Uploaded April 2026 | Updated September 2026, 2 weeks ago
What do the herbal remedy St. John’s Wort and grapefruit juice have in common? They can both interfere with the effectiveness of medications, with St. John’s Wort decreasing and grapefruit juice increasing blood levels. Such changes in blood levels can mean that a medication will not work as well as intended or will result in an overdose. Both effects were discovered serendipitously, not as a consequence of direct research.
A major problem with organ transplants is the rejection of the new organ as the body’s immune system looks on the transplanted organ as an intruder and mounts an attack against it. This can be countered with the use of anti-rejection drugs such as the fungus-derived cyclosporine which suppresses the activity of the immune system’s T cells. In the 1990s physicians noticed that some transplant patients on cyclosporin had dangerously low levels of the drug. Around the same time, it was also noted that in some AIDS patients, protease inhibitors such as Indinavir were not working because blood levels were too low.
What was going on with the transplant and AIDS patients who had the surprisingly low levels of meds in their blood? Questioning revealed that they were taking St. John’s Wort, an over-the-counter herbal medication with a long history of use as an antidepressant. An investigation of the biochemistry of this herb revealed that one of its constituents, hyperforin, has the ability to induce an enzyme known as Cytochrome P 450 that protects the body by breaking down substances, such as drugs, that it recognizes as foreign. Since hyperforin increases the activity of this enzyme, the result is lowering blood levels of drugs such as cyclosporin and Indinavir that are normally metabolized by this enzyme. Further research revealed that many other drugs are also metabolized by this enzyme, so to be on the safe side the advice is not to mix St. John’s Wort with any other medication.
Grapefruit juice has the opposite effect of St. John’s Wort. It inhibits the Cytochrome P 450 enzyme with the result that medications are more poorly metabolized and blood levels build up. This was discovered in 1989 by Canadian researcher Dr. David Bailey who was studying the effects of alcohol on the nifedipine, a blood pressure lowering drug. To mask the taste of alcohol it was mixed with grapefruit juice. Surprisingly, blood pressure dropped more than expected. It turns out that grapefruit contains compounds called furanocoumarins that block Cytochrome P450 with the result that blood levels of a medication can rise dangerously. Further experiments showed that with some drugs there is no safe amount of grapefruit juice, meaning that if the information sheet that comes with the drug says that it should not be consumed with grapefruit, then even small amounts have to be avoided. Who would have ever thought that St. John’s Wort and grapefruit juice would be instrumental in teaching us how to prevent underdosing and overdosing with medications.
What do the herbal remedy St. John’s Wort and grapefruit juice have in common? They can both interfere with the effectiveness of medications, with St. John’s Wort decreasing and grapefruit juice increasing blood levels. Such changes in blood levels can mean that a medication will not work as well as intended or will result in an overdose. Both effects were discovered serendipitously, not as a consequence of direct research.
A major problem with organ transplants is the rejection of the new organ as the body’s immune system looks on the transplanted organ as an intruder and mounts an attack against it. This can be countered with the use of anti-rejection drugs such as the fungus-derived cyclosporine which suppresses the activity of the immune system’s T cells. In the 1990s physicians noticed that some transplant patients on cyclosporin had dangerously low levels of the drug. Around the same time, it was also noted that in some AIDS patients, protease inhibitors such as Indinavir were not working because blood levels were too low.
What was going on with the transplant and AIDS patients who had the surprisingly low levels of meds in their blood? Questioning revealed that they were taking St. John’s Wort, an over-the-counter herbal medication with a long history of use as an antidepressant. An investigation of the biochemistry of this herb revealed that one of its constituents, hyperforin, has the ability to induce an enzyme known as Cytochrome P 450 that protects the body by breaking down substances, such as drugs, that it recognizes as foreign. Since hyperforin increases the activity of this enzyme, the result is lowering blood levels of drugs such as cyclosporin and Indinavir that are normally metabolized by this enzyme. Further research revealed that many other drugs are also metabolized by this enzyme, so to be on the safe side the advice is not to mix St. John’s Wort with any other medication.
Grapefruit juice has the opposite effect of St. John’s Wort. It inhibits the Cytochrome P 450 enzyme with the result that medications are more poorly metabolized and blood levels build up. This was discovered in 1989 by Canadian researcher Dr. David Bailey who was studying the effects of alcohol on the nifedipine, a blood pressure lowering drug. To mask the taste of alcohol it was mixed with grapefruit juice. Surprisingly, blood pressure dropped more than expected. It turns out that grapefruit contains compounds called furanocoumarins that block Cytochrome P450 with the result that blood levels of a medication can rise dangerously. Further experiments showed that with some drugs there is no safe amount of grapefruit juice, meaning that if the information sheet that comes with the drug says that it should not be consumed with grapefruit, then even small amounts have to be avoided. Who would have ever thought that St. John’s Wort and grapefruit juice would be instrumental in teaching us how to prevent underdosing and overdosing with medications.
