Viscum album

Viscum album

Synonyms

No documentation

Vernacular Name

European Mistletoe, Viscum, Birdlime, All-heal, Devil's Fuge, Loranthus, Mulberry Mistletoe, Golden Baugh.

Description

Viscum album or Mistletoe is a semiparasitic plant that has been used for centuries to treat a number of health conditions. Two major types of V. album, European and American, contain very similar protein constituents but have different medicinal uses. V. albumpreparations have been used medicinally in Europe, especially in Celtic tradition, for centuries to treat epilepsy, infertility, exhaustion, anxiety, vertigo, hypertension, and arthritis. The Druids and the ancient Greeks used V. album as a panacea. In the last 50 years, many laboratory, animal, and human studies have been conducted on potential anti-cancer effects thought to be caused by immuno-stimulatory effects of V. album. The Commission E Monographs list V. album as a treatment for degenerative inflammation of the joints, and as palliative therapy for malignant tumors.

The use of V. album as a cancer therapy was popularized in the 1920s by Rudolf Steiner, PhD (1861–1925) as a choice in anthroposophical medical cancer treatment. V. album is listed as a therapy in the Homeopathic Pharmacopoeia of the United States (HPUS), the officially recognized compendium for homeopathic drugs in this country. V. album injectable preparations are not commercially available in the United States and are not approved by the US Food and Drug Administration (FDA) for use in humans. However, liquid extracts and teas from V. album are still used by some herbalists and health care professionals in cancer and immune support.

While V. album is traditionally used to reduce blood pressure and as an antispasmodic agent, current uses of V. album in are reported in cancer treatment. In some European countries, extracts of V. album are among the most prescribed drugs offered to cancer patients. Injections of V. album are reported in numerous clinical studies to improve immunity, quality of life and length of survival in cancer patient. However, the use of V. album in clinical practice is still controversial. At this time no recommendation can be made using V. album extracts in cancer treatment until more clinical trials on humans are performed.

V. album is a hemi-parasitic shrub, meaning that while it can produce some chlorophyll, it needs a host plant in order to survive.  Growing on the branches of other trees, it produces stems that are from 30 to 90 centimeters in length having dichotomous branching.  The leaves are thick and leathery growing 3 to 8 centimeters in opposite pairs.  The plant produces tiny flowers and yellow or white berries which contain a thick gelatinous substance and one seed.

Origin / Habitat

V. album is native to Europe, particularly the warmer climates of the continent.  V. album is hemi-parasitic, growing as a parasite on trees, especially fruit trees such as apple and poplar trees.  V. album requires a warm, humid climate in order to thrive and needs neutral or basic soil. It can grow in direct sunlight or in partial shade.

Chemical Constituents

The major constituents of V. album include viscumin (also known as mistletoe lectin I, ML-I or VAL) and viscotoxin[2],[3] also included are phenylpropanoids syringin, syringenin-apiosylglucoside, eleutheroside E.

Plant Part Used

Leaves, young stem.

Medicinal Uses

General

Cancer treatment - adjunct

Immunomodulation

Arthritis and inflammatory conditions

Cardiotonic

HIV

Hepatitis

Recurrent respiratory infections

Most Frequently Reported Uses

Cancer treatment - adjunct

Immunomodulation

Arthritis and inflammatory conditions

Dosage

Dosage range

Traditional Dosages:

Cold Infusion: Soak 2-4 teaspoonfuls (10-20 grams) of finely chopped V. album in 2 cups (approx. 500mL) of water overnight. Strain and take the infusion first thing in the morning; it can be sweetened to taste. During the day, steep another batch similarly to be drunk at bedtime.

Hot infusion: 1 teaspoonful (5 grams) of finely chopped V. album in one cup (approx. 250mL) of hot water for 5-10 minutes. Drink this twice daily.

Tincture (1:4w/v): 1/8 teaspoonful (1/2 ml), three times per day.

