Viscum Album Therapy

Viscum album (European mistletoe) has been used for medical indications for several centuries. Hildegard von Bingen (1098-1179) gives several indications for the (oral) use of Viscum album. In the beginning of the 20th century, it was Rudolf Steiner (1861-1925), who suggested the parenteral use of Viscum album in the treatment of cancer patients. Therefore, since 1923, Viscum album has been used and initially studied in the field of oncology. In the last decade of the 20th century, Viscum album, as an immunomodulator, has also been clinically studied in chronic viral infections like in HIV/AIDS, Human Papilloma Virus (HPV) infection in women with cervix dysplasia, and hepatitis C (HCV) infection.[i],[ii],[iii]

It is well-known that the extracts of European mistletoe (Viscum album Loranthaceae) cause a variety of biological activities such as cytokine production from immune- related cells,1,2,3 enhancement of natural killer (NK) cell activity,1,[iv],[v],[vi] and immunoadjuvant activity.[vii],[viii],[ix]

The immunomodulating and anti-cancer activities of Viscum are caused by biologically active components like lectins (glucoproteins), viscotoxins, alkaloids and polysaccharides.5,[x],[xi],[xii] Especially the mistletoe lectines (ML) cause significant activities and therefore have been studied most intensively.[xiii],[xiv],[xv] Three main groups of lectins have been identified: lectin I (ML-I) has an affinity for D-galactose (D-Gal), lectin III (ML-III) for N-acetyl-galactoseamine (GalNAc), and lectin II (ML-II) for both sugars. Among the three lectins, ML-I is most well studied, so that its anti- tumor and immunomodulating activities are well recognized. The modes of action of the various components of Viscum album have been well summarized and discussed by Fischer.[xvi]

Von Laue has documented that during parenteral Viscum album therapy, there is a positive correlation between the total mistletoe lectin content and the production of anti-ML-I-IgG antibodies.[xvii] Subclasses of anti-ML-I-IgG antibodies can indicate whether a Viscum album therapy leads to an activation of Th-I lymphocytes (through production of IgG1 or/and eventually IgG3) or to an activation of Th-2 lymphocytes (through pro-duction of IgG2 or/and IgG4).17

Usually, through immune stimulation and immunomodulation with Viscum album, a Th-1 response is initiated. Through this pathway, a cytokine-dependent cytotoxity is provoked, which plays an important role in the natural defence mechanisms against tumor cells. A Th-2 response provokes the production of IL-4, IL-5, IL-10, etc., and thus, B cells increase their production of IgG2 and IgG4. The cytotoxity thus created, is (tumor) antigen-specific, and exhibits a direct lysis of tumor cells.
Therefore, monitoring of IgG subclasses during a Viscum album therapy is a very meaningful way to monitor and optimize therapeutic interventions. In addition, in the early phases of a Viscum album therapy, eosinophilia is considered to be a positive phenomenon, and positively related to a partial or complete response in cancer patients.
In general, growing older makes the circadian rhythm of the core temperature and its amplitude more and more rigid and flat. In cancer patients, the circadian rhythm of the core temperature and its amplitude have become significantly hampered. Usually, the core temperature is lowered by about 0.6°C. In addition, the amplitude is flattened. The delicate interaction between the core and peripheral temperature to maintain a stable core temperature is also inhibited.[xviii]

Therefore, one could say that the cancer patient grows old more rapidly. Parenteral administration of Viscum album will usually improve these functions significantly.18,[xix] In other words, Viscum album rejuvenates the above described circadian rhythm, and thus the warmth organization. Thus, in the Gorter Model, Viscum album is used to improve effectively the T-cell function and the functioning of the warmth organization of the patient.
Recently, pre-clinical and clinical studies have been conducted with the Korean mistletoe (Viscum coloratum). Compared to the European mistletoe, very similar activities of the Korean mistletoe in animal models have been documented.[xx]
Mistletoe is currently the most prescribed anticancer medication used in northern and central Europe. Fully 70 percent of all cancer patients receive mistletoe preparations and it is usually paid for by the national health care systems, making mistletoe a more frequently prescribed anticancer medication than any other type of medication, includind immunotherapies such as interleukin-2, all forms of chemotherapy and angiogenesis inhibitors.

