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There are always claims over fruit or fruit drinks and their health benefits. A daily glass of grapefruit juice lets patients derive the same benefits from an anti-cancer drug as they would get from more than three times as much of the drug by itself, according to a new clinical trial. The combination could help patients avoid side effects associated with high doses of the drug and reduce the cost of the medication. Researchers at the University of Chicago Medicine study the effects that foods can have on the uptake and elimination of drugs used for cancer treatment. In a study published in August in Clinical Cancer Research, they show that eight ounces a day of grapefruit juice can slow the bodys metabolism of a drug called sirolimus, which has been approved for transplant patients but may also help many people with cancer.
Grapefruit is an excellent source of many nutrients and phytochemicals that contribute to a healthy diet. Grapefruit is a good source of vitamin C, contains the fiber pectin, and the pink and red hues contain the beneficial antioxidant lycopene. Studies have shown grapefruit helps lower cholesterol, and there is evidence that the seeds have antioxidant properties.
Patients who drank eight ounces a day of grapefruit juice increased their sirolimus levels by 350 percent. A drug called ketoconazole that also slows drug metabolism increased sirolimus levels by 500 percent.
Grapefruit juices pharmaceutical prowess stems from its ability to inhibit enzymes in the intestine that break down sirolimus and several other drugs. The effect begins within a few hours of what the researchers refer to as grapefruit juice administration. It wears off gradually over a few days.
Cohen and colleagues organized three simultaneous phase-1 trials of sirolimus. Patients received only sirolimus, sirolimus plus ketoconazole, or sirolimus plus grapefruit juice. They enrolled 138 patients with incurable cancer and no known effective therapy.
The first patients started with very low sirolimus doses, but the amounts increased as the study went on, to see how much of the drug was required in each setting to reach targeted levels, so that patients got the greatest anti-cancer effect with the least side effects.
The optimal cancer-fighting dose for those taking sirolimus was about 90 mg per week. At doses above 45 mg, however, the drug caused serious gastrointestinal problems, such as nausea and diarrhea, so patients taking sirolimus alone switched to 45 mg twice a week.
The optimal doses for the other two groups were much lower. Patients taking sirolimus plus ketoconazole needed only 16 mg per week to maintain the same levels of drug in the blood. Those taking sirolimus plus grapefruit juice needed between 25 and 35 mg of sirolimus per week.
Grapefruit can have a number of interactions with drugs, often increasing the effective potency of other compounds. Grapefruit contains a number of polyphenolic compounds, including the flavanone naringin, alongside the two furanocoumarins bergamottin and dihydroxybergamottin. These inhibit the drug-metabolizing enzyme isoform CYP3A4 predominately in the small intestine, but at higher doses also inhibit hepatic CYP3A4. It is via inhibition of this enzyme that grapefruit increases the effects of a variety of drugs by increasing their bioavailability.
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Grapefruit Juice and the Fight Against Cancer
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