Proprietary Extracts:

There are a number of proprietary extracts containing low levels of mistletoe lectin-Ι (ML-Ι) that are used as adjuvant cancer therapies. V. album extracts are prepared as aqueous solutions or solutions of water and alcohol, and they can be fermented or unfermented.[1] Some extracts are prepared according to homeopathic standards, while others are liquid extracts for injection. These extracts usually are given by intravenous, subcutaneous or intrapleural injection. In most reported studies, subcutaneous injections of 1mg /kg were given 2-3 times a week, but the overall duration of treatment varied considerably. V. album preparations are administered in incrementally increasing dosages, usually including an induction phase and a maintenance phase of administration. A typical treatment course can last several months to years. V. album extracts, according to Anthroposophical medicine practice, may also be administered directly into the tumor, particularly in cancer of the liver, esophagus and cervix. V. album injections should only be given by a qualified health care professional.

Children Dosing (younger than 18 years old): Since information regarding dosing in children is limited, it is not recommended using V. album extracts in children under 18 years of age.

Injectable V. album preparations should be refrigerated until use. Ampules should be warmed in the hands before use.

Most Common Dosage

Due to the wide variety of preparations and proprietary products, there is no common dosage used in general. Homeopathic preparations are also available.

Standardized to 

Commercially available V. album products contain lectins I, II and III as one predominant group of biologically active agents. Preparations from V. album extracts are most frequently used in the treatment of cancer patients in German-speaking countries. They are not available commercially in the United States. V. album products are made and sold under brand names including: 

  • Iscador (also called Iscar) - Iscador is prepared by fermenting an aqueous extract of the whole V. album plant with the bacterium Lactobacillus plantarum.
  • Eurixor
  • Cefalektin
  • Helixor
  • Isorel (also called Vysorel)
  • Iscucin- homeopathic
  • Lektinol (also called Plenosol) - homeopathic
  • ABNOBAviscum - homeopathic

The chemical constituents, uses and dosages of each V. album product varies, depending on many factors, including:

  • The type of host tree on which the V. album plant grows. Products are typically made from V. album growing on fir, apple, elm, and pine trees. For example, IscadorM is from apple trees, IscadorP comes from pine trees, IscadorQ is from oak trees, and IscadorU comes from elm trees. Anthroposophical physicians believe that the type of V. album
  • The time of year the plant is harvested
  • The species of V. album
  • Whether the extract is fermented or unfermented
  • Whether the extract is prepared with homeopathic methods
  • The company that makes the product
extract chosen should depend on the type of tumor and the sex of the patient.

Pharmacology

Pre-clinical

V. album has been a plant of interest in cancer treatment for decades. Laboratory studies report extracts from V. album stimulate immunity and cause cancer cell death.[4],[5] Two components seem to provide the most anti-cancer activity – viscumin and viscotoxin. Viscumin is a lectin (a complex protein–sugar compound that can bind to cell surfaces) that appears to interfere with intracellular protein synthesis,[6] stimulate the production of cytokines (which increase the production of leukocytes) and activate leukocytes.[7] Viscumin may also affect the processes of metastasis and apoptosis.[8] Viscumin is known as ML-1 lectin. Viscotoxins are small proteins that appear to be more cytotoxic and more likely to induce cellular necrosis. [9]

Extracts of V. album have been reported to have a direct toxic effect on tumor cells.[10]  Another reported activity is stabilization of white blood cell DNA, including white blood cells that have been exposed to DNA-damaging chemotherapy drugs.[11] V. album stimulates production of white blood cells and improves cytokine production, such as IL-1, IL-6, and TNF-alpha.[12] Other reports suggest that V. album inhibits protein synthesis of cancer cells, thereby inducing apoptosis.[13] A laboratory study found efficacy of V. album (Iscador) treatment of various tumors to be comparable to the chemotherapy drug vincristine.[14]

Similar to European mistletoe (V. album), extracts from a type of Korean mistletoe (V. albumcoloratum Kom.) have demonstrated in vitro and in vivo cytoxocity in laboratory studies.[15]

Clinical

Reports of more than 30 clinical trials of V. album as an injectable treatment for cancer have been published since the early 1960s.[16],[17] Results of these clinical trials support the thought that use of V. album has impact on survival or leads to an improved ability to fight cancer or to withstand anticancer treatments is weak.[18] Nevertheless, these results need to be supported with more randomized, double blind placebo controlled studies.

