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to Menu Page~repeating the stings over a period of time. For example, it is suggested that the venom be injected into arthritic patients at trigger points in a daily course of treatment that lasts 4 to 8 weeks. Proponents indicate that there are typical patterns of responsiveness, depending on the ailment. A 50-year-old patient with arthritis might note pain relief in 2 weeks, mobility in 3 weeks, and freedom from symptoms in 4 weeks (Weeks, 1994).
Research on bee venom has included studies of whole venom and venom products. For example, in the 1960s and 1970s, studies on bee venom to treat rheumatic diseases were conducted by William H. Shipman of the U.S. Navy Radiological Defense Laboratory, James Vick of the Walter Reed Army Hospital Medical Research Center, and Gerald Weissman of New York University Hospital and their colleagues, with funding by private and public sources. One finding was that whole bee venom could suppress the development of an induced arthritis in rats, although it could not alleviate the illness after it had started (Zurier et al., 1973). Treatment with separate fractions of bee venom had no positive effect.
In later studies in which the components of bee venom were purified further, the various ~properties, such as anti-inflammatory and antibacterial activity (see table 1), began to be associated with specific materials.
In a more recent study (Kim, 1992), a randomized, controlled trial was conducted comparing true honeybee venom therapy with a "sham" product for 180 patients suffering from chronic pain and inflammation; solutions were injected twice weekly for 6 weeks. Significant posttreatment reductions in pain and inflammation were recorded in the true bee venom therapy group and were maintained at 6-month followups.
The American Apitherapy Society endeavors to coordinate information on bee venom research. Starting with 100 citations 12 years ago, when patients in his medical practice first interested him in the subject, Bradford Weeks, the society's president, has now acquired more than 12,000 case reports on persons treated with bee venom (Weeks, 1994). Together, these 12,000 reports are the basis for the ongoing National Multicenter Apitherapy Study. Approximately 200 physicians and 200 beekeepers voluntarily contribute reports.~At this time, the database for the multicenter study contains mostly anecdotal information, such as "I had an illness; I was stung by bees; my health improved." As Weeks notes, there is no proof in such reports that a person really had the specified illness and really improved because of the bee venom treatment.
The American Apitherapy Society would like to obtain research funds to improve the collection of both retrospective (past) information and prospective (future) data. Funding could provide research staff to search out medical records for proof of illness, training for research staff and bee venom therapists on how to gather data, and support for statistical analyses.
Meanwhile, the multicenter study has in its database some 1,300 reports on patients with multiple sclerosis (subjectively reporting increased sensation and bowel and bladder control), 2,800 with rheumatoid arthritis, and other groupings of data on such problems as gout, viral illnesses, and premenstrual syndrome--nearly 100 percent of 40 women being treated for premenstrual syndrome by apitherapy became symptom free, according to ~Weeks (1993).
In some ways, apitherapy is a classic alternative therapy. It has ancient roots and, although discarded by mainstream medicine, has survived in folk practice.
Iscador/Mistletoe
Iscador is a liquid extract from the mistletoe plant (Viscum album) that has been used to treat tumors for more than 60 years (Hajto et al., 1990a). A complex mixture, iscador has two properties that are thought to make it effective against tumors. Iscador is cytostatic and sometimes cytotoxic--that is, it can stop cell growth, sometimes even killing cells. In addition, iscador has immunostimulatory properties, affecting the immune system. Two protein components of the mistletoe extracts appear to be the major active ingredients, viscotoxins and lectins (Jung et al., 1990).
The mistletoe lectins have been studied in more detail than the viscotoxins. In general, lectins ~are a group of sugar-containing proteins that are able to bind specifically to the branching sugar molecules of complex proteins and lipids on the surface of cells. Certain lectins have both cell-killing and immunostimulatory activity. Their toxic effect occurs because they can stop protein synthesis in cells.
Viscotoxins can kill cells but do not act on the immune system. They act by injuring cell membranes. Considering the toxic properties of both major active ingredients of mistletoe extracts, it is not surprising that mistletoe itself can be poisonous and that proponents of iscador provide cautions about how much to take.
One study examined a lectin from a proprietary mistletoe extract that has been reported to show ability to affect the immune system in rabbits (Hajto et al., 1989). When a tissue culture of certain white blood cells was exposed to this lectin, increased secretion of certain immune system products resulted, including TNF alpha and interleukins 1 and 6, which are cytokines (see the glossary). In turn, there was an increase in the number and activity of certain types of white blood cells. A corroborating increase was seen in cytokine levels in ~serum of patients after injection of lectin doses (Hajto et al., 1990b).
