Overview
Questions and Answers About Mistletoe
Changes To This Summary (09/21/2006)
General CAM Information
Evaluation of CAM Approaches
Questions to Ask Your Health Care Provider About CAM
To Learn More About CAM

Overview

• Mistletoe is a plant that grows on several types of trees and has been used since ancient times to treat many ailments (see Question 1 ¹ and Question 2 ²).



• Mistletoe extract has been shown to kill cancer cells in the laboratory and to boost the immune system (see Question 3 ³).



• Animal studies have suggested that mistletoe may be useful in decreasing the side effects of standard anticancer therapy (see Question 5 ⁴).



• Many human studies using mistletoe to treat cancer have been done in Europe with unclear results, and a few clinical trials in the United States and abroad are in progress (see Question 6 ⁵).



• Very few bad side effects have been reported from the use of mistletoe extract, though mistletoe plants and berries are poisonous to humans (see Question 7 ⁶).



• 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 ⁷).



• The FDA does not allow injectable mistletoe to be imported or used except for clinical research (see Question 8 ⁷)

Questions and Answers About Mistletoe

1. 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 used mainly in Europe and Asia, where products are made and sold under brand names including Iscador, Eurixor, Helixor, Isorel, Vysorel, and ABNOBAviscum. Mistletoe products are not sold to consumers in the United States.

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

   • The type of 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.

   This summary discusses research done mainly with a mistletoe species known as Viscum album Loranthaceae.

   Mistletoe extracts are prepared as water-based solutions or solutions of water and alcohol. Mistletoe products may be named according to the type of 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.

2. 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 "cure -all." 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).

   Ingredients in mistletoe that have been studied for their usefulness in treating cancer include:

   • Alkaloids.
   • Viscotoxins.
   • Lectins.

   One of the 4 different lectins, known as ML I (or viscumin), may produce many of mistletoe's effects.

3. 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:

   • Boost the immune system.
   • Kill cancer cells in the laboratory.
   • Protect the DNA in white blood cells, including cells that have been exposed to DNA-damaging chemotherapy drugs.

   Refer to the PDQ health professional summary on Mistletoe Extracts ⁸ for more information on theory.

4. How is mistletoe administered?

   Mistletoe extracts are usually given by injection into the muscle (intramuscular), beneath the skin (subcutaneous), or into a vein (intravenous or IV). In most reported studies, injections under the skin were given 2 to 3 times a week for various lengths of time.

5. Have any preclinical (laboratory or animal) studies been conducted using mistletoe?

   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.

   Animal studies testing mistletoe's ability to stop cancer cell growth have had different 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 may protect the immune system from certain drugs.

6. Have any clinical trials (research studies with people) been conducted using mistletoe?

   Clinical trials using mistletoe to treat cancer have been done in Europe with unclear results. 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.

   Much research about using mistletoe to treat cancer has focused on its effects on the immune system. Although there is evidence that mistletoe can boost the immune system, there is no evidence that this enhanced immunity helps the body to fight cancer cells.

   The National Cancer Institute's PDQ clinical trials database contains protocol abstracts for clinical studies of mistletoe as a treatment for cancer.[1]

7. 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.

8. 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.

References

1. Mansky PJ, National Center for Complementary and Alternative Medicine: Phase I Study of Gemcitabine and Mistletoe in Patients With Advanced Solid Tumors, NCCAM-02-AT-260, Clinical trial, Closed.  [PDQ Clinical Trial] ⁹
   
   

Changes To This Summary (09/21/2006)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

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 (NCI) and the National Center for Complementary and Alternative Medicine (NCCAM) 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) Consensus Conference 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 ¹⁰, 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 Alternative Medicine (NCCAM)

The National Center for Complementary and Alternative Medicine (NCCAM) 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.

NCCAM Clearinghouse

Post Office Box 7923 Gaithersburg, MD 20898–7923

Telephone: 1–888–644–6226 (toll free) 301–519–3153 (for International callers)

TTY (for deaf and hard of hearing callers): 1–866–464–3615

Fax: 1–866–464–3616

E-mail: info@nccam.nih.gov

Web site: http://nccam.nih.gov

CAM on PubMed

NCCAM 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 Web sites 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.) CAM on PubMed is available through the NCCAM Web site ¹¹. It can also be accessed through NLM PubMed ¹² bibliographic database by selecting the "Limits" tab and choosing "Complementary Medicine" as a subset.

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 Web site ¹³.

