AIDS Treatment News No. 019 (San Francisco Sentinel) - December 7, 1986
John S. James

Published medical studies, mostly from Japan, strongly sug- gest that lentinan may be valuable. But U. S. physicians cannot obtain the medicine, because of bureaucratic and commercial barriers -- a situation unlikely to change soon since apparently no formal research is being conducted on AIDS and lentinan in the U. S., in Japan, or anywhere else.

Meanwhile, the mushrooms are available in grocery stores, and health food stores sell shiitake extracts. Researchers believe that lentinan could be effective orally if used properly. However, much of the commercial-product literature does not reflect information obtained from the scientific studies and medical trials. Anyone using lentinan should know what has been learned about how it should or should not be used.

This article will discuss the Japanese use of lentinan with cancer and with a single case of ARC, and mention some of the many immune effects of this substance. Then we will look at the shiitake preparations available now in the United States, and what should be known about using them.

In this article we can only touch on the very large subject of immune potentiators and antivirals from medicinal fungi.

Lentinan and Cancer

Japanese physicians have used highly purified lentinan as an immunotherapy in clinical trials with hundreds of patients with gastric and other cancers. Study after study found that lentinan combined with chemotherapy worked better than chemotherapy alone. For a review of the immune effects of lentinan, and its use in cancer treatment, see Aoki, 1984 (reference below). Tadao Aoki is the world's leading authority on the medical use of lentinan. Dr. Aoki has repeatedly urged that lentinan be tested for ARC or AIDS.

Early animal studies of lentinan found no anticancer effect; later, scientists realized that the cause of this failure was that too large a dose had been used. With a correct dose, lentinan caused complete regression of certain cancers in mice (see Aoki, 1984). The doses which failed were ten to 80 times too large, suggesting that the effective range may not be too critical.

Lentinan has many immune effects. Researchers are now most interested in its enhancement of "natural killer" (NK) cells, which, like T cells, are a subgroup of white blood cells. Lentinan can also increase gamma interferon production.

One study found that lentinan alone was not very effective in treating human cancer. For better results, doctors combine it with chemotherapy. The lentinan should be started first (Aoki, 1984).

In both humans and animals, lentinan did not work if there was a protein deficiency (Akimoto, 1986).

Physicians have found that to get the greatest effect, they should avoid giving lentinan every day. Aoki, 1984, suggested a dose of 1 mg twice a week. More recently, this dose has been given every other day.

Doctors usually administer lentinan by injection, either intravenous or intramuscular. It can also be taken orally, but about five times the dose is required.

We can find just one published case of lentinan used to treat KS. The patient, an 84 year old man who also had lung cancer, did not have AIDS. The KS lesions quickly improved, and disappeared in a couple months (Aoki and others, 1981).

Lentinan and AIDS

There is only one published case where doctors used lentinan for treating AIDS or ARC. But this case is crucial, because a person with ARC became antibody negative and remained that way even without the drug. She also improved clinically and is in good health today, two years later.

The published report of this case appeared two years ago in THE LANCET (Aoki and others -- LANCET). The researchers also released a more detailed report (Aoki and others -- PROCEEDINGS). This writer learned of the current status through private communication.

The patient, apparently exposed to AIDS by a transfusion, had grown progressively weaker, and repeatedly tested positive for AIDS antibodies. The T4 count was under 300, and other blood tests also suggested ARC.

One mg per day of lentinan was given daily for five months; at that time the doctors did not know that giving it less often would be more effective. The patient's condition improved, and the blood counts went in the right direction. The T4 count reached about 500, although the T4/T8 ratio declined because the T8 count increased faster.

After four months, the AIDS antibody test became negative and remained that way. Two years later, the patient is healthy. We do not know recent blood counts.

Political Problems

Obviously this case should be followed up, especially since lentinan has no serious side effects. But two years after publication in one of the most widely circulated medical journals, we know of no other person with AIDS, ARC, or a positive test who has received lentinan, anywhere in the world. U. S. physicians cannot obtain the drug; Japanese physicians can use it, but they have few AIDS/ARC patients.

At this time, the Bristol-Meyers corporation has an option to buy U. S. license rights to lentinan. We have heard that they have applied to the U. S. Food and Drug Administration for an IND -- permission to test an experimental drug -- but have not yet received it. We do not know whether Bristol-Meyers is interested in AIDS; the obvious commercial use for lentinan would be for treating cancer. Even if they are interested in trying it as an AIDS treatment, it could take years before it even gets tested on a handful of patients.

The U. S. National Institutes of Health could obtain lentinan and test it, but so far has shown little interest. A colleague of Dr. Aoki sent a thousand doses to Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, but received no reply. Perhaps the package got lost in the mail.

The U. S. National Cancer Institute has added lentinan to a list of over 80 drugs which people have suggested as possible treatments for AIDS. It's AIDS Drug Selection Committee plans to consider whether or not to follow up.

What's Available Now?

It may be possible to get lentinan treatment abroad.

We have heard conflicting reports about whether persons known to have AIDS, ARC, or a positive antibody test can enter Japan for medical treatment, or for any other reason. The Japanese consulate was non-committal, which suggests that there may be a problem, and that we might not find out until someone tries to go.

It may also be possible for clinics in Mexico or other coun- tries to buy lentinan from Japan.

