ChiroACCESS Article

Mistletoe: Holiday Friend or Foe?

This information is provided to you for use in conjunction with your clinical judgment and the specific needs of the patient.

ChiroACCESS Editorial Staff



Published on

December 16, 2009

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There are many health and other myths surrounding the popular Holiday use of mistletoe.  It has been associated with anything from a romantic unexpected kiss to a dangerous poisonous substance to avoid.  The ancient Celts believed mistletoe held the soul of the host tree.  However, there is another side to mistletoe.  It is a very well established aid to improve the immune system and is used for the care of many forms of cancer.  The 2009 scientific publications supporting the clinical use of mistletoe have been numerous (see samples below).

MistletoeWhat about the "poison" label sometimes given to mistletoe?  The toxicity of mistletoe as a poison is minimal.  Most who consume the berries (which contains more toxins than the leaves), have no adverse effect at all.  Some care should be exercised with respect to children and pets.  The (1997) abstract below exemplifies the minimal risk of problems with even children.  With the nearly 2,000 cases, there was no morbidity on over 99% of the cases and no fatalities.

As for the relationship between mistletoe and kissing, we were unable to locate any scientific studies to confirm its effectiveness; but antidotally, we have seen it work!

Happy Holidays!

American mistletoe exposures.

Am J Emerg Med. 1997 Sep;15(5):516-20.

Krenzelok EP, Jacobsen TD, Aronis J.
Pittsburgh Poison Center, Children's Hospital of Pittsburgh, PA, USA.

American mistletoe is generally considered to be extremely toxic. Although there are no data to support this contention, both the lay public and medical professionals often respond very aggressively after ingestion of any portion of this plant. To determine if American mistletoe is deserving of this reputation, the outcomes of 1,754 exposures to this plant were examined. All mistletoe data extracted from the American Association of Poison Control Centers national data collection system for the period of 1985 to 1992 were analyzed according to patient age, gastrointestinal decontamination therapy, patient outcome, and geographic region of the exposure. Pediatric exposures accounted for 92.1% of the cases, and 94.7% of the reported cases were accidental exposures. Of all cases, 99.2% had an outcome associated with no morbidity, and there were no fatalities. Apparently, patient outcome was not influenced by the use of gastrointestinal decontamination techniques-96.2% of treated patients remained asymptomatic versus 96.3% of patients who received no therapy. The accidental ingestion of American mistletoe is not associated with profound toxicity.

Difficulties and Perspectives of Immunomodulatory Therapy with Mistletoe Lectins and Standardized Mistletoe Extracts in Evidence-based Medicine.

Evid Based Complement Alternat Med. 2009 Nov 25. [Epub ahead of print]

Hajtó T, Fodor K, Perjési P, Németh P.
Department of Immunology and Biotechnology, University of Pècs, Pécs, Hungary.

Viscum album preparations are aqueous mistletoe plant extracts used in complementary and alternative medicine as immunomodulators in cancer therapy. However, evidence of immunological efficacy of mistletoe extracts (MEs) used in clinical trials is often lacking. Mechanisms involved in anti-tumor properties of ME and mistletoe lectins (MLs) modify both innate and adaptive immune systems, according to animal model experiments. In the background of these effects, a selective binding of ML on CD75 ganglioside receptors of interleukin 12 (IL-12)-producing macrophages or dendritic cells can play an important role. Immunological effects of ME correlate with their lectin activity, showing a bell-shaped dose-response curve of efficacy. Therefore, a correct determination of MLs for the standardization of commercial ME is essential. However, plant MLs exhibit heterogeneity, which most likely results from post-translational processing. In addition, amino acid analysis of ML has revealed numerous conservative substitutions along their amino acid sequence. Consequently, ML research needs new perspectives, and the advantages and disadvantages of purified and biologically better defined ML preparations are also discussed in this article.

Clinical research in anthroposophic medicine.

Altern Ther Health Med. 2009 Nov-Dec;15(6):52-5.

Hamre HJ, Kiene H, Kienle GS.
Institute for Applied Epistemology and Medical Methodology, Freiburg, Germany.

Anthroposophic medicine includes special medications and special artistic and physical therapies. More than 200 clinical studies of varying design and quality have been conducted on anthroposophic treatment. Half of these studies concern anthroposophic mistletoe therapy for cancer. Clinical effects of mistletoe products include improvement of quality of life, reduction of side effects from chemotherapy and radiation, and possibly increased survival. Apart from cancer therapy, the largest studies of anthroposophic treatment have been 2 naturalistic system evaluations: In German outpatients with mental, musculoskeletal, respiratory, and other chronic conditions, anthroposophic treatment was followed by sustained improvements of symptoms and quality of life. In primary care patients from 4 European countries and the United States treated for acute respiratory and ear infections by anthroposophic or conventional physicians, anthroposophic treatment was associated with reduced use of antibiotics and antipyretics, quicker recovery, and fewer adverse reactions; these differences remained after adjustment for relevant baseline differences.

Effects of Japanese mistletoe lectin on cytokine gene expression in human colonic carcinoma cells and in the mouse intestine.

Biomed Res. 2009 Oct;30(5):303-9.

Monira P, Koyama Y, Fukutomi R, Yasui K, Isemura M, Yokogoshi H.
Graduate School of Nutritional and Environmental Sciences, and Global COE, University of Shizuoka, Yada, Shizuoka, Japan.

