Benefits of Grapefruit

Scientific Name(S): Citrus Paradisi Macfad., Rutaceae

Common Name(S): Grapefruit

Grapefruit, named for the way the fruit grows in clusters, like grapes, is only 300 years old. It is believe to have been produced in Jamaica by the accidental pollination of a fruit called pomelo and an orange.

Botany: The grapefruit is a large, dimpled, round citrus fruit, measuring 3 to 6 inches in diameter. It descends from a cross between a pomelo (pummelo) or shaddock (C. Grandis), a large Malaysian citrus, and a sweet orange. Some believe the grapefruit could also have arisen as a mutation of another type of citrus tree. The fruit grows in clusters similar to grapes, and this may be the reason why the "grapefruit" was so named. The two main varieties of grapefruit include the Duncan (many seeds and good flavor) and the Marsh (seedless with less flavor). The pink varieties followed; the Foster (1907; seeded) and the Thompson (1913; seedless). The Ruby red-pulped grapefruit was developed in the late twenties in McAllen, Texas. Grapefruits can be considered a "New World" product, a species only a few hundred years old. The juice of the fruit, including concentrate, accounts for approximately 42% of all US processed grapefruit products.

History: In 1310 B.C., Greek historian Theophrastus wrote of how Citron was thought to be an antidote to poison and how it could also "sweeten the breath." Later, Pliny, a Roman naturalist, used the word "citrus" for the first time and labeled the fruit as a medicine. The grapefruit, then called "small shaddock," was first mentioned by Griffith Hughes in 1750, as the "forbidden fruit" of Barbados. The name "grapefruit" was said to have been first used in Jamaica in 1814. In 1823, the grapefruit was introduced in Florida by a French count, Odette Phillippe, but did not begin to gain popularity until the end of the nineteenth century. Worldwide production of grapefruit today averages 4.3 million metric tons.

In the 1930's, Hollywood's "Grapefruit Diet" came into vogue, including calorie intake to approximately 800 per day, and including grapefruit consumption at each meal. Weight was lost from this diet, but any diet based primarily on one food is too restrictive to be healthy because too many other important nutrients may be missing.

Uses and benefits of Grapefruit

Grapefruit juice is used as a nutritional supplement for potassium loss. Grapefruit pectin can help reduce cholesterol and promote regression of atherosclerosis. Other effects include induction of red cell aggregation by constituent naringin, reduction of hemocrits and possible anti-cancer effects.

Side Effects of Grapefruit

Grapefruit juice can create adverse effects by altering drugs metabolized by the CYP3A4 enzyme system (eg, some nonsedating antihistamines, benzodiazepines, selected calcium channel blockers, estrogens, quinidine, and cyclosporine). A case report exists about grapefruit juice-induced hypotension.

Toxicology: Grapefruit juice has been reported to interact with certain nonsedating antihistamines, benzodiazepines, the dihydropyridine class of calcium channel blockers, cyclosporine, estrogens and quinidine. The mechanism of the interaction probably involves inhibition of gut wall enzymes, specifically the CYP3A4 isozyme.

Antihistamines: In humans, grapefruit ingestion may increase the bioavailability of tertenadine (no longer available in US) and probably astemizole. Altered cardiac repolarization (in poor metabolizers of tertenadine) and increases in the QT interval have been reported when tertenadine was taken with grapefruit juice compared with water. More than one metabolic pathway appears to be inhibited. There is considerable patient variability in the pharmacokinetic effect of the interaction. The clinical importance of this interaction has not been determined.

Benzodiazepines: In healthy human subjects, taking midazolam or triazolam with grapefruit juice has been reported to increase plasma concentrations and the area under the plasma concentration-time curve (AUC) of these benzodiazepines. However, the clinical effects of taking midazolam or triazolam with grapefruit juice are likely to be minor.

Calcium channel blockers: In humans, the bioavailability of the dihydropyridine calcium channel blockers, including amlodipine, felodipine, nifedipine, nimodipine and nisoldipine, may be increased by concurrent ingestion of grapefruit juice. While the increases in peak plasma concentrations for amlodipine were slight (15%), peak plasma concentrations of felodipine increased more than 300%. nifedipine increased by nearly 35% and the hypotensive effects were enhanced, nimodipine levels increased by 24%, and nisoldipine plasma levels increased by 400%. The bioavailability of diltiazem, a different class of calcium channel blocker (eg, a benzothiazepine) was not affected by grapefruit juice ingestion.

Cyclosporine: Human studies have demonstrated that grapefruit juice alters the pharmacokinetics of cyclo­sporine. Taking cyclosporine with grapefruit juice may result in an increase in plasma concentrations and AUC of cyclosporine. In addition, concentrations of a cyclosporine metabolite may be increased. An increase in neurologic side effects, including tremors, was reported when cyclosporine was taken with grapefruit juice. Some patients are instructed by their physicians to take cyclosporine with grapefruit juice in order to administer a lower dose of cyclosporine and reduce cost to the patient. Thus, grapefruit juice may provide an inexpensive, nontoxic alternative to drugs given to reduce the cyclosporine dose. In this situation, patients should avoid fluctuations in their grapefruit juice ingestion.

Estrogens: In 13 healthy female volunteers, grapefruit juice increased plasma concentration of ethinyl estradiol by 37% and the AUC by 28% compared with ingestion of the estrogen with herbal tea.

Quinidine: When studied in 12 healthy male volunteers, administration of quinidine with grapefruit juice, compared with water, delayed the absorption of quinidine and inhibited the metabolism of quinidine to its major metabolite (3-hydroxyquinidine). The effects of quinidine on the QTc interval were delayed and reduced by ingestion with grapefruit juice.

Summary: The grapefruit is a popular breakfast fruit in the US. Approximately one-half of ttle world's grapefruit crop is made into juice. Grapefruit juice has been found to increase bioavailability of certain drugs by inhibition of the CYP3A4 gut wall enzyme system. Drugs affected by this system include some calcium channel blockers, tertenadine, cyclosporine and others. These drug-food interactions are important and warrant the counseling of patients by pharmacists and other healthcare workers.