Mistletoe

Scientific Name(s): Viscum album L. (European mistletoe) and Phoradendron tomentosum (DC.) Engelm. ex A. Gray (Christmas mistletoe).

Common Name(s): Mistletoe , bird lime , all heal , devil's fuge , golden bough , mistel (German), Iscador

Uses

Mistletoe has been used to treat cancer, although there is a lack of quality clinical trials and no evidence of an effect. Further study is needed. In folk medicine, it has been used for its cardiovascular properties. Clinical efficacy has not been established. Injectable mistletoe extract is widely used in Europe but is not licensed for use in the United States.

Dosing

Crude mistletoe fruit or herb is used to make a tea to treat hypertension at a dosage of 10 g/day. There are a number of proprietary extracts containing low levels of mistletoe lectin-Ι (ML-Ι) used as adjuvant cancer therapies. These extracts usually are given by intravenous (IV) or subcutaneous injection at dosages of 0.1 to 30 mg several times per week. Mistletoe preparations, produced according to anthroposophical methods, are given in incrementally increasing dosages depending on the patient's general condition and response to the injection. Use in pediatric patients has been reported. The pharmacokinetics in healthy adults has been determined.

Contraindications

Data are limited. Use of mistletoe extracts in patients with primary or secondary brain tumors, leukemia, or malignant lymphoma is contraindicated.

Pregnancy/Lactation

Mistletoe contains toxic constituents. Avoid use during pregnancy or lactation.

Interactions

None well documented.

Adverse Reactions

Local reactions following injection include redness, itching, inflammation, and induration at the injection site. Systemic reactions include mild fever or flu-like symptoms. Anaphylaxis has been reported.

Toxicology

Poison centers report toxicity of the whole plant, but especially mistletoe berries. The use of preparations standardized to small doses of ML-Ι or depleted of lectins may reduce toxicity.

Botany

The family Viscaceae (Christmas Mistletoe family) contains 5 genera and more than 50 different mistletoe species. Synonyms include Phoradendron flavescens , Phoradendron serotinum , and Viscum coloratum . Mistletoe is a hemiparasitic plant that grows on a wide variety of host trees such as pine, oak, birch, and apple. The term hemiparasitic indicates that the mistletoe plant carries out photosynthesis independently but obtains its water and minerals from the host. There are several subspecies and varieties of mistletoe, which are defined by the host that they parasitize. European mistletoe is dioecious, with male and female flowers on separate plants. They are pollinated by insects and bear small white berries on evergreen foliage. Other varieties bear red berries. 1 , 2

History

Mistletoe preparations have been used medicinally in Europe for centuries to treat epilepsy, infertility, hypertension, and arthritis. The Celtic priests, known as Druids, revered the oak tree and the mistletoe that grew upon it, according to Roman author and naturalist Gaius Plinius Secundus (also known as Pliny the Elder). At the winter celebration of Samhain, the sacred oaks were bare except for the green boughs of mistletoe. This was taken as a sign of eternal fertility. The Celts placed a sprig of mistletoe above the door of their houses. Its sacred nature prohibited fighting beneath it. This evolved over centuries into the custom of kissing underneath mistletoe at Christmas. 3 In 1921, the Austrian anthroposophical spiritual leader Rudolf Steiner suggested that mistletoe might be used to treat cancer, based on the observation that mistletoe, like cancer, is parasitic and lethal to its host. 4 Swiss and German clinics were founded to implement this idea and are still actively using a mistletoe preparation fermented with a strain of Lactobacillus for 3 days, a process that is more aligned to alchemy and homeopathy than pharmacology. 4 , 5

Chemistry

The most distinctive constituents of V. album are its proteins, which are of 2 types: the viscotoxins, which are small (5 kDa), cystine-rich basic proteins (known as thionins), and the larger mistletoe lectins. Four viscotoxins (A1, A2, A3, and B) have been isolated and sequenced. 6 They are highly homologous 46–amino acid proteins, differing from one another at a few positions. The 3-dimensional structure of viscotoxin A3 has been elucidated by nuclear magnetic resonance methods. 7 The viscotoxin profile of the 3 European subspecies of V. album has been determined. 8 Two novel viscotoxins, termed 1-PS and U-PS, were found in subspecies austriacum (pine) and subspecies abietis (fir). The viscotoxin profile of subspecies album did not vary appreciably with 7 different hosts. The American species P. tomentosum yielded a homolog known as phoratoxin. 2 The preparation Iscador has been shown to contain similar amounts of viscotoxins compared with the unfermented V. album extract. 9

