- How It Works
- Purported Uses
- Research Evidence
- Patient Warnings
- Do Not Take If
- Side Effects
- Special Point
- Dosage (Inside MSKCC Only)
Scientific Name
Viscum album, Viscum coloratum
Common Name
Viscum, all-heal, birdlime
Brand Name
Helixor®, Iscador®, Iscador Qu®, Lektinol™, Eurixor®, Abnoba-viscum Quercus
Clinical Summary
Derived from the aerial parts, except berries, of the plant, mistletoe preparations are used by patients for a variety of conditions including cancer, HIV, hepatitis, and degenerative joint disease. Polypeptides, including lectins and viscotoxins, are thought responsible for in vitro immune stimulant and tumor inhibition activities (1). Although orally administered products are available, all research reported in the literature has evaluated parenteral formulations of mistletoe, which are not approved for use in the United States by the Food and Drug Administration.
The body of published research suggesting efficacy for the treatment of cancer lacks well-designed randomized trials. A meta-analysis analyzed 11 of these clinical trials conducted before 1994 and showed no benefit from mistletoe (1), but recent sytematic reviews point to the accumulating evidence in support of mistletoe while emphasizing the need for well-designed clinical trials (17) (18).
An epidemiologic study also suggested a possible survival advantage following treatment with mistletoe, but this has not been confirmed in controlled trials (2) (3).
An injectable form of mistletoe lectins was found to reduce the frequency and intensity of clinical signs and symptoms in patients with hepatitis C (4). Mistletoe extract is not active in metastatic colorectal cancer resistant to 5-fluorouracil and leucovorin (20). Confirmed efficacy for other proposed claims is lacking (5) (6).
Possible adverse effects from treatment include injection site reactions (7), chills, fever, headache, leukocytosis, chest pain, orthostatic hypotension, bradycardia, diarrhea, and vomiting (8) (9). In addition, long-term use of mistletoe extracts may reduce T cell function in cancer patients (10). Toxic doses of mistletoe can produce coma, seizures, and death (11). Possible drug interactions include additive hypotensive effect from antihypertensives and antagonism of cardiac glycosides or antiarrhythmics.
Purported Uses
- Arthritis
- Cancer treatment
- Hepatitis
- HIV and AIDS
- Hypertension
- Immunostimulation
- Sedation
- Spasms
Constituents
- Acids: Oleic, palmitic, anisic, caffeic, para-coumaric, quinic, vanillic
- Amines: Acetycholine, choline, histamine, tyramine
- Flavonoids: Quercetin
- Lectins: Lectins I, II, and III (high molecular weight polypeptides)
- Terpenoids: Beta-amyrin, resin acids, beta-sitosterol, stigmasterol, sterol A
- Viscotoxins: Viscotoxins A2, A3, and B (low molecular weight polypeptides)
- Others: Mucilage, mannitol, inositol, fructose, glucose, starch, syringin, tannin
(11)
Mechanism of Action
Immunologic action of mistletoe is attributed to lectins. Lectins induce macrophage cytotoxicity, stimulate phagocytosis of immune cells, increase cytokine secretion (TNF-alpha, IL-1, IL-2, and IL-6), and enhance cytotoxicity effects on various cell lines in vitro (9) (12). In addition, mistletoe extracts stimulate dendritic cell maturation and activation (13) and induce apoptosis of lymphoblastic leukemia cells (14). However, analysis of mistletoe lectins and alkaloids has produced conflicting data about in vitro and animal model inhibition of cancer cell growth with mouse and human cell lines. The hypotensive effect is thought to be mediated by acetylcholine, histamine, GABA, tyramine, and flavones, although the exact mechanism of action is unknown. Controlled clinical trials in humans also yield mixed results on mistletoe’s effects (4) (5) (6) (15).
Warnings
Mistletoe berries and leaves are highly poisonous - more than 2 berries or 3 leaves can produce toxic effects.
(9)
Contraindications
Pregnant women should not consume mistletoe due to uterine stimulant activity of tyramine and unidentified constituents.
Adverse Reactions
Common: Chills, fever, headache, leukocytosis, chest pain, orthostatic hypotension, bradycardia, diarrhea, vomiting, hypersensitivity, subcutaneous infiltrates (7) (8) (9)
Long-term use of mistletoe extracts may reduce T cell function in cancer patients (10)
Toxicity: Hypotension, coma, seizures, myosis, and death (11)
Herb-Drug Interactions
- Cytochrome P450 3A4 substrates: Mistletoe inhibits CYP3A4 and can affect the intracellular concentration of drugs metabolized by this enzyme (19).
Literature Summary and Critique
Literature about mistletoe preparations consists primarily of uncontrolled trials, case report series, or studies with questionable design. Several recent publications indicate possible survival advantage with various effects on quality of life.
Steuer-Vogt MK, et al. The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomized controlled clinical trial. Eur J Cancer 2001;37:23-31.
