Can mistletoe cure cancer?

Introduction

Cancer is a leading cause of mortality worldwide. In 2020, an estimated 19.3 million new cancers were diagnosed and about 10 million people died from the disease^[1].

Because of the strong public interest in cancer cures, many claims of miraculous therapies are popular on the Internet. These cures are usually claimed to be better for people on the basis that they are “natural” or “plant-based”, as opposed to proven therapies like chemotherapy, radiotherapy or immunotherapy. Health Feedback reviewed some of these “natural cures” and found that they were based on unsupported but popular beliefs or simply scams. Cancer misinformation can have dire consequences, from misleading patients into spending money on fake treatments to discouraging them from proven, effective therapies.

One example of an herbal product presented as a cancer remedy is mistletoe. European mistletoe (Viscum album) is a parasitic plant that grows on several species of trees like oak, pine, apple trees, and elms. The European Medicines Agency (EMA) has authorized various traditional medicines containing mistletoe for cardiovascular conditions and cancer in Europe.

Mistletoe has been part of European traditional medicine for a long time, but its modern use as a cancer therapy is controversial. It is tied to anthroposophical medicine, which is the clinical application of anthroposophy, a system of spiritual beliefs developed in the early twentieth century by philosopher Rudolf Steiner. Steiner believed that cancer results from imbalances, including spiritual ones, and mistletoe would help correct these imbalances. Steiner also formulated Iscador, a product made of fermented mistletoe, which is still one of the main mistletoe formulations used as therapy for cancer patients. However, there’s scant scientific evidence supporting anthroposophical medicine.

In contrast to the EMA, the U.S. Food and Drug Administration (FDA) hasn’t approved mistletoe for any kind of medical condition. Still, mistletoe-containing preparations are marketed as supplements or alternative remedies in the U.S. for cancer and other ailments.

The claim that mistletoe effectively cures cancer endures to this day, and social media posts are a testament to this. But how much scientific evidence is actually there for this claim? In this Insight article, we’ll focus on examining the research on whether mistletoe can cure cancer or halt cancer progression, either on its own or together with conventional therapies.

Preclinical studies provide some encouraging results

In a review of the scientific literature, the U.S. National Cancer Institute explained that mistletoe or mistletoe extracts have cytotoxic effects in vitro—that is, in test tubes—and in animals. This means that molecules present in mistletoe can kill cancer cells or at least block their growth. Mistletoe also contains molecules that can stimulate the immune system, thus supporting the immune system’s ability to fight tumors^[2-5].

However, the National Cancer Institute also noted that animal studies produced “mixed and inconsistent results”, raising questions about how effective mistletoe would actually be against cancer. Furthermore, results from in vitro or animal studies cannot be extrapolated to humans. Neither cells growing in a dish nor mice fully replicate the biology of the human body, although they provide varying degrees of approximation.

Therefore, although these preclinical results are important as they provide a basis for further investigations into the effect of mistletoe on cancer patients, on their own they don’t provide sufficient evidence that mistletoe is an effective cancer treatment in people.

Clinical studies on the effect of mistletoe products in cancer patients are poorly designed, provide conflicting results

The scientific literature on mistletoe isn’t limited only to preclinical studies. There have also been clinical studies and trials investigating the effect of mistletoe products in cancer patients but the results are conflicting. Overall, the only reliable conclusion we can make at this point in time is that clinical evidence doesn’t support the use of mistletoe alone or in conjunction with conventional therapies to cure cancer or prolong patient survival.

Before we dive into a discussion of the studies, it’s important first to understand how the quality of a study’s design can influence the reliability of the study’s results and conclusions.

Research, especially in humans, is susceptible to the risk of bias and statistical artifacts^[6]. Bias can arise through many ways, such as the absence of blinding, lack of adequate and transparent criteria for excluding and including patients in the trial, and small sample sizes. A well-designed study seeks to address such deficiencies, which helps minimize these risks and thus increases confidence in the results.

Systematic reviews of available clinical trials of mistletoe in cancer found that most of them are marred by inadequate study designs, thereby providing low confidence in the studies’ conclusions. Such reviews put together all the studies on a particular research question, as long as the studies meet a pre-specified criteria to reduce bias and ensure that the studies included are of sufficient quality.