Lectins

Viscumin, a toxic lectin, was isolated from V. album and shown to be a type ΙΙ ribosome-inactivating protein. 10 Three distinct lectins (ML-Ι[viscumin], ML-ΙΙ, and ML-ΙΙΙ) were isolated by another group and shown to have different carbohydrate-binding specificities. 11 , 12 The complete amino acid sequence of ML-Ι B-chain has been obtained, showing homology to other galactose-specific lectins, such as ricin and abrin. 13 The X-ray diffraction 3-dimensional structure of ML-Ι has been obtained in the free state 14 and bound to beta-galactose. 15 ML-Ι binds to several sialylglycoproteins in addition to the galactose-binding specificity initially identified. 16 , 17 The structural features important for carbohydrate recognition have been described in detail. 18 , 19 A minor chitin-binding lectin completely distinct from ML-Ι-ΙΙΙ was isolated. 20 Examination of the commercial preparation Iscador has shown that ML-Ι is modified or degraded, while ML-ΙΙ and ML-ΙΙΙ are still present. 5 , 10 , 21

Carbohydrates

The water-soluble polysaccharides of V. album and Iscador have been purified and characterized. A highly esterified galactouronan and a complex arabinogalactan were identified, with the corresponding polysaccharides from Iscador having lower molecular weights compared with those of the native, unfermented extract. 22

Small molecular weight compounds

The phenylpropanoids syringin, syringenin-apiosylglucoside, and eleutheroside E have been found in V. album , and have been used to identify and standardize mistletoe preparations. 10 , 23 The syringin content of mistletoe growing on different host plants has been measured. 24 A number of known and novel chalcone and flavanone glycosides have been reported from European V. album . 25 , 26 Inositol derivatives are widespread in the Viscaceae family and occur at relatively high concentrations in all species of mistletoe. They are thought to play a role in osmotic balance. 27 Other miscellaneous compounds have been reported. 28 , 29 A report of alkaloids in the plant has not been substantiated by isolation in pure form or structure elucidation. 30

Uses and Pharmacology

Because of the potential toxicity of mistletoe, many studies have been done in vitro. Methodology of clinical trials is generally poor.

Cancer

Despite a plethora of experiments to determine a mechanism of action for mistletoe, no clear pathway has been identified. Proposed mechanisms generally focus on direct cytotoxic action (apoptosis induction) or immunomodulation (eg, enhanced natural killer cell activity, increased production of interleukins and tumor necrosis factor-alpha, activation of mononuclear cells, stimulation of granulocyte phagocytosis). 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 Therapeutic activity is considered to be caused by mistletoe lectins 65 ; however, other cytotoxic compounds may contribute. 66

Clinical data

Several systematic reviews of clinical trials have been published. 65 , 67 , 68 , 69 , 70 , 71 Outcome measures include survival times, tumor response, quality of life, psychological distress, adverse reactions, and safety. 65 All reviews note the poor methodology in many of the trials; the diversity of extracts (different species, different extraction methods, and different host trees) and the use of various treatment regimens make systematic analysis difficult. No evidence of effect can be shown. A positive and negative trend were found for trials included in the reviews. 65 , 67 , 68 Two quality trials of mistletoe as adjuvant to chemotherapy in breast cancer showed positive effect (quality of life, reduction of adverse reactions of chemotherapy), and 4 trials (including head and neck cancer and melanoma) with good methodology showed evidence of no effect on increased survival. 65 Reviewers considered it desirable to enroll patients in further clinical trials. 65 , 67 , 71 Injectable mistletoe is not approved as a cancer treatment in the United States. 71 Some in vitro and in vivo experiments and clinical studies suggest that interleukins can stimulate proliferation of certain cancer cells, and hence mistletoe therapy may not be without risk in cancer patients. 67 Use of mistletoe extracts in patients with primary or secondary brain tumors, leukemia, or malignant lymphoma is contraindicated. 67

Cardiovascular

In European folk medicine, a primary use of mistletoe is for its cardiovascular properties. However, clinical trials to support this use are lacking. Viscotoxins have been shown to induce reflex bradycardia and possess negative inotropic effects in the isolated animal cardiac muscle, as well as vasoconstriction at higher doses. 72 , 73 Phoratoxin demonstrates action on skeletal muscle fibers. 74 Phenylpropanoids might also play a role in mistletoe's cardiovascular effects through a postulated inhibition of cyclic adenosine monophosphate phosphodiesterase. 75 , 76

Dosage

Crude mistletoe fruit or herb is used to make a tea for hypertension at a dosage of 10 g/day.

