Mistletoe Extracts (PDQ®)
- Mistletoe is a semiparasitic plant that grows on several types of common trees such as apple, oak, pine, and elm. Mistletoe extract has been used since ancient times to treat many ailments (see Question 1).
- Mistletoe is one of the most widely studied complementary and alternative medicine therapies in people with cancer. In certain European countries, preparations made from European mistletoe are among the most prescribed drugs for patients with cancer (see Question 1).
- Mistletoe extract has been shown to kill cancer cells in the laboratory and to affect the immune system. However, there is limited evidence that mistletoe's effects on the immune system help the body fight cancer (see Question 2 and Question 3).
- Mistletoe extracts are usually given by injection under the skin or, less often, into a vein, into the pleural cavity, or into the tumor. (see Question 4).
- Animal studies have suggested that mistletoe may be useful in decreasing the side effects of standard anticancer therapy, such as chemotherapy and radiation (see Question 5).
- A large number of human studies using mistletoe to treat cancer have been done since the early 1960s, but major weaknesses in many of these have raised doubts about their findings (see Question 6).
- Very few harmful side effects have been reported from the use of mistletoe extract (see Question 7).
- The U.S. Food and Drug Administration (FDA) has not approved mistletoe as a treatment for cancer or any other medical condition (see Question 8).
- The FDA does not allow injectable mistletoe to be imported, sold, or used except for clinical research (see Question 8).
Questions and Answers About Mistletoe
What is mistletoe?
Mistletoe is a semiparasitic plant that grows on several types of trees, including apple, oak, maple, elm, pine, and birch. It has been used for centuries to treat medical conditions such as epilepsy, hypertension, headaches, menopausal symptoms, infertility, arthritis, and rheumatism.
Mistletoe is one of the most widely studied complementary and alternative medicine therapies for cancer. In certain European countries, extracts made from European mistletoe are among the most prescribed therapies for cancer patients. These products are made and sold under brand names including:
- Iscador (also called Iscar).
- Lektinol (also called Plenosol).
Brand names including Eurixor, Isorel, and Vysorel are no longer sold.
This summary discusses research done mainly with the European mistletoe species.
The chemical makeup of mistletoe products varies, depending on many factors, including:
Mistletoe extracts are prepared as water-based solutions or solutions of water and alcohol. Mistletoe products may be named according to the type of host tree on which the plant grows. For example, IscadorM is from apple trees, IscadorP comes from pine trees, IscadorQu is from oak trees, and IscadorU comes from elm trees. Some users believe that the type of mistletoe extract chosen should depend on the type of tumor and the sex of the patient.
What is the history of the discovery and use of mistletoe as a complementary or alternative treatment for cancer?
Mistletoe was used by the Druids and the ancient Greeks, and appears in legend and folklore as a panacea or "cure -all". Modern interest in mistletoe as a possible treatment for cancer began in the 1920s.
Extracts of mistletoe have been shown to kill cancer cells in the laboratory and to boost the immune system (the complex group of organs and cells that defends the body against infection or disease). For this reason, mistletoe has been classified as a type of biological response modifier (a substance that stimulates the body's response to infection and disease). Extracts of mistletoe have also been shown in the laboratory to prevent the growth of new blood vessels needed for tumors to grow.
Ingredients in mistletoe that have been studied for their usefulness in treating cancer include:
What is the theory behind the claim that mistletoe is useful in treating cancer?
Mistletoe extract is studied as a possible anticancer agent because it has been shown to:
How is mistletoe administered?
Mistletoe extracts are usually given by injection under the skin (subcutaneous). Less common ways to give mistletoe include by mouth, into a vein (intravenous or IV), into the pleural cavity, or into the tumor. In most reported studies, injections under the skin were given 2 to 3 times a week for various lengths of time.
What preclinical (laboratory or animal) studies have been conducted using mistletoe?