Mistletoe lectins have various biological activities including anti-cancer and immunomodulatory effects. We previously isolated a lectin (ML-J) from Japanese mistletoe. In the present study, we examined the effects of ML-J on cytokine gene expression in human colon adenocarcinoma Caco-2 cells and in the mouse intestine. The results of reverse transcription-polymerase chain reaction and quantitative real-time polymerase chain reaction indicated that ML-J caused an upregulation of the gene expression of the proinflammatory cytokines interleukin (IL)-8, tumor necrosis factor-alpha (TNF-alpha) and IL-6 in Caco-2 cells and TNF-alpha and IL-6 in the duodenum. This study provides the first example to show that a perorally administered plant lectin affects gene expression in the duodenum.

Immunomodulating effects of Korean mistletoe lectin in vitro and in vivo.

Int Immunopharmacol. 2009 Dec;9(13-14):1555-61. Epub 2009 Sep 27.

Lee CH, Kim JK, Kim HY, Park SM, Lee SM.
College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.

The immunomodulatory effects of Korean mistletoe lectin (KML), one of the major active components in Viscum album L. var. coloratum, were investigated in vitro in immune cell proliferation and natural killer (NK) cell- and macrophage-mediated cytotoxicity, and in vivo in the forced swim test and cold stress. In mitogen-induced lymphocyte proliferation of murine splenocytes, concanavalin A and lipopolysaccharide significantly increased the proliferation of T cell and B cell lymphocytes, respectively. KML exposure increased lymphocyte proliferation in response to mitogen. KML also increased the splenic NK cell and macrophage activities in vitro. Exposure to KML increased production of cytokines such as interleukin-1 and interleukin-6 by macrophages. Two-week treatment with KML (30, 100, 300 and 600 microg/kg) increased the recruitment of lymphocytes, monocytes and macrophages. In the forced swim test, the immobility time was significantly attenuated by treatment with KML (300 and 600 microg/kg). In a cold stress experiment, spleen and thymus weight increased in KML-treated mice, while the weight of adrenal gland was lower than that in vehicle-treated mice. The levels of serum aminotransferases, lactate dehydrogenase and alkaline phosphatase were decreased by KML treatment. KML treatment also induced increases in the percentages of CD4(+) and CD8(+) cells in thymus. Our results suggest that KML enhances the immune system through modulation of lymphocytes, NK cells, and macrophages.

Efficacy and safety of mistletoe preparations (Viscum album) for patients with cancer diseases. A systematic review.

Forsch Komplementmed. 2009 Aug;16(4):217-26. Epub 2009 Jul 17.

Melzer J, Iten F, Hostanska K, Saller R.
Institute of Complementary Medicine, Department of Internal Medicine, University Hospital Zurich, Switzerland.

BACKGROUND: Mistletoe is often used as a complementary approach in oncology. Despite experimental anti-tumour effects and several reviews there remains controversy about its clinical role.

PATIENTS AND METHODS: Potentially relevant trials were identified to perform a systematic review (databases: e.g. EMBASE, MEDLINE; hand search: e.g. bibliographies; search terms: e.g. mistletoe). To be included, randomised or comparative clinical trials at least had to examine mistletoe preparations standardized according to manufacturing process and to describe interventions explicitly. Additionally, cohort studies were included for reasons of external validity. Results were summarised in tables.

RESULTS: 18 clinical trials (>6,800 participants) were included. Their internal quality was mostly low. Due to heterogeneity between trials a meta-analysis was impossible. Regarding efficacy, findings were inconsistent regarding life expectancy, relation to tumour entity, dosing and treatment duration. Yet, studies indicate that quality of life (QoL) is improved. As these findings do not seem to be limited to one of the different parenteral mistletoe preparations reviewed the treatment may be summarised under the umbrella term 'mistletoe therapy'. Regarding safety, 1 serious adverse event (AE) related to mistletoe was described; non-serious AEs were local reactions at injection site. Allergic reactions were rare.

CONCLUSION: Supportive 'mistletoe therapy' seems safe and beneficial for QoL in adult patients with solid tumours. But there is an urgent need to confirm its efficacy in patient-centred care in a complex oncological setting. This has to be evaluated systematically in prospective observational trials with validated, multidimensional patient-rated QoL questionnaires and comparisons of different preparations and dosages.

Mistletoe lectin modulates intestinal epithelial cell-derived cytokines and B cell IgA secretion.

Arch Pharm Res. 2009 Mar;32(3):443-51. Epub 2009 Apr 23.

Lyu SY, Park WB.
Department of Herbal Medicinal Pharmacology, Daegu Haany University, Gyeongsan, 712-715, Korea.

A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. var. coloratum agglutinin, VCA), which is known for its anti-cancer activity, was isolated from Korean mistletoe. In this study, IEC-6 rat intestinal epithelial cells and IM-9 human B-cells were cultured to determine the effect of VCA on cytokine and immunoglobulin (Ig) secretion. In lipopolysaccharide (LPS)-stimulated IEC-6 cells, VCA significantly shifted the interleukin (IL)-2, IL-5, IL-6, and tumor necrosis factor-alpha (TNF-alpha) secretion toward a more immunostimulatory response. Since intestinal epithelial cell-derived secretions may be capable of affecting local B cell Ig production in a variety of ways, we mimicked this condition by deriving a 2-day culture supernatant from IEC-6 cell line which was treated VCA in the presence or absence of LPS, and adding these supernatants to cultures of IM-9 human B cells. As a result, IgA secretion was significantly enhanced at in the presence of VCA at 10(-8)-10(-4) microg/mL. This study suggests that cytokines derived from IEC by VCA may create an environment which may contribute to the enhancement of IgA secretion seen in mucosal tissues. Overall, the induction of cytokines in intestinal epithelial cells, and IgA in B cells by Korean mistletoe lectin could indicate an enhanced immunosurveillance to prevent intestinal infections or other intestinal pathologies.
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