Iscador , a proprietary fermented product with different properties to unfermented mistletoe extracts, contains low levels of ML-Ι (10 mg extract contains 750 ng lectin). 63 Iscador extract usually is given by IV or subcutaneous injection at dosages of 0.1 to 30 mg several times per week. 77 , 78 , 79 , 80 Mistletoe preparations produced according to anthroposophical methods are given in incrementally increasing dosages depending on the patient's general condition and response to the injection. 65 Therapy for solid tumors has used mistletoe preparations containing lectin 20,000 ng/mL or viscotoxins 100 mcg/mL by either the intratumoral, subcutaneous, or IV route. Iscador has not been approved for use in the United States. 81

Use in pediatric patients has been reported. 82 The pharmacokinetics in healthy adults has been determined. 83 Peak plasma concentrations were obtained 1 to 2 hours after subcutaneous injection, and mistletoe preparation was still detectable in some of the volunteers after 2 weeks. 83 An enteric-coated mistletoe-alginate/chitosan complex has been developed to overcome the poor bioavailability of oral mistletoe. 84

Pregnancy/Lactation

Mistletoe contains toxic constituents. Avoid use during pregnancy or lactation. 85 , 86

Interactions

None well documented.

Adverse Reactions

Clinical trials on adverse reactions related to mistletoe administration ranged from a few reactions to as many as 45% of trial participants experiencing some adverse reaction. 65 , 67 Local reactions following injection include redness, itching, and induration at the injection site. Subcutaneous inflammation following injection of the extract has been reported, 87 and this has been noted as a potential methodological flaw for blinding in future trials. 88 Systemic reactions include mild fever or flu-like symptoms. 65

Toxicology

Mistletoe is considered to be a toxic plant, and its content of toxic lectins lends support to this. 89 Poison centers report toxicity of the whole plant, but especially the berries. Mild gastroenteritis, seizures, hallucinations, and anaphylaxis have been reported. 70 , 90 , 91 , 92 , 93 Use of preparations standardized to small doses of ML-Ι (1 ng/injection) or depleted lectins by fermentation may reduce toxicity. 9

