This may have a role to play in multiple myeloma, see below:
“Low blood levels of this compound have been reported in patients with malignancies other than breast cancer, including myeloma, lymphoma, and cancers of the lung, prostate, pancreas, colon, kidney, and head and neck. [12,13 reviewed in 31]”
Co-enzyme Q10 in Cancer Therapy
Overview
This complementary and alternative medicine (
Although several naturally occurring forms of coenzyme Q have been identified, Q10 is the predominant form found in humans and most mammals, and it is the form most studied for therapeutic potential. Thus, it will be the only form of coenzyme Q discussed in this
General Information
Coenzyme Q10 (also known as Co Q10,Q10, vitamin Q10, ubiquinone, or ubidecarenone) is a benzoquinone compound synthesized naturally in the human body. The “Q” and the “10” in the name refer to the quinone chemical group and the 10 isoprenyl chemical subunits, respectively, that are part of this compound’s structure.
The term “coenzyme” denotes it as an organic (contains carbon atoms), nonprotein molecule necessary for the proper functioning of its protein partner (an enzyme or an enzyme complex). Coenzyme Q10 is used by cells of the body in a process known variously as aerobic respiration, aerobic metabolism, oxidative metabolism, or cell respiration.
Through this process, energy for cell growth and maintenance is created inside cells in compartments called mitochondria.[reviewed in 1-4] Coenzyme Q10 is also used by the body as an endogenous antioxidant.[reviewed in 1,2,4,5,7-9]
An antioxidant is a substance that protects cells from free radicals, which are highly reactive chemicals, often containing oxygen atoms, capable of damaging important cellular molecules such as DNA and lipids. In addition, the plasma level of coenzyme Q10 has been used, in studies, as a measure of oxidative stress (a situation in which normal antioxidant levels are reduced).[10,11]
Coenzyme Q10 is present in most tissues, but the highest concentrations are found in the heart, liver, kidneys, and pancreas.[6] The lowest concentration is found in the lungs.[6] Tissue levels of this compound decrease as people age, due to increased requirements, decreased production,[6] or insufficient intake of the chemical precursors needed for synthesis.[reviewed in 12] In humans, normal blood levels of coenzyme Q10 have been defined variably, with reported values ranging from 0.30 to 3.84 micrograms per milliliter.[13,14,reviewed in 2,4]
Given the importance of coenzyme Q10 to optimal cellular energy production, use of this compound as a treatment for diseases other than cancer has been investigated. Most of these investigations have focused on coenzyme Q10 as a treatment for cardiovascular disease.[15,reviewed in 2,4]
In patients with cancer, coenzyme Q10 has been shown to protect the heart from anthracycline-induced cardiotoxicity (anthracyclines are a family of chemotherapy drugs, including doxorubicin, that have the potential to damage the heart) [3,16-18] and to stimulate the immune system.[19, reviewed in 20]
Stimulation of the immune system by this compound has also been observed in animal studies and in humans without cancer.[21-27] In part because of its immunostimulatory potential, coenzyme Q10 has been used as an adjuvant therapy in patients with various types of cancer.[17,28,29,30, reviewed in 20,31-33]
While coenzyme Q10 may show indirect anticancer activity through its effect(s) on the immune system, there is evidence to suggest that analogs of this compound are able to suppress cancer growth directly.
Analogs of coenzyme Q10 have been shown to inhibit the proliferation of cancer cells in vitro and the growth of cancer cells transplanted into rats and mice.[12,34] In view of these findings, it has been proposed that analogs of coenzyme Q10 may function as antimetabolites to disrupt normal biochemical reactions that are required for cell growth and/or survival and, thus, that they may be useful for short periods of time as chemotherapeutic agents.[12,34]
Several companies distribute coenzyme Q10 as a dietary supplement. In the
To conduct clinical drug research in the
In animal studies, coenzyme Q10 has been administered by injection (intravenous, intraperitoneal, intramuscular, or subcutaneous). In humans, it is usually taken orally as a pill (tablet or capsule), but intravenous infusions have been given.[4] Coenzyme Q10 is absorbed best with fat; therefore, lipid preparations are better absorbed than the purified compound.[reviewed in 2,4] In human studies, supplementation doses and administration schedules have varied, but usually have been in the range of 90 to 390 milligrams per day.
