The Malarone/coQ10 question

I stopped taking coQ10 when I started taking Malarone according to my doctor’s instructions. Unfortunately, it turned out that my 400 daily mg of coQ10 was what was working for my migraines -- they have come back since I stopped taking it. I have been having a mild one almost every day, and yesterday I had a seriously bad one. Last night, I decided to make it my mission to find out whether the coq10 ban was really necessary.

I had one clue that it might not be -- a post from a Lyme doctor in Germantown, MD who maintains a public blog about his experiences treating Lyme and its coinfections. In a post from 2008, he said that

Atovaquone…also appears to work through a mitochondrial mechanism. It interferes with electron transport- the final stage of the KREBS cycle necessary for cellular energy production. This is considered a possible mechanism of action. It does not involve the coenzyme Q10 pathway. And even if it did, it inhibits an enzymatic conversion in the cell. It’s effect would be independent of the amount of Q10 present. And furthermore- there is nothing to suggest that oral Q10 supplements would have any way of getting into bacterial mitochondria.

Q10 and Mepron both have effects in the mitochondria of cells. That is all they have in common. They work on different cellular mechanisms. If Q10 is an effective supplement for Lyme symptoms, then there is no scientific rationale for stopping it when anti-Babesia therapy is prescribed.

I know this contradicts advice I have given patients in the past. But not having the time to research every recommendation, I had taken this on faith. I think it was incorrect advice.

I spent several hours last night and most of today researching it. Here is what I found:

A synthetic analog of ubiquinol, or coenzyme Q10, atovaquone is a broad-spectrum antibiotic with an elimination half-life of 2-3 days in adults. Atovaquone selectively inhibits protozoan mitochondrial electron transport at the cytochrome bc1 complex and collapses mitochondrial membrane potential (Mather MW et al, 2007). It binds to the complex's cytochrome b subunit, specifically to the ubiquinol oxidation pocket, where it interacts with the Rieske iron-sulfur protein (Kessl JJ et al, 2003).

Ubiquinol binds both to the oxidation pocket and the Rieske protein (Wikipedia, “The Q cycle”, no reference). Normally, ubiquinol then participates in a redox reaction with ubiquinone, which binds to a nearby site on the cytochrome b subunit. As part of this reaction, ubiquinol gives up an electron to the Rieske protein, which then passes it on to the cytochrome c1 subunit of the complex (Zhang Z et al, 1998; Crofts AR et al, 1999). There’s a second half to the Q cycle, which you can read about here.

Although Atovaquone and ubiquinol bind to the same sites on the cytochrome bc1 complex, they use different binding residues. When atovaquone is bound, though, it blocks movement of the Rieske protein domain by locking the protein in its cytochrome b-binding conformation, preventing the electron transfer I described above (Mather MW et al, 2005). Without the electron transfer, the Q cycle cannot be completed; thus, no need for ubiquinone…

…in bacterial mitochondria, at least. I still need it to keep my cranial blood vessels happy. It did occur to me to wonder if ubiquinone participated in any other mitochondrial reactions. It does, but since atovaquone collapses mitochondrial membrane potential I can't see how it could get in. And, as far as I can tell, even if it gets into the bacterial mitochondria, it won’t matter, thanks to Malarone's super-long half-life .

So I started taking it again. I feel a bit like a renegade, and also insecure about my biochemistry memory, so I’m going to take the coQ10 2-3 hours away from my Malarone doses (not that that will make any difference, given Malarone’s long elimination half-life -- it will either be a problem, because there's something that I've missed, or it won't). Since the Malarone has been giving me what I think are Herxheimer reactions every few days, I’ll watch to see if the Herxes stop with the addition of the coQ10. If they do, then I’ll discontinue it and start looking for another functional migraine remedy.

FUN! Wasn’t that fun? I LOVE SCIENCE. It gave me a huge rush to get even this far in understanding how this works.