Mistletoe (Viscum album)

Extracts from botanical mistletoe have been used in Europe for decades to support immune function in cancer just as in Asia many Chinese herbs are used to balance energy flow in the body.

Extracts of mistletoe are well-studied in Western science and hundreds of scientific articles have been published on practically all aspects of its clinical use. The clinical protocols for using mistletoe in cancer treatment were initially developed by Rudolf Steiner, PhD (1861-1925).

Since that time, pharmacological research and clinical studies have shown that it provides a broad spectrum of anti-tumor activities and restoration of the cellular immune system. Mistletoe is currently the most prescribed anticancer medication used in northern and central Europe.

• Benefits of Mistletoe

  Mistletoe has been found to both prolong life and improve quality of life. Researchers studying uterine cancer reported, “mistletoe preparations such as Iscador and Abnoba Viscum have the effect of prolonging overall survival of corpus uteri cancer patients.” Another study, which track patients over five-years found, “significantly improved quality of life and significantly reduced persistent signs/symptoms.” Numerous studies have affirmed these benefits. Studies have also shown a range of other clinical benefits:

  • Typically well tolerated
  • Low toxicity
  • No more than Grade I flu-like symptoms
  • Decreased pain due to higher serum endorphins ii
  • Prolonged survival of patients with breast cancer, ovarian, uterine, and cervical cancers.

  
  
  
  
  

• Enhanced Immune Function

  Recent research has confirmed enhanced immune function and healing with the use of mistletoe in patients with various types of cancer, including a broad range of cancers of the digestive tract and the genital system. Studies of immune support and restoration have also involved healthy individuals and report:

  • Higher levels of cellular immunity, our primary defense against cancer (eosinophils)
  • Greater numbers of natural killer cells and increased activity
  • Increased levels of cancer-fighting T-cells and T-helper cells
  • Increases in immune signaling chemicals (cytokines) xii xv xvii
  • Higher levels of protective immune antibodies and the B cells that make them
  • DNA repair following chemotherapy and radiation in patients with almost all types of cancers

• Normalized Body Temperature

  Therapeutic use of mistletoe helps to re-establish the body’s natural temperature rhythm and increases core temperature by about 1° F (0.6° C). This increase in temperature counters the poor circulation and slower metabolic rate experienced by many cancer patients, reflected in chronically cold hands and feet. Improvement in core body temperature and restoration of circadian rhythm seems to be an important marker of immune restoration. Normalized body temperature also correlates with improved outcome and survival. (More information: Mistletoe Use in Cancer Therapy by Katherine Aparicio)

• New Section

  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.  Like dendritic vaccinations, the mistletoe extract needs to be injected in a series to evoke and maintain a significant immune response.

  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.

Patient's experience

• I had no concerns about toxicity, because there is already broad agreement in the research literature on the safety of mistletoe. Given the findings on immune support, I felt it could actually be beneficial to me, because as we age, the immune system tends to decrease in competence. The pin prick of the needle was barely painful—it felt similar to an acupuncture needle. I noticed no response with the first series of injections—eight little shots, given every other day. It was only at the second series of injections that my body showed a reaction—a reddish welt that would take a few days to disappear. The welt told me that my immune system was responding and being activated.

  — Erik Peper, PhD

• Research

  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 i>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, i>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 i>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 albumrejuvenates 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]

• 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)

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  Grossarth-Maticek R, Ziegler R. Randomized and non-randomized prospective controlled cohort studies in matched pair design for the long-term therapy of corpus uteri cancer patients with a mistletoe preparation (Iscador). Eur J Med Res. 2008 Mar 31;13(3):107-20. Beuth J, Schneider B, Schierholz JM. Impact of complementary treatment of breast cancer patients with standardized mistletoe extract during aftercare: a controlled multicenter comparative epidemiological cohort study. Anticancer Res. 2008 Jan-Feb;28(1B):523-7. Loewe-Mesch A, Kuehn JJ, Borho K, Abel U, Bauer C, Gerhard I, Schneeweiss A, Sohn C, Strowitzki T, v Hagens C. [Adjuvant simultaneous mistletoe chemotherapy in breast cancer—influence on immunological parameters, quality of life and tolerability] [Article in German]. Forsch Komplementmed. 2008 Feb;15(1):22-30. Semiglazov VF, Stepula VV, Dudov A, Schnitker J, Mengs U. Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial. Anticancer Res. 2006 Mar-Apr;26(2B):1519-29. Elsässer-Beile U, Leiber C, Wetterauer U, Bühler P, Wolf P, Lucht M, Mengs U.Adjuvant intravesical treatment with a standardized mistletoe extract to prevent recurrence of superficial urinary bladder cancer. Anticancer Res. 2005 Nov-Dec;25(6C):4733-6.