Many laboratory and animal studies have been done with mistletoe, either alone or combined with other agents. Laboratory studies have suggested that mistletoe may support the immune system by increasing the number and activity of various types of white blood cells. One type of European mistletoe (IscadorQu) used in a 2004 laboratory study showed a strong anticancer effect on certain types of cancer cells but no anticancer effect on other types of cancer cells. While one laboratory study reported that mistletoe extract caused several types of human cancer cells to grow faster, this was not found in other recent lab studies.
Studies testing mistletoe's ability to stop cancer cell growth in animals have yielded mixed and inconsistent results, depending on the extract used, the dose tested, the way it was given, and the type of cancer studied. Results of a few animal studies have suggested that mistletoe may be useful in decreasing the side effects of standard anticancer therapy, such as chemotherapy and radiation therapy, and that it counteracts the effects of drugs used to suppress the immune system, such as cortisone.
Have any clinical trials (research studies with people) been conducted using
Most clinical trials using mistletoe to treat cancer have been done in Europe. Most study results have been published in German. Although many of these trials have reported mistletoe to be effective, there are major weaknesses in almost all that raise doubts about their findings. Weaknesses have included small numbers of patients, incomplete patient data, lack of information about mistletoe dose, and problems with study design.
Many studies involve using mistletoe as adjuvant therapy in patients with cancer. One retrospective cohort study done in Europe between 1993 and 2000 looked at the use of a mistletoe extract (Iscador) as long-term adjuvant therapy in 800 patients treated with chemotherapy and/or radiation therapy for colorectal cancer that had not spread. The study found that patients treated with Iscador had fewer adverse events, better symptom relief, and improved disease-free survival compared to patients who did not receive Iscador as adjuvant therapy.
A European study published in 2013 looked at the use of IscadorQu in advanced or metastatic pancreatic cancer. Patients received best supportive care and were randomly assigned to receive either Iscador Qu or no anticancer therapy. Results in 220 patients showed that those treated with Iscador had improved survival and less severe disease-related symptoms (including pain, weight loss, fatigue, nausea, diarrhea, and anxiety) compared with those who did not receive IscadorQu.
A European study done between 1978 and 1987 looked at the use of IscadorU and IscadorQu in non-small cell lung cancer that could not be treated with surgery. Patients were randomly assigned to receive one of 3 treatments: (1) Iscador injections; (2) Polyerga Neu injections (a sheep spleen preparation said to stimulate the immune system and have antitumor effects); or (3) placebo injections of a vitamin B mixture. Results in 312 patients showed no differences among the 3 groups in survival or tumor response. It was noted that more patients in the Iscador group reported an improved sense of well-being compared with patients in the other groups.
Before researchers can conduct clinical drug research in the United States, they must file an Investigational New Drug (IND) application with the Food and Drug Administration (FDA). The FDA does not make information public about IND applications or approvals; this information can be made public only by the applicants. In the last decade, at least two U.S. investigators were given approval to conduct clinical trials of mistletoe as a treatment for people with cancer. These clinical trials are now closed.
In 2002, the National Center for Complementary and Integrative Health (NCCIH), in cooperation with the National Cancer Institute (NCI), began enrolling patients for a phase I clinical trial of a mistletoe extract (Helixor A) and gemcitabine in patients with advanced solid tumors. This combination showed low toxicity and no botanical -drug interactions were reported.
Reviews of many clinical trials combined
Findings from over 50 clinical trials using mistletoe extracts in patients with cancer have been published. Recent reviews of many studies taken together have looked at the effects of mistletoe on quality of life, survival, and symptom relief in different types of cancer:
- Quality of life was measured in a review that included 26 randomized clinical trials. Of these, 22 trials showed patients had improved quality of life. All 10 nonrandomized, controlled clinical trials reviewed also reported the same benefits. Chemotherapy-related fatigue, nausea and vomiting, depression, emotional well-being, and concentration improved. Some of the studies were well designed, while others had weaknesses.
