Mistletoe

Our assessments of evidence for each medical benefit fall into one of these categories:

• Strong evidence: consistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analysesa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results
• Good evidence: significant effects in one large or several mid-sized and well-designed clinical studies ( randomized controlled trialsa study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects with an appropriate placebo or other strong comparison control or observational studies that control for confounds)
• Modest evidence: significant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies), or several small studies aggregated into a meta-analysis
• Preliminary evidence: significant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect
• Weak evidence: one or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects
• Insufficient evidence: preclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example)

• Fewer side effects (adverse events) among people with primary, non-metastatic breast cancer receiving conventional treatment with subcutaneous mistletoe extract injections for at least 3 months (median of 52 months) compared to conventional treatment alone in a very large RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁷Bock PR, Friedel WE, Hanisch J, Karasmann M, Schneider B. Wirksamkeit und Sicherheit der komplementären Langzeitbehandlung mit einem standardisierten Extrakt aus Europäischer Mistel (Viscum album L.) zusätzlich zur konventionellen adjuvanten onkologischen Therapie bei primäirem, nicht metastasiertem Mammakarzinom. Ergebnisse einer multizentrischen, komparativen, epidemiologischen Kohortenstudie in Deutschland und der Schweiz [Efficacy and safety of long-term complementary treatment with standardized European mistletoe extract (Viscum album L.) in addition to the conventional adjuvant oncologic therapy in patients with primary non-metastasized mammary carcinoma. Results of a multi-center, comparative, epidemiological cohort study in Germany and Switzerland]. Arzneimittelforschung. 2004;54(8):456-66. German.
• Fewer disease or therapy-related symptoms or side effects—such as mucositis, fatigue, pain, or headache—and a correlated improved quality of life up to 5 years after treatment ended among people with breast cancer using mistletoe extract after completing chemotherapy compared to controls in a very large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹⁸Beuth 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.
• Fewer adverse reactions including nausea, gastrointestinal tract symptoms, depression, fatigue, and mental symptoms induced by the conventional therapies among people with breast cancer receiving postoperative chemotherapy, radiotherapy, and/or hormone therapy compared to conventional therapies alone in a large observational study¹⁹Schumacher K, Schneider B et al. Influence of postoperative complementary treatment with lectin-standardized mistletoe extract on breast cancer patients. A controlled epidemiological multicentric retrolective cohort study. Anticancer Research. 2003 Nov-Dec;23(6D):5081-7.
• Benefits in coping, fatigue, sleep, exhaustion, energy, nausea, vomiting, appetite, depression, anxiety, ability to work, and emotional and functional well-being and, less consistently, with pain, diarrhea, general performance, and other side effects of conventional treatments among people with cancer treated with mistletoe therapy in 22 of 26 studies in a systematic review of RCTs and other clinical studies²⁰Kienle 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. Integrative Cancer Therapies. 2010 Jun;9(2):142-57.
• Better quality of life or fewer side effects of cancer treatments in 3 of 5 RCTs among people with malignant disease with anthroposophic mistletoe compared to controls in a review of controlled trialsa study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial²¹Kienle GS, Kiene H. Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts. European Journal of Medical Research. 2007 Mar 26;12(3):103-19.
• Better quality of life in relation to side effects during cancer treatment in 3 studies among 23 studies total among people with cancer with mistletoe therapy compared to controls in review of controlled studies, none of which were high quality²²Kienle GS, Berrino F et al. Mistletoe in cancer—a systematic review on controlled clinical trials. European Journal of Medical Research. 2003 Mar 27;8(3):109-19.
• Fewer adjuvant therapy-related adverse reactions and fewer persisting symptoms among people with surgically treated stage 1–3 nonmetastatic colorectal cancer receiving adjuvant therapy or conventional aftercare with mistletoe extracts compared to no mistletoe in a mid-sized observational study²³Friedel WE, Matthes H, Bock PR, Zänker KS. Systematic evaluation of the clinical effects of supportive mistletoe treatment within chemo- and/or radiotherapy protocols and long-term mistletoe application in nonmetastatic colorectal carcinoma: multicenter, controlled, observational cohort study. Journal of the Society for Integrative Oncology. 2009 Fall;7(4):137-45.
• Fewer adverse events—such as nausea and vomiting or pain—and lower rates of discontinuation of standard cancer treatment among people with cancer receiving targeted therapy with mistletoe extracts compared to targeted therapy alone in a mid-sized observational study;²⁴Thronicke 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 Sep 6;5(3). pii: E100. review note: selection bias is likely and can make interpreting results difficult

• Less anxiety among people with cancer of the digestive tract (esophagus, stomach, pancreas, colon, or rectum) receiving the mistletoe extract Isorel 2 weeks before and 2 weeks after surgery compared to controls in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²⁵Enesel MB, Acalovschi I et al. Perioperative application of the Viscum album extract Isorel in digestive tract cancer patients. Anticancer Research. 2005 Nov-Dec;25(6C):4583-90.

