Mistletoe Therapy

For thousands of years, mistletoe has been viewed as one of the most magical, mysterious, and sacred plants in nature. Mistletoe, or Viscum, was used by the Druids and the ancient Greeks, and appears in legend and folklore as a panacea. The modern tradition of kissing under the mistletoe can be traced back to ancient mistletoe lore. Mistletoe is a parasitic plant that attaches to and penetrates the branches of a tree or shrub by a structure called the haustorium, through which mistletoe absorbs water and nutrients from the host plant. Though there are hundreds of species of mistletoe worldwide, only Viscum Album is used to treat cancer. In the scientific community, mistletoe has been studied as an anticancer agent since the 1920s because its extracts have exhibited both cytotoxic and immunomodulatory properties. Currently, mistletoe extracts are used to treat a variety of conditions including cancer, HIV, hepatitis, and degenerative joint disease. In this article, I focus on the proven benefits, research, and application of injectable mistletoe extract in breast cancer treatment. Injectable mistletoe extract was first used for cancer therapy in the 1920s by Rudolf Steiner, Ph.D., and Dr. Ita Wegman based on anthroposophical medicine principles.1, 2, 3, 4 In Europe, mistletoe therapy is no longer controversial, and oncologists have continued to prescribe mistletoe extracts for the past 90 years. By some estimates, 40% of French5 and up to 60% of German cancer patients6 receive this botanical extract. The U.S. FDA, however, has not approved mistletoe as a treatment for cancer or any other medical condition. Accordingly, the FDA does not allow injectable mistletoe to be imported, sold, or used except for clinical research. Fortunately for patients in the U.S. there are still ways to obtain injectable mistletoe extracts from Europe, despite these government restrictions. Every year, Germans alone spend more than $30 million on mistletoe preparations as cancer treatment. Results of a national survey conducted in Germany in l995 by the Society for Biologic Cancer Defense found that mistletoe preparations were the most frequently prescribed botanical drug (80%) followed by trace elements, vitamins, enzymes, and xenogenic peptides like thymus preparations. In Germany, Switzerland, and Austria, mistletoe preparations are licensed medicines that are partly reimbursable through the official healthcare system. Actress, author, and breast cancer survivor Suzanne Somers revealed in her 2009 book Knockout that she opted to use mistletoe extracts in her breast cancer treatment. Despite its popularity and long usage in Europe, for many people in North America this was the first time that they had heard of mistletoe therapy. The U.S. medical media rarely covers ongoing evidence-based mistletoe research. Commercial Mistletoe Extracts

Mistletoe extracts are primarily manufactured in Europe and sold under brand names including:

  • Iscador (also called Iscar)

  • Helixor

  • Eurixor

  • Isorel (also called Vysorel)

  • Iscucin

  • Lektinol (also called Plenosol)

  • abnobaVISCUM

Though there are several types of mistletoe extracts available in Europe, the most commonly prescribed is Iscador, which is distributed by Weleda AG in Schwäbisch Gmünd, Germany. The manufacture and quality assurance of Iscador is regulated by European law. Iscador is prepared by fermenting an aqueous extract of the whole mistletoe plant with Lactobacillus plantarum. The product is filtered to remove bacteria before standardization and packaging for injection. Formulations are labeled based on the tree from which the mistletoe was harvested. For example, Iscador M for malus (apple); Iscador P for pinus (pine); Iscador A for abies (fir); Iscador Qu for quercus (oak); and Iscador U for ulmus (elm), with different effects attributed to each type. Tree varieties of mistletoe are selected for different types of cancer, with Iscador M used most often in breast cancer.7 Apple tree mistletoe extracts have also proven beneficial for tumors of the lower abdomen (colon, bladder, uterus, and ovaries), and upper abdomen (stomach, liver, and pancreas). It is also important to understand that not all mistletoe preparations are similar. Some are made from whole plant extract (Iscador, Helixor) while others contain only mistletoe Lectin I, a single chemical from the mistletoe plant (Eurixor). Many of the Iscador preparations are also available with additional homeopathic dosages (D8) of certain metal salts — for example, malachite (copper carbonite), mercury sulphate and silver carbonite. These compositions are based on anthroposophical principles of treatment and augment the specific mistletoe treatment. Mistletoe Constituents and their Effects

