INDEX

Mistletoe (Viscum album)

Indications

Hypertension, congestive heart failure, arrhythmia, cardiac weakness, atherosclerosis, and vascular inflammation. As a vagal nerve tonic, Viscum album may help strengthen weak pulse, slow tachyarrhythmia, or enliven bradycardia. Cardiac enlargement, valvular incompetence, angina, shortness of breath, dyspnea, edema, palpitation with exertion, inability to lie down, and other symptoms of congestive heart failure are also said to be indications for Viscum. Viscum album was also used for seizures and epilepsy,1 “St. Vitus’s dance,” motor twitching, spasm, and nerve hyperactivity. Traditional herbal literature notes that V. album improves carbohydrate metabolism in cases of diabetes.2 Viscum album is also a traditional medicine for cancer and inflammation. Scientific research on Viscum has led to the development of parenteral drugs, including Iscador and Helixor, both of which are used to treat leukemia and lymphoma.

Mechanism of Action

Viscum album may improve blood pressure via a variety of mechanisms. It noncompetitively inhibits Ca2+ influx through calcium-gated channels as well as Ca2+ mobilization from intracellular stores, both of which contribute to its vasorelaxant action.3 Viscum album may also reduce vascular resistance in the coronary arteries via promotion of nitric oxide and cyclic guanosine monophosphate.4,5,6 Its positive ionotropic effect may occur via β-adrenergic innervation,5 and it may reduce pressure in the jugular vein and carotid arteries via muscarinic receptor blockade.7 Viscum may improve microcirculation8 and protect against chemotherapy-induced damage to microcirculatory vessels9 and heart tissue.10

Because underlying metabolic syndrome and diabetes are leading contributors to the development of chronic vascular inflammation and heart disease, agents that improve glycemic control and vascular inflammation are important for reducing the risk of and treating heart disease. Viscum album proteins enhance insulin secretion from the pancreatic beta cells without any signs of cytotoxicity.11 Viscum may also have hyperglycemic and antioxidant effects, helping to protect vasculature and improve circulation.12

Coniferin and syringin are two phenylpropanoid glycosides believed to have vascular effects including inhibiting platelet aggregation.13 A paper published in 1959 reported that V. album contains
γ-aminobutyric acid, which contributes to its hypotensive effect, but this finding has not been replicated.14 Viscum album flavonoids have been shown to reduce tachyarrhythmias15 and to normalize electrical conduction through the Purkinje fibers, thereby decreasing ventricular excitability.16 They have also been shown to reduce noradrenalin-induced aortic contractions.17

Viscum lectins are believed to have anticancer, immune-stimulating, and anti-inflammatory effects. Lectins bind to glycoprotein receptors on blood and other cells. They also bind to inflammatory proteins and have an impact on immune response, platelet aggregation, and inflammatory pathways in various ways specific to the lectin and the tissue.18,19,20,21,22,23,24 For example, V. album lectins promote the release of inflammatory cytokines, contributing to anti-inflammatory effects in the heart and other tissues.25 Nanomolar concentrations of various lectins are required to affect mammalian protein synthesis.26 Some Viscum lectins have an affinity for endothelial cells.27 Certain Viscum lectins are known to have toxic effects and are referred to as viscotoxins. Viscotoxins are poorly absorbed in oral medications that deliver small amounts of lectins along with flavonoids and other medicinally active compounds.

Lectins that bind ribosomes and reduce their activity are known as ribosome-inactivating proteins, and lectins that bind to red blood cells and affect clotting and the release of inflammatory mediators are referred to as hemagglutinins or phytohemagglutinins. Both types of lectins are found in V. album and contribute to its vascular and anticancer effects.28 Viscum album agglutinin (VAA) induces the aggregation and activation of neutrophils, thrombocytes, and erythrocytes at a concentration of 0.1–25 µg/mL in human blood.29 Small VAA doses improve platelet response to endogenous aggregators, without inducing aggregation themselves, whereas higher doses may induce platelet aggregation.30

Evidence-Based Research

A clinical pilot study showed V. album tincture reduces blood pressure and serum triglycerides at a dosage of 10 drops of mother tincture (a 1:10 alcohol extract), 3 times per day.31

In an animal model of menopause, numerous enzyme systems involved in lipid accumulation and atherosclerosis development were found to be optimized after 8 weeks on a water extract of V. album. Carnitine palmitoyltransferase was observed to increase and fatty acid synthase to decrease.32

Safety in Pregnancy and Breastfeeding

No information was identified in the scientific or traditional literature on the safety of V. album during pregnancy or lactation.

