Grapefruit juice shown to boost drug's anti-cancer properties

Sirolimus, a drug typically used by transplant patients to prevent rejection, has been found in previous studies to have anti-cancer properties as well.  While it’s not currently used to treat cancer, there may be a way to give those properties a boost, and make the drug a feasible option for cancer patients – by adding some grapefruit juice.

A new study from the University of Chicago Medicine revealed patients taking sirolimus receive more of its anti-cancer benefits if they drink a glass of grapefruit juice every day along with the drug.  The drug-juice combination was so effective that patients who drank grapefruit juice obtained three times as many benefits than those who took the drug alone.

This is also interesting because of grapefruits’ dangerous interaction with some prescription medications, namely ones that treat high blood pressure and heart conditions.

Researchers had discovered sirolimus’ potential anti-cancer properties from previous research.

“It’s a drug that was discovered in the 70s,” Dr. Ezra Cohen, a cancer specialist at the University of Chicago Medicine and the study’s lead author, told  “It was clearly shown to have anti-cancer effects and anti-neoplastic effects, but it hadn’t been developed for cancer extensively because the patent ran out.  There wasn’t a lot of commercial interest to develop sirolimus, so it sort of was pushed aside for a while.  Eventually, sirolimus was indeed approved, but for people who got organ transplants to prevent rejection.”

Cohen and his team study how food consumption can either help or hurt the effectiveness of drugs used for cancer therapy.  They got the idea to test grapefruit juice from another previous study around two decades ago.

“Investigators were doing a study on alcohol’s effect on a certain heart drug,” Cohen said. “And to mask the taste of alcohol, they used grapefruit juice.  What they ended up finding out was that the grapefruit juice increased the blood levels of the drug.”

Putting the two studies together, the scientists enrolled 138 patients with incurable cancer, splitting them into three groups – those who received only sirolimus, sirolimus and ketoconazole (a compound that slows drug metabolism), and sirolimus and grapefruit juice.  They hoped these different combinations would boost the drug’s absorptive power.

“One of the issues with sirolimus is that it has very poor bioavailability, meaning only 14 percent gets absorbed when you take the pill,” Cohen said.  “That’s why the company that manufacturers sirolimus actually created an intravenous analog of the drug, because of the availability issue.  So we thought, ‘Why don’t we try to modify the metabolism of sirolimus by using a ketoconazole or using grapefruit juice.  If we can reduce even some of the side effects associated with the drug and develop a combination, that could be effective.”

At first, the participants were given very low doses of sirolimus, but the amounts were slowly increased as time went on in order to determine how much of the drug was need to reach goal levels and maximize its efficacy.

Ultimately, the results showed drinking eight ounces of grapefruit juice per day helped increase sirolimus levels by 350 percent.  The effect was even greater for those who took ketoconazole, with sirolimus levels increasing by 500 percent.  Overall, the optimal dose for those taking sirolimus on its own was 90 mg, while those drinking grapefruit juice only needed 25 to 35 mg of sirolimus, and those on the ketoconazole combination needed only 16 mg.

According to Cohen, the decrease in dosage helped people to avoid the drug’s unpleasant side effects, such as diarrhea and other gastrointestinal issues.  These problems seemed to surface, according to the researchers, after patients took dosages over 45 mg.

While ketoconazole was more effective, the researchers recommend the more naturally derived grapefruit juice, as it was a much less-toxic option.  Ultimately, the juice works by slowing the cancer drug’s metabolism.

“The simple way to think about it is that grapefruit juice inhibits the production of the enzymes by the cells that line our gut,” Cohen said. There’s no direct effect on the drug, instead it inhibits the enzymes that metabolize the drug.”

Cohen hopes this study encourages further research on the effects of herbal and natural compounds in combination with cancer therapy, as well as a closer look at what sirolimus can do.

“We’re realizing with these drugs, they do work very well in certain combinations, so there may be more and more approval for this class of drug,” Cohen said.