Hypericin/St. John's Wort: Experience So Far

Issue # 63 of AIDS Treatment News (August 26, 1988) published a report on hypericin, a chemical found in St. John's wort (Hypericum perforatum) and related plant species -- plants which are common around the world and have long been used as medicinal herbs. A team of researchers at New York University found that hypericin worked as an antiretroviral in animals, in tests with two retroviruses which affect mice; it also inactivated HIV in laboratory tests, and prevented infection of new cells. Hypericin is believed to cross the blood-brain barrier (Meruelo and others, 1988).
Extracts of St. John's wort with chemically standardized hypericin content have been sold over the counter for several years as an antidepressant in Germany, Austria, and Switzerland.
But at the time of our earlier report, there was no information on human use of the herbal extracts for treating AIDS or HIV. This article reports the human experience so far.
A note of caution: The information presented here shows hypericin as a promising treatment possibility. However, this information rests only on reports from eleven persons, all we could find who have used concentrated St. John's wort extracts for treating AIDS or HIV. They have used the treatment only for three months, sometimes less. Many treatments have looked good at first, and later turn out to be useless or harmful.
We were concerned about publishing this article too early, but decided it was better to go ahead than to wait. It is unclear what we would be waiting for. Clinical trials of chemically synthesized hypericin are being planned, but may take a year to even start. Since herbal extracts already available might contribute to AIDS treatment, it is urgent that they be given more attention.
Hypericin may be important as a treatment possibility for those who have no other option -- who cannot use standard treatments and do not have access to experimental ones. They might want to discuss hypericin with their healthcare providers, and consider using it with medical monitoring to minimize any risk.
But those who have other options and can afford to wait should consider doing so. In a few weeks or months, much more will be known about hypericin, whether it is safe and effective, and how best to use it.

Results with AIDS/HIV

To research this article, we tried to find every case we could locate of anyone who had used any form of St. John's wort or hypericin for AIDS or HIV infection. We interviewed either the persons themselves or their physicians.
We found 19 people overall. The cases divided themselves into two groups. Eleven had used concentrated extracts of St. John's wort, with known concentrations of hypericin; several of them had used the same preparation and same dose, for the same length of time. The other eight had only used herbal teas, or miscellaneous or unknown preparations; in all these cases, the amount of hypericin taken could not be determined. (No one used chemically purified or synthesized hypericin, probably because it was not available.)