Bibliography

1. Mistletoe. USDA, NRCS . 2008. The PLANTS Database (http://plants.usda.gov, July, 2008). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Becker H. Botany of European mistletoe ( Viscum album L.). Oncology . 1986;43 (suppl 1):2-7.
3. Bryant VM, Grider S. To kiss: why we kiss under the mistletoe at Christmas. The World & I . 1991:613.
4. Ernst E. Mistletoe as a treatment for cancer. BMJ . 2006;333(7582):1282-1283.
5. Ribéreau-Gayon G, Jung ML, Di Scala D, Beck JP. Comparison of the effects of fermented and unfermented mistletoe preparations on cultured tumor cells. Oncology . 1986;43(suppl 1):35-41.
6. Samuelsson G, Pettersson BM. The amino acid sequence of viscotoxin B from the European mistletoe ( Viscum album L., loranthaceae). Eur J Biochem . 1971;21(1):86-89.
7. Romagnoli S, Ugolini R, Fogolari F, et al. NMR structural determination of viscotoxin A3 from Viscum album L. Biochem J . 2000;350(pt 2):569-577.
8. Schaller G, Urech K, Grazi G, Giannattasio M. Viscotoxin composition of the three European subspecies of Viscum album . Planta Med . 1998;64(7):677-678.
9. Wagner H, Jordan E, Feil B. Studies on the standardization of mistletoe preparations. Oncology . 1986;43(suppl 1):16-22.
10. Olsnes S, Stirpe F, Sandvig K, Pihl A. Isolation and characterization of viscumin, a toxic lectin from Viscum album L. (mistletoe). J Biol Chem . 1982;257(22):13263-13270.
11. Franz H, Ziska P, Kindt A. Isolation and properties of three lectins from mistletoe ( Viscum album L.). Biochem J . 1981;195(2):481-484.
12. Müthing J, Meisen I, Bulau P, et al. Mistletoe lectin I is a sialic acid-specific lectin with strict preference to gangliosides and glycoproteins with terminal Neu5Ac alpha 2-6Gal beta 1-4GlcNAc residues. Biochemistry . 2004;43(11):2996-3007.
13. Soler MH, Stoeva S, Voelter W. Complete amino acid sequence of the B chain of mistletoe lectin I. Biochem Biophys Res Commun . 1998;246(3):596-601.
14. Krauspenhaar R, Eschenburg S, Perbandt M, et al. Crystal structure of mistletoe lectin I from Viscum album . Biochem Biophys Res Commun . 1999;257(2):418-424.
15. Sweeney EC, Palmer RA, Pfüller U. Crystallization of the ribosome inactivating protein ML1 from Viscum album (mistletoe) complexed with beta-D-galactose. J Mol Biol . 1993;234(4):1279-1281.
16. Wu AM, Song SC, Hwang PY, Wu JH, Pfüller U. Interaction of mistletoe toxic lectin-I with sialoglycoproteins. Biochem Biophys Res Commun . 1995;214(2):396-402.
17. Wu AM, Chin LK, Franz H, Pfüller U, Herp A. Carbohydrate specificity of the receptor sites of mistletoe toxic lectin-I. Biochim Biophys Acta . 1992;1117(2):232-234.
18. Lee RT, Gabius HJ, Lee YC. Ligand binding characteristics of the major mistletoe lectin. J Biol Chem . 1992;267(33):23722-23727.
19. Galanina OE, Kaltner H, Khraltsova LS, Bovin NV, Gabius HJ. Further refinement of the description of the ligand-binding characteristics for the galactoside-binding mistletoe lectin, a plant agglutinin with immunomodulatory potency. J Mol Recognit . 1997;10(3):139-147.
20. Peumans WJ, Verhaert P, Pfüller U, Van Damme EJ. Isolation and partial characterization of a small chitin-binding lectin from mistletoe ( Viscum album ). FEBS Lett . 1996;396(2-3):261-265.
21. Holtskog R, Sandvig K, Olsnes S. Characterization of a toxic lectin in Iscador , a mistletoe preparation with alleged cancerostatic properties. Oncology . 1988;45(3):172-179.
22. Jordan E, Wagner H. Structure and properties of polysaccharides from Viscum album (L.). Oncology . 1986;43(suppl 1):8-15.
23. Deliorman D, Calis I, Ergun F, Tamer U. The comparative studies on phenylpropanoid glycosides of Viscum album subspecies by high performance liquid chromatography. J Liq Chromatogr Relat Technol . 1999;22(20):3101-3114.
24. Deliorman D, Ergun F. High performance liquid chromatographic determination of syringin in Viscum album L. ssp. album samples collected from different host plants. J Liq Chromatogr Relat Technol . 2000;23(19):3033-3042.
25. Fukunaga T, Kajikawa I, Nishiya K, Watanabe Y, Takeya K, Itokawa H. Studies on the constituents of the European mistletoe, Viscum album L. Chem Pharm Bull . 1987;35(8):3292-3297.