No mutagenic or cytogenic changes were demonstrated with both therapeutic and extremely high dosages of V. album on human amniotic fluid cells.33

Some Early American physicians reported that V. album exerts an oxytocin-like effect on the uterus, helping to control excessive bleeding as well as improving the contractile rhythm and pattern of the uterine muscles. Viscum album was therefore used in early labor as a uterine tonic and as an oxytocic for stalled labor. Viscum is reported to promote involution of the uterus after delivery of the placenta and reduce chances of postpartum hemorrhage.

There are no published studies investigating the use of V. album in lactation, but its lectin content means it is probably best used with caution.

General Safety

At physiologically appropriate doses, V. album is generally well tolerated and without significant side effects. German hospitals and clinics using injectable preparations of V. album for cancer and for patients with human immunodeficiency virus (HIV) report few side effects overall and excellent tolerability.34 Side effects were more common in HIV-positive patients than in healthy controls, and the most common side effects noted were flu-like malaise, fever, and gingivitis, none of which were severe.

One toxicity study in patients with advanced solid tumors reported that no herb–drug interactions were seen in patients receiving an injectable combination therapy that delivered 250 mg of V. album. All 44 patients were observed to develop antibodies to V. album lectins, and approximately half experienced fever and flu-like symptoms.35 Another study comparing the use of V. album as an adjuvant to the fluorouracil prodrug doxifluridine in the treatment of recently operated on gastric cancer patients reported that the addition of V. album resulted in less diarrhea than in those receiving the chemotherapy drug alone, along with significant increases in leukocyte and eosinophil counts.36

In vitro studies have shown cytogenetic damage or mutagenic effects from V. album preparations.37,38

Viscum species are potentially toxic and must be used with caution and at the appropriate dose. The plant has harsh emetic properties and can cause bloody diarrhea and tenesmus, vomiting, and prostration. It can be fatal if overdosed. Overdose presents as contraction of the pupils, muscular spasms and convulsions, coma, and eventually death. The German literature cites pregnancy and hyperthyroidism as contraindications to using parenteral Viscum (Helixor) in the treatment of cancer.39 There has been one published case report of anaphylaxis where follow-up studies revealed the individual had developed anti-immunoglobulin E antibodies to V. album.40

Dosage

Oral doses of V. album powder (usually encapsulated) used for cardiovascular issues vary from 650 mg twice per day to 4 g four times per day. Smaller amounts can be taken in formulas when combining
V. album with other similarly acting herbs.

Traditional Uses

Viscum album is traditionally used for the symptoms of congestive heart failure, arrhythmia, and cardiac weakness and for the underlying causes such as atherosclerosis and vascular inflammation. Viscum album is specifically indicated for the hypotensive patient who has a weak, feeble pulse and a weak heart; however, because of its many complex mechanisms of action, V. album may also be used for hypertension.41 Viscum album was used for seizures and epilepsy,1 St. Vitus’s dance, motor twitching, spasm, and nerve hyperactivity. Traditional herbal literature notes that V. album improves carbohydrate metabolism in people with diabetes.2 Viscum album is also a traditional medicine for cancer and inflammation.

References

1

J Ethnopharmacol. 1998;61(3):237–41. Antimicrobial and anticonvulsant activities of Viscum capense. Amabeoku GJ, et al.

2J Endocrinol. 1999;160(3):409–14. Insulin-secreting activity of the traditional antidiabetic plant Viscum album. Gray AM, et al.

3 Niger J Physiol Sci. 2008;23(1–2):115–20. The vasorelaxant effect of Viscum album leaf extract is mediated by calcium-dependent mechanism. Mojiminiyi FB, Owolabi ME, Igbokwe UV, Ajagbonna OP.

4 Nat Prod Res. 2006;20(13):1176–82. Viscum album aqueous extract induces NOS-2 and NOS-3 overexpression in Guinea pig hearts. Tenorio-Lopez FA, Valle Mondragon LD, Olvera GZ, Torres Narvaez JC, Pastelin G.

