As you might expect, the situation is more complicated than it first seems.
“A chance finding of our study on ethanol-drug interactions was that citrus fruit juices may greatly augment the bioavailability of some drugs.” So began a paper published in 1991 in The Lancet, one of the most respected medical journals in the world. Dr. David Bailey and colleagues at the University of Western Ontario had been studying felodipine, a blood pressure–lowering drug, and wondered if it interacted with alcohol. They decided on a double-blind trial in which some subjects were to take the drug with alcohol and some without. This meant that the taste of alcohol had to be masked, and after some experimentation Dr. Bailey concluded that grapefruit juice was up to the task. To the researchers’ surprise, the alcohol had no effect, but in both groups the blood levels of felodipine were three times higher than expected. Bailey knew he was on to something. And he certainly liked a challenge. After all, he had been the first Canadian to run a sub-four-minute mile!
At this point, the eager scientist decided to become his own guinea pig. One day he took felodipine with water, the next day with grapefruit juice; each time he drew blood, and sent it for analysis of drug levels. He didn’t have to wait for the results to confirm the “grapefruit effect.” After taking the medication with grapefruit juice, he began to feel faint and lightheaded, classic symptoms of low blood pressure. Clearly, when taken with grapefruit juice, felodipine lowered blood pressure more than expected. A number of questions immediately arose. By what mechanism was grapefruit juice increasing the drug’s effectiveness? Did other juices have such an effect? What about interactions with other drugs? What would happen if the juice were consumed not with the drug but at some other time during the day? Was there a silver lining to this cloud? Could dosages of medications be reduced if they were taken with grapefruit juice?
Predictably, The Lancet paper unleashed a cavalcade of research. It wasn’t long before studies showed that only grapefruit juice had this unusual effect. Some compound specific to grapefruit inhibited the action of CYP3A4, an enzyme found in the wall of the intestine. This enzyme is part of the body’s detoxicating system and tackles intruders, such as medications. If its action is impaired, blood levels of these foreign substances can be expected to rise. Since CYP3A4 is known to be involved in the metabolism of numerous drugs, researchers suspected that felodipine would not be the sole medication to show a “grapefruit effect.” Indeed it was not. Various oral medications, ranging from heart-rhythm regulators and immunosuppressants to estrogen supplements and AIDS treatments, all interact with grapefruit juice. And the effect can last as long as 24 hours, meaning that drinking grapefruit juice at any time is contraindicated when taking drugs metabolized by CYP3A4. Since it isn’t completely clear which drugs fall into this category and which do not, and because of the known variation in CYP3A4 levels in different individuals, some experts suggest that grapefruit juice be avoided when taking any medication. Accordingly, many hospitals have taken grapefruit juice off the menu.
The grapefruit industry has complained that it is being unfairly singled out. Spokespeople maintain, correctly, that there are numerous drug-food interactions. Dairy foods can interfere with some antibiotics, broccoli can reduce the effect of anticoagulants, foods high in tyramine (aged cheese, red wine, soy sauce, sauerkraut, salami) can cause dramatic rises in blood pressure when coupled with antidepressants of the monoamine oxidase (MAO) inhibitor variety, and the absorption of digoxin (taken for congestive heart disease) is impaired by cereals such as oatmeal. While all of this information is factual, the existence of such effects doesn’t let grapefruit off the hook.
So if, as mentioned earlier, grapefruit juice lowers cholesterol, why not forget the statin and just drink grapefruit juice? That’s exactly what some people are asking after reading about Israeli researcher Shela Gorinstein’s study showing that just one red grapefruit a day can reduce LDL, the “bad cholesterol” by as much as 20 percent. Furthermore, red grapefruit reduces tri-glycerides significantly. But wait a minute. Gorinstein’s subjects all had recently undergone bypass surgery, had been resistant to statins and were on a diet with only 9 percent of calories coming from fat. So these results cannot be readily extrapolated to your average North American who is diagnosed with elevated cholesterol. What can he or she do? First, eat a diet low in saturated and trans fats, with plenty of fruits, vegetables and oat bran. And yes, grapefruit too! Throw in some persimmons, some pomelits (a cross between a grapefruit and a pomelo) and pale lager beer, all of which have been shown by Gorinstein to reduce the risk of heart disease. And if that doesn’t work, well, bring on the statins. But for now, not with grapefruit juice. That restriction may change in the future, thanks to researchers at the University of North Carolina who have identified furanocoumarins as the troublesome compounds in grapefruit juice and have shown that they can be removed. The resulting juice had no effect on blood levels of medications. This research may yet have another benefit. Perhaps furanocoumarins can be added to medications, reducing the dose needed and reducing the risk of side effects. These developments should make grapefruit growers somewhat less sour.
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