(a) Using Known Hypericin Preparations

This is the information collected so far about human use of St. John's wort extracts containing known, significant concentrations of hypericin.
Of the eleven who used known concentrations of hypericin, nine reported successful, often dramatic results. The only failure was a patient near death, who was given the treatment as a desperation measure; it was too late and he died within several days. (One other patient was asymptomatic and had no after-treatment blood work, so there was no indicator of whether the treatment had been helpful or not.)
None of these persons reported any adverse effects from the treatment -- except for one who experienced drowsiness when taking very large doses. All ten patients are still using it.
Four of them are patients of one physician, David Payne, D.O., an osteopathic physician in Mesa, Arizona. Dr. Payne's patients used a standardized German tincture, "Hyperforat" (see "Available Extracts Containing Hypericin", below), which is sold over the counter in Germany for use as an antidepressant. They are taking 40 drops three times a day -- 120 drops per day total. (The recommended antidepressant dose is 20 to 30 drops three times a day; Dr. Payne increased this amount after discussion with the New York University researchers who had conducted antiviral tests in animals.)
We interviewed Dr. Payne about his experience with hypericin in treating these patients. The following is from the transcript of our phone interview of February 9, 1989.
Dr. Payne: "The clinical experience I've had so far has been very, very good. Every one of the people benefitted -- except as I said, one patient who only started the treatment for a few days before he died; he was too far gone to help. But I have had other people who were almost that sick make dramatic recoveries. I called all the patients yesterday, to see how they were doing and make sure there were no side effects. None of them report any side effects from the medication. They say it is very easy to take, causes no distress, no problems. And since starting the therapy around mid-November, they all reported major improvements in symptoms: increase in energy, and so forth."
(Dr. Payne noted that all of these patients had a T- 4 (T-helper) count less than 10 when they started, and there have been no major increases. But with counts starting that low, any increase would take time.)
AIDS Treatment News: That's understandable. But what about P24 levels?
Dr. Payne: "We haven't received the P24 back except for one patient. His P24 went from 47 picograms down to 7 (positive to negative)."
AIDS Treatment News: That's good. How much time was there between the tests?
Dr. Payne: "About six weeks."
(AIDS Treatment News: asked about the individual patients.)
Dr. Payne: "The four patients are Andy, Dan, Chris, and John (the names have been changed). Every one of them is doing very well. Every one of them reports increases in energy. None of them has any symptoms right now. One, Andy, the last T-4 cell count we did on him was nine. He has nine T-4 cells in a white count of one thousand. But he has absolutely no symptoms. He has gone skiing, he is doing everything. So symptomatically, it seems to work very quickly. Their symptoms improve within a matter of weeks. The (T-cell) numbers, however, do not seem to improve as rapidly. Their symptoms, in almost every case, within two weeks had improved."
(Just before we went to press, Dr. Payne reported that Andy's white count is now 2300. It had not been above 1100 for six months.)
"Dan, for instance was bedfast. He was getting almost all of his nutrition through a catheter. He had to be wheeled into my office in a wheelchair; he was very sick, could not keep anything in his stomach. He was wasting away, fatigued, had no strength or energy in his legs at all. He had mild peripheral neuropathy, not bad. I started him on the hypericin. Two weeks later, he came with his wife, but he walked into the office without any help. He was down to only thirty percent of his nutrition administered through the catheter.
"And two weeks after that, his wife was working, so he drove himself down (a two and a half hour trip), hopped into the office looking like a perfectly normal human being, like there was nothing ever wrong with him, which is astounding. He said he'd been hiking a little bit. He was eating a full diet. His nausea and vomiting had gone away. His energy level was coming up.
"When I saw him a month after that, he was fine, perfectly fine. He had energy, he was happy. He looked like he'd never had anything wrong with him. Really strange. As sick as he was, I thought eight weeks to change from that bad, being bedfast and wheeled in in a wheelchair, to driving himself and walking into the office by himself feeling good -- that was dramatic. And I don't know if it is coincidental, but he was not using much else. He could not tolerate AZT, he could not tolerate dextran sulfate. Hypericin is about all he was doing.
"And John had pneumocystis when we started him on the hypericin. So he was not feeling good at the time; we started him on it anyway. We treated him for pneumocystis and continued him on the hypericin. I talked to him yesterday to get an update on it, and he said that he had a little bit of a cold now, but that was it. He said before he got his cold, he had just been in San Diego, and had tons of energy, and was walking all around San Diego. John had also been very sick. He had had pneumocystis over and over again. He was very weak, losing weight. He's gained eight pounds recently.
"Those are the kinds of stories. What is doing it I'm not sure. But I have to attribute some of the improvement to the hypericin. That is the only thing different they are using."
The rest of the interview concerned technical matters such as the possibility of testing for blood levels of hypericin.
Of the other six persons known to AIDS Treatment News who used known extracts of hypericin for HIV:
* One had less than ten T-helper cells, and severe diarrhea for several months; the diarrhea could not be diagnosed or controlled. Two days after starting the hypericin (Psychotonin M tincture), the diarrhea stopped. Later, as a test, the patient stopped taking the hypericin, and the diarrhea returned. We do not have other details of this case.
* Another person used very large doses of St. John's wort tinctures (first Psychotonin M, then Jarrow Formulas), several times the recommended dose, in order to test for side effects before suggesting the treatment to friends. He had had severe hairy leukoplakia for a year; it went away completely with the treatment, but later it returned, despite continuing use of hypericin.
Drowsiness was his only consistent side effect. This patient was also using Ativan, which may have contributed to the drowsiness.
* One person used low doses of two different extracts available in the U.S., for two and a half weeks. He reported that swelling in lymph glands was completely gone, after he had had the problem for a year. Also, HIV- related arthritis symptoms in his feet were greatly relieved. (He had used 40 drops per day of a tincture (Jarrow Formulas) for one week, followed by one tablet per day of standardized St. John's wort extract (Yerba Prima Botanicals) for 10 days. For more information on these preparations, see "Available Extracts Containing Hypericin", below.) This person was also taking dextran sulfate (which he had been using for ten months), aa German treatment called "adaptogen", but the
improvements mentioned above occurred after he started using the St. John's wort extracts.
This person also reported one side effect of the hypericin -- an increase in sun sensitivity, resulting in a mild but unexpected sunburn after being in the sun for about half an hour.
* That person's lover, who has AIDS, took the same preparations and reported significant reduction in peripheral neuropathy (numbness in feet). He also commented that the St. John's wort was the easiest AIDS treatment he had ever taken. He often had stomach problems, but had none whatever resulting from the St. John's wort. The only other HIV treatment he was using was adaptogen.
The following two reports give little information, but we included them for completeness:
* One person took a small amount of a tincture (Jarrow Formulas), together with St. John's wort herbal tea. He was using several other treatments at the same time: acyclovir, ciprofloxicin, isoprinosine, and aloe vera juice (de Veras beverage). He reported increased energy, and also clearing of mucus, making it easier to breathe. He also has KS, and reported that the treatment did not seem to help.
* The final report is from a person who is asymptomatic but who recently became P24 antigen positive. He has been using St. John's wort tinctures for three weeks, and has not yet been re-tested for P24 antigen. There have been no side effects. But because the patient has no symptoms, and has not yet had blood work after the treatment began, there is no way to tell if there has been any benefit.
No other side effects were reported by any of these patients -- only the drowsiness and the increased sensitivity to sunlight, each mentioned by one person as noted above.

