In the realm of functional medicine, mistletoe isn’t just a festive decoration; it’s also recognized for its potential as a cancer therapy. While conventional treatments like chemotherapy, radiation, and immunotherapy remain primary options, interest in complementary and integrated therapies continues to grow. Mistletoe emerges as a promising natural, integrative approach to cancer care.
Mistletoe (Viscum album) has been used for centuries for its medicinal properties. Mistletoe is a parasitic plant that grows on various types of trees, such as fir, apple, and pine trees. Depending on which tree it grows on, the compounds, or lectins, will vary.
Although mistletoe has been used long-term in Europe, its role in cancer treatment has garnered significant attention in recent years in North America. Excitingly, in 2023, John Hopkins University completed a phase I clinical trial of intravenous mistletoe, demonstrating both safety and clinical benefit, warranting additional phase II studies in combination with chemotherapy as the next step. (1)
Cancer often evades immune surveillance, allowing tumors to thrive unchecked. Mistletoe extracts have long been recognized for their immunomodulatory effects and containing compounds that enhance immune surveillance. Numerous studies have demonstrated its ability to stimulate various components of the immune system, including natural killer cells and T cells. (2, 3, 4). Furthermore, mistletoe extracts in vitro and in vivo have been found to have direct cytotoxicity and induce apoptosis, or programmed cell death, in cancer cells. (5). This targeted cytotoxic effect helps to reduce tumor burden without harming healthy cells.
Beyond its direct anti-cancer properties, mistletoe has also been shown to aid with conventional treatment-related adverse effects and improve the quality of life for cancer patients. Studies have shown that mistletoe therapy can mitigate chemotherapy-induced nausea and vomiting, boost energy levels, and enhance overall well-being and quality of life. (6, 7)
Side effects mistletoe may help with (6-10):
- Fatigue
- Pain
- Nausea and vomiting
- Appetite
- Insomnia
- Depression
- Neutropenia
- Overall quality of life
In 2018, Thronicke et al. studied the use of targeted therapies alone versus in combination with a botanical extract of mistletoe, Viscum album. They concluded that combining targeted therapies with mistletoe reduced the number of adverse events associated with the drugs. Specifically, the adverse events were reported in 19.8% of patients in the drug group and only 9.2% in the combination mistletoe group, a statistically significant reduction. But perhaps most importantly, they found a reduction in the need to abort treatment due to adverse events. 60.5% of subjects in the drug group had to discontinue treatment for this reason, versus just 35% in the combination group. (11)
In addition to improving the side effects of conventional treatment, there is also some evidence of mistletoe improving survival. A 2024 study of advanced or metastatic NSCLC patients treated with PD-1/PD-L1 inhibitor therapy in combination with mistletoe or alone found that the mistletoe group had a reduced hazard of death by 40%. Additionally, the combination group had 13.8 months of survival vs 6.8 in the control group. (12)
Mistletoe can be administered intravenously and subcutaneously. It is not administered orally due to potential hepatotoxicity. Some expected side effects of mistletoe are: For example, once an adequate dose of subcutaneous mistletoe is established, we expect a 5cm, red, potentially pruritic reaction at the site of injection. Additionally, there may also be cold—and flu-like symptoms.
For more information on how to support your cancer patients, potentially with mistletoe, consider the Advanced Integrative Oncology Palliative Care Course by the Integrative Oncology Institute.
- Paller CJ, Wang L, Fu W, et al. Phase I Trial of Intravenous Mistletoe Extract in Advanced Cancer. Cancer Res Commun. 2023;3(2):338-346. Published 2023 Feb 28. doi:10.1158/2767-9764.CRC-23-0002
- Büssing A., Rosenberger A., Stumpf C., Schietzel M. Development of lymphocyte subsets in tumor patients after subcutaneous administration of mistletoe extracts. Forsch Komplementarmed. 1999;6(4):196–204. doi: 10.1159/000021253
- Beuth J, Ko HL, Gabius HJ, Burrichter H, Oette K, Pulverer G. Behavior of lymphocyte subsets and expression of activation markers in response to immunotherapy with galactoside-specific lectin from mistletoe in breast cancer patients. Clin Investig. 1992;70(8):658-661. doi:10.1007/BF00180280
- Oei SL, Thronicke A, Schad F. Mistletoe and Immunomodulation: Insights and Implications for Anticancer Therapies. Evid Based Complement Alternat Med. 2019;2019:5893017. Published 2019 Apr 17. doi:10.1155/2019/5893017
- Choi SH, Lyu SY, Park WB. Mistletoe lectin induces apoptosis and telomerase inhibition in human A253 cancer cells through dephosphorylation of Akt. Arch Pharm Res. 2004;27(1):68-76. doi:10.1007/BF02980049
- Loef M, Walach H. Quality of life in cancer patients treated with mistletoe: a systematic review and meta-analysis. BMC Complement Med Ther. 2020;20(1):227. Published 2020 Jul 20. doi:10.1186/s12906-020-03013-3
- Pelzer F, Loef M, Martin DD, Baumgartner S. Cancer-related fatigue in patients treated with mistletoe extracts: a systematic review and meta-analysis. Support Care Cancer. 2022;30(8):6405-6418. doi:10.1007/s00520-022-06921-x
- Pelzer F, Tröger W, Nat DR. Complementary Treatment with Mistletoe Extracts During Chemotherapy: Safety, Neutropenia, Fever, and Quality of Life Assessed in a Randomized Study. J Altern Complement Med. 2018;24(9-10):954-961. doi:10.1089/acm.2018.0159
- Tröger W, Jezdić S, Zdrale Z, Tišma N, Hamre HJ, Matijašević M. Quality of life and neutropenia in patients with early-stage breast cancer: a randomized pilot study comparing additional treatment with mistletoe extract to chemotherapy alone. Breast Cancer (Auckl). 2009;3:35-45. Published 2009 Jul 6. doi:10.4137/bcbcr.s2905
- Kienle GS, Kiene H. Review article: Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Integr Cancer Ther. 2010;9(2):142-157. doi:10.1177/1534735410369673
- Thronicke A, Oei SL, Merkle A, Matthes H, Schad F. Clinical Safety of Combined Targeted and Viscum album L. Therapy in Oncological Patients. Medicines (Basel). 2018;5(3):100. Published 2018 Sep 6. doi:10.3390/medicines5030100
- Schad F, Thronicke A, Hofheinz RD, Matthes H, Grah C. Patients with Advanced or Metastasised Non-Small-Cell Lung Cancer with Viscum album L. Therapy in Addition to PD-1/PD-L1 Blockade: A Real-World Data Study. Cancers (Basel). 2024;16(8):1609. Published 2024 Apr 22. doi:10.3390/cancers16081609
