Mistletoe Extracts - National Cancer Institute

Mistletoe Extracts - National Cancer Institute

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, products 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).
Eurixor.
Helixor.
Isorel (also called Vysorel).
Iscucin.
Lektinol (also called Plenosol).
ABNOBAviscum.
This summary discusses research done mainly with this mistletoe species.

The chemical makeup of mistletoe products varies, depending on many factors, including:

The type of host tree on which the mistletoe plant grows.
The time of year the plant is harvested.
The species of mistletoe.
Whether the extract is fermented or unfermented.
Whether the extract is prepared with homeopathic methods.
The company that makes the product.
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, IscadorQ 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:

Alkaloids.
Viscotoxins.
Lectins.
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:

Have effects on the immune system.
Kill mouse, rat, and human cancer cells in the laboratory.
Protect the DNA in white blood cells in the laboratory, including cells that have been exposed to DNA-damaging chemotherapy drugs.
There is no evidence that mistletoe's effects on the immune system help the body fight cancer.

See the PDQ health professional summary on Mistletoe Extracts for more information on theory.

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 mistletoe?
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 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.

In 2002, the National Center for Complementary and Alternative Medicine (NCCAM), 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. The trial is now closed and the data is being analyzed.

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. At present, at least two U.S. investigators have IND approval to study mistletoe as a treatment for cancer.

The National Cancer Institute's PDQ clinical trials database contains protocol abstracts for clinical studies of mistletoe as a treatment for cancer.

Have any side effects or risks been reported from mistletoe?
Very few bad side effects have been reported from the use of mistletoe extract products. Common side effects include soreness and inflammation at injection sites, headache, fever, and chills. A few cases of severe allergic reactions, including anaphylactic shock, have been reported.

Although mistletoe extracts appear to be safe, mistletoe plants and berries are toxic (poisonous) to humans. Side effects caused by eating mistletoe plants and berries include seizures, slowing of the heart rate, abnormal blood pressure, vomiting, and death. These toxic effects may be more or less severe depending on the amount and the type of mistletoe plant eaten.

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.

At this time, there is not enough evidence to recommend the use of mistletoe as a treatment for cancer except in carefully designed clinical trials. These trials will give more information about whether mistletoe can be useful in treating certain types of cancer