26. Fukunaga T, Kajikawa I, Nishiya K, et al. Studies on the constituents of the European mistletoe, Viscum album L. II. Chem Pharm Bull . 1988;36(3):1185-1189.
27. Richter A. Viscumitol, a dimethyl-ether of muco-inositol from Viscum album . Phytochemistry . 1992;31(11):3925-3927.
28. Deliorman D, Calis I, Ergun F. A new acyclic monoterpene glucoside from Viscum album ssp. album. Fitoterapia . 2001;72(2):101-105.
29. Errenst M, Scheffler A. Photohaemolytic activity of chlorophyll degradation products in a mistletoe extract. Planta Med . 1999;65(7):627-631.
30. Khwaja TA, Dias CB, Pentecost S. Recent studies on the anticancer activities of mistletoe ( Viscum album ) and its alkaloids. Oncology . 1986;43(suppl 1):42-50.
31. Stirpe F, Legg RF, Onyon LJ, Ziska P, Franz H. Inhibition of protein synthesis by a toxic lectin from Viscum album L. (mistletoe). Biochem J . 1980;190(3):843-845.
32. Ribéreau-Gayon G, Jung M, Beck J, Anton R. Effect of fetal calf serum on the cytotoxic activity of mistletoe ( Viscum album L.) lectins in cell culture. Phytother Res . 1995;9(5):336-339.
33. Urech K, Schaller G, Ziska P, Giannattasio M. Comparative study on the cytotoxic effect of viscotoxin and mistletoe lectin on tumour cells in culture. Phytother Res . 1995;9(1):49-55.
34. Schaller G, Urech K, Giannattasio M. Cytotoxicity of different viscotoxins and extracts from the European subspecies of Viscum album L. Phytother Res . 1996;10(6):473-477.
35. Ribéreau-Gayon G, Jung ML, Baudino S, Sallé G, Beck JP. Effects of mistletoe ( Viscum album L.) extracts on cultured tumor cells. Experientia . 1986;42(6):594-599.
36. Jung ML, Baudino S, Ribéreau-Gayon G, Beck JP. Characterization of cytotoxic proteins from mistletoe ( Viscum album L.). Cancer Lett . 1990;51(2):103-108.
37. Kuttan G, Vasudevan DM, Kuttan R. Isolation and identification of a tumour reducing component from mistletoe extract ( Iscador ). Cancer Lett . 1988;41(3):307-314.
38. Büssing A, Suzart K, Bergmann J, Pfüller U, Schietzel M, Schweizer K. Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins. Cancer Lett . 1996;99(1):59-72.
39. Bantel H, Engels IH, Voelter W, Schulze-Osthoff K, Wesselborg S. Mistletoe lectin activates caspase-8/FLICE independently of death receptor signaling and enhances anticancer drug-induced apoptosis. Cancer Res . 1999;59(9):2083-2090.
40. Büssing A, Multani AS, Pathak S, Pfüller U, Schietzel M. Induction of apoptosis by the N-acetyl-galactosamine-specific toxic lectin from Viscum album L. is associated with a decrease of nuclear p53 and Bcl-2 proteins and induction of telomeric associations. Cancer Lett . 1998;130(1-2):57-68.
41. Park R, Kim MS, So HS, et al. Activation of c-Jun N-terminal kinase 1 (JNK1) in mistletoe lectin II-induced apoptosis of human myeloleukemic U937 cells. Biochem Pharmacol . 2000;60(11):1685-1691.
42. Rentea R, Lyon E, Hunter R. Biologic properties of iscador: a Viscum album preparation I. Hyperplasia of the thymic cortex and accelerated regeneration of hematopoietic cells following X-irradiation. Lab Invest . 1981;44(1):43-48.
43. Bloksma N, Schmiermann P, de Reuver M, van Dijk H, Willers J. Stimulation of humoral and cellular immunity by Viscum preparations. Planta Med . 1982;46(4):221-227.
44. Mueller EA, Anderer FA. Synergistic action of a plant rhamnogalacturonan enhancing antitumor cytotoxicity of human natural killer and lymphokine-activated killer cells: chemical specificity of target cell recognition. Cancer Res . 1990;50(12):3646-3651. Erratum in: Cancer Res . 1990;50(18):6115.
45. Büssing A, Regnery A, Schweizer K. Effects of Viscum album L. on cyclophosphamide-treated peripheral blood mononuclear cells in vitro: sister chromatid exchanges and activation/proliferation marker expression. Cancer Lett . 1995;94(2):199-205.
46. Ribéreau-Gayon G, Dumont S, Muller C, Jung ML, Poindron P, Anton R. Mistletoe lectins I, II and III induce the production of cytokines by cultured human monocytes. Cancer Lett . 1996;109(1-2):33-38.
47. Stein GM, Berg PA. Flow cytometric analyses of the specific activation of peripheral blood mononuclear cells from healthy donors after in vitro stimulation with a fermented mistletoe extract and mistletoe lectins. Eur J Cancer . 1998;34(7):1105-1110.
