Viscum album (L.) in experimental animal tumors: A meta-analysis

Abstract

Mistletoe (Viscum album L.) has been used as complementary anticancer treatment for ~100 years. Although the clinical efficacy of mistletoe in cancer and associated survival benefits remain contested, several studies point to its effectiveness and others have reported antitumor and immunomodulatory properties. In the present review, a search was conducted for original articles reporting the outcomes of treatments for experimental animal tumors with mistletoe. The inclusion criteria were: Publication in English, from 1996 onwards and in peer-reviewed journals included in the database PubMed. The parameters analyzed were: Provenance and time of publication, rationale, methods (animal species used, mistletoe preparation, treatment protocol, tumor lineage, blinding, randomization, controls and concomitant treatments), outcomes and investigated mechanisms of action. A total of 37 studies met the inclusion criteria. The quality of the studies was adequate in the terms of sample size and use of controls, and the only animal species employed were mice and rats. However, few studies reported having performed random allocation and none reported blinding. There was wide variation in the type and preparation of mistletoe used, route of administration, regimen, tumor type and the mechanism of action assessed. A temporal trend was identified; earlier studies sought to establish the antitumor effect of mistletoe and its possible mechanisms, cytotoxicity and immunomodulation in particular, whereas the later ones tended to focus more on biologically active principles, genomics and oxidative stress. A total of 32/37 studies reported an antitumor effect, 3 of which had mixed results. A total of 2 studies did not detect any antitumor effect and a further 2 found stimulation of tumor growth in the treated groups. One study did not assess antitumor effects, investigating immunomodulation action instead. The quality of the studies was satisfactory and the majority reported positive outcomes. Nevertheless, there is a great deal of methodological heterogeneity among the studies, which precludes conclusive comparisons. Based on these results, the present authors strongly suggest developing guidelines for reporting in vivo mistletoe cancer treatment experiments.

Phytochemical analysis and in vitro anti-proliferative activity of Viscum album ethanolic extracts

“…Most investigations into V. album are based on aqueous extracts [2][3][4][5][6]. The active compounds that have been identified are proteins commonly classified as viscotoxins (VT) and mistletoe lectins [7,8].…”

Comprehensive Metabolome Analysis of Fermented Aqueous Extracts of Viscum album L. by Liquid Chromatography−High Resolution Tandem Mass Spectrometry

“…However, only in the decade of 1920 it was introduced for cancer treatment by Steiner and Wegman [ 7 ]. After this, a boom in the amount of scientific reports was observed, for example botanical [ 2 , 3 ], phytochemical [ 5 , 8 ], pharmacological [ 6 , 8 , 9 ], pre-clinical [ 10 ], and clinical [ 11 , 12 ] studies. Many clinical studies demonstrated the efficacy of V. album extracts as adjuvant in cancer therapy to treat different types of tumors (gastrointestinal, breast, pancreas, lungs, kidneys, etc.…”

Homoeopathic Viscum album (10-3) is More Cytotoxic to in vitro Culture of Human Breast Cancer Cell Line than to Human Mesenchymal Stem Cells

“…Thus, it is well-known fact that there is an action of the components of the VA extract on cancer cells [11,18,19]. However, the literature still does not present data about the in vitro evaluation of homoeopathic VA, with only 7 articles in Pubmed database using the terms "Viscum album and homeopathic" (in May-2020) which are of especial relevance due to the low frequency of occurrence of side effects produced by homoeopathic formulations.…”

“…The current application as an injection preparation for tumor patients is based on the first suggestions of Rudolf Steiner, founder of anthroposophy, over 100 years ago [10]. Even though the intrinsic cellular mechanisms involving the antitumor action of VA are still poorly understood, intense use of this complementary therapy is being made in the last decades [11].…”