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The dangers of grapefruit juice--seen with orally taken drugs only
The dangers of grapefruit juice
By Nicholas Bakalar The New York Times
WEDNESDAY, MARCH 22, 2006
In 1989, a group of Canadian researchers studying a blood pressure drug were astonished to discover that drinking a glass of grapefruit juice dangerously increased the drug's potency.
They were testing the effects of drinking alcohol on a medicine called Plendil. The scientists needed something that would hide the taste of alcohol so that subjects would know only that they were taking the drug and not know whether they were drinking alcohol with it.
"One Saturday night, my wife and I tested everything in the refrigerator," said Dr. David Bailey, a research scientist at the London Health Sciences Center in London, Ontario, and the lead author on the study. "The only thing that covered the taste was grapefruit juice."
So they used it in their experiment, expecting the grapefruit juice to be irrelevant to their results. But blood levels of the drug went up significantly in the control group that drank just grapefruit juice, without alcohol.
"People didn't believe us," Bailey said. "They thought it was a joke. We had trouble getting it published in a major medical journal."
Eventually the paper was published by Lancet, in February 1991.
Finding why juice had that effect was the next question.
The answer, it turned out, lay in a family of enzymes called the cytochrome P-450 system, in particular one known as CYP 3A4. This enzyme metabolizes many drugs, and toxins as well, into substances that are less potent or more easily excreted or both.
Grapefruit juice interferes with the ability of CYP 3A4 to do that, increasing the potency of a drug by letting more of it enter the bloodstream, in effect producing an excessive dose.
Grapefruit interacts with this enzyme only in the intestines, not in the liver or other places where it is found. As a result, the effect is seen only with medicines taken orally, not with injected drugs.
Numerous studies now show the interaction of grapefruit juice with many widely used medicines. Most interactions have no serious consequences, but a few do. For example, drugs used to lower cholesterol, like Lipitor, Mevacor and Zocor, have increased potency when taken with grapefruit juice. Excessive levels of those drugs can lead to a serious and sometimes fatal muscle disorder called rhabdomyolysis.
Does this mean a person could reduce the amount of medicine required simply by drinking grapefruit juice? No, according to Bailey.
"The problem is the unpredictability of the effect," he said. "There's no uniformity from one individual to another or from one bottle of grapefruit juice to the next.
"There's huge variation in the amount of enzyme people have in their guts. Fooling around with grapefruit juice is not a good idea."
Grapefruit juice can also interfere with the metabolism of selective serotonin reuptake inhibitors, or SSRIs, like Prozac, used to treat depression.
Dr. Marshall Forstein, an associate professor of psychiatry at Harvard, said he told patients to switch from grapefruit juice to something else because most oranges and other citrus fruits do not have the same effect.
Among fruit juices, grapefruit has the strongest effect, but lime juice and orange juice made from Seville oranges similarly inhibit the CYP 3A4 enzyme. With some drugs, apple juice may interact in the same way.
While Bailey suggests avoiding grapefruit juice entirely when taking medicine, some experts say the effect of the juice should not be exaggerated.
"The circumstances under which an interaction will occur are relatively unusual," said David Greenblatt, a professor of pharmacology at Tufts University School of Medicine in Boston. First, he said, the drug has to be metabolized significantly by intestinal CYP 3A4, and relatively few are. "When you look at the actual data for each drug, the scientific conclusions are that the interactions are unusual, sometimes quite small and not of clinical importance. But there are some cases in which it's significant."
Greenblatt and his co-investigators at Tufts have conducted research sponsored by the National Institutes of Health in this field for years, and he has been a paid consultant to the Florida Citrus Commission.
Dr. Richard Kim, a professor of medicine and pharmacology at Vanderbilt University in Nashville, Tennessee agreed that the interaction was a serious health concern in some patients.
"Grapefruit consumption is a clinically relevant issue, especially for the elderly, who are most likely to be taking the drugs affected by it," Kim said. "If you're taking multiple medications, or have recently switched to a different type of medication, you should be particularly careful. The easiest thing to do under those circumstances is to take the medicine with water and avoid the juice completely."