- Tumor response, quality of life, and psychological distress were measured in a review of 21 randomized clinical trials in patients with different types of cancer. A variety of mistletoe extracts were used either alone, with chemotherapy, or with radiation therapy. Most of the studies reported benefits for patients, although this review had weaknesses in design and size.
- Quality of life and survival were measured in a review of 10 randomized clinical trials which used a variety of mistletoe extracts in patients with different types of cancer. There was no difference in survival or quality of life measures in patients who received mistletoe compared to those who did not.
Have any side effects or risks been reported from mistletoe?
One review surveyed many animal and human studies that used European mistletoe and mistletoe lectins. Different doses and ways to give mistletoe were used. Treatment was not found to lessen immune system responses. High doses of mistletoe lectins damaged the liver in some cases; this damage was correctable. Another review of clinical trials reported adverse effects that included increased circulatory problems, thrombophlebitis, swelling of lymph nodes, and allergic reactions.
A few cases of severe allergic reactions, including anaphylactic shock, have been reported.
Is mistletoe approved by the U. S. Food and Drug Administration (FDA) for use as a cancer treatment in the United States?
The United States Food and Drug Administration (FDA) has not approved the use of mistletoe as a treatment for cancer or any other medical condition. The FDA does not allow injectable mistletoe extracts to be imported or used except for clinical research.
Current Clinical Trials
Check the list of NCI-supported cancer clinical trials for cancer CAM clinical trials on mistletoe extract that are actively enrolling patients.
General information about clinical trials is available from the NCI website.
Changes To This Summary (03/24/2015)
Editorial changes were made to this summary
About This PDQ Summary
Physician Data Query (PDQ) is the National Cancer Institute's (NCI's) comprehensive cancer information database. The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries come in two versions. The health professional versions have detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions have cancer information that is accurate and up to date and most versions are also available in Spanish.
PDQ is a service of the NCI. The NCI is part of the National Institutes of Health (NIH). NIH is the federal government’s center of biomedical research. The PDQ summaries are based on an independent review of the medical literature. They are not policy statements of the NCI or the NIH.
Purpose of This Summary
This PDQ cancer information summary has current information about the use of mistletoe extracts in the treatment of people with cancer. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.
Reviewers and Updates
Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change.
The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Cancer Complementary and Alternative Medicine Editorial Board.
Clinical Trial Information
A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Clinical trials are listed in PDQ and can be found online at NCI's website. Many cancer doctors who take part in clinical trials are also listed in PDQ. For more information, call the Cancer Information Service 1-800-4-CANCER (1-800-422-6237).
Permission to Use This Summary
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The best way to cite this PDQ summary is:
National Cancer Institute: PDQ® Mistletoe Extracts. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://www.cancer.gov/about-cancer/treatment/cam/patient/mistletoe-pdq. Accessed <MM/DD/YYYY>.
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General CAM Information
Complementary and alternative medicine (CAM)—also referred to as integrative medicine—includes a broad range of healing philosophies, approaches, and therapies. A therapy is generally called complementary when it is used in addition to conventional treatments; it is often called alternative when it is used instead of conventional treatment. (Conventional treatments are those that are widely accepted and practiced by the mainstream medical community.) Depending on how they are used, some therapies can be considered either complementary or alternative. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease.
Unlike conventional treatments for cancer, complementary and alternative therapies are often not covered by insurance companies. Patients should check with their insurance provider to find out about coverage for complementary and alternative therapies.
Cancer patients considering complementary and alternative therapies should discuss this decision with their doctor, nurse, or pharmacist as they would any therapeutic approach, because some complementary and alternative therapies may interfere with their standard treatment or may be harmful when used with conventional treatment.
Evaluation of CAM Approaches
It is important that the same rigorous scientific evaluation used to assess conventional approaches be used to evaluate CAM therapies. The National Cancer Institute and the National Center for Complementary and Integrative Health (NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to evaluate CAM therapies for cancer.
Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a rigorous scientific process that includes clinical trials with large numbers of patients. Less is known about the safety and effectiveness of complementary and alternative methods. Few CAM therapies have undergone rigorous evaluation. A small number of CAM therapies originally considered to be purely alternative approaches are finding a place in cancer treatment—not as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) in November 1997, acupuncture has been found to be effective in the management of chemotherapy-associated nausea and vomiting and in controlling pain associated with surgery. In contrast, some approaches, such as the use of laetrile, have been studied and found ineffective or potentially harmful.
The NCI Best Case Series Program which was started in 1991, is one way CAM approaches that are being used in practice are being investigated. The program is overseen by the NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM). Health care professionals who offer alternative cancer therapies submit their patients’ medical records and related materials to OCCAM. OCCAM conducts a critical review of the materials and develops follow-up research strategies for approaches deemed to warrant NCI-initiated research.
Questions to Ask Your Health Care Provider About CAM
When considering complementary and alternative therapies, patients should ask their health care provider the following questions:
- What side effects can be expected?
- What are the risks associated with this therapy?
- Do the known benefits outweigh the risks?
- What benefits can be expected from this therapy?
- Will the therapy interfere with conventional treatment?
- Is this therapy part of a clinical trial?
- If so, who is sponsoring the trial?
- Will the therapy be covered by health insurance?
To Learn More About CAM
National Center for Complementary and Integrative Health (NCCIH)
The National Center for Complementary and Integrative Health (NCCIH) at the National Institutes of Health (NIH) facilitates research and evaluation of complementary and alternative practices, and provides information about a variety of approaches to health professionals and the public.
- NCCIH Clearinghouse
- Post Office Box 7923 Gaithersburg, MD 20898–7923
- Telephone: 1-888-644-6226 (toll free)
- TTY (for deaf and hard of hearing callers): 1-866-464-3615
- E-mail: firstname.lastname@example.org
- Website: https://nccih.nih.gov
CAM on PubMed
NCCIH and the NIH National Library of Medicine (NLM) jointly developed CAM on PubMed, a free and easy-to-use search tool for finding CAM-related journal citations. As a subset of the NLM's PubMed bibliographic database, CAM on PubMed features more than 230,000 references and abstracts for CAM-related articles from scientific journals. This database also provides links to the websites of over 1,800 journals, allowing users to view full-text articles. (A subscription or other fee may be required to access full-text articles.)
Office of Cancer Complementary and Alternative Medicine
The NCI Office of Cancer Complementary and Alternative Medicine (OCCAM) coordinates the activities of the NCI in the area of complementary and alternative medicine (CAM). OCCAM supports CAM cancer research and provides information about cancer-related CAM to health providers and the general public via the NCI website.
National Cancer Institute (NCI) Cancer Information Service
U.S. residents may call the NCI Cancer Information Service toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 am to 8:00 pm. A trained Cancer Information Specialist is available to answer your questions.
Food and Drug Administration
The Food and Drug Administration (FDA) regulates drugs and medical devices to ensure that they are safe and effective.
- Food and Drug Administration
- 10903 New Hampshire Avenue
- Silver Spring, MD 20993
- Telephone: 1-888-463-6332 (toll free)
- Website: http://www.fda.gov
Federal Trade Commission
The Federal Trade Commission (FTC) enforces consumer protection laws. Publications available from the FTC include:
- Who Cares: Sources of Information About Health Care Products and Services
- Fraudulent Health Claims: Don’t Be Fooled
- Consumer Response Center
- Federal Trade Commission
- 600 Pennsylvania Avenue, NW
- Washington, DC 20580
- Telephone: 1-877-FTC-HELP (1-877-382-4357) (toll free)
- TTY (for deaf and hard of hearing callers): 202-326-2502
- Website: http://www.ftc.gov