Constituents of mistletoe with tumor-reducing components include specific lectins such as viscumin and viscotoxins, alkaloids, polysaccharides, and polyphenolic substances. Other components include carbohydrates, phenolic compounds, sterols, triterpenes, and amines.8 Isolation of lectin and alkaloid components of mistletoe extracts has yielded reproducible tumor-reducing properties. Mistletoe lectins are the most investigated single component of mistletoe extracts, with cytotoxic effects attributed in part to ribosome-inactivating properties and apoptotic induction.9 Lectins are proteins or glycoproteins with specific binding sites for sugars which are not antibodies or enzymes. Mistletoe lectins have been shown to induce macrophage and natural killer cell cytotoxicity10, stimulate phagocytosis of immune cells, increase TNFα, IL-1, IL-2, and IL-6 cytokine secretion, and enhance cytotoxicity effects on various cell lines in vitro.11 Mistletoe lectins also react with red blood cells and certain immunoglobulins, and have experimentally induced cytotoxicity by inhibiting protein synthesis on the ribosomal level. Their “A-chain properties” exhibit mitogenicity and inhibit synthesis in cell-free systems. A-chain properties are also candidates for construction of immuotoxins. Their “B-chain properties” activate macrophages and release lymphokines from lymphocytes, as well as inhibit allergen-induced histamine release from leukocytes and collagen-induced serotonin release from platelets.12 Hence, mistletoe lectins activate the immune system in several ways to reduce tumor growth. Specifically, three different mistletoe lectins have been isolated, and of these, viscumin and viscotoxins are the most researched. Viscumin has been shown to interfere with intracellular protein synthesis13, 14, stimulate the production of tumor necrosis factor15, 16, and activate leukocytes.17 Viscumin may also affect the processes of metastasis and apoptosis.18 Viscotoxins, or thionins, are cytotoxic, small molecular weight proteins that have a molecular structure similar to that of viscumin, but are more cytotoxic and able to induce cellular necrosis of tumors. Mistletoe viscotoxins are responsible for immunostimulant and tumor-inhibiting activities.19 Mistletoe alkaloids are also toxic for tumor cells, but have not been as extensively researched as the lectins. Mistletoe polysaccharides may have an immune boosting effect, by the stimulation of the neutrophil granulocytes.20 Mistletoe Extract Research

Mistletoe extracts have been extensively researched over the last 70 years. Numerous in vivo, in vitro and human studies have confirmed that mistletoe extracts can boost the immune system which enhances tumor destruction or shrinkage.21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 Most of the clinical studies on the efficacy of mistletoe extract on health-related quality of life and survival time have been conducted in Germany and Switzerland, with some in Russia, Serbia, and the Ukraine. Of the commercial mistletoe extracts, Iscador and Helixor are the most thoroughly researched. Iscador has produced the following results in breast cancer patients after one intravenous infusion: enhancement of phagocytic activity of white blood cells; significant increase in natural killer cell and antibody-dependent cell mediated cytotoxicity; and augmented levels of large granular lymphocytes.38 In 2007, in vitro research with Iscador Q, Iscador M, and Iscador P indicated that different Iscador preparations can induce cell cycle inhibition and tumor cell regression. Researchers observed complete inhibition of S-phase progression in MCF7 breast cancer cell line.39 Several human studies support the use of mistletoe extracts for cancer care. Most have shown mistletoe to reduce side effects of cytotoxic chemotherapy and radiotherapy, and to prolong survival.40, 41, 42 In human studies, mistletoe improved cancer-treatment related toxicities in patients with advanced non-small cell lung cancer43 and colorectal cancer44, and reduced symptoms and improved quality of life in patients with pancreatic45 and breast cancers.46 Mistletoe administered in conjunction with gemcitabine in patients with advanced solid tumors allowed higher gemcitabine doses to be used without apparent effects from mistletoe on gemcitabine pharmacokinetics.47 Epidemiological data also suggests a survival advantage following mistletoe treatment. In 2001, German researchers performed a multi-cancer prospective long-term epidemiological cohort study on the efficacy and effectiveness of Iscador on survival times including 10,226 patients with dif