Novel Strategy for COVID-19: Methylene Blue

April 27, 2020

References:  Vine Health Care, Am Council on Science and Health, CBS News, Oxygen Saturation Sensor, Science Direct NAD,

Ever heard of Methylene Blue?  Possibly as a cheap party trick for making your pee look green on St. Patrick's Day.  Don't do that.  It does interfere with some other drugs that folks may be taking.  But what about COVID'19 and methylene blue.  In the frantic rush to find things that work, here is a though that is cheap, easily available, widely tested and well known.  And unstudied.  Could it work against COVID-19?

One of the known markers of severe disease with COVID-19 is an odd low oxygen level in folks that don't have a sense of being short of breath.  Normally your oxygen saturation is around 98-99% and you feel good.  If your saturation drops to 92-93% quickly, you feel awful.  Folks with COVID-19 show up with oxygen saturations of 70-80%, and look fine.  Something is dramatically remiss.  In fact, it appears this is a marker of future risk, walking around for days with very low oxygen saturation and not feeling it.  It is something you can measure yourself at home with an inexpensive oxygen saturation sensor.  What's going on?

The virus is thought to attack the hemoglobin molecule and damage the heme part of it, where iron is attached.  Iron is a very toxic compound when let loose.  It is tightly bound to hemoglobin where it binds oxygen in the lungs, drops it off in the tissue where it then binds carbon dioxide.  In that process it switches back and forth between it's Fe+2 state and its Fe+3 state. A pulse oximetry device measures oxygenated vs deoxygenated blood indirectly, while PaO2 (the partial gas pressure of oxygen) is measured with an arterial blood gas.  Damaged hemoglobin syndromes such as sulfhemoglobinemia, methemoglobinemia and carbon monoxide poisoning cause a low oxygen saturation on pulse oximetry with a normal PaO2, just like COVID-19.   This is called a saturation gap.  Like the London subway, "Mind the Gap".  This is called an acquired methemoglobinemia and can be the result of medication or toxin exposures which cause iron to flip from the Fe2+ (ferrous) state, where it can carry oxygen to the Fe3+ (ferric) state. where it can't.   If the percentage of methemoglobinemia is elevated enough, the patient becomes “functionally anemic” and feels short of breath.

That's where methylene blue comes in.  We referred to nicotinamide riboside in a prior posting as a possible helpful adjunct in COVID because of its NAD link.  Follow me here.  There is an enzyme called cytochrome-b5 reductase utilizes NADH formed during glycolysis to reduce methemoglobin back to functional hemoglobin.  This pathway is not normally used in baseline human physiology.  But it's there.  Methylene blue is an electron donor which can be taken orally or administered intravenously.  It upregulates the restoration of met-hemoglobin through the NADPH-MetHb pathway back to functional hemoglobin.  High dose IV vitamin C does the same thing.  Not as efficiently.  But that may be where IV Vitamin C has some benefit.  

Has this been studied in COVID-19?  No!!!  It is just known to work in other situations where you have this "Gap" and it is a way of addressing it.  "Mind the Gap".   Is methylene blue dangerous?  Well, most of the time not really unless you are G6PD deficient or on some antidepressants.  Can you buy it?  Well, yes.  It's on Amazon at 1% concentration and is what Frat Parties do to freak out folks with the resultant green pee.

I think this is a very interesting concept.  It has not been studied.  None of us should go out and buy it and start taking it.  The purpose of this blog is to spark curiosity and initiate a conversation.  We are all in a frantic global rush to explore and consider new ideas.   But the saturation gap is there.  Every ER doctor knows about it. And the first thing you will have done when you go to an ER is have your finger placed in a saturation pulse oximetry device.  And THAT is something you can do, at home.  

WWW.What will work for me?   I have a pulse oximetry device.  I just checked mine.  At age 70 it's not unusual to putz along at 96-97.  I was 98% so I'm quite happy with myself.  I did take my nicotinomide riboside this morning.  That is something else you can do.   

Pop Quiz

1.  What does methylene blue do?  Answer: it restores a broken hemoglobin molecule that has had carbon monoxide abnormally attached to it, making it impossible to transport oxygen.  If you are carbon monoxide poisoned.  Not common.  But curiously we are seeing a similar thing happen in COVID-19.

2.   What is that curious thing we are seeing in COVID-19?     Answer: Folks walking around with very low oxygen levels as measured by pulse oximetry meters.  Instead of 97-99 levels, which are normal,. folks will have 70-80s and feel fine, supposedly.   Very odd and quite remarkable.

3.   Do I have to go to an ER to measure that?    Answer:   No, you can buy one at home.  The price has gone up dramatically in the last three weeks, so buy one now before it doubles again.  Or buy 10,000 and double the price yourself (and get yourself a paid vacation by Uncle Sam for price gouging.).

4.   Methylene blue has been shown to help folks with COVID-19.     Answer:  No, it hasn 't.  It just fits the bill if you understand the physiology.

5.   What happens to the color of your pee if you take it orally?       Answer:  Irish green.  If you don't get sick from it by having a reaction.  So don't do it, yet.