Hypericum and HIV

by Paul Bergner

Medical Herbalism 2(1):1,3,6

In 1988, researchers found that hypericin, isolated from Hypericum perforatum (St. Johnswort) inhibited retroviruses in mice. (Meruelo et al.) Some physicians, herbal practitioners and AIDS patients immediately questioned whether herbal preparations of St. Johnswort, widely available, inexpensive, and without significant side effects, would work clinically to cure or otherwise benefit AIDS, ARC, and HIV positive patients. Hypericum preparations, with standardized hypericin content, are recognized antidepressants in Germany, described as non-toxic by government drug monographs. (Hobbs 1989)

Normally the move from animal studies to human studies would have taken years, subject to strict FDA guidelines. Due in part to the efforts of activist AIDS organizations, and in part to well-established safety of the herb, some physicians and individuals began experimenting with the herb immediately. Preliminary data is now available on the efficacy of presently available products at up to triple the normal dose ranges. Community-based clinical trials have recently been funded and will soon be underway in several cities, to more formally test different dose ranges.

Most patients report benefits

Hypericum appears to make most AIDS patients feel better, even those who are seriously ill (James 1989a). David Payne D.O. of Arizona, who has used Hypericum with his AIDS/ARC patients, and who has done a formal six-month study (Payne 1989), states that 80-90% of patients report at least some benefit. John S. James, publisher of Aids Treatment News, who compiled a survey of 112 patients taking Hypericum, found that 65 of the 112 reported some benefits. He notes that the actual percentage of people benefited is higher than this, because of the 47 who reported no benefit, some were asymptomatic to begin with (James 1989b). Furthermore, 27 of the respondents had been taking Hypericum for less than 4 weeks, and only a third of these reported benefits. The most common benefits are: improved outlook, more energy, less fatigue, and feeling better, reported by forty-one of the 65 respondents in James’ survey.

Not a wonder-cure for HIV

The observed benefits of Hypericum appear to be due to its anti-depressant effect rather than to action against the HIV virus. It is difficult to isolate the action of Hypericum from presently available data. In most cases patients were taking other medications, such as AZT in either high or low doses. Dr. Payne’s measured results in groups taking Hypericum alone, (or in conjunction with AZT), and although there was improvement of T-cell parameters or P-24 antigen (a marker AIDS antibodies) in some patients in the Hypericum group, there was no overall trend toward improvement. In James survey, of those taking Hypericum without other antiviral drugs, 3 reported improvement of T-cell measurements, and 2 reported worsening. It appears that Hypericum preparations, at least those available now, and in the doses studied, are not a wonder-cure for AIDS

Higher doses, products standardized with higher amounts of hypericin, or purified hypericin may still prove to be effective against HIV. Dr. Payne notes that blood levels of hypericin in his studies only reached about a third of the levels found to inhibit retroviruses in animals. Even the present products and doses may prove beneficial to some groups, such as asymptomatic HIV positive patients. One such patient in James’ survey became P-24 antigen negative while apparently taking no other medications. The number of patients studied so far is too small to rule out benefit to some people, although it is clear that not everyone will benefit from current preparations.

Other possible benefits

In analyzing the toxicity of Hypericum in 24 patients, Dr. Payne noted that liver enzymes seemed to improve in almost every case. No known activity of Hypericum can account for this, and it remains to be seen whether this is only a random result in a small sample of patients. This does allay concerns about the possible liver toxicity of Hypericum at elevated doses (three times the antidepressant dose) however.


Most people involved in studies took standardized German or American preparations. The German product, Hyperofat, should not be confused with a similar product, Hyperofat Forte, which also contains Rauwolfia serpentina and could have significant side effects if taken in high doses. Alcohol tinctures, if well made from fresh material, may contain significant amounts of hypericin. They should have a deep blood-red color (not merely pink or light red) if they are made properly. Because the hypericin content of Hypericum is so low (.24% in dried plant material),(Hobbs 1989), it is this author’s opinion that products standardized for hypericin content are most desirable for use with HIV infected patients.

