For more than a decade, doctors have known that some compound in grapefruit juice interacts with a small number of drugs to triple the amount of that drug absorbed into the bloodstream. While the compound has remained a mystery, doctors simply tell their patients to avoid grapefruit juice while on the medication.
In a study published in the May issue of the American Journal of Clinical Nutrition, however, Paul Watkins, MD, and his colleagues, finally tracked down furanocoumarins as the active ingredient in grapefruit juice causing this unusual reaction. Watkins, the Dr. Verne S. Caviness distinguished professor of medicine at the University of North Carolina, explained that furanocoumarins block an enzyme called CYP3A4 in the wall of the intestine.
“This enzyme normally chews up certain drugs when they are absorbed,” he says. “When you inhibit the enzyme, however, it doesn’t chew up the drug, which means that more of the drug gets absorbed into the bloodstream.
“Research shows it can boost levels of the drug three times. That’s like taking three pills instead of one. This is an average. Some people would not be boosted as much. Others, however, would be boosted more.”
As startling as this sounds, Watkins points out that of the hundreds of different medications that people are treated with, there are only about 10 with any kind of warning about grapefruit juice in the labeling.
“Fortunately, these drugs are safe enough that boosting absorption for most people will be of no consequence. It appears, however, that a rare patient may have adverse symptoms — for example, muscle tenderness with certain cholesterol medications.
“To my knowledge there have been no confirmed reports of deaths occurring as a result of patients taking their medications with grapefruit juice.”
Classes of drugs that interact with grapefruit juice.
Watkins, who is also director of UNC’s General Clinical Research Center and who led the research team, says that grapefruit juice interacts with four major classes of drugs. One class includes some of the medications used to control anxiety.
Another class comprises a minority of drugs used to lower blood pressure, called calcium channel blockers.
Yet another class are those cholesterol-lowering drugs called statins — particularly Nevacor, Zocor and, to a lesser extent, Lipitor.
Finally, grapefruit juice interacts with immunosuppressants — predominantly Cyclosporine A — which is used mainly to prevent transplanted organs from being rejected.
“Grapefruit juice clearly boosts the absorption of these drugs,” says Watkins, again commenting on the general safety of the drug, so the boosting effect for most individuals is not an issue. The only exception to this blanket cloak of safety might be for individuals taking Cyclosporine A, he adds. “Kidney transplant patients, for example, will be taking this drug.”
It was originally assumed that the ingredients responsible for drug interactions were the flavonoids that give grapefruit juice its bitter taste, Watkins says.
“What we did with our study with the Florida Department of Citrus, however, was to remove the furanocoumarins, leaving in the major flavonoids to see if that got rid of the problem — and it did.
“This is the best evidence, to date, that the active ingredient causing drug interactions is not flavonoids, but these compounds called furanocoumarins that appear to be tasteless and are present in very low amounts in grapefruit juice.”
The story doesn’t end here, because each discovery opens doors to other possibilities, one being that it is now technically possible to market furanocoumarin-free grapefruit juice to patients who would otherwise have to avoid grapefruit.
Much more important, it may be possible to add furanocoumarins to the formulations of certain drugs that tend to be poorly or erratically absorbed to improve their oral delivery.
Watkins explained that if you are a drug company and you develop a drug and only 10 percent of it gets into the body, then you do not have a very good drug, so you usually stop developing it.
“The market for adding furanocoumarins to these pills would be primarily for drugs that had been abandoned in development, or given only by intramuscular injection or intravenously, or promising drugs that might be developed in the future.
“Since furanocoumarins are in grapefruit, it seems reasonable to assume that they are safe, so this should be a safe way to improve oral delivery of drugs.”
Safety: The bottom line
“I personally feel that if you have been taking medicine with grapefruit juice every morning, and the drug is working fine, and your physician is happy, then there is no reason to change.”
According to Watkins, there are many people who enjoy grapefruit juice. And there are others whose economic well being depends upon making it. With the hurricanes the south has experienced over the past couple of years, in particular, the citrus industry is really in tough shape.
“The reality is that a rare patient would get into trouble because of the interaction between a drug and grapefruit juice. This is not a public health issue.”