Last month, the FDA issued an unusual warning. It wasn’t about counterfeit prescription drugs, an unsafe medicine, or a recalled product. Rather, the warning was for something that grows naturally in the groves of Florida: the sour, juicy grapefruit.

The FDA consumer update confirmed what users of drugs like statins have known for a long time—you shouldn’t eat grapefruit or drink grapefruit juice if you’re taking any of a number of medications. In the report, Shiew Mei Huang, the acting director of the FDA’s Office of Clinical Pharmacology, noted that for many drugs, “the juice increases the absorption of the drug into the bloodstream. When there is a higher concentration of a drug, you tend to have more adverse events.”

The strange “grapefruit effect” was first discovered entirely by accident. As part of a 1989 study, scientists at London’s Victoria Hospital were attempting to discover whether ethanol—the molecule responsible for the intoxicating effects of alcoholic drinks—could negatively interact with a drug called felodipine, developed to treat high blood pressure. They happened to use grapefruit juice to mask the taste of the alcohol, and discovered unexpectedly high levels of the drug in the blood. After further investigation, they realized it wasn’t the alcohol causing the surge—it was grapefruit.

The danger of mixing grapefruit and medication is most widely known for cholesterol-lowering statin drugs like Zocor and Lipitor, but recent studies have indicated grapefruit can interact with a longer list of medicines, including those prescribed to treat high blood pressure (like Nifediac and Afeditab), depression or anxiey (Zoloft and BuSpar) and erectile dysfunction (Viagara and Cialis). Even some over-the-counter antihistamines, like Allegra, may be affected. The negative interactions are greatest if the grapefruit is consumed less than four hours before the drugs are ingested, the FDA says.

What are the adverse effects? Increased concentration of the medications force the liver to work harder, increasing the risk of liver damage, potentially leading to muscle breakdown and kidney failure. But surprisingly, for a few drugs, including Allegra, grapefruit actually lowers the concentration of the medicine in the blood, reducing its effectiveness.

These opposite effects of grapefruit work via entirely different biological mechanisms. In the first case—when drug concentrations are dangerously increased—certain compounds in the fruit known as furanocoumarins inhibit the action of an enzyme, called CYP3A4, which occurs in the small intestine. Normally, CYP3A4 starts to break down the drugs, so they are somewhat metabolized by the time they hit the bloodstream. But with CYP3A4 inhibited, larger amounts pass into the blood.

The consequences of this can vary widely among individuals, who naturally start out with different levels of the enzyme. The particular drug’s potential for toxic effects also plays a role. For some drugs, habitually taking them with grapefruit can lead to liver and kidney damage over the long term. For others, a single episode may lead to toxic levels of the medication in the blood.

The mechanism by which grapefruit reduces the effectiveness of other drugs—antihistamines, such as Benadryl and Allegra, in particular—is less well understood. In this case, substances in the fruit interfere with transporter proteins on the surfaces of cells. Because of this interference, the medication does not enter cells as efficiently and is less effective.

The FDA notes that it has begun requiring certain medications to be labeled if they are not to be taken with grapefruit, and advises consumers to ask their doctor or pharmacist if they are unsure.

Still, grapefruit lovers can take heart: A team of citrus breeders at the University of Florida is at work developing grapefruit-pummelo hybrids that contain little or no furanocourmarins, which should be able to be eaten safely with any medication. The researchers predict they will be able to release commercial varieties of the new fruit within a few years.