“Pulsed dose” may be best

The normal antidepressant dose of Hypericum is 20-100 mg of hypericin per day, or about 20-30 drops of the tincture three times a day. For AIDS treatment, this dose has been more than tripled. (Payne 1989) Dr. Payne and others have also used a “pulsed dose”, a method common in clinical trials where active substances have long half-lives in the blood. (Hypericin blood levels tend to drop by 1/2 every 7-10 days.) With a pulsed dose, the patient receives a very large dose over a short period of time, rather than small doses daily. The pulsed dose is repeated at intervals. The pulsed dose yields higher blood levels quickly, while maintaining the same average levels as with a daily dose. Periods of low blood levels accompanying the pulsed dose may reduce potential toxicity. The accompanying graph shows the comparative blood levels of an active ingredient with a long half-life when given in a daily or a pulsed dose.

Dr. Payne administered a daily dose equivalent to 70 mg hypericin (Yerba Prima tablets) three times a day, or a pulsed dose of 70 mg every four hours for two consecutive days of each week, but not on the other days of the week. Dr Payne concluded from his study that the pulsed dose seemed to have the most effect and the least toxicity.


Hypericum preparations do not have any of the side effects normally associated with monoamine oxidase (MAO) inhibitors, even though the German government monograph for Hypericum states that it acts as a MAO inhibitor. (Hobbs 1989) Research has shown that hypericin has a MAO-inhibitor effect. (Suzuki et al. 1984; Muldner and Zoller 1984) This raises alarm among those familiar with these drugs, because of their serious side effects. MAO inhibitors presumably work by blocking the action of MAO in the brain, thereby increasing amounts of neurotransmitters there. MAO dependent reactions occur throughout the body, however, and drug doses effective in the brain have invariably caused side effects elsewhere. The most significant is a potentially fatal hypertensive crises when MAO inhibitors interact with foods containing tyramine, or with certain over-the-counter drugs.

The complete lack of such side effects, even with doses about triple the normal antidepressant dose, calls into question whether the antidepressant effects of Hypericum are in fact due to the MAO-inhibiting effects of hypericin. If Hypericum is inhibiting MAO in the brain, then why is it not inhibiting other MAO reactions and causing side effects? Other constituents of Hypericum (flavonoids and xanthones) may be responsible for the antidepressant effect. (Hobbs 1989) The length of time for Hypericum to exhibit its antidepressant effect (3 weeks-2 months) (Weiss 1988) is characteristic of the action of many flavonoids. Regardless of the mechanism, there is no need for concern about MAO-inhibitor side effects with the use of Hypericum at up to 280 mg hypericin content per day for up to six months.

Summary and conclusion

Hypericum preparations subjectively benefit most AIDS and ARC patients, even those seriously ill, without major side effects. The main effects seem to be from their antidepressant action. The reported improvement of outlook with increased energy and reduced fatigue are important improvements in the quality of life, contributing to the overall state of health and happiness. Currently available preparations do not appear to universally affect HIV or T-cell status. Improvements in some individual have been observed, however, and the potential benefit to some classes of patients, or of stronger preparations or isolated hypericin has not been ruled out. Currently scheduled formal clinical trials may yield new information. The pulsed dose may be the most effective.


Hobbs, C. “St John’s Wort: Hypericum perforatum L.” (review article) HerbalGram (1989) No.18/19. p. 24-33

Muldner, Von H., Zoller, M. 1984 “Antidepressive wirkung eines auf den wirkstoffcomplex hypericin standardisierten hypericum-extraktes.” Arzneim.-Forsch. 37:10-13 as reported by Hobbs, 1989.

James, John S. AIDS treatment news. Issue #74, Feb 24, 1989.

_____________. AIDS treatment news. Issue #91, Nov 17, 1989

Muruelo et al/ “Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin.” Proc natl acad sci (1988) 85:5230-5234

Payne, David L. Personal communication. Study completed in Nov. 1989.

Suzuki, O. et al. 1984. “Inhibition of monoamine oxidase by hypericin” Planta medica 50: 272-4. as reported by Hobbs, 1989.

Weiss, Rudolph F. Herbal medicine Beaconsfield Publishers, Beaconsfield, England (1988) (Translated from the sixth German edition of Lerhbuch der Phytotherapie.
Copyright 2001 Paul Bergner  

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