Major Research Findings

A study published in 1 found that European mistletoe (Viscum album) extract is cytotoxic to canine high-grade astrocytoma cells in vitro and has additive effects with mebendazole. The study used the canine astrocytoma cell line SDT-3G and found that the IC50 for mistletoe alone was 5.644 ± 0.09 SD μg/mL. The addition of mistletoe at 5 μg/mL to mebendazole at 0.03 μM led to increased cell death compared to what would be expected for each drug separately.

Another study published in 2 found that European mistletoe extract can induce cellular stress responses in Ewing sarcoma cells. This study showed that mistletoe lectins and triterpene acids, which are both found in European mistletoe extract, are effective against Ewing sarcoma in vitro, ex vivo, and in vivo.

A study published in 3 found that multiple active compounds from European mistletoe (Viscum album) synergistically converge to promote apoptosis in Ewing sarcoma cells. This study recreated the total mistletoe effect by combining an aqueous extract (viscum) and a triterpene extract (TT) solubilized with cyclodextrins. They found that viscumTT treatment shifted the balance of apoptotic regulatory proteins towards apoptosis, mainly via CLSPN, MCL1, BIRC5, and XIAP downregulation. ViscumTT also demonstrated strong antitumor activity in a cell line- and patient-derived mouse model, and may be considered an adjuvant therapy option for pediatric patients with Ewing sarcoma.

A systematic review and meta-analysis published in 4 aimed to evaluate the safety and efficacy of mistletoe extract (ME) use during the oncological perioperative period. The results suggested that ME may be safe and effective for use in this setting.

A review article published in 5 focused on the antioxidant activity of mistletoe. It highlighted the controversial medical story of European mistletoe regarding its antioxidant activity and the potentiality of other species of mistletoe.

A review article published in 6 discussed the anti-inflammatory activity of European mistletoe. It proposed a relationship between the recent uses of mistletoe, based on its antioxidant properties, which are supported by phytochemical and pharmacological data. This review highlighted the unique metabolism of mistletoe as a key interpretation element to explain its biological properties and steer its consequent therapeutic uses.

A real-world data study published in 7 evaluated the quality of life in lung cancer patients receiving radiation and Viscum album L. The study suggested that add-on treatment with extracts of Viscum album L. (white-berry European mistletoe, VA) may be feasible and safe and to improve the QoL of cancer patients.

A study published in 8 isolated five undescribed dihydroflavonoid glycoside derivatives, namely albvisosides A-E, together with two known compounds from the roots and stem leaves of Viscum album L. var. album (European mistletoe). Albvisoside B exhibited significant inhibitory effect on hepatic lipid accumulation in HepG2 cells at very low concentrations (EC₅₀: 0.7 nM). The study elucidated the direct targets or downstream effectors of albvisoside B using proteome integral solubility alteration assay.

A review article published in 9 provided an update on current evidence regarding Viscum album L. therapy in oncology. It highlighted the various antitumor, pro-apoptotic, anti-proliferative, and immunomodulatory effects of Viscum album extracts. Two current meta-analyses attribute life-prolonging and HRQL-improving properties to additive Viscum album therapy.

A study published in 10 made advances on the visualization of the internal structures of the European mistletoe using microtomography for 3D reconstruction. The study investigated the attachment mode and host penetration of the European mistletoe, and found that the diameter and length of the branch hypertrophy showed a positive linear correlation with the age of the mistletoe.

A study published in 11 described the chemical profiles and biological activities of homogenizer-assisted extract (HAE) and ultrasound-assisted extract (UAE) of V. album parts (leaf, fruits, and seeds). The leaf extracts exhibited the best antioxidant and enzyme inhibitory effects in the study.

A study published in 12 evaluated the effect of extract of the European mistletoe - Viscum album quercus L. on spermatozoa motility and viability in vitro. The results showed that Viscum album quercus had a negative dose- and time-dependent effect on spermatozoa motility and viability parameters in vitro.

A case report published in 13 reported long-term tumor-free survival in a patient with Stage IV epithelial ovarian cancer undergoing high-dose chemotherapy and Viscum album extract treatment. This report suggested that Viscum album may lead to improved quality of life and reduced chemotherapy side effects, and may have synergistic cytotoxic and proliferation-inhibiting effects when used together with chemotherapy.

A CARE compliant case report published in 14 described the intralesional and subcutaneous application of Viscum album L. (European mistletoe) extract in cervical carcinoma in situ. This report suggested that Viscum album may be a useful treatment option for cervical carcinoma in situ.

A randomized study published in 15 evaluated the safety and clinical response of complementary treatment with European mistletoe extracts during chemotherapy. The results suggested that European mistletoe extracts are safe and can be used as a complementary therapy during chemotherapy.

A study published in 16 evaluated the efficacy and safety of Viscum album extract (Helixor-M) to treat malignant pleural effusion in patients with lung cancer. The results suggested that Helixor-M may be an effective and safe treatment option for malignant pleural effusion.

