Unexpected Lescol Interaction with Citrus Sparkling Water

[flacorps]

I started on LescolXL (80mg timed-release fluvastatin) an athlete, and quit it a near-invalid ... and went downhill even after that from acquired hypogonadism (low Testosterone) that I blame largely on the Lescol.

I was on Lescol (with layoffs due to becoming ill) for about a year and a half until I finally became so foggy I fell and hit my head on a big wheeled trash bin and needed 25 staples to close my scalp.

During my time on the drug I had several incidents of gastrointestinal distress that resulted each time in passing black pigment stones--once I even had pancreatitis. This had actually happened once or twice in the years before I began taking Lescol (I believe while taking erythromycin and either OJ or nefazodone or paxil, none of which I tolerated well), and therein lies the tale. I amassed more than 500 pages of research from Google scholar before I was drawn inevitably to the conclusion that my hypogonadism was not genetic, or from hitting my head, or an early sign of the lymphoma that killed my father, or associated with CFIDS/HHV-6/EBV/CMV or Hep C (all viable candidates), it was in fact due to 10 years of overconsumption of Lacroix lemon and lime sparkling waters that interacted with just about every prescription I've been on in the last 10 years. To make a long story short, I believe they contain furanocoumarins that accumulated in my liver and prevented my body from clearing Lescol as it should have. The really acute effects didn't kick in, however, until I either drank orange juice (which has flavonoids but not furanocoumarins and hence won't cause the "grapefruit juice effect" on its own) or used say clarithromycin, also a potent inhibitor of P-glycoprotein like the flavonoids (as well as CYP3A4).

While the grapefruit juice effect can happen with statins that use the CYP3A4 enzyme route for clearance, Lescol is supposed to not be subject to it because it uses mainly CYP2C9. Well guess what? Bergamottin, one of the furanocoumarins, inhibits that one too, and another furanocoumarin knocks out the third supposed P450 metabolic pathway. A lot of these furanocoumarins are broken down by citric acid in juices and sodas so they're not so bad. Guess what's missing from sparkling water ... citric acid!

In short, at 80mg a day, by virtue of the sparkling water mangling my P450 metabolic pathways I was giving myself a chronic overdose that I occasionally spiked with a mega-overdose (perhaps by virtue of P-glycoprotein inhibition shutting Lescol's last escape route through the kidneys instead of the liver--my lower back really hurt during these attacks). It was "The Perfect Storm", and I'm pretty sure it damaged something (perhaps irreversibly) in the anterior pituitary or the gonads.

In short, this is less a report about a deficiency in Lescol than it is a plea to get some research done so that people understand that lemon and lime flavorings contain the half of the grapefruit juice effect that can accumulate silently in the liver, while waiting for something to come along and trigger the rest of the effect by inhibiting P-glycoprotein.

And if you're on Lescol, don't accidentally assemble the same dieteray components I did.

If you question any aspect of this post, I have access to the appropriate articles that back up my assertion.

[prof]

Flacorps--A very instructive story indeed; thank you for posting it, very sorry you have to live it.

As far as you know, do the flavonoids (e.g., in red wine, lycopene, etc.) also affect statin metabolism?

If you're out there, thanks for your thoughts. You've obviously "done the work."

prof

[flacorps]

I'm writing from memory here because I haven't gone back and reviewed any of the stuff I printed, but I maintain that the flavonoids in OJ inhibited p-glycoprotein and in so doing prevented the kidneys from clearing the Lescol through excretion in the urine--and if the liver didn't metabolize the stuff, the only remaining way out was through the kidneys, so the Lescol kept circulating and building up with each dose.

I am unsure whether the flavonoids in any other food or beverage (except, presumably oranges) would have the same effect, but keep in mind that if the P450 system is intact it shouldn't matter much to a drug that is also metabolized by it. IMHO, the renal system is an escape hatch used to clear Lescol when the necessary hepatic enzymes are absent due to being bound with and inhibited by the bergamottins.

A few keywords put in at scholar.google.com should give you some idea.

[june_nmexico]

flacorps -
Interesting information. I've been taking Lescol XL for a year and a half with no problems (that I'm aware of). I take no other meds. I do drink a very modest amount of a lemon-lime soda that I usually mix with pure blueberry juice for the extra vitamins. I'm not sure that citric acid is present in the soda, at least it's not listed on the ingredients. I'll be more aware of what I drink from now on.

I also have been taking the Lescol XL five times a week instead of daily. I'm very small at 108 lbs. and thought the 80 mg dose seemed high for my size, especially since I don't know how long the time released formulation stays in the system. I'm due for a check up and new blood work in a few weeks and will see what shows up.