Another approach is to develop this treatment from available materials, outside of the official research system. The shi- itake mushrooms, which contain lentinan, and various extracts sold in health-food stores, are readily available.

Researchers believe that lentinan can be effective when taken orally, if five times the injected dose is used. In November 1986, Dr. Aoki visited the U. S. National Institutes of Health and reported on the treatment of 59 patients for an immune deficiency called low natural killer cell condition; they received intravenous lentinan in the hospital, then took mainte- nance doses orally as outpatients. The natural killer cell activity improved greatly, an effect likely to be important for treating KS and other cancer.

What we don`t know is how much lentinan is in the mushrooms or the commercial preparations. We don't yet know of any company which has tested its material and calibrated its pills or powder so that users know what they are getting. The chemical test is not available commercially, but could be done in a university lab.

It is important that the products be tested, because too much lentinan can be not only ineffective, but harmful, because it can have the opposite of the intended effect. In one of the cancer studies, overdoses ten times too high markedly depressed the immune response (Aoki, 1984). But side effects of proper doses, which can include skin rashes and a feeling of heaviness in the chest, are rare and not serious when they do occur (Aoki, 1984). They clear up when the lentinan is stopped.

Lentinan is "heat stable" (Aoki, 1984), which probably means it survives normal cooking. One paper reported 30 cases of skin rashes and itching, seen by dermatologists over nine years, caused by eating shiitake as an ingredient of oriental cooking (Nakamura and Kobayashi, 1985). The dermatologists believe that these effects were caused by lentinan, suggesting that it may be possible to get an effective dose through normal use of shiitake as food. Shiitake has long been a folk medicine for cancer in Japan and other Asian countries; and until U. S. physicians can get lentinan, traditional ways of using the mushroom may be the best available.

Much of the commercial health-product literature for shi- itake preparations fails to inspire confidence. One flyer claims that its shiitake tablet "may be effective" for "allergy, hypertension, liver trouble, tumor, kidney trouble, post-operative discomfort, lymphnode, infectious hepatitis (B) (sic), collagen disease, rheumatism, gout, diabetes mellitus, gonorrhea, AIDS, common cold or flu, loss of energy". Another suggests what might be called the Godzilla theory of medicine:

"It is believed that the mycelium in the earth had the strength to push its way through a thick layer of concrete. Obviously, if this tremendous power could be utilized for the good of the human body, amazing results could be expected."

People facing death deserve better. We can let the public and professionals know the importance of this potential AIDS/ARC treatment, and the fact that it has been neglected for two years for no medical or scientific reason. A medicine known to be safe, easy to use, and outstandingly effective in the single case tried, at least deserves a second look. If more people were close enough to AIDS treatment research to know what is going on, they would insist that some way be found through the red tape and commercial obstacles which now block testing of some of the most promising treatment leads.

****** References

Akimoto M, Nishihira T, and Kasai M.: Modulation of the Anti- Tumor Effects of BRM Under Various Nutritional or Endocrine Conditions. GAN TO KAGAKU RYOHO, Volume 13 Number 4 Part 2, pages 1270-1276, April 1986 (English summary).

Aoki T. Lentinan. In Fenishel RL and Chirgis MA, editors, IMMUNE MODULATION AGENTS AND THEIR MECHANISMS, pages 63-77. Marcel Dekker, Inc., New York and Basel, 1984.

Aoki T, Miyakoshi H, Horikawa Y, and Usuda Y. Staphage Lysate and Lentinan as Immunomodulators and/or Immunopotentiators in Clinical and Experimental Systems. In Hersh EM, Chirigos MA, and Mastrangelo M, editors, AUGMENTING AGENTS IN CANCER THERAPY, page 101-112, Raven Press, New York, 1981.

Aoki T, Miyakoshi H, Usuda Y, Chermann JC, Barre-Sinoussi F, Ting RC, and Gallo RC. Antibodies to HTLV I and III In Sera From Two Japanese Patients, One With Possible Pre-AIDS. THE LANCET, page 936-937, October 20, 1984.

Aoki T, Miyakoshi H, Usuda Y, Ting RC, and Gallo RC. Lentinan Treatment of Japanese Cases Infected With Human T-Lymphotropic Retroviruses (HTLV-I and -III). PROCEEDINGS OF THE SIXTH SYMPOSIUM ON RATIONALE OF BIOLOGICAL RESPONSE MODIFIERS IN CANCER TREATMENT, Hakone, Japan, August 31-September 1, 1984.

Nakamura T and Kobayashi A. Toxicoderma caused by the edible mushroom shiitake (lentinus edodes). HAUTARZT, pages 591-593, October 1985 (English summary).

Wakui A and others. Randomized Study of Lentinan On Patients With Advanced Gastric and Colorectal Cancer. GAN TO KAGAKU RYOHO, April 1986 (English summary).

For More Information:

To find out more about lentinan, you can call Ivan John, (212) 288-2952. Call between 8 and 9 PM, New York time (5-6 PM in San Francisco). Ivan John is a medical student working with Nathaniel Pier, M. D., to get lentinan tested for AIDS or ARC.

This article is the 16th in the author's series on experimental AIDS/ ARC treatments. Other treatments covered include DNCB, AL 721, naltrexone, BHT, glycyrrhizin, and AZT.

861207
ATN01901

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1986. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .