Mistletoe therapy

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Viscum album

Mistletoe therapy is the therapeutic use of mistletoe (this article discusses mainly the therapeutic use of viscum album or European mistletoe).

Botany

Mistletoe is the general term given to the parasitic and hemi-parasitic tree dwelling genuses of the family Viscaceae which contains three genera of mistletoe:

  1. Arceuthobium (dwarf mistletoe)
  2. Phoradendron (American mistletoe)
  3. Viscum (mistletoe)[1]

American Mistletoe (Phoradendron serotinum) has a history of use in Mexican and South American traditional medicine for the treatment of cancer.[2]

History of Clinical Use

European Mistletoe (Viscum Album) is the genus with the most scientific interest. It was used historically in traditional European herbal medicine for non-oncologic conditions including epilepsy, hypertension, and heart failure. In 1917 Rudolf Steiner together with the physician Ita Wegman developed and used extracts of mistletoe successfully in a case of metastatic breast cancer.[3]

Scientific Evidence

Cumulative PubMed articles by year with the terms "Mistletoe" and "Cancer"

Safety Trials

There have been several peer reviewed studies on the safety of viscum album extracts. These have all shown that mistletoe therapy is safe in a variety of routes (subcutaneous, intravenous, intralesional, and intrathecal) as well as doses, and along with many types of conventional modalities.

  • A US based study led by Johns Hopkins looked at the safety of intravenous Helixor viscum album extracts in stage 4 cancer patients heavily pretreated with chemotherapy. It concluded "Intravenous mistletoe demonstrated manageable toxicities with disease control and improved Quality of Life in a heavily pretreated solid tumor population."[4]
  • A 2017 phase 1 dose escalation trial of intravenous mistletoe found that "weekly infusions of 2000 mg of the pine-mistletoe extract were tolerated and can be used in further studies but had a risk for allergic reactions and fever."[5]
  • A 2018 randomized controlled study looked at breast cancer patients treated with subcutaneous Iscador or Helixor compared to controls. Both arms received conventional dosed chemotherapy with cyclophosphamide, adriamycin, and 5-fluorouracil. The study found that "Mistletoe extracts were safe in this clinical study... mistletoe extracts had no adverse interactions with the anticancer agents used in this study. Furthermore, certain side effects of chemotherapy decreased under this complementary treatment in breast cancer patients."[6]
  • A 2011 review of 69 human and 48 animal trials using up to 1500mg of VAE extracts in humans found that "Application of higher dosages of VAE or Mistletoe Lectins is not accompanied by immunosuppression; altogether VAE seems to exhibit low risk but should be monitored by clinicians when applied in high dosages."[7]
  • In 2011 a 3-armed randomized, double blind clinical trial looked specifically at IL-6 and CRP production in relationship to mistletoe as there was concern that there may be an unfavorable impact on lymphoma. It concluded "Treatment with (mistletoe) results in eosinophilia and an increase of CD4 cells but not in an increase of IL-6 or CRP. No safety concerns regarding the two mistletoe preparations have been raised by this study."[8]
  • A 2014 multicentre, observational study on subcutaneous injection of mistletoe extracts found that there were no serious adverse drug reactions. "The results of this study indicate that mistletoe therapy is safe. Adverse drug reactions were mostly mild to moderate in intensity and appear to be dose-related and explained by the immune-stimulating, pharmacological activity of mistletoe."[9]
  • A 2014 observational study on higher dose intravenous mistletoe found that this therapy was generally safe.[10]
  • A 2018 safety trial looked at the concurrent use of mistletoe with conventional targeted therapies such as avastin and herceptin. There were 4.1 times less side effects in the viscum album group compared to the control group. "Addition of viscum album to targeted therapy significantly reduced the probability of oncological treatment discontinuation by 70%"[11]
  • A 2017 trial found no differences between patients using checkpoint inhibitors alone versus with mistletoe extracts.[12]
  • A 2014 in vitro study looked at drug-herb interactions between mistletoe components and common chemotherapy agents and found no danger of drug-herb interactions. "VAE did not inhibit chemotherapy induced cytostasis and cytotoxicity in any of our experimental settings. At higher concentrations VAE showed an additive inhibitory effect."[13]
  • A 2018 case series of salvage very high dose viscum album extract in palliative pediatric cancer found some clinical effect and reported safety in a controlled inpatient facility. This study also used intrathecal injection of mistletoe extracts. "Our study underpinned the safety and feasibility of high-dose mistletoe infusion in children with advanced stages of cancer and showed noteworthy antineoplastic effects, which should be verified in a prospective clinical phase II/III-study. Because of possible side effects, the treatment should be implemented only in an in-patient setting in experienced pediatric oncology centers."[14]
  • A 2019 study found no additional autoimmunity flares in cancer patients with pre-existing autoimmune conditions. "Our findings suggest that add-on viscum album therapy in cancer patients with preexisting autoimmune diseases as Hashimoto’s thyroiditis, psoriasis, ulcerative colitis, Grave’s disease, and some rheumatic diseases is safe. No higher rates of viscum album associated adverse effects were observed and the overall adverse effect rates were significantly lowered in viscum album therapy periods."[15]
  • A 2014 study found that intratumoral injection of mistletoe gave an anticipated amount of local inflammation around the tumor as well as fever. These side effects were generally tolerable and intratumoral mistletoe was found to be safe and the side effects part of the anticancer working of mistletoe. "Intratumoral injection of mistletoe preparations resulted in a relatively high frequency of adverse drug reactions. Nearly all adverse drug reactions were mild to moderate however, and no serious adverse drug reactions occurred. Furthermore, it is possible that immune-related adverse drug reactions such as pyrexia and local inflammatory reactions might be critical for tumor response."[16]

Current Clinical Use

A main field of use in anthroposophic medicine is the treatment of cancer, there is also nononcological uses for example in rheumatic disorders.

Pharmacologic Extraction

Currently there are four companies that extract mistletoe: Abnoba, Helixor, Iscador, and Iscucin. They each use refined extraction and preparation techniques and use extracts of mistletoe from different host trees. Their final products vary greatly in concentration of lectins and viscotoxins as well as host tree specific compounds.

Literature

  • Johnson, Steven; Winters, Nasha; Blanning, Adam; Debus, Marion; Faust, Paul; Hancock, Mark; Hinderberger, Peter (2022-02-25). Mistletoe and the Emerging Future of Integrative Oncology. SteinerBooks, Incorporated. ISBN 978-1-938685-33-0.

Weblinks

References

  1. ↑ Agrios, G. N. (2005). "Plant Pathology". PLANT DISEASES CAUSED BY PARASITIC HIGHER PLANTS, INVASIVE CLIMBING PLANTS, AND PARASITIC GREEN ALGAE. Elsevier. pp. 705–722. doi:10.1016/B978-0-08-047378-9.50019-1. ISBN 9780120445653.
  2. ↑ Alonso-Castro, A. J., Juárez-Vázquez, M. del C., Domínguez, F., González-Sánchez, I., Estrada-Castillón, E., López-Toledo, G., Chávez, M., Cerbón, M. A., García-Carranca, A. (1 August 2012). "The antitumoral effect of the American mistletoe Phoradendron serotinum (Raf.) M.C. Johnst. (Viscaceae) is associated with the release of immunity-related cytokines". Journal of Ethnopharmacology. 142 (3): 857–864. doi:10.1016/j.jep.2012.06.018. Retrieved 13 March 2023.
  3. ↑ van Emmichoven: Wer War Ita Wegman - Google Scholar, retrieved 13 March 2023
  4. ↑ Paller, C. J., Wang, L., Fu, W., Kumar, R., Durham, J. N., Azad, N. S., Laheru, D. A., Browner, I., Kachhap, S. K., Boyapati, K., Odeny, T., Armstrong, D. K., Meyer, C. F., Gaillard, S., Brahmer, J. R., Page, I., Wang, H., Diaz, L. A., Jr. (28 February 2023). "Phase I Trial of Intravenous Mistletoe Extract in Advanced Cancer". Cancer Research Communications. 3 (2): 338–346. doi:10.1158/2767-9764.CRC-23-0002. Retrieved 13 March 2023.
  5. ↑ Huber, R., Schlodder, D., Effertz, C., Rieger, S., Tröger, W. (18 September 2017). "Safety of intravenously applied mistletoe extract – results from a phase I dose escalation study in patients with advanced cancer". BMC Complementary and Alternative Medicine. 17 (1): 465. doi:10.1186/s12906-017-1971-1. Retrieved 15 January 2023.
  6. ↑ Pelzer, F., Tröger, W. (1 September 2018). "Complementary Treatment with Mistletoe Extracts During Chemotherapy: Safety, Neutropenia, Fever, and Quality of Life Assessed in a Randomized Study". Journal of Alternative and Complementary Medicine. 24 (9–10): 954–961. doi:10.1089/acm.2018.0159. Retrieved 15 January 2023.
  7. ↑ Kienle, G. S., Grugel, R., Kiene, H. (28 August 2011). "Safety of higher dosages of Viscum album L. in animals and humans--systematic review of immune changes and safety parameters". BMC complementary and alternative medicine. 11: 72. doi:10.1186/1472-6882-11-72.
  8. ↑ Huber, R., Lüdtke, H., Wieber, J., Beckmann, C. (24 November 2011). "Safety and effects of two mistletoe preparations on production of Interleukin-6 and other immune parameters - a placebo controlled clinical trial in healthy subjects". BMC complementary and alternative medicine. 11: 116. doi:10.1186/1472-6882-11-116.
  9. ↑ Steele, M. L., Axtner, J., Happe, A., Kröz, M., Matthes, H., Schad, F. (2014). "Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous Mistletoe Extracts (Viscum album L.) in Cancer Patients". Evidence-Based Complementary and Alternative Medicine: eCAM. 2014: 724258. doi:10.1155/2014/724258.
  10. ↑ Steele, M. L., Axtner, J., Happe, A., Kröz, M., Matthes, H., Schad, F. (2014). "Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study". Evidence-Based Complementary and Alternative Medicine: eCAM. 2014: 236310. doi:10.1155/2014/236310.
  11. ↑ Thronicke, A., Oei, S. L., Merkle, A., Matthes, H., Schad, F. (6 September 2018). "Clinical Safety of Combined Targeted and Viscum album L. Therapy in Oncological Patients". Medicines. 5 (3): 100. doi:10.3390/medicines5030100. Retrieved 15 January 2023.
  12. ↑ Thronicke, A., Steele, M. L., Grah, C., Matthes, B., Schad, F. (13 December 2017). "Clinical safety of combined therapy of immune checkpoint inhibitors and Viscum album L. therapy in patients with advanced or metastatic cancer". BMC complementary and alternative medicine. 17 (1): 534. doi:10.1186/s12906-017-2045-0.
  13. ↑ Weissenstein, U., Kunz, M., Urech, K., Baumgartner, S. (8 January 2014). "Interaction of standardized mistletoe (Viscum album) extracts with chemotherapeutic drugs regarding cytostatic and cytotoxic effects in vitro". BMC Complementary and Alternative Medicine. 14 (1): 6. doi:10.1186/1472-6882-14-6. Retrieved 15 January 2023.
  14. ↑ Zuzak, T. J., Wasmuth, A., Bernitzki, S., Schwermer, M., Längler, A. (October 2018). "Safety of high-dose intravenous mistletoe therapy in pediatric cancer patients: A case series". Complementary Therapies in Medicine. 40: 198–202. doi:10.1016/j.ctim.2018.01.002.
  15. ↑ Oei, S. L., Thronicke, A., Kröz, M., Matthes, H., Schad, F. (26 February 2019). "Use and Safety of Viscum album L Applications in Cancer Patients With Preexisting Autoimmune Diseases: Findings From the Network Oncology Study". Integrative Cancer Therapies. 18: 1534735419832367. doi:10.1177/1534735419832367. Retrieved 15 January 2023.
  16. ↑ Steele, M. L., Axtner, J., Happe, A., Kröz, M., Matthes, H., Schad, F. (1 March 2015). "Use and Safety of Intratumoral Application of European Mistletoe (Viscum album L) Preparations in Oncology". Integrative Cancer Therapies. 14 (2): 140–148. doi:10.1177/1534735414563977. Retrieved 15 January 2023.
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