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  Mabed M, El-Helw L, Shamaa S. Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma. Br J Cancer. 2004 Jan 12;90(1):65-9. Gorter RW, van Wely M, Reif M, Stoss M. Tolerability of an extract of European mistletoe among immunocompromised and healthy individuals. Altern Ther Health Med. 1999 Nov;5(6):37-44, 47-8. Grossarth-Maticek R, Ziegler R. Randomised and non-randomised prospective controlled cohort studies in matched-pair design for the long-term therapy of breast cancer patients with a mistletoe preparation (Iscador): a re-analysis. Eur J Med Res. 2006 Nov 30;11(11):485-95. Grossarth-Maticek R, Ziegler R. Prospective controlled cohort studies on long-term therapy of ovairian cancer patients with mistletoe (Viscum album L.) extracts iscador. Arzneimittelforschung. 2007;57(10):665-78. Grossarth-Maticek R, Ziegler R. Randomized and non-randomized prospective controlled cohort studies in matched pair design for the long-term therapy of corpus uteri cancer patients with a mistletoe preparation (Iscador). Eur J Med Res. 2008 Mar 31;13(3):107-20. Grossarth-Maticek R, Ziegler R. Prospective controlled cohort studies on long-term therapy of cervical cancer patients with a mistletoe preparation (Iscador). Forsch Komplementmed. 2007 Jun;14(3):140-7. Epub 2007 Jun 22. Huber R, Rostock M, Goedl R, Lüdtke R, Urech K, Klein R. Immunologic effects of mistletoe lectins: a placebo-controlled study in healthy subjects. J Soc Integr Oncol. 2006 Winter;4(1):3-7.

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  Dohmen W, Breier M, Mengs U. Cellular immunomodulation and safety of standardized aqueous mistletoe extract PS76A2 in tumor patients treated for 48 weeks. Anticancer Res. 2004 Mar-Apr;24(2C):1231-7. Schink M, Tröger W, Dabidian A, Goyert A, Scheuerecker H, Meyer J, Fischer IU, Glaser F. Mistletoe extract reduces the surgical suppression of natural killer cell activity in cancer patients. a randomized phase III trial. Forsch Komplementmed. 2007 Feb;14(1):9-17. Epub 2007 Mar 6. Heinzerling L, von Baehr V, Liebenthal C, von Baehr R, Volk HD. Immunologic effector mechanisms of a standardized mistletoe extract on the function of human monocytes and lymphocytes in vitro, ex vivo, and in vivo. J Clin Immunol. 2006 Jul;26(4):347-59. Epub 2006 May 17. Beuth J, Stoffel B, Ko HL, Buss G, Tunggal L, Pulverer G. [Immunoactive effects of various mistletoe lectin-1 dosages in mammary carcinoma patients] [Article in German]. Arzneimittelforschung. 1995 Apr;45(4):505-7. Schöffski P, Riggert S, Fumoleau P, Campone M, Bolte O, Marreaud S, Lacombe D, Baron B, Herold M, Zwierzina H, Wilhelm-Ogunbiyi K, Lentzen H, Twelves C; European Organization for Research and Treatment of Cancer New Drug Development Group. Phase I trial of 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. 2004 Dec;15(12):1816-24. Klein R, Classen K, Berg PA, Lüdtke R, Werner M, Huber R. In vivo-induction of antibodies to mistletoe lectin-1 and viscotoxin by exposure to aqueous mistletoe extracts: a randomised double-blinded placebo controlled phase I study in healthy individuals. Eur J Med Res. 2002 Apr 30;7(4):155-63. Kovacs E, Hajto T, Hostanska K. Improvement of DNA repair in lymphocytes of breast cancer patients treated with Viscum album extract (Iscador). Eur J Cancer. 1991;27(12):1672-6. Kovacs E. The in vitro effect of Viscum album (VA) extract on DNA repair of peripheral blood mononuclear cells (PBMC) in cancer patients. Phytother Res. 2002 Mar;16(2):143-7.