Mistletoe Therapy

Mistletoe (Viscum album L.) is a medicinal herb that has been used as a cancer therapy in modern medicine for over a hundred years. It is a semi parasitic evergreen plant that is native to Asia and Europe. It grows on certain species of trees and draws out water and nutrients for its growth and survival.

Mistletoe is a historic folk remedy that has been used for a wide range of conditions, including cancer. The first documented clinical application of mistletoe as a cancer therapy was in 1920 by Dutch physician Ita Wegman. He prescribed a mistletoe extraction to treat a breast cancer patient following a recommendation by Rudolph Steiner [1].

In Europe, mistletoe extracts are currently one of the most common types of treatment used in integrative medicine for cancer [1]. In many German-speaking countries it is the number one alternative therapy prescribed for cancer patients and is often covered by health insurance [2]. However, the therapy is not currently approved by the FDA in the USA.

Clinical research shows that mistletoe activates the immune system in ways that may be beneficial for treating cancer. Studies show that it helps to reduce the often severe side effects from conventional treatments, improves quality of life, and may potentially increase survival times [3].

Mistletoe extract is most commonly applied as an adjuvant (supportive) treatment for people suffering with cancer. This means it is used alongside or after standard of care treatments such as surgery, chemotherapy and radiation.

History of Mistletoe Therapy

Plants of the Viscum species such as mistletoe (Viscum album L.) have been used in the traditional medicine systems of Europe for centuries [9]. The medicinal properties of mistletoe have been known since ancient times. In fact, the Druids and ancient Greeks are reported to have used mistletoe as a medicine. It is also described in legend and folklore as a panacea for many diseases [4].

Mistletoe has been applied traditionally for a wide range of ailments such as epilepsy, infertility, menopausal issues, nervous tension, asthma, hypertension, headaches, dermatitis, and as a cancer therapy in various different forms [4]. Hippocrates used mistletoe to treat diseases of the spleen and also to help with menstruation problems. In the Middle Ages, the prominent figures Hildegard von Bingen and Paracelsus recommended mistletoe as a treatment for conditions such as gout, leprosy, mumps, hepatitis, liver disorders, and lung diseases. It was even recommended for “weakness of the heart” [9].

By the end of the 19th century mistletoe was rejected by scientists and deemed a folklore remedy. Nevertheless, interest in mistletoe was revived in the 20th century. From 1920 onwards mistletoe began to garner attention in the medical community after Rudolph Steiner recommended a mistletoe extraction as a therapy for cancer. The extract was produced in a complex manufacturing process that combined the sap from mistletoe harvested in summer and winter [9].

The first recorded use of mistletoe in modern oncology was by the Dutch physician Ita Wegman. He was the first person to implement Rudolph Steiner’s recommendation and used his mistletoe extraction to treat a patient with breast cancer [1]. It was Steiner’s astute intuition that led him to conceive of mistletoe as a cancer therapy. Similar to cancer, mistletoe is a parasitic growth that kills its host. Guided by Hahnemann's principle of “like cures like”, Steiner came to the conclusion that a mistletoe extract would have anticancer effects [21].

Despite the implausible and unusual nature of the origins of mistletoe therapy for cancer, there are currently thousands of scientific preclinical studies that support Steiner’s hypothesis and show that mistletoe’s primary compounds (alkaloids, lectins, and viscotoxins) do have potent anticancer properties, while the extracts have been shown to have a wide range of scientifically-validated benefits for cancer patients [21].

Mistletoe Therapy Research

Research suggests that mistletoe extract may be beneficial for cancer patients in terms of improving quality of life, increasing survival rates, mitigating disease-related symptoms and reducing side effects from conventional treatment. However, there have been some concerns about the reliability and mixed results of the clinical studies on mistletoe for cancer [12].

Several studies show that mistletoe therapy positively affects the quality of life of cancer patients by improving fatigue, sleep, exhaustion, nausea, vomiting, appetite, depression, anxiety, pain and other common side effects of standard of care treatments such as chemotherapy, radiation and surgery [9] [13] [14].

The clinical efficacy of mistletoe regarding tumor control and survival has been contested in certain studies [15]. However, a 2013 randomized control trial reported an increase in survival rates for patients with pancreatic cancer [16]. A meta-analysis from 2010 concluded that mistletoe extract (under the brand name Iscador) may prolong overall survival and improve psychosomatic self-regulation (mental and emotional stress management) in breast cancer patients [17]. A more recent meta-analysis from 2020 found that adjuvant treatment of cancer patients with Iscador was associated with better survival rates, but acknowledged the possibility of performance bias since the studies were unblinded (information that may influence results was not withheld from patients or doctors) [18].