Comment

These reports, obtained from informal interviews, omit many details. We did not try to take medical histories; instead we asked people to tell us what seemed important to them. Taken together, we find the reports striking for three reasons:
* Consistency. Except for the patient near death who was given hypericin as a desperation measure, in almost every case there was major, unexpected improvement in symptoms, leading at least to improved quality of life. These people are in different parts of the country, often with different physicians, generally not knowing each other, and using different hypericin products from unrelated manufacturers.
* Working for patients who are seriously ill. Most treatments work best for those who are healthy to begin with. But here, patients benefitted greatly despite being seriously ill to start (needing a wheelchair and tube feeding, pneumocystis again and again, T-helper counts less than 10, etc.).
* Speed of improvement. Clear improvements in symptoms were usually seen within two to three weeks.
In blood work, no significant improvement in T- cells was found in about three months -- the longest time anyone has used the treatment so far. Only one person's P24 antigen result is available, and it went from positive to negative (47 to 7 picograms) during the treatment -- a good sign, but little can be concluded from a single case.

(b) Using Unknown Hypericin Preparations

The rest of our information on human use of St. John's wort extracts concerns those who only used herbal teas (or in one case, a homemade extract in brandy, and in another a medicine in France with no labeling for hypericin content and which we could not obtain for analysis). In these cases there was no way to estimate the amount of hypericin taken.
Among the eight persons who used only these preparations, there were no reports of benefits as dramatic as those above. Most believed or suspected it was helping. Most of these people were healthy to begin with, and did not have any before-and-after blood work- -meaning that usually there was no indicator to show whether the treatment was helping or not.
Until recently, it was difficult to obtain any St. John's wort extract with a known hypericin concentration in the United States. Most of the patients discussed above obtained theirs by having somebody bring it from Germany; the other two started the treatment in February 1989, when it was possible to obtain apparently comparable preparations in the U.S. But dried hypericin herb (which can differ greatly in quality from one batch to another), as well as a number of tincture and oil extracts, have long been sold in the U.S. in health-food stores. Some of them have only tiny amounts of
hypericin -- ten times as little as some of the German preparations, or even less. (Some European preparations have very little hypericin, too.)
The eight cases of persons using herbal teas or unknown preparations include two or three treatment failures. In one case the treatment was discontinued because of a drug reaction, a severe rash probably caused by use of St. John's wort; we do not know what kind of preparation was used (herbal tea, tincture, etc.). The rash started about two weeks after the treatment was begun, and went away a week after it was discontinued.
In another case, a person prepared a homemade extract by gathering St. John's wort from nearby fields, and soaking it in brandy. There were no side effects, but after several months of using the preparation, his helper T-cell count had declined from about 400 to 252. He decided that the treatment was unsuccessful, and discontinued it.
In the third case, an older patient developed kidney problems a week and a half after starting using St. John's wort tea; his first symptom was severe swelling in the legs. His infectious disease physician doubted that the herb had anything to do with the problem, because he had seen similar cases where no herb had been used. The patient stopped all medicines he was taking, was treated by kidney specialists, and has largely recovered.
The apparent lack of benefit from herbal teas or other unknown preparations may have resulted from low levels of hypericin in the treatment. On the other hand, they may have resulted from self-selection of healthier patients in the herbal-tea group -- healthy enough that they had no symptoms to serve as indicators of
. Those motivated enough to obtain an extract from Germany were those who had symptoms in which improvement could be seen.
Still, the great difference in the results between those who used concentrated, standardized extracts and those who used the herbal teas suggests that at least until more is known, it would be better to stay with extracts which are standardized for hypericin content, or else have been chemically tested and found to contain significant amounts of the chemical.

