Mistletoe is a hemi- parasitic plant belonging to the family Santalales. It grows on the branches of several trees like apple, elm, oak, pine, poplar, and spruce, etc. It is considered to be an important medicinal herb and has been traditionally used to treat many types of cancers, especially breast and gynecological cancers. In Europe, extracts of European mistletoe (Viscum album Loranthacea) have been used as complementary medications along with conventional cancer therapy. It is said to improve the host’s immune system, improve survival after cancer therapy, enhance the quality of life and reduce the adverse reactions to chemotherapy and radiation therapy.
A systematic review of the various case controlled studies and the randomized clinical trials done on the efficacy of mistletoe extracts have shown consistent improvement in the fatigue associated with the chemotherapy as well as improvement in other measures of the quality of life.
Important biological compounds present in European mistletoe
European mistletoe contains a variety of biologically active compounds, the most important of which are lectins. Mistletoe lectins consist of two polypeptide chains:
- A carbohydrate binding B-chain which enables proteins to enter cells by binding with the receptors present on the surface of the cells.
- A catalytic A-chain which inactivates the ribosomes by removing an adenine residue from the 28S RNA of the 60S subunit of the ribosome and thus, inhibits the protein synthesis.
European mistletoe contains another important compounds called as viscotoxins, which are small proteins that have a stimulatory effect on the immune system and a cytotoxic action on the cancer cells.
Apart from lectins and viscotoxins, European mistletoe contains Viscum album chitin binding agglutinin, several oligosaccharides and polysaccharides, flavonoids, vesicles and triterpene acids which possess a strong apoptosis inducing effect. They enhance the cytotoxic actions of various anticancer drugs and stimulate the immune system by activating monocytes/macrophages, granulocytes, natural killer (NK) cells, T-cells, dendritic cells, and inducing a variety of cytokines such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, GM-CSF, TNF-?, IFN-?. Because of its immuno-stimulatory action, European mistletoe is classified as a Biological response modifier.
Commercial preparations of mistletoe
Extracts from European mistletoe are available in the European markets under the brand names of Iscador, Eurixor, Helixor, Isorel, Iscucin, Plenosol, and ABNOBAviscum. The composition of these extracts varies, depending upon the species of the host tree, the time of the year when the herb is harvested, the method of preparing the extract and lastly, upon the commercial producer. These extracts are usually marketed in the form of injectable prescription drugs.
Mistletoe improves survival time of breast cancer patients
Mistletoe is the most commonly used anti- cancer drug in Germany. A large, prospective cohort study was undertaken there to determine whether treatment with Iscador (commercially available extract of European mistletoe) prolongs survival time in patients with cancer of colon, rectum, stomach, breast cancer with or without to axillary or distant metastasis, or bronchogenic carcinoma. The researches also tried to find out any relationship between treatment with Iscador and self regulation of the cancer. The study included 10, 226 cancer patients, of which 1668 were treated with Iscador, while 8475 patients received only conventional cancer therapy. The researchers found that the mean survival time in patients who received Iscador was 40% longer than the control groups. Patients receiving Iscador exhibited good self regulation of the cancer (56% relative to the control group) which led to a longer survival time.
Patients receiving mistletoe in addition to conventional therapy report fewer side effects
Another study was carried out to compare the efficacy and safety of long term complementary therapy with standardized European mistletoe extract (Iscador) in addition to the conventional cancer therapy in patients of primary, non- metastatic breast cancer, with a control group consisting of patients who received only conventional therapy. The multicenter, pharmaco-epidemiological study involved administering mistletoe extract subcutaneously to the test group for three months apart from the regular conventional therapy. The patients were followed up for at least 3 years or until death, whichever was earlier. At the beginning of the study, the patients from the test group had a more advanced disease with a poorer prognosis. At the end of the study, it was seen that significantly fewer number of patients who received mistletoe developed adverse drug reactions to conventional therapy compared to patients who received only conventional therapy. The symptoms related to breast cancer disappeared faster in the test group and overall mortality hazard was lowered.
Mistletoe improves the quality of life during chemotherapy for breast cancer
Another large Cochrane study was undertaken to determine the effectiveness, tolerability and safety of mistletoe when used alone or in conjunction with other therapies to treat cancer. It involved a meta-analysis of twenty one studies, of which 13 provided data on patient survival, 7 on the response of the tumor, 16 on the quality of life, and 12 on the side effects of mistletoe. The meta-analysis covered 3484 cancer patients in all. The researchers concluded that mistletoe extracts offer benefits on measures of quality of life during chemotherapy for breast cancer.
Side effects of mistletoe therapy
Despite the many beneficial effects that mistletoe therapy has to offer, its use is limited because of the adverse reactions caused by it. It can cause soreness and inflammation at injection site apart from mild headache, lymphadenopathy, fever with chills, and transient flu like symptoms. However, in certain sensitive patients, mistletoe can even cause anaphylactic shock. The side effects are usually dose related and depend upon the type of mistletoe plant from which the extract has been taken.
However, keeping in view the various side effects that mistletoe can cause, and in the absence of studies that firmly establish its efficacy, the U.S. government has not recommended its use by the general public. Although, multiple studies have been carried out to establish the beneficial effect of mistletoe in cancer treatment, most of these studies have had one or many major weaknesses and hence, there have been doubts about their reliability. Either the number of patients involved in the studies has been small, or there was failure to document the exact amount and duration of mistletoe use. Many studies have lacked control subjects or used historical control subjects or have measured mean survival period instead of the recommended median survival period.
Further clinical studies which prescribe to the different procedures required while performing such studies are the need of the hour. It is only when the results of these studies are suitably reliable that they will become commercially available to all the cancer patients.