• A very weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward less reduction in neutrophils (neutropeniaan abnormally low number of neutrophils in the blood, leading to increased susceptibility to infection) after surgery among people with breast cancer treated with mistletoe extracts 3 times a week during 18 weeks of adjuvanttreatment applied after initial treatment for cancer, especially to suppress secondary tumor formation chemotherapy compared to controls in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects;²⁶Pelzer F, Tröger W, Nat DR. 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. 2018 Sep/Oct;24(9-10):954-961. review note: the reduction in neutropenia is small primarily because neutropenia was at a very low level
• Better counts of some types of white blood cells during oral chemotherapy after surgery among people with stomach cancer treated with mistletoe extracts injected subcutaneously 3 times per week from postoperative day 7 to week 24 in increasing doses compared to chemotherapy alone in a small RCT²⁷Kim KC, Yook JH, Eisenbraun J, Kim BS, Huber R. Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma – a randomized, controlled pilot study. BMC Complementary and Alternative Medicine. 2012 Oct 3;12:172.
• A smaller reduction in natural killer cell activity 24 hours after open tumor resection among people with colorectal cancer treated with perioperative mistletoe infusion compared to controls in a small RCT²⁸Schink M, Tröger W et al. Mistletoe extract reduces the surgical suppression of natural killer cell activity in cancer patients. a randomized phase III trial. Complementary Medicine Research. 2007 Feb;14(1):9-17.
• Less suppression of immune activity from surgery among people with cancer of the digestive tract (esophagus, stomach, pancreas, colon, or rectum) treated with the mistletoe extract Isorel 2 weeks before and 2 weeks after surgery compared to controls in a small RCT²⁹Enesel MB, Acalovschi I et al. Perioperative application of the Viscum album extract Isorel in digestive tract cancer patients. Anticancer Research. 2005 Nov-Dec;25(6C):4583-90.
• Fewer adverse effects on white blood cells during radiotherapy and chemotherapy after surgery among men with squamous cell carcinomas of the larynx and pharynx treated with subcutaneous injections of standardized mistletoe extract in escalating doses in the abdominal region compared to standard treatment alone in a small RCT³⁰Klopp R, Schmidt W et al. Influence of complementary Viscum album (Iscador) administration on microcirculation and immune system of ear, nose and throat carcinoma patients treated with radiation and chemotherapy. Anticancer Research. 2005 Jan-Feb;25(1B):601-10.
• Less reduction in granulocyte function among people with breast cancer treated with a mistletoe infusion before the start of surgery compared to controls in a small observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods trial³¹Büssing A. Immune modulation using mistletoe (Viscum album L.) extracts Iscador. Arzneimittelforschung. 2006 Jun;56(6A):508-15.

• Substantially better weight (gain in the treatment group and loss in the control group) among people with locally advanced or metastatic pancreatic cancer receiving no further conventional treatment and treated with mistletoe extract in escalating doses by subcutaneous injection three times a week compared to controls in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects³²Tröger W, Galun Det al. Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. Deutsches Arzteblatt International. 2014 Jul 21;111(29-30):493-502, 33 p following 502.

• Better appetite after surgery among people with breast cancer treated with mistletoe extracts 3 times a week during 18 weeks of adjuvanttreatment applied after initial treatment for cancer, especially to suppress secondary tumor formation chemotherapy compared to controls in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects³³Pelzer F, Tröger W, Nat DR. 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. 2018 Sep/Oct;24(9-10):954-961.
• Better appetite among people with locally advanced or metastatic pancreatic cancer receiving no further conventional treatment and treated with mistletoe extract in escalating doses by subcutaneous injection three times a week compared to controls in a mid-sized RCT³⁴Tröger W, Galun Det al. Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. Deutsches Arzteblatt International. 2014 Jul 21;111(29-30):493-502, 33 p following 502.

• Less fatigue among people with locally advanced or metastatic pancreatic cancer receiving no further conventional treatment and treated with mistletoe extract in escalating doses by subcutaneous injection three times a week compared to controls in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects³⁵Tröger W, Galun Det al. Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. Deutsches Arzteblatt International. 2014 Jul 21;111(29-30):493-502, 33 p following 502.
• Less cancer-related fatigue during standard chemotherapy or radiochemotherapy among people with non-metastasized colorectal cancer treated with mistletoe interventions compared to standard treatment alone in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study³⁶Bock PR, Hanisch J, Matthes H, Zänker KS. Targeting inflammation in cancer-related-fatigue: a rationale for mistletoe therapy as supportive care in colorectal cancer patients. Inflammation & Allergy Drug Targets. 2014;13(2):105-11.

• Less diarrhea during oral chemotherapy after surgery among people with stomach cancer treated with mistletoe extracts injected subcutaneously 3 times per week from postoperative day 7 to week 24 in increasing doses compared to chemotherapy alone in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects³⁷Kim KC, Yook JH, Eisenbraun J, Kim BS, Huber R. Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma – a randomized, controlled pilot study. BMC Complementary and Alternative Medicine. 2012 Oct 3;12:172.

