Why you Should not have Grapefruit

Grapefruit interacts with a wide variety of medications, potentially causing serious side effects.

Grapefruit Is One of the Weirdest Fruits on the Planet

In the clinical trial, grapefruit was screwing something up, and screwing it up good.

The effects of grapefruit on medication were surreptitiously discovered during a clinical trial for something else 

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,

Bailey first tested a new theory on himself. Felodipine doesn’t really have any ill effects at high dosages, 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 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.

In some of these cases, the grapefruit interaction is not a big deal, because they’re safe drugs and even having several times the normal dosage is not particularly dangerous. In other cases, it’s exceedingly dangerous. “There are a fair number of drugs that have the potential to produce very serious side effects,” says Bailey. “Kidney failure, a cardiac arrhythmia that’s life-threatening, gastrointestinal bleeding, respiratory depression.” A cardiac arrhythmia messes with how the heart pumps, and if it stops pumping, the mortality rate is about 20 percent. It’s hard to tell from the statistics, but it seems all but certain that people have died from eating grapefruit.

This is even more dangerous because grapefruit is a favorite of older Americans. The grapefruit’s flavor, that trademark bitterness, is so strong that it can cut through the decreased taste sensitivity of an aged palate, providing flavor for those who can’t taste a lot of other foods very well. And older Americans are also much more likely to take a variety of pills, some of which may interact with grapefruit.

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.

This is not a universally accepted conclusion. In Canada, where Bailey lives and works, warnings are universal. “Oh yeah, it’s right on the prescription bottles, in patient information,” he says. “Or they have a yellow sticker that says, ‘Avoid consumption of grapefruit when taking