MEDICAL HERBALISM: A Journal for the Clinical Practitioner

Copyright 2000 Paul Bergner

by Paul Bergner
(Bergner, P. Hypericum, drug interactions, and liver effects. Medical Herbalism (2000)11(2):16)

Two articles published in the February 14, 2000 issue of The Lancet have identified potentially
serious interactions between concentrated extracts of St Johnswort (Hypericum perforatum) and
several drugs used in AIDS and organ transplant patients. Hypericum apparently increases the
activity of the liver enzymes that metabolize and inactivate the drugs, lowering effective blood
levels. In the case of the AIDS drug indinavir, hypericum standardized extracts at a dose of 300 mg
three times a day lowered blood levels by 57-82%, rendering it therapeutically ineffective. In two
patients with heart transplants, hypericum extracts in the same dosage  reduced circulating levels of
the anti-rejection drug cyclosporin to the point that both patients began to reject the transplanted
heart. Hypericum had reduced circulating cyclosporin levels to approximately 50-70% of their pre-
hypericum levels within two weeks.
The specific enzyme system whose activity was increased in the test subjects is the CYP3A, part of
the p450 microsomal enzyme system, responsible for Phase I detoxification in the liver and also
present in intestinal and kidney cells. The CYP3A subfamily is the most abundant group of p450
enzymes in the liver.  Many drugs are mainly metabolized by the CYP3A enzymes, as are many fat
soluble hormones, including estrogens and cortisol. Thus hypericum could have similar actions to
those reported with many drugs. Depending on whether the drugs are metabolized to their active
form or inactive forms by the enzymes, simultaneous consumption of hypericum extracts may either
increase of decrease blood levels. Consequences could range from innocuous to fatal depending on
the nature of the drug and how critical the drug dose is to the patient's health.Interactions with the
two drugs reported in Lancet present a strong hazard for patient injury because of the critical nature
of the drugs, the widespread promotion of concentrated extracts of hypericum for depression, and
because depression frequently accompanies AIDS and organ transplantation.  The reports should
prompt modern herbalist to use caution in prescribing hypericum for depression in patient receiving
simultaneous pharmaceutical drug prescriptions.

Some drugs metabolized by the CYP3A enzyme system
aldrin, carbamazepine, corticosteroids cyclosporine, erythromycin, indinavir, lidocaine, lovastatin,
methadone, midazolam, nefedipine, quinidine,
Endogenous hormones metabolized by the CYP3A enzyme system
estradiol, estriol, testosterone, cortisol
More drugs which are most likely to have some interaction with St Johnswort can be found online
at   Herbs in the last column,
labeled 3A4,5,7 may be affected by St. Johnswort which could either increase or decrease their
The reports may also explain some traditional uses of hypericum. Older texts in European
herbalism describe hypericum as a liver herb. Sebastian Kneipp; in My Water Cure, for instance,
states: "This medicinal herb has a particular influence on the liver; its tea is an excellent remedy
for it." Andrew Chevallier's contemporary Encyclopedia of Medicinal Plants states that
hypericum is a cholagogue and tonic for the liver and gallbladder. The liver effects of hypericum
are hardly taught today, with the herbs antidepressant effects taking the spotlight after clinical
trials and intensive marketing of the herb for that reason. Liver effects and antidepressant effects
may in fact be related. In traditional Greek/Arabic medicine, as well as in traditional Chinese
medicine, some forms of depression are considered as arising from impaired function of the liver,
and the same CPY3A system that hypericum stimulates is responsible for clearing cortisol from
the system. Elevated cortisol, the adrenal stress hormone, is associated with depression.
The CPY3A system is also responsible for clearing estrogen from the system, and the recent
findings may explain the traditional use of hypericum for female complaints associated with
hyperestrogenism. Finley Ellingwood, MD classified hypericum as a "sedative especially useful
in the diseases of women" in the 1919 version of his materia medica. More recently, Malcolm
Stuart said of hypericum in his Encyclopedia of Herbs and Herbalism that "Certainly when taken
internally, the herb stimulates both gastric and bile secretions, and is effective for irregular
Chevallier, Andrew. The Encyclopedia of Medicinal Plants. New York: DK Publishing, 1996
Ellingwood, Finley. American materia Medica, Therapeutics and Pharmacognosy. Portland,
Oregon: Eclectic Medical Publications, 1983 [Reprint of 1919 original]
Kneipp, Sebastian. My Water Cure. 62nd Edition [translation reprint]. Pomeroy Washington:
Health Research, 1972
Piscitelli, SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St
John's wort. Lancet 355(9203)
Ruschitzka F, Meier PJ, Turina M, L?scher TF, Noll G. Acute heart transplant rejection due to
Saint John's wort Acute heart transplant rejection due to Saint John's wort. Lancet 355(9203)
Stuart, Malcolm [editor]. The Encyclopedia of Herbs and Herbalism. New York: Grosset and
Dunlap, 1979

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