In 1989, a group of Canadian researchers studying a blood pressure drug were astonished to discover that drinking a glass of grapefruit juice dangerously increased the drug's potency.
They were testing the effects of drinking alcohol on a medicine called Plendil. The scientists needed something that would hide the taste of alcohol so that subjects would know only that they were taking the drug and not know whether they were drinking alcohol with it.
"One Saturday night, my wife and I tested everything in the refrigerator," said Dr. David Bailey, a research scientist at the London Health Sciences Center in London, Ontario, and the lead author on the study. "The only thing that covered the taste was grapefruit juice."
So they used it in their experiment, expecting the grapefruit juice to be irrelevant to their results. But blood levels of the drug went up significantly in the control group that drank just grapefruit juice, without alcohol.
"People didn't believe us," Bailey said. "They thought it was a joke. We had trouble getting it published in a major medical journal."
Eventually the paper was published by Lancet, in February 1991.
Finding why juice had that effect was the next question.
The answer, it turned out, lay in a family of enzymes called the cytochrome P-450 system, in particular one known as CYP 3A4. This enzyme metabolizes many drugs, and toxins as well, into substances that are less potent or more easily excreted or both.
Grapefruit juice interferes with the ability of CYP 3A4 to do that, increasing the potency of a drug by letting more of it enter the bloodstream, in effect producing an excessive dose.
Grapefruit interacts with this enzyme only in the intestines, not in the liver or other places where it is found. As a result, the effect is seen only with medicines taken orally, not with injected drugs.
Numerous studies now show the interaction of grapefruit juice with many widely used medicines. Most interactions have no serious consequences, but a few do. For example, drugs used to lower cholesterol, like Lipitor, Mevacor and Zocor, have increased potency when taken with grapefruit juice. Excessive levels of those drugs can lead to a serious and sometimes fatal muscle disorder called rhabdomyolysis.
Does this mean a person could reduce the amount of medicine required simply by drinking grapefruit juice? No, according to Bailey.
"The problem is the unpredictability of the effect," he said. "There's no uniformity from one individual to another or from one bottle of grapefruit juice to the next.
"There's huge variation in the amount of enzyme people have in their guts. Fooling around with grapefruit juice is not a good idea."
Grapefruit juice can also interfere with the metabolism of selective serotonin reuptake inhibitors, or SSRIs, like Prozac, used to treat depression.
Dr. Marshall Forstein, an associate professor of psychiatry at Harvard, said he told patients to switch from grapefruit juice to something else because most oranges and other citrus fruits do not have the same effect.
Among fruit juices, grapefruit has the strongest effect, but lime juice and orange juice made from Seville oranges similarly inhibit the CYP 3A4 enzyme. With some drugs, apple juice may interact in the same way.
While Bailey suggests avoiding grapefruit juice entirely when taking medicine, some experts say the effect of the juice should not be exaggerated.
"The circumstances under which an interaction will occur are relatively unusual," said David Greenblatt, a professor of pharmacology at Tufts University School of Medicine in Boston. First, he said, the drug has to be metabolized significantly by intestinal CYP 3A4, and relatively few are. "When you look at the actual data for each drug, the scientific conclusions are that the interactions are unusual, sometimes quite small and not of clinical importance. But there are some cases in which it's significant."
Greenblatt and his co-investigators at Tufts have conducted research sponsored by the National Institutes of Health in this field for years, and he has been a paid consultant to the Florida Citrus Commission.
Dr. Richard Kim, a professor of medicine and pharmacology at Vanderbilt University in Nashville, Tennessee agreed that the interaction was a serious health concern in some patients.
"Grapefruit consumption is a clinically relevant issue, especially for the elderly, who are most likely to be taking the drugs affected by it," Kim said. "If you're taking multiple medications, or have recently switched to a different type of medication, you should be particularly careful. The easiest thing to do under those circumstances is to take the medicine with water and avoid the juice completely."