Available Extracts Containing Hypericin

So far there is more clinical experience for HIV with the Hyperforat product (the one used by Dr. Payne) than with any other; ideally, therefore, that would be the kind to use. Hyperforat has a chemically standardized hypericin content, so every batch of the preparation should be equivalent. But at this time there is no organized way to obtain the tincture from Germany.
To test alternatives which are more readily available, AIDS Treatment News bought several U.S. preparations and sent them to a chemist for analysis of the hypericin content. Three may be roughly comparable to Hyperforat; two others failed the test. We suspect that most of the St. John's wort extracts sold in health-food stores are worthless against HIV, as there is no testing or regulation of hypericin content. One of the samples we tested had less than a tenth of the hypericin expected.
Unfortunately there are several inconsistencies in the chemical test results we have seen. Therefore we cannot reliably estimate how much of the tinctures which are more readily available in the U.S. would be needed to be equivalent to the 120 drops per day used by Dr. Payne. All we can say is that the preparations listed below do appear to contain significant amounts of hypericin. We hope to get more precise chemical measurements in the future -- and also results for other preparations which we have not tested. Perhaps buyers clubs could work together to organize such a testing program.
The two German products mentioned favorably by the people we interviewed for this article were Hyperforat, used by Dr. Payne's patients, and Psychotonin M, used by some of the others. Hyperforat is standardized at 0.2 mg (200 micrograms) per ml. We do not know the concentration of Psychotonin M.
If it becomes possible to purchase these products in the U.S., they will probably cost twice as much as in Germany because of shipping expense. It may cost about a dollar and fifty cents per day for the dose Dr. Payne's patients used.
Not all German St. John's wort extracts are satisfactory. Some have only tiny amounts of hypericin.
In the U.S., a St. John's wort tablet from Yerba Prima Botanicals (see below) contains a standardized herbal extract obtained from Germany. According to the product label, each tablet contains 250 mg of St. John's wort extract, standardized at 0.14 percent hypericin. Using these specifications, we calculated that three and one half tablets contain about the same amount of hypericin (1.225 mg) as 120 drops of Hyperforat (1.2 mg, assuming 20 drops per ml). The tablets cost about $7. for 60 (retail price), so the total cost of this daily dose is about 40 cents. (The suggested adult dose on the label is less, one tablet twice a day.)
The St. John's wort tinctures from Jarrow Formulas, and from Herb Pharm, were found in our testing to contain significant amounts of hypericin. However, our test results had unexplained inconsistencies, so we do not trust them for computing doses. We do not know at this time what dose would be equivalent to 120 drops of Hyperforat.
Those who have used the tinctures but who cannot take alcohol have been putting the tincture into boiling water and letting it stand for at least two minutes to allow the alcohol to evaporate (instructions on Jarrow Formulas bottle). The heat cannot hurt the hypericin.

How to Order

As explained above, we do not yet know how to order Hyperforat (or Psychotonin M) St. John's wort extracts. The PWA Health Group in New York (phone number below) hopes to carry them. Meanwhile, the herbal extracts listed below are readily available.

When ordering any of these preparations, ask for St. John's wort extract, not hypericin. The people taking the orders seldom know what hypericin is.
Yerba Prima tablets: call 800/421-9972 or 415/632-7477, ask for "St. John's wort standardized extract" tablets. Yerba Prima is also distributed nationally in health-food stores.
Herb Pharm tincture: call 503/846-7178, ask for "St. John's wort tincture".
Jarrow Formulas: To find locations of health-food stores which carry the product, or to ask other questions about it, call Jarrow Formulas, 213/204-6936. To order by mail, call The Vitamin Trader, 800/334-9300 from California, 800/334-9310 from other states.. Ask for "St. John's wort herbal tincture extract".
Note: You can also purchase St. John's wort extracts through buyers' clubs. We suggest keeping in touch with these groups and seeing what they recommend. The ones we know which are already selling St. John's wort extracts, or will be very soon, are the PWA Health Group in New York, 212/532-0280; the Healing Alternatives Foundation in San Francisco, 415/626-2316; the Nutritional Products Buyers' Club in Los Angeles,

213/855-0533; and Alliance 7 in San Diego, 619/281- 5360. The New York, Los Angeles, and San Diego groups can ship orders.

