Safety of higher dosages of Viscum album L. in animals and humans - systematic review of immune changes and safety parameters

Systematic review of all experiments and clinical studies investigating higher dosages of VAE in animals and humans (Viscum album > 1 mg in humans corresponding to > 0.02 mg/kg in animals or ML > 1 ng/kg) and assessing immune parameters or infections or adverse drug reactions.69 clinical studies and 48 animal experiments reported application of higher doses of VAE or ML and had assessed immune changes and/or harm. In these studies, Viscum album was applied in dosages up to 1500 mg in humans and 1400 mg/kg in animals, ML was applied up to 6.4 μg/kg in humans and in animals up to 14 μg/kg subcutaneously, 50 μg/kg nasally and 500 μg/kg orally. A variety of immune parameters showed fluctuating or rising outcomes, but no immunosuppressive effect. Side effects consisted mainly of dose-dependent flu-like symptoms (FLS), fever, local reactions at the injection site and various mild unspecific effects. Occasionally, allergic reactions were reported. After application of high doses of recombinant ML, reversible hepatotoxicity was observed in some cases.Application of higher dosages of VAE or ML is not accompanied by immunosuppression; altogether VAE seems to exhibit low risk but should be monitored by clinicians when applied in high dosages.Complementary cancer treatment is utilised by 15-73% of all cancer patients in Europe, in addition to well established oncological treatments [1]. Most of these complementary treatments are herbal remedies and among these, Viscum album L extracts (VAE, European mistletoe, a hemiparasitic shrub, not to be confused with the Phoradendron species or "American mistletoe") are frequently used [1]. Physicians in Germany consider VAE to have a relevant therapeutic benefit [2].VAE contains a variety of biologically active compounds. Of these, mistletoe lectins (ML I, II and III) have been most thoroughly investigated. ML consist of two polypeptide chains: a carbohydrate-binding B-chain that can bind to cell surface receptors and thus enable the pro