Without regard to treatment phase: modest evidence of better quality of life among people treated with mistletoe

• Better quality of life among people with cancer treated with mistletoe extracts compared to controls, with stronger effects for younger people or with longer treatment, in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 26 controlled trialsa study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial³⁸Loef M, Walach H. Quality of life in cancer patients treated with mistletoe: a systematic review and meta-analysis. BMC Complementary Medicine and Therapies. 2020 Jul 20;20(1):227.
• Better quality of life among people with cancer treated with mistletoe therapy in 22 of 26 studies in a systematic review of RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects and other clinical studies³⁹Kienle 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. Integrative Cancer Therapies. 2010 Jun;9(2):142-57.
• Better quality of life in 21 of 24 studies among people with gynecological or breast cancers (and including lung cancer in 1 study) treated with mistletoe therapy in a review of clinical and preclinical studiestesting a drug, a procedure, or another medical treatment in isolated cells or in animals; preclinical evidence is considered only an initial indication of possible effects in people⁴⁰Kienle GS, Glockmann A, Schink M, Kiene H. Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research. Journal of Experimental & Clinical Cancer Research. 2009 Jun 11;28:79.
• Better overall quality of life in 3 studies among 23 studies total among people with cancer treated with mistletoe therapy compared to controls in review of controlled studies, none of which were high quality⁴¹Kienle GS, Berrino F et al. Mistletoe in cancer—a systematic review on controlled clinical trials. European Journal of Medical Research. 2003 Mar 27;8(3):109-19.

During chemotherapy: modest evidence of better quality of life in general among people treated with mistletoe

• Better quality of life among people with breast cancer treated with chemotherapy and mistletoe therapy compared to chemotherapy alone in a systematic review of 4 RCTs⁴²Lange-Lindberg AM, Velasco Garrido M, Busse R. Mistletoe treatments for minimising side effects of anticancer chemotherapy. GMS Health Technology Assessment. 2006 Sep 19;2:Doc18.

• Less pain during surgery and adjuvanttreatment applied after initial treatment for cancer, especially to suppress secondary tumor formation chemotherapy among people with breast cancer treated with mistletoe extracts 3 times a week during 18 weeks of chemotherapy compared to controls in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁴³Pelzer F, Tröger W, Nat DR. 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. 2018 Sep/Oct;24(9-10):954-961.
• Less pain among people with locally advanced or metastatic pancreatic cancer receiving no further conventional treatment, and treated with mistletoe extract in escalating doses by subcutaneous injection three times a week compared to controls in a mid-sized RCT⁴⁴Tröger W, Galun Det al. Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. Deutsches Arzteblatt International. 2014 Jul 21;111(29-30):493-502, 33 p following 502.

• Less insomnia among people with locally advanced or metastatic pancreatic cancer receiving no further conventional treatment and treated with mistletoe extract in escalating doses by subcutaneous injection three times a week compared to controls in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁴⁵Tröger W, Galun Det al. Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. Deutsches Arzteblatt International. 2014 Jul 21;111(29-30):493-502, 33 p following 502.

• Longer intervals between repeated punctures to drain ascites among people with advanced cancer with mistletoe injected into the peritoneal cavity compared to baseline in a small uncontrolled studya study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁴⁶Bar-Sela G, Goldberg H, Beck D, Amit A, Kuten A. Reducing malignant ascites accumulation by repeated intraperitoneal administrations of a Viscum album extract. Anticancer Research. 2006 Jan-Feb;26(1B):709-13.

• No lower risk of recurrence among people with malignant disease treated with anthroposophic mistletoe compared to controls in a review of controlled trialsa study design in which people are assigned to either an experimental group or a control group to compare the outcomes from different treatment; assignment is not random, and so this is not as strong a study design as a randomized controlled trial, but still stronger than an uncontrolled trial⁴⁷Kienle GS, Kiene H. Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts. European Journal of Medical Research. 2007 Mar 26;12(3):103-19.

• Comparable tumor recurrence at 12 months among people with noninvasive superficial urothelial bladder carcinomas of stages pTa and pT1, grades 1 to 2 after resection treated with mistletoe extracts inserted in the bladder (intravesically) compared to local historical controls treated with adjuvanttreatment applied after initial treatment for cancer, especially to suppress secondary tumor formation Bacillus Calmette-Guerin (BCG), without local or systemic side effects in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁴⁸Elsässer-Beile U, Leiber C et al. Adjuvant intravesical treatment with a standardized mistletoe extract to prevent recurrence of superficial urinary bladder cancer. Anticancer Research. 2005 Nov-Dec;25(6C):4733-6.
• Fewer frequently recurring tumors in 5 of 8 people with resectable bladder cancer treated with high-dose mistletoe treatment compared to baseline in a small uncontrolled trial⁴⁹von Schoen-Angerer T, Wilkens J, Kienle GS, Kiene H, Vagedes J. High-dose Viscum album extract treatment in the prevention of recurrent bladder cancer: a retrospective case series. Permanente Journal. 2015 Fall;19(4):76-83.