48. Stein GM, Schaller G, Pfüller U, et al. Characterisation of granulocyte stimulation by thionins from European mistletoe and from wheat. Biochim Biophys Acta . 1999;1426(1):80-90.
49. Schumacher U, Feldhaus S, Mengs U. Recombinant mistletoe lectin (rML) is successful in treating human ovarian cancer cells transplanted into severe combined immunodeficient (SCID) mice. Cancer Lett . 2000;150(2):171-175.
50. Elsässer-Beile U, Ruhnau T, Freudenberg N, Wetterauer U, Mengs U. Antitumoral effect of recombinant mistletoe lectin on chemically induced urinary bladder carcinogenesis in a rat model. Cancer . 2001;91(5):998-1004.
51. Kunze E, Schulz H, Gabius HJ. Inability of galactoside-specific mistletoe lectin to inhibit N-methyl-N-nitrosourea-induced tumor development in the urinary bladder of rats and to mediate a local cellular immune response after long-term administration. J Cancer Res Clin Oncol . 1998;124(2):73-87.
52. Kunze E, Schulz H, Adamek M, Gabius HJ. Long-term administration of galactoside-specific mistletoe lectin in an animal model: no protection against N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis in rats and no induction of a relevant local cellular immune response. J Cancer Res Clin Oncol . 2000;126(3):125-138.
53. Kuttan G, Menon LG, Kuttan R. Prevention of 20-methylcholanthrene-induced sarcoma by a mistletoe extract, Iscador. Carcinogenesis . 1996;17(5):1107-1109.
54. Jurin M, Zarkovic N, Hrzenjak M, Ilic Z. Antitumorous and immunomodulatory effects of the Viscum album L. preparation Isorel. Oncology . 1993;50(6):393-398.
55. Hajto T. Immunomodulatory effects of iscador: a Viscum album preparation. Oncology . 1986;43(suppl 1):51-65.
56. Salzer G. Pleura carcinosis. Cytomorphological findings with the mistletoe preparation iscador and other pharmaceuticals. Oncology . 1986;43(suppl 1):66-70.
57. Hajto T, Hostanska K, Frei K, Rordorf C, Gabius HJ. Increased secretion of tumor necrosis factors alpha, interleukin 1, and interleukin 6 by human mononuclear cells exposed to beta-galactoside-specific lectin from clinically applied mistletoe extract. Cancer Res . 1990;50(11):3322-3326.
58. Kelter G, Schierholz JM, Fischer IU, Fiebig HH. Cytotoxic activity and absence of tumor growth stimulation of standardized mistletoe extracts in human tumor models in vitro. Anticancer Res . 2007;27(1A):223-233.
59. Lyu SY, Park WB. Effects of Korean mistletoe lectin ( Viscum album coloratum) on proliferation and cytokine expression in human peripheral blood mononuclear cells and T-lymphocytes. Arch Pharm Res . 2007;30(10):1252-1264.
60. Lee SJ, Son YO, Kim H, et al. Suppressive effect of a standardized mistletoe extract on the expression of activatory NK receptors and function of human NK cells. J Clin Immunol . 2007;27(5):477-485.
61. Gong F, Ma Y, Ma A, et al. A lectin from Chinese mistletoe increases gammadelta T cell-mediated cytotoxicity through induction of caspase-dependent apoptosis. Acta Biochim Biophys Sin (Shanghai) . 2007;39(6):445-452.
62. Heinzerling L, von Baehr V, Liebenthal C, von Baehr R, Volk HD. Immunologic effector mechanisms of a standardized mistletoe extract on the function of human monocytes and lymphocytes in vitro, ex vivo, and in vivo. J Clin Immunol . 2006;26(4):347-359.
63. Tusenius KJ, Spoek AM, van Hattum J. Exploratory study on the effects of treatment with two mistletoe preparations on chronic hepatitis C. Arzneimittelforschung . 2005;55(12):749-753.
64. Wacker R, Stoeva S, Betzel C, Voelter W. Complete structure determination of N-acetyl-D-galactosamine-binding mistletoe lectin-3 from Viscum album L. album. J Pept Sci . 2005;11(6):289-302.
65. Horneber MA, Bueschel G, Huber R, Linde K, Rostock M. Mistletoe therapy in oncology. Cochrane Database Syst Rev . 2008;(2):CD003297.
66. Eggenschwiler J, von Balthazar L, Stritt B, et al. Mistletoe lectin is not the only cytotoxic component in fermented preparations of Viscum album from white fir ( Abies pectinata ). BMC Complement Altern Med . 2007;7:14.
67. Ernst E, Schmidt K, Steuer-Vogt MK. Mistletoe for cancer? A systematic review of randomised clinical trials. Int J Cancer . 2003;107(2):262-267.
