| St. Johnswort and Anti-HIV Proteases |
Answered by: Conrad Richter
Question from: David
Posted on: February 17, 2000
I am a practicing acupuncturist and herbalist here in San Francisco. I have also been a subscriber of your publications for many years and continue to support your mission and professional approach, as well as , your factual knowledge base. This is why I turn to you in regards to my question.
I am in a quandary over a rumor that is unfortunately spreading through the HIV community like wildfire. The rumor is that St. John’s Wort, when taken in conjunction with certain HIV medicines - i.e. Protease Inhibitors, that the antagonistic effect is that St. John’s Wort actually leaches out or detoxifies the system of the Protease Inhibitors. A study has been cited but no one has shown said study to me. I can neither prove or disprove this rumor.
As this effects many of my clients I am very curious to know if you people have ever heard of any research being done on the particular use of the herb as cited above. If so please let me know. Thank you very much.
Here is what my herbalist colleagues reported back to me when I asked them about this. As you will see, the FDA recently (Feb. 2000) issued a warning based on findings reported recently in Lancet.
From Robin Klein, Herbalist AHG (Instructor, Sweetgrass School of Herbalism):
Basically, this new warning is taken out of context as usual. Many food and other drug substances can interfere with prescription drugs. As we discussed on herbal hall, foods in the Cruciferae/Brassicaceae family can also induce or stimulate CYP450 enzymes as well. Therefore, Brocolli should not be eaten with protease inhibitors either! Of course, the researchers didn’t study brocolli, so they are not going to mention it.
We herbalists must take the research and see where the holes are. For instance, we have yet to discover the dose used in the study, the form of the product, etc. How much brocolli would have to be eaten? How much St. Johnswort (SJW) would have to be taken? Maybe the dose used in the study is ridiculously high? We don’t know yet. But this is what one should look for.
As Jim Duke points out, the researchers knew all this. They just aren’t explaining it. They intended to find the most controversial drug to add to SJW to make their point. HIV is a perfect scenario for them because HIV folks take SJW in the hopes that it is an antiviral. Unfortunately, HIV patients are taking this antiviral property out of context too. SJW will work as an antiviral but only in a petri dish exposed to ultraviolet light. This effect has never been proven to be therapeutically relevant.
The media just LOVES this sort of press release. They will run with it and all the folks who are afraid of herbs will point their fingers and say, ‘see, told you so!’ But will the real truth come out? I doubt it. One has to dig deep and know a thing or two about herbs, detoxification and drugs in order to know the REST OF THE STORY.
SJW is safer than hundreds of other drugs, including Tylenol. But THAT does not make good headlines.
From Aaron Young (CEO, Integrative Medical Arts) and Mitchell B. Stargrove, N.D., L.Ac. (Founder and Chief Medical Officer, Integrative Medical Arts):
St. John’s Wort and Other Supplements Interacting With Drugs: Sorting Fears, Fact and Fiction with www.InteractionReport.org.
Recent studies have found that St. John’s Wort (Hypericum perforatum) may interact with several prescription drugs. This emerging research has raised significant concern due to the widespread use of the herb. The February 12, 2000 issue of the British journal Lancet featured two reports and some correspondence on St. John’s Wort (SJW) interactions. The US FDA followed quickly with an advisory concerning the use of the anti-HIV protease inhibitor Indinavir concurrently with products containing St. John’s Wort. Safety concerns have also been raised recently about SJW interacting with Digoxin and the emerging potential for interaction with a wide range of other medications. Repeated warnings have also been voiced that SJW could contribute to the dangerous phenomenon known as serotonin syndrome when taken with anti-depressants such as Prozac (SSRI’s). Coverage in the popular press headlining safety concerns about herbs has contributed to an atmosphere of fear and uncertainty among consumers and focused attention on the need for appropriate clinical research, education and regulation. Even so, numerous studies have confirmed the value of SJW for individuals suffering from moderate depression and reaffirmed its minimal risk of adverse effects. Thus, the overall safety profile of SJW remains excellent, and clinical reports of interactions will only enhance the safety of the SJW preparations when used appropriately.
Few physicians are professionally trained or clinically experienced in the therapeutic use of herbal medicines and dietary supplements, and awareness of the potential for interactions has only recently become a subject of concern in the medical literature, although drug-drug interactions have long been a subject of study. The limited research into herbs and supplements has contributed to a severe shortage of authoritative information, as does a lack of reporting mechanisms for adverse events associated with herbs and nutriceutical consumption. Surveys have also shown that, while a significant shift is underway, a majority of patients consuming herbs and supplements do not inform their physicians about usage of these products. Information about interactions and adequate reporting procedures are therefore crucial in developing a framework of information about interactions which can serve to further research, product safety, consumer and health professional education, and regulatory initiatives such as accurate product labeling.
[Integrative Medical Arts established www.InteractionReport.org, an internet-based resource for reporting interactions and adverse reactions involving herbs and nutritional supplements. For more information contact: Interactions@IBISmedical.com - 503.526.1972 - www.IBISmedical.com.]
From Richard W. Noble MD (Clinical Consultant, Herbal Medicine):
Here’s the FDA alert sent out to physicians. Check out the full article in Lancet.
