That food was grapefruit, a seemingly ordinary fruit that is, in truth, anything but ordinary. Right from the moment of its discovery, the grapefruit has been a true oddball. Its journey started in a place where it didn’t belong, and ended up in a lab in a place where it doesn’t grow. Hell, even the name doesn’t make any sense. (...)
This is especially ironic, because the grapefruit, as Bailey would show, is actually one of the most destructive foes of modern medicine in the entire food world.
Bailey works with the Canadian government, among others, testing various medications in different circumstances to see how humans react to them. In 1989, he was working on a blood pressure drug called felodipine, trying to figure out if alcohol affected response to the drug. The obvious way to test that sort of thing is to have a control group and experimental group—one that takes the drug with alcohol and one that takes it with water or nothing at all. But good clinical science calls for the study to be double-blind—that is, that both the tester and subjects don’t know which group they belong to. But how do you disguise the taste of alcohol so thoroughly that subjects don’t know they’re drinking it?
“It was really my wife Barbara and I, one Saturday night, we decided to try everything in the refrigerator,” says Bailey. They mixed pharmaceutical-grade booze with all kinds of juices, but nothing was really working; the alcohol always came through. “Finally at the very end, she said, ‘You know, we’ve got a can of grapefruit juice. Why don’t you try that?’ And by golly, you couldn’t tell!” says Bailey. So he decided to give his experimental subjects a cocktail of alcohol and grapefruit juice (a greyhound, when made with vodka), and his control group a glass of unadulterated grapefruit juice.
The blinding worked, but the results of the study were … strange. There was a slight difference in blood pressure between the groups, which isn’t that unusual, but then Bailey looked at the amount of the drug in the subjects’ bloodstreams. “The levels were about four times higher than I would have expected for the doses they were taking,” he says. This was true of both the control and experimental groups. Bailey checked every possible thing that could have gone wrong—his figures, whether the pharmacist gave him the wrong dosage—but nothing was off. Except the grapefruit juice.
Bailey first tested a new theory on himself. Felodipine doesn’t really have any ill effects at high dosage, so he figured it’d be safe, and he was curious. “I remember the research nurse who was helping me, she thought this was the dumbest idea she’d ever heard,” he recalls. But after taking his grapefruit-and-felodipine cocktail, his bloodstream showed that he had a whopping five times as much felodipine in his system than he should have had. More testing confirmed it. Grapefruit was screwing something up, and screwing it up good.
Eventually, with Bailey leading the effort, the mechanism became clear. The human body has mechanisms to break down stuff that ends up in the stomach. The one involved here is cytochrome P450, a group of enzymes that are tremendously important for converting various substances to inactive forms. Drugmakers factor this into their dosage formulation as they try to figure out what’s called the bioavailability of a drug, which is how much of a medication gets to your bloodstream after running the gauntlet of enzymes in your stomach. For most drugs, it is surprisingly little—sometimes as little as 10 percent.
Grapefruit has a high volume of compounds called furanocoumarins, which are designed to protect the fruit from fungal infections. When you ingest grapefruit, those furanocoumarins permanently take your cytochrome P450 enzymes offline. There’s no coming back. Grapefruit is powerful, and those cytochromes are donezo. So the body, when it encounters grapefruit, basically sighs, throws up its hands, and starts producing entirely new sets of cytochrome P450s. This can take over 12 hours.
This rather suddenly takes away one of the body’s main defense mechanisms. If you have a drug with 10 percent bioavailability, for example, the drugmakers, assuming you have intact cytochrome P450s, will prescribe you 10 times the amount of the drug you actually need, because so little will actually make it to your bloodstream. But in the presence of grapefruit, without those cytochrome P450s, you’re not getting 10 percent of that drug. You’re getting 100 percent. You’re overdosing.
And it does not take an excessive amount of grapefruit juice to have this effect: Less than a single cup can be enough, and the effect doesn’t seem to change as long as you hit that minimum.
None of this is a mystery, at this point, and it’s shockingly common. Here’s a brief and incomplete list of some of the medications that research indicates get screwed up by grapefruit:
- Benzodiazepines (Xanax, Klonopin, and Valium)
- Amphetamines (Adderall and Ritalin)
- Anti-anxiety SSRIs (Zoloft and Paxil)
- Cholesterol-lowering statins (Lipitor and Crestor)
- Erectile-dysfunction drugs (Cialis and Viagra)
- Various over-the-counter meds (Tylenol, Allegra, and Prilosec)
- And about a hundred others.
by Dan Nosowitz, Atlas Obscura | Read more:
Image: Stella Murphy
[ed. We used cytochrome P450 during the Exxon Valdez oil spill as a bio-marker for exposure. Interestingly, the by-products of it's metabolizing function can be more toxic than the original pollutant.]