A prospective evaluation of head and neck cancer patients stratified based on intervention (surgery with or without radiotherapy) and randomized to receive either placebo or mistletoe 1ng/kg Eurixor® subcutaneously twice a week for up to 60 weeks. A total of 447 patients were enrolled: Group A consisted of 105 patients receiving surgery alone compared to 97 receiving surgery and mistletoe; Group B contained 137 patients receiving surgery and radiotherapy compared to 138 receiving concomitant mistletoe. The study did not demonstrate any difference in lymphocyte subsets, quality of life, efficacy, or survival for either Group A or B. Injection site reactions were noted in 45% of all patients receiving mistletoe. Other reactions noted included myalgia, mild fever, fatigue, and sneezing. Sixteen percent of patients in Group A and 20% in Group B discontinued mistletoe due to adverse events. The authors failed to find any benefit for mistletoe injections for head and neck cancer.
Grossarth-Maticek R, et al. Use of Iscador, an extract of European mistletoe (Viscum album) in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study. Altern Ther Health Med 2001;7:57-78.
A large epidemiologic matched-pair evaluation of survival in patients receiving standard chemotherapy with or without mistletoe for the treatment of various oncologic diagnoses. Patients received treatment between 1971 and 1988 throughout Germany. A total of 1668 patients received Iscador® brand mistletoe injections in combination with standard chemotherapy. The authors matched patients for comparison in an unblinded fashion allowing no more than 2 minor deviations in criteria between patients. Final data analysis revealed a statistically significant survival advantage for patients receiving Iscador®. All types of cancer appeared to benefit with added survival ranging from 0.48 to 1.72 years. The authors make no mention of adverse events or toxicity. The authors also did not match for the type or number of previous chemotherapy regimens that patients received.
Tusenius KJ, Spoek JM, Kramers CW. Iscador Qu for chronic hepaptis C: an exploratory study. Complement Ther Med 2001;9:12-6.
A case report series of 5 patients administered 5 mg Iscador® subcutaneously three times a week for 12 months. All patients had serologically confirmed Hepatitis C. Changes in viral load and improvement in liver function tests were noted in two patients, but elevated viral load and stable or elevated liver functions tests were noted in another 3 patients. The only side effect reported was injection site reaction. Improvements in quality of life were shown after treatment and persisted up to 6 months following treatment. Additional studies are needed to confirm this effect.
References
- Kleijnen J, Knipschild P. Mistletoe treatment for cancer: Review of controlled trials in humans. Phytomedicine 1994;1:255-60.
- Grossarth-Maticek R, et al. Use of Iscador, an extract of European mistletoe (Viscum album) in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study. Altern Ther Health Med 2001;7:57-78.
- 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. Nov 30 2006;11(11):485-495.
- Huber R, et al. Effects of a mistletoe preparation with defined lectin content on chronic hepatitis C: an individually controlled cohort study. Eur J Med Res 2001;6:399-405.
- Kleeberg UR, et al. Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis. Eur J Cancer. 2004 Feb;40(3):390-402.
- Steuer-Vogt MK, et al. The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial. Eur J Cancer 2001;37:23-31.
- Finall AI, McIntosh SA, Thompson WD. Subcutaneous inflammation mimicking metastatic malignancy induced by injection of mistletoe extract. BMJ 2006:333:1293-4.
- Gorter RW, et al. Subcutaneous infiltrates induced by injection of mistletoe extracts (Iscador). Am J Ther 1998;5:181-7.
- Schulz V, et al. Rational Phytotherapy: A Physician’s Guide to Herbal Medicine, 4th ed. New York: Springer; 2001.
- Bussing A, Stumpf C, Troger W, Schietzel M. Course of mitogen-stimulated T lymphocytes in cancer patients treated with Viscum album extracts. Anticancer Res. Jul-Aug 2007;27(4C):2903-2910.
- Newall CA. Herbal medicines: A Guide for Health Care Professionals. London: Pharmaceutical Press; 1996.
- Goebell P, et al. Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial. J Urol. 2002 Jul;168(1):72-5.
- Elluru SR, van Huyen JP, Delignat S, et al. Induction of maturation and activation of human dendritic cells: a mechanism underlying the beneficial effect of Viscum album as complimentary therapy in cancer. BMC Cancer. 2008;8:161.
- Seifert G, Jesse P, Laengler A, et al. Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro.Cancer Lett. Jun 18 2008;264(2):218-228.
- Mengs U, Gothel D, Leng-Peschlow E. Mistletoe extracts standardized to mistletoe lectins in oncology: review on current status of preclinical research. Anticancer Res 2002;22:1399-407.
- Tusenius KJ, Spoek JM, Kramers CW. Iscador Qu for chronic hepaptis C: an exploratory study. Complement Ther Med 2001;9:12-6.
- Ostermann T, Raak C, Büssing A. Survival of cancer patients treated with mistletoe extract (Iscador): a systematic literature review. BMC Cancer. 2009 Dec 18;9:451.
