwater breath hold, it is probably ending when all the methylene blue is reduced and there is no more oxygen to facilitate its turnover.

Under conditions of a long flight with marginally lower oxygen availability, methylene blue creates an opportunity to increase ATP production and reactive oxygen species (ROS) production simultaneously. ROS enhance the adaptive response to hypoxia. Usually hypoxia generates ROS in proportion to the decrease in ATP production, so the adaptive response to hypoxia correlates with you feeling worse. By coupling the increased ATP production to the ROS production, methylene blue reduces the stress you feel from hypoxia, but increases the rate of adaptation. The hypoxia response will elicit a gene expression protocol to improve oxygen delivery to cells, sequestration of oxygen by complex IV, and total capacity for oxygen utilization and ATP production.

This is educational in nature and not medical or dietetic advice. See terms for additional and more complete disclaimers.

Contraindications for methylene blue include glucose 6-phosphate dehydrogenase deficiency, use of SSRIs; hydroxylamine toxicity; renal failure; caution should be used in cases of methemoglobinemia caused by dapsone or aniline; and methylene blue can make a pulse oximeter inaccurate.

Dosing methylene blue should start with 0.5 milligrams and titrate upwards in 0.5-milligram amounts. The reported dose used above preceding the swimming session was 30 milligrams. Methylene blue at this dose can cause MAO inhibition with effects on mood and risk of excess serotonin.

Methylene blue rewires mitochondria and does not “turbo charge” them or “heal them” and this should be regarded as a biohack with the long-term implications of regular use being unclear. If your mitochondria work great, regular use of methylene blue will make them work less efficiently.

Full details about methylene blue can be found in Methylene Blue: Biohacker’s Delight or Playing With Fire?