Both the cell-killing and the immunostimulatory activities of iscador could potentially affect tumor cells. Whether iscador is an appropriate treatment for cancer has been the subject of at least 46 published clinical studies (6 collective reports, 5 small historical studies, 9 large historical studies, 14 retrospective studies, 10 prospective studies, and 2 randomized studies), which were reviewed by Helmut Kiene (Kiene, 1989). None of the studies fit the format of a controlled, randomized, double-blind clinical trial (see app. F). Kiene points out that such studies would be difficult to do because visible local skin irritations appear early in mistletoe treatments; thus both patient and doctor would know about the treatment.8
Of 36 studies that Kiene decided were evaluable, he reported that 9 showed positive, statistically significant effects against diverse cancers, including ovarian, cervical, breast, stomach (postoperative), colorectal, and bronchial cancers and liver metastases. Usually the effect was to lengthen the survival time of the patient, commonly measured as median or average survival time; in one study, a significant reduction in the use of painkillers and ~psychopharmaceuticals was observed (see the glossary). The reviewer noted that the effect of mistletoe therapy tended to appear in situations involving patients with advanced stages of disease rather than patients with less advanced illness.
The antitumor effects observed in these studies with people are supported by studies with animal tumors. Furthermore, except for skin irritations, few uncomfortable side effects are reported by patients. This finding contrasts with the discomforts associated with more traditional anticancer radiation treatments and chemotherapy.
Much of the previous research was conducted in Germany, and the lead organization for a new study is also based there. NCI's Physicians' Data Query index identifies this study as a Phase III randomized trial of adjuvant treatment with INF-A (interferon alpha) versus INF-G (interferon gamma) versus mistletoe extract (iscador M) versus no further treatment following curative resection of high-risk stage I/IIB malignant melanoma.9 A three-volume compendium of research papers on iscador, including translations of some from German, is available (Scharff, 1991).~Revici's Guided Chemotherapy
Emmanuel Revici, a Romanian-born physician, is still practicing in New York City in his late nineties. (His license was suspended in November 1993, but that is being challenged.) Revici has developed an approach to illness (particularly cancers) that he calls biologically guided chemotherapy (Lerner, 1994; Revici, 1961). The basis of Revici's approach is a concept that disease involves a biological dualism. While in a healthy body anabolism and catabolism balance, in a diseased body their imbalance results in diseases that are either anabolic (see the glossary) or catabolic. Correspondingly, the way the diseased body responds to treatment differs depending on the type of imbalance. In their choices of therapies, physicians must therefore be guided by which condition predominates.
Revici ascribes the effects of tumor cells to lipid imbalances. If fatty acids predominate--a catabolic condition--the tumor tissues are described as having an electrolytic imbalance and alkaline environment. If, instead, sterols predominate--an anabolic condition--there is a reduction in cell membrane permeability, according to Revici.~The patients Revici determines to have a predominance of fatty acids are treated with sterols and other agents with positive electrical charges that can theorectically counteract the negatively charged fatty acids. If sterols are predominant, treatment is with fatty acids and other agents that can increase the metabolic activity of fatty acids. The determination of anabolic (rich in sterols) or catabolic (rich in fatty acids) character is based on a series of medical tests and judgments about body type. For example, a lean individual would be more likely to have a catabolic condition, and a rounded individual, an anabolic one; Revici also considers females more likely to have an anabolic character, and males, a catabolic one. Based on the various tests, an individualized chemotherapy program is designed for each patient with cancer. (This individualization makes it harder to conduct controlled studies of treatment effectiveness.)
Along with Revici's choice of type of lipid to administer, he may incorporate other materials, such as selenium, in his lipid envelope. According to his theory, the additional agent will be delivered ("guided") directly to the tumor site because of the site's affinity for the selected lipid carrier. Because of this specificity, lower systemic drug toxicity is expected.~OAM has expressed interest in an evaluation of Revici's approach as a cancer treatment. Besides anecdotal reports concerning Revici's patients, one independent clinical trial was already conducted by Joseph Maisin, director of the Cancer Institute of the University of Louvain, Belgium. Although the results were never published, Maisin is reported to have written to Revici that dramatic improvements occurred in 75 percent of 12 terminal cancer patients. These improvements included tumor regression, disappearance of metastases, and cessation of hemorrhage.
Revici has applied his dualistic theory to other conditions besides cancer. He first developed therapies for different kinds of pain. Among the other conditions he is reported to have addressed are itching, insomnia, vertigo, migraine, radiation burns, osteoarthritis, rheumatoid arthritis, convulsions, postoperative bleeding, AIDS, ileitis, colitis, and drug addiction.
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