A controversial medicinal plant

The main field of application of mistletoe is as a supplementary treatment in oncology. Here it is used today mainly to improve the quality of life.

Viscum album L., mistletoe or white-berried mistletoe, is a parasitic shrub of the sandalwood family (Fig. 1) . In relation to the host tree, several subspecies are distinguished:

Hardwood mistletoe (Viscum album subspecies album)
Fir mistletoe (Viscum album subspecies abietis)
Pine or pine mistletoe (Viscum album subspecies austriacum).

Mistletoe is spread by birds, which eat the sticky fruits, but they cannot digest the inner part with the seeds. When the seeds are shed on an appropriate tree, they can settle on it and germinate. In the process, they extract water and minerals from the host, allowing the mistletoe germ to grow slowly on the tree. Over the course of many years, spherical formations of up to one meter in diameter can form.

In this way, mistletoe spreads in temperate zones of northern and central Europe. Mistletoe was also introduced to the United States in the early 20th century and grows in the San Francisco area.

Ingredients

Among the ingredients of Viscum album, whose effects are so controversially discussed, sugar-containing mistletoe lectins, i.e. glycoproteins, are at the center. About 20 different lectins are known to be present in mistletoe in various compositions.

In addition to lectins, viscotoxins, small cystine-rich cationic peptides belonging to the thione group, play another important role [1]. In addition, mistletoe contains various flavonoids and a thousand times higher content of thiols (e.g. glutathione) than other plants, which have a very good antioxidant effect.

Cardiovascular and Anthroposophy

Mistletoe has some importance in traditional medicine because studies indicate cardioprotective and antihypertensive effects. In anthroposophic medicine, various mistletoe preparations are used to treat various tumor diseases. Depending on the tumor, preparations with mistletoe grown on different host trees are used. With hardly any other medicinal plant are studies published with such controversial results. While for some not the slightest evidence can be discerned for tumor treatment with mistletoe preparations [2], for others, especially in anthroposophical circles, mistletoe represents an important and effective contribution to tumor treatment [3].

Heart, blood pressure

Mistletoe has a long folk medical tradition in various countries for the treatment of mild heart failure and elevated blood pressure [4]. And already among the Celts mistletoe was considered sacred, especially if it grew on an oak tree sacred to the Celts, which is rather rare. Therefore, it was cut only with golden sickles and used for cult purposes.

A pharmacological study published in 2014 addressed the cardioprotective properties of Viscum album [5]. Here, isolated rat hearts in which ischemia was induced experimentally were treated with Viscum album extract before and during ischemia, and the results were compared with untreated hearts. The infarct extent in treated hearts was significantly lower compared to untreated hearts (p<0.01). The efficacy of mistletoe extract for the treatment of hypertension was established in a 2014 open clinical trial [6]. Patients with a systolic BP up to 180 mmHg and a diastolic BP up to 110 mmHg received ten drops of Viscum album mother tincture three times daily for twelve weeks and no other antihypertensive drugs. Data from 42 patients could be analyzed. After twelve weeks of treatment, systolic BP decreased on average from 155.8 mmHg to 141.1 mmHg (p<0.001) and diastolic BP from 84.4 mmHg to 79.5 mmHg (p<0.00177) compared to baseline. Thus, the results were significant.

Tumors

Libraries could be filled with papers on the tumor-inhibiting effects of mistletoe preparations, and views on this are, as already mentioned, very controversial. It seems difficult to prove efficacy with today’s clinical trial rules. This is why there are many authors who dismiss mistletoe therapy as a mere placebo treatment [2]. Without questioning the importance of clinical trials, there are arguments that point to difficulties in making the efficacy of mistletoe treatments dependent on trial results. This is what Markus Reif of the IKF Berlin said in a presentation at the 28th Swiss Conference on Phytotherapy:

“The conduct of new RCTs suffers, on the one hand, from the fact that mistletoe extracts cannot really be blinded to a placebo because of their sometimes marked local side effects, until which the dose of mistletoe administration is increased. Second, there is little willingness to participate in mistletoe studies among both physicians and patients. Advocates of mistletoe therapy in the medical profession cannot justify withholding it from their patients suffering from a tumor. Appropriate patients simply have a mistletoe preparation prescribed by their treating physician; conversely, patients who reject mistletoe therapy are all the more unwilling to participate in a relevant RCT” [7].