A recent clinical trial involving subQ injections of 20mg V. album twice weekly was reported to enhance humoral and cellular immune responses in 4 cancer patients.[19] A case report and objective and subjective results from clinical trials suggests that V. album may have a dose-dependent effect on cancer-related fatigue, helping patients to have more energy.[20]

A review of the safety and efficacy of standardized V. album extract  (HELIXOR) in 681 cancer patients revealed the V. album extract was beneficial for breast cancer patients since it significantly improved quality of life and significantly reduced persistent signs/symptoms of the disease/treatment for 5 years during aftercare.[21]

A 2008 review of the current clinical trials for all V. album extracts in the treatment of various cancers (overall comprising 3484 randomized cancer patients) found the evidence of V. album extracts improving the survival or leading to an improved ability to fight cancer or to withstand anticancer treatments to be weak. The authors concluded that although weak, there is some evidence that V. album extracts may offer benefits on measures of QOL during chemotherapy for breast cancer.[22],[23]

Interaction and Depletions

Interaction with other Herbs

No documentation

Interaction with Drugs

There are no known drug interactions with the use of V. album in recommended dosages.

Based on pharmacology, V. album may increase the effects of blood pressure lowering medications. Use with caution if taking antihypertensive medications.

Based on pharmacology, using of V. album with CNS depressants may enhance the sedative effects. Use with caution if taking CNS depressants and sedative medications.

Based on pharmacology, do not use with individuals taking MAO inhibitors. V. album contains tyramine-like constituents that may interact with MAOIs and lead to hypertensive crisis.

Based on pharmacology, the use of V. album with anti-diabetic medications including insulin may result in further lowering of blood sugar levels. Use with caution if taking anti-diabetic and blood sugar lowering medications.

Based on pharmacology, avoid use of V. album in individuals taking thyroid medications.

Precautions and Contraindications

Side effects

V. album preparations have been reported safe in recommended doses. Common side effects include soreness and inflammation at injection sites, headache, fever, and chills.[25],[26] A few cases of severe allergic reactions, including anaphylactic shock, have been reported. [27] If allergy or rash occurs, discontinue use immediately.

V. album, which includes various species of Phoradendron, are similar in constituents but have not been widely studied.

Avoid use of V. album extract in individuals with cardiovascular diseases.

Avoid use of V. album in active/uncontrolled hyperthyroid patients, as metabolism may be altered.

Use with caution in individuals with diabetes and blood sugar regulation problems, as V. album may alter blood sugar levels.

V. album may increase liver enzymes in high dosages. Use with caution in those with liver impairment or disease.

Use cautiously in individuals with glaucoma or in those on cholinergics.

V. album's white berries are potentially toxic and should be avoided. Seizures, vomiting, and death have been reported following ingestion of these substances.[24] The severity of the toxic effects associated with V. album ingestion may depend on the amount consumed and the type of V. album plant.

Pregnancy

Due to the potential of uterine stimulation of constituents found in V. album, avoid during pregnancy and lactation.