In 1989, a group of Canadian researchers studying a blood pressure drug were astonished to discover that drinking a glass of grapefruit juice dangerously increased the drug's potency.
They were testing the effects of drinking alcohol on a medicine called Plendil. The scientists needed something that would hide the taste of alcohol so that subjects would know only that they were taking the drug and not know whether they were drinking alcohol with it.
"One Saturday night, my wife and I tested everything in the refrigerator," said Dr. David Bailey, a research scientist at the London Health Sciences Center in London, Ontario, and the lead author on the study. "The only thing that covered the taste was grapefruit juice."
So they used it in their experiment, expecting the grapefruit juice to be irrelevant to their results. But blood levels of the drug went up significantly in the control group that drank just grapefruit juice, without alcohol.
"People didn't believe us," Bailey said. "They thought it was a joke. We had trouble getting it published in a major medical journal."
Eventually the paper was published by Lancet, in February 1991.
Finding why juice had that effect was the next question.
The answer, it turned out, lay in a family of enzymes called the cytochrome P-450 system, in particular one known as CYP 3A4. This enzyme metabolizes many drugs, and toxins as well, into substances that are less potent or more easily excreted or both.
Grapefruit juice interferes with the ability of CYP 3A4 to do that, increasing the potency of a drug by letting more of it enter the bloodstream, in effect producing an excessive dose.
Grapefruit interacts with this enzyme only in the intestines, not in the liver or other places where it is found. As a result, the effect is seen only with medicines taken orally, not with injected drugs.
Numerous studies now show the interaction of grapefruit juice with many widely used medicines. Most interactions have no serious consequences, but a few do. For example, drugs used to lower cholesterol, like Lipitor, Mevacor and Zocor, have increased potency when taken with grapefruit juice. Excessive levels of those drugs can lead to a serious and sometimes fatal muscle disorder called rhabdomyolysis.
Does this mean a person could reduce the amount of medicine required simply by drinking grapefruit juice? No, according to Bailey.
"The problem is the unpredictability of the effect," he said. "There's no uniformity from one individual to another or from one bottle of grapefruit juice to the next.
"There's huge variation in the amount of enzyme people have in their guts. Fooling around with grapefruit juice is not a good idea."
Grapefruit juice can also interfere with the metabolism of selective serotonin reuptake inhibitors, or SSRIs, like Prozac, used to treat depression.
Dr. Marshall Forstein, an associate professor of psychiatry at Harvard, said he told patients to switch from grapefruit juice to something else because most oranges and other citrus fruits do not have the same effect.
Among fruit juices, grapefruit has the strongest effect, but lime juice and orange juice made from Seville oranges similarly inhibit the CYP 3A4 enzyme. With some drugs, apple juice may interact in the same way.
While Bailey suggests avoiding grapefruit juice entirely when taking medicine, some experts say the effect of the juice should not be exaggerated.
"The circumstances under which an interaction will occur are relatively unusual," said David Greenblatt, a professor of pharmacology at Tufts University School of Medicine in Boston. First, he said, the drug has to be metabolized significantly by intestinal CYP 3A4, and relatively few are. "When you look at the actual data for each drug, the scientific conclusions are that the interactions are unusual, sometimes quite small and not of clinical importance. But there are some cases in which it's significant."
Greenblatt and his co-investigators at Tufts have conducted research sponsored by the National Institutes of Health in this field for years, and he has been a paid consultant to the Florida Citrus Commission.
Dr. Richard Kim, a professor of medicine and pharmacology at Vanderbilt University in Nashville, Tennessee agreed that the interaction was a serious health concern in some patients.
"Grapefruit consumption is a clinically relevant issue, especially for the elderly, who are most likely to be taking the drugs affected by it," Kim said. "If you're taking multiple medications, or have recently switched to a different type of medication, you should be particularly careful. The easiest thing to do under those circumstances is to take the medicine with water and avoid the juice completely."
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