This is an in-depth assessment of the current evidence for mistletoe for cancer-related quality of life. Follow the links for other information regarding mistletoe for cancer:
The findings of reliable systematic reviews (SRs) on mistletoe-based interventions for cancer-related quality of life published in the past five years (2021-2026) have been summarized below. CAM Cancer appraised the quality of the SRs with the AMSTAR2 tool and only included SRs of moderate or high quality, while SRs of low or critically low quality were excluded. The full description of the included studies can be viewed in the evidence tables.
General characteristics of included studies
Number of studies
Three systematic reviews with meta-analysis were identified: one in various cancer populations (Loef 2020), one in breast cancer patients (Loef 2023) and one focusing on fatigue (Pelzer 2022).
Number of RCTs per SR; participants per SR
Overall quality of life in patients with various cancers was evaluated in 26 publications comprising 30 datasets (25 RCTs, 5 non-randomized controlled studies). 2,500+ participants across studies.
Quality of life in breast cancer patients was evaluated in 16 studies (15 publications; 9 RCTs, 7 nRCTs) with approximately 833 participants in RCTs and 2,831 participants in nRCTs
Cancer-related fatigue was evaluated in 19 studies (12 RCTs, 7 nRCTs). 1,494 participants in RCTs and 2,668 participants in nRCTs
Participants
Adults with various cancer types, including breast cancer and mixed solid tumour populations. Cancer stages varied across reviews, ranging from early-stage disease to advanced cancer.
Interventions: Mistletoe extracts (Viscum album preparations), including Iscador, Helixor, Eurixor, Lektinol, AbnobaVISCUM, other mistletoe preparations.
Used either as adjuncts to conventional cancer treatment or as stand-alone supportive interventions.
Comparators
Conventional cancer treatment alone (chemotherapy, radiotherapy, surgery, hormone therapy); no additional treatment/supportive care only;
Placebo injections; active comparators in some studies.
Outcomes
Global quality of life (QoL); QoL subdomains (physical, emotional, social, role and cognitive functioning, symptom scales); cancer-related fatigue; treatment-related adverse events and tolerability.
Effects of the intervention
Global quality of life
Across systematic reviews, mistletoe therapy was consistently associated with improvements in overall quality of life among cancer patients. Effects were generally of moderate magnitude and were observed both in mixed cancer populations and in breast cancer-specific analyses. However, confidence in the findings is limited by substantial methodological weaknesses and risk of bias in the underlying studies.
Various cancers: Significant improvement in global QoL with effect sizes of SMD = 0.61 (95% CI 0.41 to 0.81; p < 0.00001). Certainty of evidence: No formal GRADE assessment is reported but confidence is reduced by high risk of bias and substantial heterogeneity. (Loef 2020)
The SR found improvements in several symptoms and functional domains, but effects were not observed consistently across all QoL dimensions.
Seven of fourteen QoL domains showed statistically significant improvement: role functioning, social functioning, pain, nausea and vomiting, dyspnoea, diarrhoea, financial difficulties. No statistically significant effects were observed for: Physical functioning, emotional functioning, cognitive functioning, fatigue, insomnia, appetite loss, and constipation.
Breast cancer
In the RCTs, moderate effect size with low heterogeneity were reported, SMD = 0.61 (95% CI 0.47 to 0.75); moderate-certainty evidence. In the nRCTs: Small effect sizes with considerable heterogeneity were reported, SMD = 0.46 (95% CI 0.10 to 0.82); very low-certainty evidence (Loef 2023).
Cancer-related fatigue
Evidence from one SR focusing on fatigue suggests that mistletoe extracts may reduce cancer-related fatigue. (Pelzer 2022) Meta-analyses of both randomized and non-randomized studies showed statistically significant improvements. However, heterogeneity and risk of bias were substantial.
Small to moderate effect sizes were reported in the RCTs: SMD = -0.48 (95% CI -0.82 to -0.14; p = 0.006). Fourteen of 23 effect estimates were statistically significant.
Smaller effect sizes were reported in the nRCTs OR = 0.36 (95% CI 0.20 to 0.66; p = 0.0008).
No formal GRADE assessment was conducted but the overall certainty is likely low because most studies were judged at high or serious risk of bias and statistical heterogeneity was substantial.
Adverse events of mistletoe treatment
Safety reporting was inconsistent across reviews and only one of the SRs assessed adverse events. The available evidence indicates that mistletoe therapy is generally well tolerated. Adverse events were primarily mild local injection-site reactions, fever, flu-like symptoms, nausea, diarrhoea, hypotension, allergic reactions. Grade 3 events were reported mainly as local injection-site reactions. Serious adverse events attributable to treatment were uncommon.
Adverse events were reported in 18 of 20 studies included in the fatigue review. Mean adverse-event rate: 1.20 ± 0.19 adverse events per 1,000 prescribed doses.
Limitations of the evidence
Quality of systematic reviews
Overall review quality was judged moderate to high according to AMSTAR 2. Despite substantial methodological limitations in the primary studies included in the SRs, the SR authors interpreted the findings optimistically. GRADE assessment was conducted only in the breast cancer review.
Common limitations across included studies
Most quantitative syntheses were based on studies with substantial methodological limitations.
In the general QoL review 65% of studies were rated high risk of bias; In the breast cancer review 67% of RCTs were high risk of bias and all nRCTs were judged at serious risk of bias; in the fatigue review, 92% of RCTs were rated high risk of bias and all nRCTs had serious risk of bias. High risk of bias in outcome measurement: lack of blinding, particularly problematic because outcomes were largely patient reported.
Clinical heterogeneity was substantial with great variations in cancer type, disease stage; conventional cancer treatments; mistletoe preparations used, treatment duration and dosing; use of multiple and sometimes non-standardized QoL instruments; small sample sizes in several studies, inclusion of retrospective and non-randomized studies with serious confounding risk, high statistical heterogeneity that could not be fully explained through subgroup or sensitivity analyses,
Limited formal assessment of certainty of evidence across reviews.
