How useful is a therapy? How certain are we about this? Where do we collect our information? In order to come to a personal judgment about a therapy, we need to look at the results of scientific studies. However, the body of scientific information keeps growing, the results are widely scattered and often not easy to obtain.
These web pages offer an updated overview of the scientific studies of the clinical use of mistletoe products for cancer. Our information platform is meant for medical doctors, scientists, journalists, decision makers in regulatory agencies and health insurance companies, interested students, and patients who are looking for information on the state of the art of clinical research and relevant clinical experience.
These information pages have been prepared and compiled according to scientific criteria. They do not in any way recommend or endorse specific products or manufacturing companies, they do not host any form of advertisement.
Mistletoe extracts (Viscum album L., VAE) are a complementary treatment of cancer, widely used in integrative cancer care. In Europe, 40% (15 -73%, depending on country) of cancer patients make use of complementary medical therapies - mostly herbal remedies ; in Central Europe most frequently prescribed are mistletoe extracts [9a, 16, 19, 24]; this also includes children with cancer diseases [15c]. Mistletoe treatment is appraised by German physicians as a beneficial oncological treatment .
Mistletoe treatment for cancer was introduced in 1920 by Rudolf Steiner and Ita Wegman, founders of Anthroposophical Medicine . Since the 1920s, a substantial amount of diverse research projects have been undertaken to investigate the influence of mistletoe extracts on tumour behaviour: on tumours in animals or plants; on tumour cells in vitro; on the course of disease in cancer patients; and on other relevant biological processes. From about 1980 onwards, oncological mistletoe research gained considerable momentum and, as a result, a wealth of scientific research from a multitude of international scientific institutions is available, particularly with regard to basic research (reviewed in [2, 12]).
The biological and pharmacological properties of Viscum album L. extracts (VAE) have been subject to extended scientific investigations [reviewed in [2, 12]). Several pharmacologically active compounds have been isolated, such as mistletoe lectins (ML I, II and III) [9b], viscotoxins [25, 26] oligo- and polysaccharides [15a, 18], lipophilic extracts  and various others [2, 12]. The most prominent properties of VAE are their cytotoxic and growth-inhibiting effects, in vitro, on a variety of human tumour cell lines, lymphocytes and fibroblasts [2, 12]. The cytotoxic effects of VAE are mainly due to the apoptosis-inducing mistletoe lectins [7, 8, 10], while the viscotoxins induce necrotic cell death [6, 8]. VAE are also recognized for their immune-modulating activity: In vitro and in vivo studies have demonstrated activation of monocytes/macrophages, granulocytes, natural killer (NK) cells, T-cells (especially T-helper-cells) and the induction of various cytokines [2, 12]. VAE also possess DNA stabilizing properties, they reduce chromosome damage and improve DNA repair [3-5, 15b]. In animals, VAE displays potent antitumoural effects when administered either directly into the tumour or systemically [2, 12]. Currently, mistletoe lectin I, an important compound of mistletoe extract, is also being produced as a recombinant and being tested for application in clinical oncology . (See basic research)
For the treatment of cancer, mistletoe extracts are usually injected subcutaneously, but sometimes they are applied locally, around or directly into the tumour or into body cavities (intrapleural, intraperitoneal, intrapericardial) or administered as an intravenous infusion. Occasionally they are given orally or intravesically. In principle, mistletoe extracts are used to treat all types of cancer, either alone or as an adjuvant to conventional cancer treatments (surgery, chemotherapy, radiotherapy, hormone treatment), in both curative and palliative situations, as a short-term therapy over a few weeks or months or as long-term therapy over many years. On the one hand, dosage is adapted according to the individual situation, diagnosis, stage, pretreatment, general condition, immune status and response to therapy, often also considering rhythmological characteristics; treatment is generally commencing with low dosage and gradually increasing thereafter; occasionally a high dosage is given at the start of therapy (see Cohort Studies). Alternatively, the mistletoe extracts are administered in a standardised manner, according to their lectin content, for example. (See Standardisation – Dosage)
The clinical effectiveness of mistletoe is a subject of controversial debate. A large number of clinical studies have been carried out in recent decades in order to shed light on this matter. There are to date a multitude of studies employing different designs. On anthroposophic preparations 30 prospective randomised controlled trials, 18 non-randomised prospective comparative studies, 42 retrospective comparative studies , and 40 single-arm studies are available. Nevertheless, if only double-blind, randomised controlled trials with large case numbers are regarded as acceptable evidence, a frequently encountered opinion today, satisfying answers will not be found for a great number of questions. (In these studies, for instance the validity of double-blinding - where neither doctor nor patient are informed whether mistletoe extract or a placebo is being injected - is questionable because subcutaneous administration of mistletoe are unblinded through both the patient and the doctor [1, 20]). However, those who also acknowledge other types of well-conducted research - medium-sized and smaller RCTs, carefully conducted comparative studies without randomised therapy allocation, cohort studies and case series - will discover a broad spectrum of interesting evidence and significant clinical observations. (See Clinical Trials)
Different mistletoe preparations are available for the treatment of cancer. Abnobaviscum®, Helixor, Iscador®, Iscucin® and Isorel® are produced according to anthroposophical methods; other mistletoe preparations include Cefalektin®, Eurixor® and Lektinol®. In the past, Plenosol has also been used in cancer therapy. The anthroposophical preparations are available from different host trees such as oak, apple, pine and others (see Overview Table). Harvesting procedure is standardized, and the juices from summer and winter harvests are mixed together. The total extract of VAE is considered essential for full effectiveness and concentration of its compounds is ensured through process standardisation. The non-anthroposophical preparations are harvested in winter from poplars (see Overview Table); they are standardized and dosed according to mistletoe lectin content (ranging from 1 ng/kg up to 15 ng/kg bodyweight) on the premise that mistletoe lectin is the main active ingredient. (See Standardisation – Dosage and Standardisation – Single substance vs. Total Extract).
