Mistletoe (European)

Health Care Professional Information

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.

Mistletoe extracts have anticancer effects in vitro (21). But well-designed randomized trials are lacking. A meta-analysis analyzed 11 of these clinical trials conducted before 1994 and showed no benefit from mistletoe (1), but recent systematic reviews point to the accumulating evidence in support of mistletoe while emphasizing the need for well-designed clinical trials (17) (18). Epidemiologic data also suggest survival advantage following treatment with mistletoe (2) (3). When used in conjuction with chemotherapy, a mistletoe extract improved quality of life in a study of breast cancer patients (22). However, mistletoe was not active in metastatic colorectal cancer resistant to 5-fluorouracil and leucovorin (20).
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). 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.
A recent study indicates that solubilized triterpene acid- or lectin-containing mistletoe extracts induce dose-dependent apoptosis in acute lymphoblastic leukemia cell line NALM-6 through caspase-8 and -9 dependent pathways (23).
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)
 

Herb-Drug Interactions
  • Cytochrome P450 3A4 substrates: Mistletoe inhibits CYP3A4 and can affect the intracellular concentration of drugs metabolized by this enzyme (19).
Dosage (Inside MSKCC Only)
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References
  1. Kleijnen J, Knipschild P. Mistletoe treatment for cancer: Review of controlled trials in humans. Phytomedicine. 1994;1:255-60.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Finall AI, McIntosh SA, Thompson WD. Subcutaneous inflammation mimicking metastatic malignancy induced by injection of mistletoe extract. BMJ. 2006:333:1293-4.
  8. Gorter RW, et al. Subcutaneous infiltrates induced by injection of mistletoe extracts (Iscador). Am J Ther. 1998;5:181-7.
  9. Schulz V, et al. Rational Phytotherapy: A Physician's Guide to Herbal Medicine, 4th ed. New York: Springer; 2001.
  10. 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.
  11. Newall CA. Herbal medicines: A Guide for Health Care Professionals. London: Pharmaceutical Press; 1996.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. Tusenius KJ, Spoek JM, Kramers CW. Iscador Qu for chronic hepatitis C: an exploratory study. Complement Ther Med. 2001;9:12-6.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. Strüh CM, Jäger S, Schempp CM, Scheffler A, Martin SF. A novel triterpene extract from mistletoe induces rapid apoptosis in murine b16.f10 melanoma cells. Phytother Res. 2012 Oct;26(10):1507-12.
  22. Eisenbraun J, Scheer R, Kröz M, Schad F, Huber R. Quality of life in breast cancer patients during chemotherapy and concurrent therapy with a mistletoe extract. Phytomedicine. 2011 Jan 15;18(2-3):151-7.
  23. Delebinski CI, Jaeger S, Kemnitz-Hassanin K, et al. A new development of triterpene acid-containing extracts from Viscum album L. displays synergistic induction of apoptosis in acute lymphoblastic leukaemia. Cell Prolif. 2012 Apr;45(2):176-87.

Consumer Information

How It Works

Bottom Line: Mistletoe has not been shown to treat or prevent cancer.

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 support this use, but clinical trials have not been conducted.
  • To treat arthritis
    There are 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.
  • 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. Human data are lacking.
  • For sedation
    There are no studies to validate this claim.
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.

E-mail your questions and comments to aboutherbs@mskcc.org.