A new study published in the August issue of Clinical Cancer Research shows that cancer patients who take one glass of grapefruit juice a day can get the same benefits as (taking) three times the amount of anti-cancer drugs. It also helps to avoid side effects caused by applying high doses of drugs, while also reducing treatment costs. Scientists at the University of Chicago Medical Center studied the potential effects of food on the absorption and elimination of anticancer drugs and found that drinking 8 ounces of grapefruit juice per day slowed down the body’s metabolism of rapamycin. Rapamycin is approved for use in transplant patients, while it may be beneficial for many cancer treatments. Wang Jun t, Intensive Care Unit, Nanping No. 1 Hospital Researchers found that patients who consumed 8 ounces of grapefruit juice a day had 350 percent elevated levels of rapamycin in their bodies; after taking ketoconazole, a drug that slows down the metabolism of rapamycin, rapamycin levels could be as much as 500 percent elevated. Ezra Cohen, M.D., cancer specialist and study director at the University of Chicago Medical Center, said, “Grapefruit juice and drugs with similar mechanisms of action can significantly increase blood levels of many drugs, but this has long been recognized as a drug overdose risk. In contrast, we wanted to see if grapefruit juice could improve rapamycin bioavailability and effectiveness when taken in a controlled way. There are enzymes in the gut that break down rapamycin as well as other drugs, and grapefruit juice inhibits these enzymes. The inhibitory effect can be seen within hours of giving grapefruit juice and gradually disappears over the next few days.Cohen and his team conducted three concurrent phase 1 trials of rapamycin, which included 138 patients with incurable cancer or lack of effective treatment who received rapamycin, rapamycin + ketoconazole, or rapamycin + grapefruit juice. In order to maximize anticancer effects while minimizing side effects, the team gave the initial patients a very low dose of rapamycin and gradually increased the dose of rapamycin as the study progressed, thereby evaluating the amount of medication needed to achieve a given level of the drug under each treatment condition. They noted that the optimal anticancer dose of rapamycin alone is approximately 90 mg/wk, although they observed that the 45 mg dose triggered severe gastrointestinal symptoms (e.g., diarrhea and nausea) and adjusted the dose to 45 mg twice weekly in this group. In comparison, the dose required to maintain the same blood levels in the rapamycin + ketoconazole group was 16 mg/wk. 25-35 mg/wk in the rapamycin + grapefruit juice group. both drug doses were quite low. The team commented, “This is the first cancer study of tandem food-drug interactions.” Although no 1 study subject showed a complete therapeutic response, about 30% of the cancer patients had stable disease-meaning that the disease did not progress, and 1 subject in the grapefruit juice group had a partial response, which manifested itself as a substantial reduction in tumor size, and the effect was sustained for more than 3 years. The advantage of grapefruit juice over ketoconazole’s slight increase in drug retention in the body is that it is non-toxic and has no risk of overdose. The researchers declared, “We therefore have at hand a substance capable of significantly increasing the bioavailability of the drug (by approximately 350% in the present study). Critically, under current conditions, it could reduce the cost of prescription drugs metabolized by the P450 enzyme. Rapamycin is the first mTOR inhibitor for the prevention of organ transplant rejection and also has anticancer properties. As the first drug of its kind, rapamycin is also the first to have its patent expire, which could make the drug more economical. “Further cost savings are achievable by combining rapamycin with its metabolic inhibitors,” commented the research team. The amount of rapamycin catabolic enzyme produced in vivo varies from person to person, which means that the effect of grapefruit juice also varies from patient to patient. However, individual patient response can be predicted by testing enzyme levels.” Cohen said, “Individual differences in the effect of grapefruit juice may be greater than individual differences in rapamycin-degrading enzymes.” At the beginning of the study, the research team used canned grapefruit juice, but studies showed that its active ingredient was insufficient. Therefore, the research team then switched to a frozen concentrated product. The research team emphasized that their research grant came from the National Institutes of Health and not from any pharmaceutical company. The team said that dose-finding studies are “not necessarily profitable” for pharmaceutical companies, especially if the drug is approved and the price is fixed, and even less so if the study results suggest that the dose of the drug recommended by the developer should be lowered.