Age limitation

No documentation

Adverse reaction

No documentation

References

  1. Ribéreau-Gayon G, Jung ML, Di Scala D, et al. Comparison of the effects of fermented and unfermented mistletoe preparations on cultured tumor cells. Oncology. 1986;43(1):35-41.
  2. Wagner H, Jordan E, Feil B. Studies on the standardization of mistletoe preparations. Oncology 1986;43(1):16-22.
  3. Jung ML, Baudino S, Ribéreau-Gayon G, et al. Characterization of cytotoxic proteins from mistletoe (Viscum album L.). Cancer Lett. 1990;51(2):103-108.
  4. Mengs U, Göthel D, Leng-Peschlow E. Mistletoe extracts standardized to mistletoe lectins in oncology: review on current status of preclinical research. Anticancer Res. May-Jun2002;22(3):1399-1407.
  5. Hajto T, Hostanska K, Frei K, et al. 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.
  6. Stirpe F, Sandvig K, Olsnes S, Pihl A. Action of viscumin, a toxic lectin from mistletoe, on cells in culture. J Biol Chem. 1982;257(22):13271-13277.
  7. Mannel DN, Becker H, Gundt A, Kist A, Franz H. Induction of tumor necrosis factor expression by a lectin from Viscum album. Cancer Immunol Immunother. 1991;33:177-182.
  8. Stirpe F, Sandvig K, Olsnes S, et al. Action of viscumin, a toxic lectin from mistletoe, on cells in culture. J Biol Chem. 1982;257(22):13271-13277.
  9. Khwaja TA, Dias CB, Pentecost S. Recent studies on the anticancer activities of mistletoe (Viscum album) and its alkaloids. Oncology. 1986;43(1):42-50.
  10. Stauder H, Kreuser ED. Mistletoe extracts standardised in terms of mistletoe lectins (ML I) in oncology: current state of clinical research. Onkologie. 2002;25(4):374-380.
  11. Büssing A, Azhari T, Ostendorp H, et al. Viscum album L. extracts reduce sister chromatid exchanges in cultured peripheral blood mononuclear cells. Eur J Cancer. 1994;30A(12):1836-1841.
  12. Hajto T. Immunomodulatory effects of iscador: a Viscum album preparation. Oncology. 1986;43(1):51-65.
  13. Zarkovic N, Vukovic T, Loncaric I, et al. An overview on anticancer activities of the Viscum album extract Isorel. Cancer Biother Radiopharm. 2001;16(1):55-62.
  14. Kovacs E, Link S, Toffol-Schmidt U. Comparison of Viscum album QuFrF extract with vincristine in an in vitro model of human B cell lymphoma WSU-1. Arzneimittelforschung. 2008;58(11):592-597.
  15. Khil LY, Kim W, Lyu S, et al. Mechanisms involved in Korean mistletoe lectin-induced apoptosis of cancer cells. World J Gastroenterol. 2007;13(20):2811-2818.
  16. Kleijnen J, Knipschild P. Mistletoe treatment for cancer: review of controlled trials in humans. Phytomedicine. 1994;1:255-260.
  17. Schöffski P, Riggert S, Fumoleau P, et al. Phase I trial of intravenous aviscumine (rViscumin) in patients with solid tumors: a study of the European Organization for Research and Treatment of Cancer New Drug Development Group. Ann Oncol. 2004;15(12):1816-1824.
  18. Horneber MA, Bueschel G, Huber R, Linde K, Rostock M. Mistletoe therapy in oncology. Cochrane Database Syst Rev. 16Apr2008;(2):CD00329.
  19. Gardin NE. Immunological response to mistletoe (Viscum album L.) in cancer patients: a four-case series. Phytother Res. Mar2009;23(3):407-411.
  20. Wode K, Schneider T, Lundberg I, Kienle GS. Mistletoe treatment in cancer-related fatigue: a case report. Cases J. 22Jan2009;2(1):77. [Epub ahead of print]
  21. Beuth 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. Jan-Feb2008;28(1B):523-527.
  22. Horneber MA, Bueschel G, Huber R, Linde K, Rostock M. Mistletoe therapy in oncology. Cochrane Database Syst Rev. 16Apr2008;(2):CD00329
  23. onnweiler O. Mistletoe in tumour therapy. Abstracts of the 4th Mistletoe Symposium, 8-10 November 2007. Germany Phytomedicine. 2007;14(7):1-54,37-43.
  24. Hall AH, Spoerke DG, Rumack BH. Assessing mistletoe toxicity. Ann Emerg Med. 1986;15(11):1320-1323.
  25. Bock PR, Friedel WE, Hanisch J, et al. 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):456-466.
  26. Stauder H, Kreuser ED. Mistletoe extracts standardised in terms of mistletoe lectins (ML I) in oncology: current state of clinical research. Onkologie. 2002;25(4):374-380.
  27. Hutt N, Kopferschmitt-Kubler M, Cabalion J, et al. Anaphylactic reactions after therapeutic injection of mistletoe (Viscum album L.). Allergol Immunopathol (Madr). Sep-Oct2001;29(5):201-203.