Mistletoe is provided as a simple subcutaneous injection twice a week, preferably in the early morning. Like dendritic vaccinations, the mistletoe extract needs to be injected in a series to evoke and maintain a significant immune response. At the Medical Center Cologne, approximately 85 percent of patients receive mistletoe. Usually, after some instruction, they find it easy to give themselves these injections, which are applied just beneath the surface of the skin using a small insulin syringe and a very fine needle.
Initially, the injection is repeated every three days. In most protocols, mistletoe is injected subcutaneously twice a week, for a period of several months to several years. Injections are typically applied in the morning, when the core temperature is lower. Based on each patient’s progress, the injections may then be prescribed periodically at six-week intervals.
(More information: Mistletoe Use in Cancer Therapy by Katherine Aparicio)

References:

[i] Gorter R, Stein J, Stoss M, Linder M: Prospektive, longitudinale, dosis-eskalierende, randomisierte Phase I/II Studie mit Iscador QuFrF und Iscador Qu Spezial mit HIV-positiven, Krebspatienten und gesunden, nicht- rauchenden Probanden. Forsch Komplementärmed (1996) 3: 169-175
[ii] Van Wely M, Stoss M, Gorter RW: Toxicity of a standardized mistletoe extract in immunocompromized and in healthy individuals. Am J Therapeutics (1996) 6(1): 37-43
[iii] Stoss M, van Wely M, Musielsky H, Gorter RW: Study on local inflammatory reactions and other parameters during subcutaneous mistletoe application in HIV-positive patients and HIV-negative subjects over a period of 18 weeks. Arzneim Forsch/Drug Res (1999) 49(I) 4: 366-373
[iv] Müller EA: Viscum album oligosaccharide activating human natural cytotoxicity is an interferon production inducer. Cancer Immunol Immunother (1990) 32: 221-227
[v] Hajto T, Hostanska K, Feri K, Rordorf C, Gabius HJ: Increased secretion of tumor necrosis factor-alpha and interleukin-1, and interleukin-6 by human mononuclear cells, exposed to galactoside lectin from clinically applied mistletoe extract. Cancer Res (1990) 50: 3322-3326
[vi] Mannel DN, Becker H, Gundt A, Kist A, Franz H: Induction of tumor necrosis factor expression by a lectin from Viscum album. Cancer Immunol Immunother (1991) 33:177-182
[vii] Müller EA, Hamprecht K, Anderer FA: Biological characterization of a common extract of Viscum album enhancing human NK cytotoxicity. Immunopharmacology (1989) 19: 69-77 [viii] Hamprecht K, Handgretinger R, Voetsch W, Anderer FA: Mediation of human NK-activity by component in extract of Viscum album. Int J Immunopharmacol (1987) 9: 199-209[ix] Bloksma N, Dijk HV, Korst P, Willer JM: Cellular and humoral adjuvant activity of mistletoe extract. Immunobiol (1979) 156: 309-319
[x] Metzner G, Franz H, Kindt A, Fahlbusch G, Suus J: The in vitro activity of lectin-1 from mistletoe (ML-1) and its isolated A and B chains in functions of macrophages and polymorphonuclear cells, Immunobiol (1985) 169: 461- 471
[xi] Hajto T, Immunomodualatory effect of Iscador: a Viscum album preparation. Oncology (1986) 43 (suppl. 1): 51-61
[xii] Hajto T et al: Modulatory potency of the S-galactoside-specific lectin from mistletoe extract (Iscador) on the host defence system in vitro in rabbits and patients. Cancer Res (1989) 49: 4803-4808
[xiii] Kuttan G, Vasudevan DM, Kuttan R: Tumour reducing activity of an isolated active ingredient from mistletoe extract and its
possible mechanism of action. J Exp Clinical Cancer Research (1992) 11: 7-12
[xiv] Bussing A, Suzart K, Schweizer K: Differences in the apoptosis-inducing properties of Viscum album extracts. Anti-cancer Drugs (1997) 8 (suppl. 1): 9-14
[xv] Riberau G, Jung MI, Dominique DS, Beck JP: Comparison of the effects of fermented and unfermented mistletoe preparations on cultured tumor cells. Oncology (1986) 45: 172-179
[xvi] Fischer S: Stimulation der Immunabwehr durch
Mistelinhaltsstoffe. Hippokrates Verlag, Stuttgart (1996) [xvii] Laue HB: Kontrollparameter während der Viscum-Therapie. In: Scheer R, Becker H, Berg PA: Grundlagen der Misteltherapie. Hippokrates Verlag, Stuttgart (1996): 399-418
[xviii] Laue B v: Wärmeorganisation und Krebserkrankung. Erfahrungsheilkunde (1994) 43(2): 63-70 [xix] Fintelmann V: Intuitive Medizin. Hippokrates Verlag, Stuttgart (1987)