Grapefruit Is One of the Weirdest Fruits on the Planet {Drug interactions ! } (Atlas Obscura)

by Dan Nosowitz October 6, 2020

In 1989, David Bailey, a researcher in the field of clinical pharmacology (the study of how drugs affect humans), accidentally stumbled on perhaps the biggest discovery of his career, in his lab in London, Ontario. Follow-up testing confirmed his findings, and today there is not really any doubt that he was correct. “The hard part about it was that most people didn’t believe our data, because it was so unexpected,” he says. “A food had never been shown to produce a drug interaction like this, as large as this, ever.”
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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.
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Despite this, the Food and Drug Administration does not place warnings on many of the drugs known to have adverse interactions with grapefruit. Lipitor and Xanax have warnings about this in the official FDA recommendations, which you can find online and are generally provided with every prescription. But Zoloft, Viagra, Adderall, and others do not. “Currently, there is not enough clinical evidence to require Zoloft, Viagra, or Adderall to have a grapefruit juice interaction listed on the drug label,” wrote an FDA representative in an email.
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more: https://www.atlasobscura.com/articles/grapefruit-history-and-drug-interactions