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New Concerns About Citrus Fruits And Medicines

Amanda J. Trangsrud
Doctor of Pharmacy Candidate 2001
The University of Arizona, Tucson, Arizona

Doctors are now paying special attention to certain medicines that seem to interact with grapefruit juice. A recent article in the Washington Post warned that "drinking grapefruit juice can make the body absorb extra amounts of some medications." Now, researchers are finding that a certain type of orange, called the Seville orange, may interact the same way with some medicines.1, 2

The Seville orange, a relative of the grapefruit, is also known as the sour or bitter orange. It is about 3 inches round and has a rough, bright red-orange bitter peel.3 The sour Seville orange skin and juice are usually used in the preparation of foods, such as orange marmalade, and "bitter orange oil" is used to flavor some candies, liqueurs, and chewing gum.3 Usually the Seville orange is too sour to eat by itself. However, in Mexico, sour oranges are often cut in half, salted, and coated with a paste of hot chili peppers. In Spain, the juice from the Seville orange is used as a flavoring when cooking fish. In Yucatan, it is used like vinegar on foods, and in Egypt, the juice has been fermented to make wine.3 Researchers are trying to determine if there is enough sour orange in these foods to cause harmful interactions with some medicines.

Are all oranges a threat? No. Studies have found that the skin and juice of sweet oranges, which are commonly used for commercial orange juices, do not contain the same compounds as grapefruit and sour Seville oranges. This appears to be the reason why orange juice as well as the sweet oranges most people buy in the grocery store seem to be safe to consume and do not have the potential to interact with medicines.4

What about other citrus fruits, such as limes and lemons? The sour Seville orange and the grapefruit have been found to be relatives to the round, sweet green citrus fruit called the pummelo.2, 5 Researchers know that the skin and juice from the pummelo contain several of the same furanocoumarins that are found in the peels and juice of the grapefruit and Seville orange. It is highly possible that lemons and limes could be related to the pummelo and could cause the same type of food-drug interactions.2 Currently, more research is being conducted to determine if any of the other sour citrus fruits can interact with medicines.

What is so special about grapefruits and the Seville oranges to make it possible for them to interact with medicines? The skin of the Seville orange and grapefruit contain compounds called furanocoumarins. When these fruits are squeezed under high pressures to make juice, the furanocoumarins are forced from the peel into the juice. These furanocoumarins can then prevent natural enzymes in your body called cytochrome P450 (or CYP450) from working correctly.2 The CYP450 enzymes are needed to break down certain medicines so that your body can get rid of them. When these enzymes are not able to work properly, certain drugs could build up to dangerous levels within your body and can cause many dangerous side effects.

Be an informed patient

It is always wise to ask your doctor or pharmacist if your medicines have the potential to interact with grapefruit juice. If your medicines can interact with grapefruit juice, then there is concern that they have the potential to interact with foods made with the Seville orange. Pharmacists have computerized drug interaction programs and can find out whether it is safe for you to include grapefruit juice, or sour orange marmalade in your diet with your medicines your doctor has prescribed.


1. Stoltz C, Otto MA. Washington Post health section: More juice. Washington Post newspaper Mar 27, 2001.

2. Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther 2001 Jan;69(1):14-23.

3. Morton JF. Sour orange, in: Fruits of warm climates. Miami, FL:1987, pg 130-33.

4. Guo LQ, Fukuda K, Ohta T, Yamazoe Y. Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity. Drug Metab Dispos 2000 Jul;28(7):766-71.

5. Morton JF. Pummelo, in: Fruits of warm climates. Miami, FL: 1987 pg 147-51.

© 2001 Consumer Health Information Corporation. All rights reserved.