Precautions

The following precautions for using St. John's wort extracts were suggested by one or more of the people we interviewed for this article.
* Let your doctor know what you are doing. At this time, few physicians know anything about this treatment. But if side effects develop, or if the medical community learns other information about St. John's wort which you should know, your physician can pass on the information if he or she knows that you need it.
* People can become abnormally sensitive to sunlight while using St. John's wort. Persons using the treatment should minimize exposure to sunlight or other ultraviolet light.
* We reported some side effects above -- especially one case of a severe skin rash apparently caused by using St. John's wort.
* Dr. Meruelo (whose team conducted the animal antiviral experiments mentioned above) suggested using a blood-chemistry panel, such as SMA 25, as an additional precaution. His group found slight, temporary changes in transaminases, LDH, and platelets in some rhesus monkeys, possibly caused by the pure hypericin used. All values returned to normal within 48 hours.
* One paper suggested the theory that hypericin works as a kind of antidepressant called an MAO inhibitor. Certain prescription antidepressants which are MAO inhibitors require avoidance of certain drugs and even certain foods, to avoid dangerous interactions. No one we talked to thought that any foods needed to be avoided with St. John's wort. While this problem seems remote, we thought we should mention the possibility.
* Dr. Rollo Hebert, a naturopathic physician in Seattle, Washington who is familiar with St. John's wort, cautioned that the antidepressant effect might give a false sense of well being, causing people to undertake tasks which are too stressful for them.
* No one knows the effects of long-term use of high doses of hypericin. It is known that the chemical can stay in the body for two weeks or more; therefore harmful concentrations might build up. Two people we talked to speculated that it might be better to take hypericin intermittently, not every day. There is no data yet to either support or contradict this possibility.

Clinical Trial Plans

Researchers at New York University, and at the Weizmann Institute in Israel, together applied for worldwide patent rights for antiviral use of hypericin. With the rights secured, they have been able to find funding for animal studies using chemically synthesized pure hypericin, and later clinical trials. A small Phase I trial may start later this year.
Meanwhile, Dr. Payne has written a protocol and already begun a formal trial of hypericin herbal extracts with and without half-dose AZT. He recruited 20 patients in the first few days, and expects to have 100 in as little as two weeks. Even though he is located in Arizona, where there are fewer persons with AIDS or HIV, recruiting has been no problem because the four patients he has already treated have many friends.
The trial with and without AZT is important, because hypericin appeared to be synergistic with AZT in an animal study -- meaning that both together might work better than either one by itself.
For more information, researchers and physicians can contact Dr. Payne in Mesa, Arizona.
Doctors Rollo Hebert and Don Brown, both naturopathic physicians in Seattle, Washington, are developing a protocol to test the effect of hypericin on P24 antigen levels and other measures of viral activity.
Keith Barton, M.D., in private practice in Berkeley, California, is interested in monitoring P24 antigen levels. Persons must be located close enough to visit the office, and be P24 positive. Dr. Barton is currently monitoring P24 levels of patients using certain Chinese herbs.
There may also be trials through community-based research organizations such as New York's Community Research Initiative, or San Francisco's County Community Consortium, or Community Research Alliance. There are
no detailed plans at the time of this writing, however, because the first human results (reported in this article) are so new.

Call for Information


If you use hypericin, even for a short time, AIDS Treatment News would like to hear about your experience. We are especially interested in laboratory test results, including P24 antigen, standard tests including T-helper count and white count, and (if possible) HIV cultures. Call or write John James or Denny Smith, AIDS Treatment News, P.O. Box 411256, San Francisco, CA 94141, 415/255-0588.

Conclusion

At this time hypericin looks promising as a possible AIDS/HIV treatment. It deserves prompt attention.
But many treatments have looked good at first, then proved disappointing later. With only three months' experience and anecdotal reports from a handful of patients, it is too early to know whether hypericin will prove valuable, or how much risk is involved.
People should be cautious, especially until more is known.

References

Meruelo D, Lavie G, and Lavie D. Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: Aromatic polycyclic diones hypericin and pseudohypericin. Proceedings of the National Academy of Sciences, USA, vol. 85, pages 5230- 5234, July 1988.
Note: We are preparing a list of technical references. For a copy, send a self-addressed stamped envelope to: Hypericin References, AIDS Treatment News, P.O. Box 411256, San Francisco, CA 94141.