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 9:00 am to 4:30 pm. Deaf and hearing impaired callers with TTY equipment may call 1-800-332-8615. 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

5600 Fishers Lane

Rockville, MD 20857

Telephone: 1–888–463–6332 (toll free)

Web site: 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

CRC-240

Washington, DC 20580

Telephone: 1-877-FTC-HELP (1-877-382-4357) (toll free)

TTY (for deaf and hearing impaired callers): 202-326-2502

Web site: http://www.ftc.gov/

Glossary Terms

Not normal. An abnormal lesion or growth may be cancerous, premalignant (likely to become cancer), or benign.

A chemical substance found in beer, wine, and liquor. Alcohol is also found in some medicines, mouthwashes, essential oils (scented liquid taken from plants), and household products.

A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer.

A hypersensitive immune reaction to a substance that normally is harmless or would not cause an immune response in most people. An allergic response may cause harmful symptoms such as itching or inflammation or tissue injury.

A severe and sometimes life-threatening immune system reaction to an antigen that a person has been previously exposed to. The reaction may include itchy skin, edema, collapsed blood vessels, fainting, difficulty in breathing, and death.

A laboratory experiment using animals to study the development and progression of diseases. Animal studies also test how safe and effective new treatments are before they are tested in people.

A disease that causes inflammation and pain in the joints.

BRM therapy. Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in biological response modifier therapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called immunotherapy, biological therapy, biotherapy, and BRM therapy.

The force of circulating blood on the walls of the arteries. Blood pressure is taken using two measurements: systolic (measured when the heart beats, when blood pressure is at its highest) and diastolic (measured between heart beats, when blood pressure is at its lowest). Blood pressure is written with the systolic blood pressure first, followed by the diastolic blood pressure (for example 120/80).

A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Treatment with drugs that kill cancer cells.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical trial.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical study.

To heal or restore health; a treatment to restore health.

Deoxyribonucleic acid. The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

The amount of medicine taken, or radiation given, at one time.

A group of disorders marked by problems in the normal functioning of the brain. These problems can produce seizures, unusual body movements, a loss of consciousness or changes in consciousness, as well as mental problems or problems with the senses.

In medicine, a preparation of a substance obtained from plants, animals, or bacteria and used as a drug or in drugs.

An increase in body temperature above normal (98.6 degrees F), usually caused by disease.

FDA. An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The Food and Drug Administration also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called FDA.

An alternative approach to medicine based on the belief that natural substances, prepared in a special way and used most often in very small amounts, restore health. According to these beliefs, in order for a remedy to be effective, it must cause in a healthy person the same symptoms being treated in the patient. Also called homeopathy.

A blood pressure of 140/90 or higher. Hypertension usually has no symptoms. It can harm the arteries and cause an increase in the risk of stroke, heart attack, kidney failure, and blindness. Also called high blood pressure.

The complex group of organs and cells that defends the body against infections and other diseases.

Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.

The inability to produce children.

Redness, swelling, pain, and/or a feeling of heat in an area of the body. This is a protective reaction to injury, disease, or irritation of the tissues.

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

IM. Within or into muscle. Also called IM.

Into or within a vein. Intravenous usually refers to a way of giving a drug or other substance through a needle or tube inserted into a vein. Also called I.V.

Research done in a laboratory. These studies may use test tubes or animals to find out if a drug, procedure, or treatment is likely to be useful. Laboratory studies take place before any testing is done in humans.

The time of life when a woman's menstrual periods stop. A woman is in menopause when she hasn't had a period for 12 months in a row. Also called change of life.

A semiparasitic plant that grows on some types of trees. Mistletoe extracts are being studied as treatments for cancer.

A substance that comes from the mistletoe plant and that is being studied as a treatment for cancer. A lectin is a complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants.

A part of the body that performs a specific function. For example, the heart is an organ.

PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI's Web site at http://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.

An action plan for a clinical trial. The plan states what the study will do, how, and why. It explains how many people will be in it, who is eligible to participate, what study agents or other interventions they will be given, what tests they will receive and how often, and what information will be gathered.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called radiotherapy and irradiation.

A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat.

Convulsion; a sudden, involuntary movement of the muscles.

In botany, a plant that gets food from a host but also contains chlorophyll and is capable of photosynthesis.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called standard of care or best practice.

Beneath the skin.

An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

Treatment.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.

A member of a group of small proteins produced by mistletoe plants that are able to kill cells and may stimulate the immune system.

To eject some or all of the contents of the stomach through the mouth.

Refers to a blood cell that does not contain hemoglobin. White blood cells include lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. These cells are made by bone marrow and help the body fight infections and other diseases. Also called WBC.