FDA PUBLIC HEALTH ADVISORY
February 10, 2000
RISK OF DRUG INTERACTIONS WITH ST JOHN’S WORT AND INDINAVIR AND OTHER DRUGS
Dear Health Care Professional:
The Food and Drug Administration would like to inform you about results from a study conducted by The National Institutes of Health (NIH) that showed a significant drug interaction between St John’s wort (hypericum perforatum), an herbal product sold as a dietary supplement, and indinavir, a protease inhibitor used to treat HIV infection. In this study, concomitant administration of St.John’s wort and indinavir substantially decreased indinavir plasma concentrations, potentially due to induction of the cytochrome P450 metabolic pathway.
For additional information on this study please refer to the February 12, 2000 Lancet publication (Piscitelli, et al).
- Indinavir and other antiretroviral agents -
At this time, pharmacokinetic data are available only for concomitant administration of indinavir with St. John’s wort. However, based on these results, it is expected that St John’s wort may significantly decrease blood concentrations of all of the currently marketed HIV protease inhibitors (PIs) and possibly other drugs (to varying degrees) that are similarly metabolized, including the nonnucleoside reverse transcriptase inhibitors (NNRTIs).
Consequently, concomitant use of St John’s wort with PIs or NNRTIs is not recommended because this may result in suboptimal antiretroviral drug concentrations, leading to loss of virologic response and development of resistance or class cross-resistance.
Because herbal products are widely used in the United States and are available in various forms such as combination products and teas, it is important that health care professionals ask patients about concomitant use of products that could contain St. John’s wort (hypericum perforatum).
In addition, FDA is working closely with drug manufacturers to ensure that product labeling of antiretrovirals is revised to highlight the potential for drug interactions with St. John’s wort.
- Other drugs -
Based on this study and reports in the medical literature, St. John’s wort appears to be an inducer of an important metabolic pathway, cytochrome P450. As many prescription drugs used to treat conditions such as heart disease, depression, seizures, certain cancers or to prevent conditions such as transplant rejection or pregnancy (oral contraceptives) are metabolized via this pathway, health care providers should alert patients about these potential drug interactions to prevent loss of therapeutic effect of any drug metabolized via the cytochrome P450 pathway.
All health care professionals are encouraged to report any serious adverse event associated with the concomitant use of prescription drugs and St. John’s wort products to the FDA’s MedWatch program at 1-800-FDA-1088 (fax 1-800-FDA-0178).
Murray M. Lumpkin, M.D Deputy Center Director (Review Management) Center for Drug Evaluation and Research
Susan Alpert, Ph.D., M.D. Director of Food Safety Center for Food Safety and Applied Nutrition
From Susan Eagles (Professional Herbalist):
Here is the recent discussion on the Lancet article on the interference of SJW with drugs for AIDS.
By Maggie Fox, Health and Science Correspondent
WASHINGTON (Reuters) - St. John’s wort, an herb commonly used by people to treat themselves for depression and anxiety, can interfere with a key drug used in AIDS cocktails, as well as a drug used for transplant patients, researchers said Thursday.
They said patients taking the drug indinavir, sold by Merck under the name Crixivan, should be careful about taking St. John’s wort.
"When St. John’s wort and the protease inhibitor indinavir are taken together, the levels of indinavir in the blood drop dramatically," Dr. Stephen Piscitelli of the National Institutes of Health, who led the study, said in a statement.
This could allow the virus to come back and, worse, start developing resistance.
"Patients and health-care professionals need to be aware of this interaction," added Dr. Judith Falloon of the National Institute of Allergy and Infectious Diseases (NIAID), one of the institutes at the NIH. "Most people taking medications to treat HIV infection should avoid using St. John’s wort."
It is well known that what patients eat and drink can affect the way drugs are absorbed and used by the body. For example, grapefruit juice is known to increase the effectiveness of some HIV drugs, and some of the drugs must be taken with food while others must be taken on an empty stomach.
Other research has also shown that patients who take alternative or herbal medicine often do not tell their doctors about it, in part for fear the doctors will disapprove.
"There is a misconception that herbal products like St. John’s wort are safe, but this study demonstrates that there can be dangerous interactions when taken with other drugs prescribed to treat medical conditions. It is important for patients to tell their health-care providers about their use of herbal products and complementary medicines," Piscitelli told the Lancet medical journal, which published the study.
The NIH researchers saw reports on how St. John’s wort affects the body and feared it might affect the protease inhibitor class of drugs used in treating HIV infection.
They tested eight healthy volunteers, first giving them three daily doses of Crixivan alone on an empty stomach, testing their blood levels of the drug, and then adding St. John’s wort capsules.
"The results were dramatically conclusive," Piscitelli said. "All the participants showed a marked drop in blood levels of indinavir after taking St. John’s wort. The drop ranged from 49 percent to 99 percent."
Protease inhibitors are often key to making HIV drug cocktails work. They can keep the virus suppressed and keep patients healthy, although they are not cured, but only if all the drugs are taken correctly.
If drug levels fall for instance if something like St. John’s wort interferes or if the patient misses a few doses -- the virus not only comes back with a vengeance but can mutate into forms that resist the drugs.
"Resistance to indinavir can decrease the response to other protease inhibitors," Piscitelli said.
In a second study, Frank Ruschitzka and colleagues from University Hospital, Zurich, in Switzerland said St. John’s wort can also interfere with cyclosporine, a drug used to keep patients from "rejecting" organ transplants.
Two patients who got heart transplants started suffering acute rejection of their hearts and had to be hospitalized after taking the herb. When they stopped taking St. John’s wort, the cyclosporine levels in their bodies returned to normal and their conditions improved, Ruschitzka reported.