68. Kienle GS, Berrino F, Büssing A, Portalupi E, Rosenzweig S, Kiene H. Mistletoe in cancer - a systematic review on controlled clinical trials. Eur J Med Res . 2003;8(3):109-119.
69. Kleijnen J, Knipschild P. Mistletoe treatment for cancer: review of controlled trials in humans. Phytomedicine . 1994;1:255-260.
70. Ernst E. Mistletoe for cancer? Eur J Cancer . 2001;37(1):9-11.
71. Mistletoe Extracts (PDQ). National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/cam/mistletoe/patient Accessed November 10, 2008.
72. Rosell S, Samuelsson G. Effect of mistletoe viscotoxin and phoratoxin on blood circulation. Toxicon . 1966;4(2):107-110.
73. Andersson KE, Jóhannsson M. Effects of viscotoxin on rabbit heart and aorta, and on frog skeletal muscle. Eur J Pharmacol . 1973;23(3):223-231.
74. Sauviat MP. Effect of phoratoxin B, a toxin isolated from mistletoe, on frog skeletal muscle fibres. Toxicon . 1990;28(1):83-89.
75. Wagner H, Feil B, Seligmann O, Petricic J, Kalogjera Z. Phenylpropanes and lignans of Viscum album cardioactive drugs V. Planta Med . 1986;(2):102-104.
76. Deliorman D, Calis I, Ergun F, et al. Studies on the vascular effects of the fractions and phenolic compounds isolated from Viscum album ssp. album. J Ethnopharmacol . 2000;72(1-2):323-329.
77. Hajto T, Lanzrein C. Natural killer and antibody-dependent cell-mediated cytotoxicity activities and large granular lymphocyte frequencies in Viscum album -treated breast cancer patients. Oncology . 1986;43(2):93-97.
78. Hajto T, Hostanska K, Gabius HJ. Modulatory potency of the beta-galactoside-specific lectin from mistletoe extract ( Iscador ) on the host defense system in vivo in rabbits and patients. Cancer Res . 1989;49(17):4803-4808.
79. Kovacs E, Hajto T, Hostanska K. Improvement of DNA repair in lymphocytes of breast cancer patients treated with Viscum album extract ( Iscador ). Eur J Cancer . 1991;27(12):1672-1676.
80. Schaefermeyer G, Schaefermeyer H. Treatment of pancreatic cancer with Viscum album ( Iscador ): A retrospective study of 292 patients 1986-1996. Complement Ther Med . 1998;6(4):172-177.
81. Orange M, Lace A, von Laue HB. Abstracts of the 4th Mistletoe Symposium, Mistletoe in Tumour Therapy. Basic Research and Medicinal Use, 8-10 November 2007. Phytomedicine . 2007;14(suppl 2):1-54.
82. Seifert G, Laengler A, Tautz C, Seeger K, Henze G. Response to subcutaneous therapy with mistletoe in recurrent multisystem Langerhans cell histiocytosis. Pediatr Blood Cancer . 2007;48(5):591-592.
83. Huber R, Rostock M, Goedl R, et al. Mistletoe treatment induces GM-CSF- and IL-5 production by PBMC and increases blood granulocyte- and eosinophil counts: a placebo controlled randomized study in healthy subjects. Eur J Med Res . 2005;10(10):411-418.
84. Lyu SY, Kwon YJ, Joo HJ, Park WB. Preparation of alginate/chitosan microcapsules and enteric coated granules of mistletoe lectin. Arch Pharm Res . 2004;27(1):118-126.
85. Brinker FJ. Herb Contraindications and Drug Interactions . 2nd ed. Sandy, OR: Eclectic Medical Publications; 1998.
86. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;109(3):227-235.
87. Finall AI, McIntosh SA, Thompson WD. Subcutaneous inflammation mimicking metastatic malignancy induced by injection of mistletoe extract. BMJ . 2006;333(7582):1293-1294.
88. Rostock M, Huber R. Randomized and double-blind studies—demands and reality as demonstrated by two examples of mistletoe research. Forsch Komplementarmed Klass Naturheilkd . 2004;11(suppl 1):18-22.
89. Stirpe F. Mistletoe toxicity. Lancet . 1983;1(8319):295.
90. [No authors listed]. Holiday hint: poison plant prevention. Child Health Alert . 2004;22:2.
91. Courtemanche J, Peterson RG. Beware the mistletoe. CMAJ . 2006;175(12):1523-1524.
92. Bauer C, Oppel T, Ruëff F, Przybilla B. Anaphylaxis to viscotoxins of mistletoe ( Viscum album ) extracts. Ann Allergy Asthma Immunol . 2005;94(1):86-89.
93. Spiller HA, Willias DB, Gorman SE, Sanftleban J. Retrospective study of mistletoe ingestion. J Toxicol Clin Toxicol . 1996;34(4):405-408.

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