Profiling mistletoe therapy research and identifying evidence gaps: A systematic review of conditions treated, mode of application and outcomes

Introduction: Mistletoe has been used as a medicine since prehistoric times. Modern Western herbal practice continues to use mistletoe. This systematic review aimed to profile mistletoe therapy in research studies and to understand the gaps in the evidence to inform future research. Methods: We used standard systematic review methodology, searching three databases (Medline, Central and Anthromed) from inception to June 2020. Results: The search identified 31 relevant trials, and 10 systematic reviews published between 1996-2020. These trials comprised 14 randomised controlled trials, 15 controlled trials and 2 cohort studies. The most common country for monocentric trials was Germany. Most of the trials declared direct or indirect financial support from companies that produce mistletoe products. All the included trials involved cancer patients, with breast cancer being the most common condition treated (n = 10). Subcutaneous injections were the most common route of administration (27/31). Quality of life was the most reported outcome. Quality appraisal of the individual trials shows that there was a lack of reporting on blinding of participants and blinding of assessors. A third of the trials did not adequately describe how they dealt with incomplete data. Recent published systematic reviews do not concur on the efficacy of mistletoe and patients' quality of life; with the risk of bias of these publications being rated as 'unclear' overall. There were insufficient data to conduct a novel meta-analysis on mistletoe therapy efficacy. Conclusion: This systematic review identified gaps in mistletoe research for improving the evidence base for mistletoe therapy in supportive cancer care.