A 2008 Cochrane review on mistletoe treatment for cancer found that “most trials were found to have major methodological drawbacks that raise doubts about the validity and generalizability of the findings”^[7]. Analyzing thirteen randomized clinical trials (RCTs) that evaluated the effect of mistletoe on cancer patients’ survival, the authors reported that “six showed some evidence of a benefit, but none of them was of high methodological quality”. The review concluded that “there was no consistent effect of mistletoe extracts on [patient survival] for any of the included malignant diseases and for any of the applied preparations of mistletoe extracts”.

A 2019 systematic review by Freuding et al. that included 14 RCTs concluded that “the majority of studies did not show any effect of mistletoe on survival”. This review reported that many studies suffered from design weaknesses, like absence of blinding, small sample size, or incomplete data reporting^[8]. Furthermore, the authors cited other causes for concern, stating that most studies presented a risk of conflict of interest because they received funding from companies or institutions promoting the use of herbal products.

Freuding et al. also noted that just two research groups produced one-third of the studies analyzed. This is a concern because in research, replication of the findings by several independent laboratories using different methodologies increases the scientific confidence in the results. By contrast, the fact that a significant portion of the research originates from just two sources introduces another risk of bias—through potential conflicts of interest—that reduces the confidence in the reliability of the results.

In particular, the first author from one of the overrepresented research groups, medical sociologist Ronald Grossarth-Maticek, came under heavy criticism for the lack of validity and plausibility of his past research on other topics^[9].

Another systematic review published in 2020 by Ostermann et al. examined 32 clinical studies spanning decades of research. The authors reported that using mistletoe extracts in combination with other treatments increased patients’ survival time. However, many of the studies included in this review were at risk of bias due to the absence of blinding and randomization. Here too, research from Grossarth-Maticek was overrepresented, in fact accounting for half of the randomized studies included.

Even though the authors claimed that the studies’ design flaws didn’t change the overall conclusion, these are still significant limitations that warrant caution in interpreting the review’s findings and conclusion. In fact, the authors called for “studies based on sound methodological designs”. In particular, the authors noted that more recent studies investigating the use of mistletoe within the context of up-to-date anticancer therapies only provided a “vague” conclusion. Out of five studies, three had suboptimal designs, one reported a positive effect, and one reported no effect of mistletoe^[10].

Finally, scientific institutions have weighed in on the matter. The U.S. National Cancer Institute concluded that there was no evidence that mistletoe could stimulate the immune system to fight cancer. It also said that the conflicting results between studies as well as the numerous methodological weaknesses jeopardized the reliability of the results.

The U.S. National Center for Complementary and Integrative Health also raised doubts about the findings from clinical trials, again pointing out “major weaknesses” in the studies’ designs. It concluded that “mistletoe is not a proven cancer treatment. It should not be used as a treatment for cancer outside of clinical trials”.

Conclusion

In summary, while a fair amount of research on the use of mistletoe as cancer treatment exists, it has provided inconclusive results as many studies on the subject carry important methodological flaws and limitations. Overall, the results of the most robust trials available don’t indicate that mistletoe cures cancer or improves the chances of patients’ survival. But new clinical trials are underway which, if better designed, may provide clearer answers.

REFERENCES

• 1 – Sung et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians.
• 2 – Duong Van Huyen et al. (2006) Interleukin-12 is associated with the in vivo anti-tumor effect of mistletoe extracts in B16 mouse melanoma. Cancer Letters.
• 3 – Seifert et al. (2008) Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro. Cancer Letters.
• 4 – Zarkovic et al. (2001) An overview on anticancer activities of the Viscum album extract Isorel. Cancer Biotherapy and Radiopharmaceuticals
• 5 – Szurpnicka et al. (2001) Biological activity of mistletoe: in vitro and in vivo studies and mechanisms of action. Archives of Pharmacal Research.
• 6 – Evans (2010) Common statistical concerns in clinical trials. Journal of Experimental Stroke and Translational Medicine.
• 7 – Ackeren et al. (2008) Mistletoe therapy in oncology. Cochrane database of systematic reviews.
• 8 – Freuding et al. (2019) Mistletoe in oncological treatment: a systematic review : Part 1: survival and safety. Journal of Cancer Research and Clinical Oncology.
• 9 – Pelosi (2019) Personality and fatal diseases: Revisiting a scientific scandal. Journal of Health Psychology.
• 10 – Ostermann et al. (2020) A Systematic Review and Meta-Analysis on the Survival of Cancer Patients Treated with a Fermented Viscum album L. Extract (Iscador): An Update of Findings. Complementary Medicine Research.