Research Shows Grapefruit Cancer Promise & Potential Drug Overdose

Contributor- D. Chandler

How many remember the grapefruit diet that was tremendously popular many years ago? It was one of those mysterious urban diet legends. Some dieters might be surprised that the “Grapefruit”” Diet has been around since the 1930s. Though it emerged approximately eighty two years ago, the weight-loss strategy continues to attract legions of fans that usually receive and pass along the details by word of mouth.  Interested people will find it tricky to nail down a specific plan as there are a host of versions now circulating online, each with its own set of menus and food list; however it was supposed to be the magic enzymes contained in the grapefruit that triggered the weight loss.

Today, researchers have discovered a totally different benefit resulting with the use of grapefruit juice. Recent scientific reports demonstrate that grapefruit can actually improve the use of a promising cancer drug.

Specifically, researchers at University of Chicago Medicine found that a glass of grapefruit juice significantly helped the body’s acceptance of a potent drug called sirolimus that they could cut drug dosage by a third to reach the same desired effect as a full dose.

In a study published in August in Clinical Cancer Research, students at the University of Chicago show that eight ounces a day of grapefruit juice can slow the body’s metabolism of sirolimus, which has been approved for transplant patients and cancer.

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 juice, and drugs with a similar mechanism, can significantly increase blood levels of many drugs,” says study director Ezra Cohen, a cancer specialist at the University of Chicago Medicine, “but this has long been considered an overdose hazard. Instead, we wanted to see if grapefruit juice can be used in a controlled fashion to increase the availability and efficacy of sirolimus.”

Grapefruit juice’s 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.

“This is the first cancer study to harness this drug-food interaction,” the authors note.

No patients in the study had a complete response, but about 30 percent of patients in the three trials had stable disease, meaning a period when their cancers did not advance. One patient receiving grapefruit juice had a partial response—significant tumor shrinkage—that lasted for more than three years.

Although Ketoconazole produced a slightly stronger drug-retention effect, grapefruit juice has the advantage that it is non-toxic, with no risk of overdose. “Therefore,” the authors wrote, “we have at our disposal an agent that can markedly increase bioavailability (in this study by approximately 350 percent) and, critically in the current environment, decrease prescription drug spending on many agents metabolized by P450 enzymes.”

Sirolimus was the first of a series of drugs, known as mTOR inhibitors, that were developed to prevent rejection of transplanted organs but that also have anti-cancer effects. As the first of its class, it was also the first to come off patent, making it less costly.

“Further cost savings,” the authors suggest, could be realized “by combining the drug with agents that inhibit its metabolism.”

Because different people produce varied amounts of the enzymes that break down sirolimus, the effect of grapefruit juice can vary, but tests of enzyme levels may be able to predict how an individual patient will respond.

“The variation in potency of the grapefruit juice itself may be far greater than the variation in the enzymes that break down sirolimus,” Cohen says.

An early version of the study used canned grapefruit juice, generously donated by a Chicago-based grocery chain. But tests of the product found it lacked the active ingredients. So the researchers shifted to a frozen concentrate product supplied by the Florida Department of Citrus.

This study was supported by the National Institutes of Health—and not by a pharmaceutical company. Dose-finding studies are “not necessarily profitable” for drug makers, the authors note, especially if the study results in lower recommended doses after the drug has been approved and priced.

While the use of grapefruit in these studies show great promise, it is equally important to be aware the potentially dangerous interactions grapefruit has shown when used in conjunction with other pharmaceutical drugs. Without fully elaborating on the subject, you can imagine that if grapefruit is preventing absorption of certain enzymes, it is therefore able to effectively reduce the proper functioning of one’s metabolism. In other words, it interferes with the enzymes that break down various medications in your digestive system. As a result, more medication stays in your body, increasing the potency of your medication to potentially dangerous levels causing serious side effects and subsequent illness. Thus, higher drug levels could be understood as the same thing as drug overdose.

Such a far cry from the days of taking grapefruit to loss weight.

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