- Melzer J, Iten F, Hostanska K, Saller R. Efficacy and safety of mistletoe preparations (Viscum album) for patients with cancer diseases. A systematic review. Forsch Komplementmed. 2009 Aug;16(4):217-26.
- Engdal S, Nilsen OG. In vitro inhibition of CYP3A4 by herbal remedies frequently used by cancer patients. Phytother Res. 2009 Jul;23(7):906-12.
- Bar-Sela G, Haim N. Abnoba-viscum (mistletoe extract) in metastatic colorectal carcinoma resistant to 5-fluorouracil and leucovorin-based chemotherapy. Med Oncol. 2004;21(3):251-4.
How It Works
Bottom Line: Because there is no solid proof that it works, mistletoe should not be used to treat cancer, hepatitis, or any other disease.
Extensive laboratory research has been performed with mistletoe, its extracts, and the product Iscador®. These experiments show that mistletoe extracts are able to stimulate the activity of several cells and factors of the immune system. In addition, mistletoe extracts show anti-tumor activity in mice implanted with cancers of the lung, colon, and breast. Researchers think this may be due to mistletoe’s ability to prevent healthy cells from turning into cancer cells (differentiation). Mistletoe has been observed to lower blood pressure, but researchers are unsure exactly how this effect takes place.
Purported Uses
- To calm muscle spasms
No scientific evidence supports this use. - To slow the heart rate
This claim is not backed by research. - To lower high blood pressure
Laboratory data supports this use, but there is no proof from clinical trials that this effect occurs in humans. - To treat arthritis
There is no data to substantiate this claim. - To treat cancer
Laboratory and animal studies show some anti-cancer activity, but clinical trials have not been able to confirm the same effect in humans. In general, clinical trials do not support this use. - To treat hepatitis
Clinical trials show conflicting results. - To treat AIDS
No scientific evidence supports this use. - As an immune stimulant
Laboratory and animal studies support this use, but these results are not always transferable to the human body. There is no proof from clinical trials that mistletoe can help the body fight infections or disease. - For sedation
There are no studies to validate this claim.
Research Evidence
Cancer treatment
A clinical trial in Europe used mistletoe (Eurixor®) in combination with mainstream therapies to treat patients with head and neck cancer. Patients were split into four groups: 105 patients had just surgery, 97 patients underwent surgery and received injections of mistletoe twice a week; 137 patients received surgery and radiotherapy alone, and 138 patients received surgery, radiotherapy, and twice weekly mistletoe injections. At the end of the study, mistletoe had no detectable effect on clinical response, quality of life, or survival, but did result in a greater number of side effects (e.g., injection site reaction, muscle pain, mild fever, fatigue, and sneezing). This trial does not support the use of mistletoe in head and neck cancers.
A large survey in Germany assayed the survival of 1668 patients with various forms of cancer who underwent mainstream therapy combined with mistletoe (Iscador®) injections. When the survival of these patients was compared to that of a group of similar patients who only used mainstream cancer therapy, they were found to live on average a half a year to almost 2 years longer. This survival benefit applied to all types of cancer studied. This type of matched-patient study is not as reliable as a “blinded” randomized controlled trial, in which the researcher is unaware which patients are taking mistletoe and therefore can make unbiased analysis of the data.
Hepatitis C
The use of mistletoe (Iscador®) to treat hepatitis C was examined in five patients. Patients received 5 mg of Iscador® in a subcutaneous injection three times a week for twelve months. Two patients showed long-lasting improvements in liver function, viral load, and quality of life, while Iscador® therapy seemed to have no effect in the other three patients. These results are very preliminary; larger clinical trials are needed to verify if mistletoe is generally helpful in treating hepatitis C.
Patient Warnings
- Mistletoe berries and leaves are highly poisonous - more than two berries or three leaves can produce toxic effects.
Do Not Take If
- You are pregnant (Some compounds in mistletoe can stimulate the uterus to contract, which can increase the risk of abortion).
- You are taking drugs that are substrates of Cytochrome P450 3A4 (mistletoe may increase the risk of side effects of these drugs).
Side Effects
- Headache
- Chills
- Fever
- Leukocytosis (abnormal elevation of the white blood cell count)
- Chest pain
- Orthostatic hypotension (low blood pressure upon sitting from reclining)
- Bradycardia (low heart rate)
- Diarrhea, vomiting
- Hypersensitivity
- Signs of toxicity include Low blood pressure, coma, seizures, myosis (long-continued contraction of the pupil of the eye), and death.
Special Point
Although orally administered mistletoe products are available, all clinical trials have evaluated only the injected forms of mistletoe, which are not approved for use in the United States by the Food and Drug Administration.
Dosage (Inside MSKCC Only)
This field is only visible to only Inside MSKCC users.
Aliases
Eurixor®
Helixor®
Iscador®
Viscum Album
E-mail your questions and comments to aboutherbs@mskcc.org.