5 Arch Cardiol Mex. 2006;76(2):130–9. Viscum album aqueous extract induces inducible and endothelial nitric oxide synthases expression in isolated and perfused guinea pig heart. Evidence of the coronary vasodilation mechanism. Tenorio López FA, del Valle Mondragón L, Zarco Olvera G, Torres Narváez JC, Pastelín Hernández G.

6 Fitoterapia. 2005;76(2):204–9. Vasodilator activity of the aqueous extract of Viscum album. Tenorio FA, del Valle L, González A, Pastelín G.

7 Clin Exp Hypertens. 2009;31(1):11–9. Effects of mistletoe (Viscum album L., Loranthaceae) extracts on arterial blood pressure in rats treated with atropine sulfate and hexocycline. Radenkovic M, Ivetic V, Popovic M, Brankovic S, Gvozdenovic L.

8 In Vivo. 2001;15(6):447–57. Changes in immunological characteristics of white blood cells after administration of standardized mistletoe extract. Klopp R, Schmidt W, Niemer W, Werner M, Beuth J.

9 Anticancer Res. 2005;25(1B):601–10. Influence of complementary Viscum album (Iscador) administration on microcirculation and immune system of ear, nose and throat carcinoma patients treated with radiation and chemotherapy. Klopp R, Schmidt W, Werner E, Werner M, Niemer W, Beuth J.

10 Asian Pac J Cancer Prev. 2011;12(11):2925–31. Viscum album L. extract and quercetin reduce cyclophosphamide-induced cardiotoxicity, urotoxicity and genotoxicity in mice. Sekeroğlu V, Aydin B, Sekeroğlu ZA.

11 Evid Based Complement Alternat Med. 2014;2014:703624. Protein fractions from Korean Mistletoe (Viscum album coloratum) extract induce insulin secretion from pancreatic beta cells. Kim KW, Yang SH, Kim JB.

12 J Ethnopharmacol. 2005;98(1–2):95–102. Evaluation of the hypoglycemic effect and antioxidant activity of three Viscum album subspecies (European mistletoe) in streptozotocin-diabetic rats. Orhan DD, Aslan M, Sendogdu N, Ergun F, Yesilada E.

13 Phytomedicine. 1998;5(1):11–7. Pharmacological activity of phenylpropanoids of the mistletoe, Viscum album L., host: Pyrus caucasica Fed. Panossian A, Kocharian A, Matinian K, Amroyan E, Gabrielian E, Mayr C, Wagner H.

14 Sven Farm Tidskr. 1959;63:545–53. Phytochemical and pharmacological studies on Viscum album L. III. Isolation of a hypotensive substance: gamma-aminobutyric acid. Samuelsson G.

15 Chung Kuo Chung His I Cheih Ho Tsa Chih. 1994;14(7):421–3. Experimental study on cellular electrophysiology of Viscum coloratum flavonoid in treating tachyarrhythmias. Wu JX, Yu GR, Wang BY.

16 Chung Kuo Yao Li Hsueh Pao. 1994;15(2):169–72. Effects of Viscum coloratum flavonoids on fast responder action potentials of hearts. Wu JX, Yu GR, Wang BY, et al.

17 J Ethnopharmacol. 2000;72(1–2):323–9. Studies on the vascular effects of the fractions and phenolic compounds isolated from Viscum album ssp. album. Deliorman D, Caliş I, Ergun F, Doğan BS, Buharalioğlu CK, Kanzik I.

18 Anticancer Res. 1993;13(5c):1789–92. Modulation of lectin-triggered superoxide release from neutrophils of tumor patients with and without chemotherapy. Timoshenko AV, et al.

19 Arzneim Forschung. 1989;39(12):1580–5. Activation of natural killer cell cytotoxicity of human blood monocytes by a low molecular weight component from Viscum album extract. Klett CY, Anderer FA.

20 Cancer Immunol Innumother. 1990;32(4):221–7. A Viscum album oligosaccharide activating human natural cytotoxicity is an interferon gamma inducer. Mueller EA, Anderer FA.

21 Cancer Immunol Immunother. 1991;33(3):177–82. Induction of tumor necrosis factor expression by a lectin from Viscum album. Mannel DN, Becker H, Gundt A, et al.

22 Cancer Lett. 1996;99(1):59–72. Induction of apoptosis in human lymphocytes treated with Viscum album L is mediated by the mistletoes lectins. Bussing A, et al.