A real-world observational multicenter analysis published in 17 evaluated the overall survival of stage IV non-small cell lung cancer patients treated with Viscum album L. in addition to chemotherapy. The results suggested that Viscum album L. may have a beneficial effect on survival in cancer patients.

A study published in 18 used high content imaging to quantitatively analyze receptor-mediated uptake and pro-apoptotic activity of mistletoe lectin-1 (ML1). This study revealed that ML1 displays very fast binding to sugar residues on the membrane and energy-dependent uptake in CT26 cells. ML1 cytotoxicity was less affected in multidrug resistant tumor cell line 4T1 in contrast to commonly used chemotherapeutic drug (ML1 resistance index 6.9 vs 13.4 for doxorubicin; IC₅₀: ML1 1.4 ng/ml vs doxorubicin 24000 ng/ml), opening new opportunities for the use of ML1 as an alternative treatment in multidrug resistant cancers.

A meta-analysis published in 20 examined 18 studies that compared cognitive-behavioral therapy with the same therapy supplemented by hypnosis. The results indicated that the addition of hypnosis substantially enhanced treatment outcome. Effects seemed particularly pronounced for treatments of obesity, especially at long-term follow-up.

A systematic review and meta-analysis published in 22 used literature searches to obtain 47 articles to examine the efficacy of hypnotherapy in the treatment of PTSD. A fixed-effects meta-analysis was applied to postintervention assessment results and 4-week follow-ups, showing a large effect in favor of hypnosis-based (especially manualized abreactive hypnosis) treatment.

A study published in 21 compared hypnotherapy (HT), group therapy (GT), and individual desensitization (SD) for dental anxiety. The results showed that all three treatments reduced dental anxiety and improved dental beliefs compared with a control group. For patients completing treatment, HT reduced dental anxiety to the same degree as GT and SD.

A two-phase constructive design study published in 19 compared hypnotherapy (future oriented hypnotic imagery) and autogenic training in the treatment of tension headaches. The results showed that both treatments were equally effective at post-treatment, but after a 6-month follow-up period, the future oriented hypnotic imagery which had been explicitly presented as hypnosis was superior to autogenic training.

A systematic review published in 23 comprehensively identified studies and evidence regarding hypnotherapy for sleep disturbances. The results suggested that hypnotherapy appears to be a promising treatment for sleep disturbance.

Benefits and Risks

Benefit Summary

European mistletoe extract has been shown to be cytotoxic to cancer cells in vitro and in vivo, and may have synergistic cytotoxic and proliferation-inhibiting effects when used together with chemotherapy. It may also reduce chemotherapy side effects and improve quality of life. European mistletoe extract has antioxidant and anti-inflammatory properties.

Risk Summary

A study published in 12 suggested that Viscum album quercus can have a negative dose- and time-dependent effect on spermatozoa motility and viability in vitro. European mistletoe extract may also interact with other medications.

Comparison Between Studies

Similarities Between Studies

Multiple studies have shown that European mistletoe extract is cytotoxic to cancer cells. European mistletoe extract has a variety of effects, including antioxidant, anti-inflammatory, and immunomodulatory effects.

Differences Between Studies

The types of cancer studied, the types of mistletoe extracts used, the study design, and the evaluation methods have all varied across studies. Therefore, further research is needed to comprehensively evaluate the effectiveness and safety of European mistletoe extract.

Consistency and Contradictions in Findings

The effects of European mistletoe extract on cancer treatment have been suggested in several studies, but its effects may vary depending on the type of cancer, the type of extract used, the dosage, and the patient's condition. The possibility that European mistletoe extract could have a negative impact on sperm motility and viability has been reported. More research is needed to clarify the use of European mistletoe extract.

Points to Note Regarding Practical Applications

While European mistletoe extract may be used as an adjunct therapy for cancer treatment, it is dangerous to use it without consulting a doctor. It is important to always consult a doctor before using European mistletoe extract, and follow their instructions. Pregnant or breastfeeding women, and people taking other medications, should consult their doctor before using European mistletoe extract.

Limitations of Current Research

Research on European mistletoe extract is still insufficient. More research is needed, particularly in the form of large-scale clinical trials in humans, to better understand the long-term effects and safety of European mistletoe extract. Further research is needed to establish the appropriate use of European mistletoe extract, as its effectiveness may vary depending on the type of cancer and the patient's condition.

Directions for Future Research

Future research on European mistletoe extract should include large-scale clinical trials in humans to more thoroughly evaluate its effectiveness and safety. It is also important to consider the optimal use of European mistletoe extract to enhance its effectiveness. Furthermore, research should investigate the mechanism by which European mistletoe extract affects sperm motility and viability, and establish safe usage practices.

Conclusion

European mistletoe extract may be useful as an adjunct therapy for cancer treatment, but there is not enough scientific evidence to fully support its effectiveness and safety at this time. It is important to consult with a doctor before using European mistletoe extract and to follow their instructions.

Research on European mistletoe extract is still in its early stages, but the potential of this treatment is high. Further research may lead to the development of new drugs that can help treat cancer.