Grapefruit and its close relatives such as Seville oranges (for marmalade), tangelos, and pomegranates contain chemicals called furanocoumarins. These disrupt the function of enzymes that break down medications in your liver and small intestine, increasing their blood levels.

These medications include cholesterol, antidepressants, sedatives, heart medications, and the popular erectile dysfunction medication Viagra Jelly. This drug-grapefruit juice interaction is well known to pharmaceutical researchers but is underappreciated by general physicians.

Phytonutrients

Grapefruit and grapefruit juice contain health-beneficial flavonoids such as limonin, naringenin, narirutin, and 5-methoxy-7-geroxycoumarin (bergamottin). Juice processed by blending and hand squeezing generally provides higher levels of these phytochemicals than juice from whole grapefruit. These compounds are known to reduce blood pressure and inhibit nitrite-induced methemoglobin formation. They also have anti-viral and anti-bacterial activity.

One study found that drinking 250 ml (1 cup) of grapefruit juice before taking sildenafil (Viagra) increased the drug’s absorption by 23%. This occurred because grapefruit juice inhibits the intestinal cytochrome P-450 (CYP) enzyme system. This system is involved in the metabolism of many drugs, including erectile dysfunction medications. The inhibition of CYP3A4 by grapefruit juice can lead to increased blood levels of the medication, which may cause side effects such as flushing and headaches.

Another potential issue is the fact that grapefruit juice can interact with several common medications, causing them to be less effective or triggering side effects. Medications that can be affected include narcotic pain relievers, calcium channel blockers, statins, immunosuppressants, and Entocort, which is used to treat Crohn’s disease. Those who use these medications should avoid grapefruit juice or consume it only in small amounts.

Contraindications

A few classes of drugs are known to interact with grapefruit or its juice, particularly those that are broken down (metabolized) by a vital enzyme in the small intestine called CYP3A4. Grapefruit juice contains natural chemicals called furanocoumarins that inhibit CYP3A4, meaning less of a drug enters the bloodstream and stays in the body. This can cause dangerous side effects, especially in the heart, respiratory and gastrointestinal tracts.

This interaction also affects some anti-cholesterol statin drugs, such as ezetimibe and sildenafil, and certain antibiotics like itraconazole and erythromycin. Generally, the interaction is not very strong and can vary widely from one person to another, but there have been cases of serious toxicity.

Pomegranate juice also inhibits CYP3A4 to some degree, although to a much lesser extent than grapefruit juice. Consequently, pomegranate juice should not be consumed with erectile dysfunction medication such as sildenafil, or with any other medication that is known to interact with this enzyme.

Heil’s father adores grapefruit juice and is currently taking a medication that can interact with it. He can still enjoy it, though, by having a splash of the juice in the morning and then waiting a few hours before swallowing his pills at bedtime. This helps reduce the risk that a smidge of grapefruit or its juice will affect his medicine in the wrong way.

Interactions

Grapefruit juice is rich in vitamin C, potassium, and dietary fiber. The acidity of the fruit also contributes to a healthy pH in your digestive tract, which supports good gut health. Despite its many benefits, it is important to talk with your doctor before drinking grapefruit juice while on medication. The juice can interfere with the effectiveness of certain drugs and increase the risk of adverse side effects.

Some medications are metabolized by a key enzyme in the small intestine, called CYP3A4. If grapefruit juice is consumed with these drugs, more of the medication enters the bloodstream and remains there longer, which increases your drug exposure. In one study, ingesting 250 ml (approximately 1 cup) of grapefruit juice an hour before and with sildenafil increased the amount of the drug absorbed by 23%.

Some common drugs that interact with grapefruit include cholesterol-lowering statins, antibiotics, and calcium channel blockers used to treat high blood pressure. Grapefruit juice can also decrease the absorption of antacids and some antidepressants. Other medications, such as probiotics and antiviral agents, may also interact with grapefruit. The juice can inhibit intestinal CYP3A4, although the degree of inhibition differs between different types of grapefruit and between individual fruits. In addition to grapefruit, other sour citrus fruits such as Seville oranges and tangelos contain flavonoids similar to those of grapefruit that can interfere with some medications. Pomegranate juice has also been shown to inhibit CYP3A4.

Side Effects

The drug interaction with grapefruit juice is caused by compounds in the fruit called furanocoumarins, such as bergamottin. These are thought to block the enzymes in the intestines that normally break down many drugs, including cholesterol medication, anti-anxiety medications, and some corticosteroids, such as Entocort EC and Uceris tablet (both budesonide). One glass of grapefruit juice can block this enzyme for up to 24 hours. This increases the level of drugs in the bloodstream, which can cause side effects such as headache, flushing, and low blood pressure.

The most well-known drug-grapefruit juice interaction is with sildenafil, sold as Viagra. Sildenafil is a phosphodiesterase type 5 inhibitor that works by blocking the actions of cGMP, which causes erections. Because the metabolizing enzymes of the liver are inhibited by grapefruit, this may cause the drug to work faster and more effectively, but it can also increase the risk of side effects such as headache, flushing, and high blood pressure.

Other drugs interact with grapefruit juice in similar ways, so it is important to check the drug facts label on any prescription medications you take to see if it is listed as a contraindication with the fruit or its juice. Some over-the-counter medications, such as fexofenadine (Allegra), are affected by grapefruit as well. Sour oranges, such as Seville oranges used for marmalade, and pomelos and tangelos, a cross between tangerines and grapefruit, can also interfere with certain drugs. Read More…