Fruit is among the select foods that aren’t just tasty, they’re also healthy. In fact, fruit consumption, in moderation, is recommended to maintain a healthy diet. But there’s one fruit that can be harmful if you’re not careful: Grapefruit.
Before reaching for this tangy, tropical citrus fruit, you might want to exercise some caution, because behind the vitamin C, magnesium, potassium, and dietary fiber lies a more sinister effect: Grapefruit can interfere with several kinds of prescription and over-the-counter medications.
Researchers estimate that grapefruit consumption creates a nutrient-drug interaction with more than 85 different medications. The list is diverse and includes drugs for high blood pressure, cancer, anxiety, and Crohn disease, along with certain birth control, antihistamines, and statins. All of these interactions can be dangerous, and some even life-threatening.
How does grapefruit interact with medications?
When drugs are consumed orally, they are broken down in the gastrointestinal tract, where CYP3A4b—an enzyme that helps deactivate the drugs—allows traces of the drug’s active ingredients to be absorbed into the bloodstream and dispersed throughout the body. The problem with grapefruit is that it contains natural chemicals called furanocoumarins, which can block CYP3A4 enzyme activity, allowing too much of the drug to enter the blood.
One study published in the British Journal of Pharmacology investigated how grapefruit juice affected the body’s absorption of simvastatin. In the study, 10 healthy participants drank 200 ml of grapefruit juice or water for 3 days, followed by a single dose of the statin. For those who drank grapefruit juice, concentrations of the statin in the blood tripled.
In a review published in the European Journal of Clinical Nutrition, researchers from the Hebrew University of Jerusalem’s School of Pharmacy wrote that a single glass of grapefruit juice is enough to produce the maximum impact on medications and that, “grapefruit juice does not need to be taken simultaneously with the medication in order to produce the interaction.” This is consistent with clinical recommendations that patients do not consume grapefruit for 72 hours prior to taking a medication that may interact with it.
“The greatest hazards may come from consuming grapefruit repeatedly during the day, which can cause a further increase in blood levels of affected drugs,” said David Bailey, MD, a professor emeritus of clinical pharmacology, University of California, San Diego, in an interview with The New York Times.
The medications in question
Here are some examples of medications that don’t mix with grapefruit or grapefruit juice:
Statins: Atorvastatin, lovastatin, simvastatin
Side effect: Rhabdomyolysis
Side effects: Hypotension, peripheral edema
Psychiatric medications: Buspirone, lurasidone, diazepam
Side effects: Dizziness, sedation, torsade de pointes, orthostatic hypotension, syncope
Blood thinners: Apixaban, rivaroxaban, clopidogrel
Side effects: GI bleeding, loss of drug efficacy
Pain medications: Fentanyl, oxycodone, colchicine
Side effects: Respiratory depression, neutropenia, neuropathy
Side effects: Torsade de pointes
Side effects: Loss of drug efficacy
The effects of grapefruit-drug interaction
When grapefruit changes how medications are metabolized, there is an increased risk of toxicity and other adverse events like the ones in the list above. That list is not exhaustive, however. Side effects range from headaches to hypotension to torsade de pointes—an irregular heart rhythm that can cause sudden death—and even enhanced HIV efficacy (when taken with antivirals), rash, hypoglycemia, and myelotoxicity.
An expanded record of more than 85 medications that may interact with grapefruit, including each drug's side effects and level of severity when consumed, was released by the Canadian Medical Association for quick reference.
Here are a few more examples:
When consumed with grapefruit juice, dronedarone, a drug used to treat heart rhythm disorders, is linked to ventricular arrhythmia, cardiac arrest, and torsade de pointes.
Possible side effects in statins include headaches, gastrointestinal complaints, hepatic inflammation, and rhabdomyolysis—a condition that can lead to kidney failure.
When calcium channel blockers interact with grapefruit, similar effects follow, including flushing, peripheral edema, hypotension, and a blockage of blood flow to the heart muscle (myocardial infarction).
Who is at highest risk?
Adverse drug events cause 1.3 million hospital visits a year, according to the CDC and, therefore, should not be taken lightly. Individual susceptibilities for drug-grapefruit interactions vary widely, but those at highest risk include older populations or patients taking multiple medications concurrently. The 45-plus age bracket is most vulnerable because they are more likely to be consuming grapefruit and taking multiple medications. According to the US Department of Health, more than 50% of people over the age of 65 reported use of at least five medications.
When taking a drug with known grapefruit interactions, it is best to abstain from the fruit altogether. Because the furanocoumarins in grapefruit juice are the primary culprits in drug interaction, it is important to note that furanocoumarins are also found in other citrus fruits such as pomelos, Seville oranges, and limes.
As the understanding of grapefruit’s nutrient-drug interaction evolves, it is likely that the fruit will be evaluated in diets on a patient-by-patient basis. For example, the CYP3A4 enzyme responsible for breaking down medications varies by individual and does not cause a uniform interaction response.
Until more is known, when taking a medication that is suspected to cause interaction, it is best to err on the side of caution and stay away from furanocoumarin-rich fruits.