Studies from 2004 and 2006 on mistletoe as an adjuvant therapy administered alongside conventional treatments showed a reduction in adverse effects and improvements in quality of life for patients with breast cancer, ovarian cancer, and lung cancer [1][19] [20].

Overall, despite some promising findings and reported benefits of mistletoe as a cancer therapy, more high-quality clinical research is needed to accurately assess the safety and efficacy of mistletoe extracts. Researchers encourage patients receiving mistletoe therapy to take part in future clinical trials [15].

Potential Applications of Mistletoe Therapy

Mistletoe therapy has several potential clinical benefits for cancer patients. Many clinical studies have been carried out on mistletoe therapy for patients with a range of different types of cancer such as bladder cancer, breast cancer, colorectal cancer, glioma, lung cancer, and melanoma [9].

The scientific research indicates possible therapeutic benefits as an adjuvant therapy to help improve quality of life, increase survival times, and reduce the side effects of standard of care treatments [4]. However, more well-designed clinical research is still needed to better understand the full scope of potential clinical benefits and anticancer effects of mistletoe therapy in humans.

There appears to be a variety of possible therapeutic effects of mistletoe therapy as reported in the scientific literature (in preclinical and clinical studies) and by proponents in alternative and integrative healthcare settings. However, not all have been proven by clinical research.

The list below is a summary of these purported benefits [5] [9] [10] [11] [13] [14]:

• Improved quality of life
• Activates the immune system and defense chemicals to fight cancer
• Induces apoptosis (programmed cell death) in cancer cells
• Prevents angiogenesis (formation of new blood vessels)
• Antitumor effects
• Selectively toxic to cancer cells
• Helps mitigate side effects of conventional treatments
• Protects against DNA damage from chemotherapy
• Reduces fatigue
• Improves anxiety and depression
• Better sleep
• Increased appetite
• Lowers levels of exhaustion
• Reduced nausea and vomiting
• Decreased sensitivity to pain
• Increased energy
• Enhanced mood
• Improves wound healing
• Antibacterial and antifungal properties
• Reduces inflammation
• Patients report less fear and more positive outlook
• Increases overall wellbeing

Clinical research shows that mistletoe has the ability to stimulate the immune system and is classified as a biological response modifier [4]. Biological response modifiers are commonly used as anticancer agents to treat cancer or to help mitigate the side effects of other anticancer drugs [4]. Mistletoe’s immunomodulatory effects appear to help prime the immune system to fight cancer [4].

Mistletoe has been shown in preclinical research to have antitumor effects [11]. Preclinical research indicates it may kill cancer cells, reduce inflammation, prevent angiogenesis (blood vessel formation) and down-regulate genes involved in tumor growth [4] [11]. It may therefore help to prevent metastases (spread of cancer) by killing cancer cells and stopping new blood vessels from forming, which in turn cuts off blood flow to tumors and inhibits growth [11]. However, this has not yet been proven in humans.

Mistletoe contains a range of biologically active molecules including lectins, flavonoids, viscotoxins, polysaccharides, alkaloids, and other substances with potential anticancer effects [4]. The mechanisms of action behind the benefits of mistletoe therapy have not been fully defined, but there is a growing body of research on lectins and viscotoxins as anticancer agents [5].

Lectins are carbohydrate-binding proteins found on cell-surfaces that play a key role in how cells interact with their environment. Lectins can bind to the outside of cells and have been shown to modulate the immune system, increase natural killer and dendritic cell activity, activate and increase numbers of lymphocytes, macrophages, leukocytes, eosinophils, and induce apoptosis (programmed cell death) in cancer cells [5] [6] [7]. Viscotoxins are small proteins that have been shown to exhibit cancer cell-killing activity and may also play a role in stimulating the immune system to fight cancer [8] [9] [4].

Laboratory and animal studies show that full-spectrum mistletoe extracts have more potent anticancer effects than isolated compounds. This suggests that there is potentially a synergistic action between the different active compounds found in mistletoe and that extracts rather than isolated compounds will have more powerful therapeutic benefits [9] [10].

Risks and Side Effects of Mistletoe Therapy

Mistletoe therapy is well-tolerated in most instances. Reported side effects are generally mild. There have been very few serious or life-threatening adverse reactions documented. Some common side effects include [22]:

• Fever
• Chills
• Elevated white blood cell count
• Reaction at injection site
• Hypersensitivity

Less common side effects include:

• Diarrhea
• Vomiting
• Headache
• Low blood pressure
• Low heart rate
• Fainting or passing out
• Increased blood sugar
• Itching
• Rash

When administered in a clinical setting mistletoe extracts appear to be safe. However, there have been some rare cases of severe toxicity and even death when self-administered or from ingesting raw mistletoe. It is important to be aware that the raw plant and berries are poisonous [3].