The scientific information presented on this website regarding mistletoe therapy is substantiated by existing scientific research, specifically by means of a systematic compilation and evaluation of the clinical trials, the basic research, the assessments of tolerance and risk aspects and a discussion of the diverse underlying conceptions of cancer and its treatment [2, 11-14]. For the purpose of this information website, the studies have been summarised, systematically presented and annotated. Since the most recent work in this regard - a methodical review and critical evaluation of available scientific evidence concerning anthroposophical medicine (Health Technology Assessment Report) [13, 14] - is limited to the field of anthroposophical medicine (most existing research concerns anthroposophical preparations), the following detailed overview of clinical trials also concentrates on anthroposophical mistletoe preparations to begin with. Most systematic reviews also include studies regarding non-anthroposophical mistletoe preparations.
Gunver S. Kienle, MD
 Auerbach, L., V. Dostal, I. Václavik-Fleck, E. Kubista, A. Rosenberger, S. Rieger, W. Tröger and J. M. Schierholz, Signifikant höherer Anteil aktivierter NK-Zellen durch additive Misteltherapie bei chemotherapierten Mamma-Ca-Patientinnen in einer prospektiven randomisierten doppelblinden Studie. In. Fortschritte in der Misteltherapie. Aktueller Stand der Forschung und klinischen Anwendung. (Ed. R. Scheer et al.) pp. 543-554, KCV Verlag, Essen (2005).
 Büssing, A. and (ed.), Mistletoe.The Genus Viscum. pp. 1-265, Hardwood Academic Publishers, Amsterdam (2000).
 Büssing, A., T. Azhari, K. Ostendorp, A. Lehnert and K. Schweizer, Viscum album L. extracts reduce sister chromatid exchanges in cultured peripheral blood mononuclear cells. Eur J Cancer 30A, 1836-1841 (1994).
 Büssing, A., H. Jungmann, K. Suzart and K. Schweizer, Suppression of sister chromatid exchange-including DNA lesions in cultured peripheral blood mononuclear cells by Viscum album L. J Exp Clin Cancer Res 15, 107-114 (1996).
 Büssing, A., A. Regnery and K. Schweizer, Effects of Viscum album L. on cyclophosphamide-treated peripheral blood mononuclear cells in vitro: sister chromatid exchanges and activation/proliferation marker expression. Cancer Lett 199-205 (1995).
 Büssing, A., G. Schaller and U. Pfüller, Generation of reactive oxygen intermediates (ROI) by the thionins from Viscum album L. Anticancer Res 18, 4291-4296 (1998).
 Büssing, A., K. Suzart, J. Bergmann, U. Pfüller, M. Schietzel and K. Schweizer, Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins. Cancer Lett 59-72 (1996).
 Büssing, A., W. Vervecken, M. Wagner, B. Wagner, U. Pfüller and M. Schietzel, Expression of mitochondrial Apo2.7 molecules and Caspase-3 activation in human lymphocytes treated with the ribosome-inhibiting mistletoe lectins and the cell membrane permeabilizing viscotoxins. Cytometry 37, 133-139 (1999).
[9a] Fasching, P.A., F. Thiel, K. Nicolaisen-Murmann, C. Rauh, J. Engel, M.P. Lux, et al. Association of complementary methods with quality of life and life satisfaction in patients with gynecologic and breast malignancies. Support Care Cancer 55 (11), 1277-84 (2007).