23 Eur J Clion Pharmacol. 1994;47(1):33–8. Non-lectin component in a fermented extract from Viscum album frown of pines induces proliferation of lymphocytes from health and allergic individuals in vitro. Stein G, Berg PA.

24 Biol Chem Hppe Seyler. 192;374(4):237–43. Efficient induction of superoxide release from human neutrophils by the galactoside-specific lectin from Viscum album. Timoskenko AV, Gabius HJ.

25 Cancer Lett. 1996;109(1–2):33–8. Mistletoe lectins I,II and III induce the production of cytokines by cultured human monocytes. Ribereau-Gayon G, et al.

26 FEBS Lett. 1993;329(1–2):59–62. Molecular mechanisms of inhibition of mammalian protein synthesis by some 4 chain hemagglutinins. Proposal of an extended classification of plant ribosome-inactivating proteins. Citores L, Ferreras JM, Iglesias R, et al.

27 Anat Embryol (Berl). 1995;191(1):47–9. Characterization of glycoconjugate expression during development of Meckel’s cartilage in the rat. Zschäbitz A, Weiser H, Stofft E, Krahn V, Gabius HJ, Khaw A, Biesalski HK.

28 Dev Oncol. 1984;15:142–6. Ribosome inactivating proteins as possible chemotherapeutic agents. Stirpe F, Barbieri l.

29 Biomed Pharmcother. 1995;49(3):253–8. Viscum album agglutinin-induced aggregation of blood cells and the lectin effects on neutrophil function. Timoshenko AV, Cherenkevich SN, Gabius HJ.

30 Anticancer Res. 1995;15(2):361–7. Galactose-specific lectin from Viscum album as a mediator of aggregation and priming of human platelets. Samal AB, Gavius HJ, Timoshenso AV.

31 J Evid Based Complementary Altern Med. 2014;19(1):31–5. 2013 Nov 5. Clinical evaluation of Viscum album mother tincture as an antihypertensive: a pilot study. Poruthukaren KJ, Palatty PL, Baliga MS, Suresh S.

32 Exp Biol Med (Maywood). 2015;240(4)477–87. The supplementation of Korean mistletoe water extracts reduces hot flushes, dyslipidemia, hepatic steatosis, and muscle loss in ovariectomized rats. Kim MJ, Park JH, Kwon DY, Yang HJ, Kim DS, Kang S, Shin BK, Moon NR, Song BS, Kim JH, Park S.

33 Arzneimittelforschung. 1995;45(1):81–3. Effect of Viscum album L. on rapidly proliferating amniotic fluid cells. Sister chromatid exchange frequency and proliferation index. Büssing A, Lehnert A, Schink M, Mertens R, Schweizer K.

34 Am J Ther. 1999;6(1):37–43. Toxicity of a standardized mistletoe extract in immunocompromised and healthy individuals. Van Wely M, Stoss M, Gorter RW.

35 Evid Based Complement Alternat Med. 2013;2013:964592. NCCAM/NCI phase 1 study of mistletoe extract and gemcitabine in patients with advanced solid tumors. Mansky PJ, Wallerstedt DB, Sannes TS, Stagl J, Johnson LL, Blackman MR, Grem JL, Swain SM, Monahan BP.

36 BMC Complement Altern Med. 2012;12:172. Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma – a randomized, controlled pilot study. Kim KC, Yook JH, Eisenbraun J, Kim BS, Huber R.

37 Arzneim Forschung. 1995;45(1):81–3. Effect of Viscum album on rapidly proliferating amniotic fluid cells. Sister chromatid exchange frequency and proliferation index. Bussing A, Lehner A, Schink M, et al.

38 Ann Pharm Fr. 1990;484:192–9. Subchronic toxicity of Viscum cruciatum Sieber. Galego Q, Ayso G, Garcia R.

39 Schweiz Rundsh Med Prax. 1990;79(10):291–5. Helixor – mistletoe preparation for cancer therapy. Document No. 19. Kast A, Hauser SP.

40 Ann Allergy Asthma Immunol. 2005;94(1):86–9. Anaphylaxis to viscotoxins of mistletoe (Viscum album) extracts. Bauer C, Oppel T, Ruëff F, Przybilla B.

41 Orv Hetil. 1953;94(3):80–1. Hypotensive effect of Viscum album. Greiner A.