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, where 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.

   All of these products are prepared from a mistletoe species known as Viscum album Loranthaceae (Viscum album L. or European mistletoe). Some of the products have been approved for medical uses in Europe. 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.

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 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).

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

   • Alkaloids.
   • Viscotoxins.
   • Lectins.
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:

   • 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 ¹ for more information on theory.

4. 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), or into the pleural cavity. In most reported studies, injections under the skin were given 2 to 3 times a week for various lengths of time.

5. 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.

6. 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.

   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. 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 ² contains protocol abstracts for clinical studies of mistletoe as a treatment for cancer.

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.

Glossary Terms

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

Cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment.

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.

Having to do with the examination and treatment of patients.

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.

A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses.

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.

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

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.

A drug that is used to treat certain types of breast cancer, pancreatic cancer, ovarian cancer, and lung cancer and is being studied in the treatment of other types of cancer. Gemcitabine is a type of antimetabolite. Also called gemcitabine hydrochloride and Gemzar.

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."

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.

A researcher in a clinical trial or clinical study.

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.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

NCCAM. A federal agency that uses science to explore complementary and alternative medicine (CAM) practices, trains CAM researchers, and provides authoritative information about CAM to professionals and the public. NCCAM awards grants for research projects, training, and career development in CAM; sponsors conferences, educational programs, and exhibits; studies ways to use proven CAM practices along with conventional medical practice; and supports adding CAM to medical, dental, and nursing school programs. NCCAM is part of the National Institutes of Health. Also called NCCAM.

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.

The first step in testing a new treatment in humans. These studies test the best way to give a new treatment (for example, by mouth, intravenous infusion, or injection) and the best dose. The dose is usually increased a little at a time in order to find the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of the treatments being tested, phase I trials usually include only a small number of patients who have not been helped by other treatments.

The space enclosed by the pleura, which is a thin layer of tissue that covers the lungs and lines the interior wall of the chest cavity.

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.

An abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors may be benign (not cancerous), or malignant (cancerous). Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, and lymphomas. Leukemias (cancers of the blood) generally do not form solid tumors.

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.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancerous), or malignant (cancerous). Also called neoplasm.

A blood vessel that carries blood to the heart from tissues and organs in the body.

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.