[9b] Franz, H., P. Ziska and A. Kindt, Isolation and properties of three lectins from mistletoe (Viscum album L.). Biochem J 195, 481-484 (1981).
 Janssen, O., A. Scheffler and D. Kabelitz, In vitro effects of mistletoe extracts and mistletoe lectins. Cytotoxicity towards tumor cells due to the induction of programmed cell death (apoptosis). Arzneim -Forsch /Drug Res 43(II), 1221-1227 (1993).
 Kienle, G. S., F. Berrino, A. Büssing, E. Portalupi, S. Rosenzweig and H. Kiene, Mistletoe in cancer - a systematic review on controlled clinical trials. Eur J Med Res 8, 109-119 (2003).
 Kienle, G. S. and H. Kiene, Die Mistel in der Onkologie - Fakten und konzeptionelle Grundlagen. Schattauer Verlag, Stuttgart, New York (2003).
 Kienle, G. S., Kiene, H. and Albonico, H. U., Health Technology Assessment Bericht Anthroposophische Medizin. Erstellt im Rahmen des Programm Evaluation Komplementärmedizin (PEK) des Schweizer Bundesamtes für Sozialversicherung. (2005).
 Kienle, G. S., H. Kiene and H. U. Albonico, Anthroposophic Medicine: Effectiveness, Utility, Costs, Safety. Schattauer Verlag, Stuttgart, New York (2006).
[15a] Klett, C. Y. and F. A. Anderer, Activation of natural killer cell cytotoxicity of human blood monocytes by a low molecular weight component from Viscum album extract. Arzneim -Forsch /Drug Res 39 (II), 1-20 (1989).
[15b] Kovacs, E., T. Hajto and K. Hostanska, Improvement of DNA repair in lymphocytes of breast cancer patients treated with Viscum album extract (Iscador®). Eur J Cancer 27, 1672-1676 (1991).
[15c] Längler A., C. Spix, G. Seifert, S. Gottschling, N. Graf, P. Kaatsch, Complementary and alternative treatment methods in children with cancer: A population-based retrospective survey on the prevalence of use in Germany. Eur J Cancer 44:2233-2240 (2008)
 Molassiotis, A., P. Fernandez-Ortega, D. Pud, G. Ozden, J. A. Scott, V. Panteli and et al., Use of complementary and alternative medicine in cancer patients: a European survey. Ann Oncol Advance Access published online on February 2, doi:10.1093/annonc/mdi110 (2005).
 Münstedt K., R. von Georgi. Unkonventionelle Krebstherapien – Vergleich von Einstellungen und Kenntnissen bei Ärzten in Deutschland und Griechenland. Forsch Komplementärmed Klass Naturheilkd 12:254-260 (2005)
 Mueller, E. A. and F. A. Anderer, A Viscum album oligosaccharide activating human natural cytotoxicity is an interferon gamma inducer. Cancer Immunol Immunother 32, 221-227 (1990).
 Petru, E., P. Schmied and C. Petru, [Complementary Measures Used by Patients With Gynecologic Cancers Undergoing Cytotoxic or Hormonal Chemotherapy]. Geburtshilfe Frauenheilkd 61, 75-78 (2001).
 Rostock, M. and R. Huber, Randomized and double-blind studies - demands and reality as demonstrated by two examples of mistletoe research. Forsch Komplementärmed 11, 18-22 (2004).
 Schöffski, P., S. Riggert, P. Fumoleau, M. Campone, O. Bolte, S. Marreaud, D. Lacombe and et al., Phase I trial on intravenous aviscumine (rViscumin) in patients with solid tumors: a study of the European Organization for Research and Treatment of Cancer New Drug Development Group. Ann Oncol 15, 1816-1824 (2004).
 Steiner, R., Geisteswissenschaft und Medizin. (1920), Rudolf Steiner Verlag, Dornach 1985.
 Urech, K., J. M. Scher, K. Hostanska and H. Becker, Apoptosis inducing activity of viscin, a lipophilic extract from Viscum album L. J Pharm Pharmacol 57, 101-109 (2005).
 Weis, J., H. H. Bartsch, F. Hennies, M. Rietschel, M. Heim, G. Adam, U. Gärtner and A. Ammon, Complementary medicine in cancer patients: demand, patients’ attitudes and psychological beliefs. Onkologie 21, 144-149 (1998).
 Winterfeld, K. and A. B. Bijnen, Viscotoxin, ein neuer Inhaltsstoff der Mistel (Viscum album L.). Liebigs Ann Chem 561, 107-115 (1948).
 Winterfeld, K. and A. Kronenthaler, Zur Chemie des blutdrucksenkenden Bestandteils der Mistel. (Viscum album). Arch Pharm 280, 103-115 (1942).