Further, in this presentation, Reif mentioned that the decades-long use of mistletoe extracts to treat tumor diseases represents a significant body of information that provides clues about tumor disease symptom control, patient compliance, quality of life, study outcomes, and potential benefits of a holistic therapeutic approach.

Quality of life

Whereas in the past, i.e. until about the end of the 1980s, primarily the antitumor efficacy of mistletoe preparations was discussed, with survival time and remissions being the focus of research, since about 1990 more and more interest has been paid to quality of life. At the 21st Swiss Conference on Phytotherapy, a paper dealt with quality of life in mistletoe therapy [8]. In this context, the term “quality of life,” which is often understood in different ways, is equated with an individual’s satisfaction with his or her physical, emotional, spiritual, and social situation [9]. It follows that multidimensional questionnaires completed by the patients concerned themselves are more reliable than data supplied by physicians or nursing staff. In his presentation, Melzer presented several studies that provide data on the quality of life of people with cancer and concluded:

“The clinical studies on mistletoe treatment to date […] suggest […] that mistletoe extracts in addition to oncological treatments […] can improve the quality of life of patients with cancer.”

Since then, several studies have appeared confirming this statement [10–13]. Of course, there were also studies and statements with negative results [14] – or voices pointing out gaps in positive studies [15].

Summary

The mysterious medicinal plant Viscum album, mistletoe, has evolved from a plant sacred to the Germanic tribes to a frequently used and controversial medicinal plant. Folk medicine use for cardioprotection has been investigated in pharmacological studies. A clinical pilot study speaks for the blood pressure lowering effect.

Mistletoe is much more widespread in oncology, where corresponding preparations are used as tumor-inhibiting therapy and nowadays increasingly to improve the quality of life. Skeptics of mistletoe therapies repeatedly point out that positive results come primarily from specialists who are well-disposed toward mistletoe therapy. Negative results, however, often come from scientists who know too little about phytotherapy – a well-known dilemma of phytotherapy. A review of the existing literature without bias argues primarily for efficacy of mistletoe treatments in the area of quality of life for cancer patients.

Literature:

Society of Anthroposophic Physicians in Germany (GAÄD). www.mistel-therapie.de
de Giorgio A, Stebbing J: Mistletoe: for Cancer or just for Christmas? Lancet Oncol 2013; 14(13): 1264-1265.
Kienle GS, Kiene H: Review article: Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Integrative Cancer Therapies 2010; 9(2): 142-157.
Carpernaros Z: The golden bough: The case for mistletoe. Eur J Herbal Med 1994; 1: 19-24.
Suveren E, et al: Cardioprotective effects of Viscum album L. subsp. album (European misletoe) leaf extracts in myocardial ischemia and reperfusion. J Ethnopharmacol 2017; 209: 203-209.
Poruthukaren KJ, et al: Clinical Evaluation of Viscum album Mother Tincture as an Antihypertensive: A Pilot Study. J Evid Based Complementary Altern Med 2014; 19(1): 31-35.
Reif M: Cohort studies as a basis for extended knowledge of the efficacy of herbal preparations using mistletoe as an example. AM thema Phytotherapy 2014; 14: 12-16.
Melzer J: Quality of life and mistletoe therapy in oncology. AM thema Phytotherapy 2007; 7: 2-4.
Donelly S, et al: Quality of life measurement in the palliative management of advanced cancer. Support Care Cancer 2001; 9: 361-365.
Kienle GS, et al: Intravenous Mistletoe Treatment in Integrative Cancer Care: A Qualitative Study Exploring the Procedures, Concepts, and Observations of Expert Doctors. Evid Based Complement Alternat Med 2016; 2016: 4628287.
Tröger W, et al: Additional Therapy with a Mistletoe Product during Adjuvant Chemotherapy of Breast Cancer Patients Improves Quality of Life: An Open Randomized Clinical Pilot Trial. Evid Based Complement Alternat Med 2014; 2014: 430518.
Tröger W, et al: Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. Dtsch Arztebl Int 2014; 111(29-30): 493-502.
Kim KC, et al: Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma – a randomized, controlled pilot study. BMC Complement Altern Med 2012; 12: 172.
Evans M: Cancer Patients’ Experiences of Using Mistletoe (Viscum album): A Qualitative Systematic Review and Synthesis. J Altern Complement Med 2016; 22: 134-144.
Shneerson C, et al: The effect of complementary and alternative medicine on the quality of life of cancer survivors: a systematic review and meta-analyses. Complement Ther Med 2013; 21: 417-429.