History
Coenzyme Q10 was first isolated in 1957,[reviewed in 2] and its chemical structure (benzoquinone compound) was determined in 1958. [reviewed in 13] Interest in coenzyme Q10 as a therapeutic agent in cancer began in 1961, when a deficiency was noted in the blood of both Swedish and American cancer patients, especially in the blood of patients with breast cancer.[13, reviewed in 30,32]
A subsequent study showed a statistically significant relationship between the level of plasma coenzyme Q10 deficiency and breast cancer prognosis.[14] Low blood levels of this compound have been reported in patients with malignancies other than breast cancer, including myeloma, lymphoma, and cancers of the lung, prostate, pancreas, colon, kidney, and head and neck.[12,13 reviewed in 31] Furthermore, decreased levels of coenzyme Q10 have been detected in malignant human tissue,[35-38] but increased levels have been reported as well.[35]
A large amount of laboratory and animal model data on coenzyme Q10 has accumulated since 1962.[reviewed in 13] Research into cellular energy producing mechanisms involving this compound was awarded the Nobel Prize in chemistry in 1978.
Some of the accumulated data show that coenzyme Q10 stimulates animal immune systems, leading to higher antibody levels,[21] greater numbers and/or activities of macrophages and T cells (T lymphocytes),[21,23] and increased resistance to infection.[24-26] Coenzyme Q10 has also been reported to increase IgG (immunoglobulin G) antibody levels and to increase the CD4 to CD8 T-cell ratio in humans.[19,22,27] CD4 and CD8 are proteins found on the surface of T cells, with CD4 and CD8 identifying “helper” T cells and “cytotoxic T cells”, respectively; decreased CD4 to CD8 T-cell ratios have been reported for cancer patients.[39,40] Research subsequently delineated the antioxidant properties of coenzyme Q10.[10,11, reviewed in1,4,6]
Proposed mechanisms of action for coenzyme Q10 that are relevant to cancer include its essential function in cellular energy production and its stimulation of the immune system (the two of which may be related), as well as its role as an antioxidant.
Coenzyme Q10 is essential to aerobic energy production,[reviewed in 1-3] and it has been suggested that increased cell energy may lead to increased antibody synthesis in B cells (B lymphocytes).[12,19] As noted previously (General Information section), coenzyme Q10 can also behave as an antioxidant.[reviewed in 1,2,4-9]
In this capacity, coenzyme Q10 is thought to stabilize cell membranes (lipid-containing structures essential to maintaining cell integrity) and to prevent free radical damage to other important cellular components.[reviewed in 1,2,6,9] Free radical damage to DNA (and possibly to other cellular molecules) may be a factor in cancer development.[reviewed in 7,10,38,41-44]
Laboratory/Animal/Preclinical Studies
Laboratory work on coenzyme Q10 has focused primarily on its structure and its function in cell respiration. Studies in animals have demonstrated that coenzyme Q10 is capable of stimulating the immune system, with treated animals showing increased resistance to protozoal infections [25,26] and to viral and chemically induced neoplasia.[24-26, reviewed in 13]
Early studies of coenzyme Q10 showed increased hematopoiesis (the formation of new blood cells) in monkeys,[reviewed in 13,17] rabbits,[45] and poultry.[reviewed in 17] Coenzyme Q10 demonstrated a protective effect on the heart muscle of mice, rats, and rabbits given the anthracycline anticancer drug doxorubicin.[46-51] Although another study confirmed this protective effect with intraperitoneal administration of doxorubicin in mice, it failed to demonstrate a protective effect when the anthracycline was given intravenously, which is the route of administration in humans.[52]
Researchers in one study sounded a cautionary note when they found that coadministration of coenzyme Q10 and radiation therapy decreased the effectiveness of the radiotherapy.[53] In this study, mice inoculated with human small cell lung cancer cells (a xenograft study), and then given coenzyme Q10 and single-dose radiation therapy, showed substantially less inhibition of tumor growth than mice in the control group that received radiotherapy alone.
Since radiation leads to the production of free radicals, and since antioxidants protect against free radical damage, the effect in this study might be explained by coenzyme Q10 acting as an antioxidant. As noted previously (General Information section), there is some evidence from laboratory and animal studies that analogs of coenzyme Q10 may exhibit direct anticancer activity.[12,34]
Human/Clinical Studies
The use of coenzyme Q10 as a treatment for cancer in humans has been investigated in only a limited fashion. With the exception of a single randomized trial,[18] which involved 20 patients and tested the ability of coenzyme Q10 to reduce anthracycline-induced cardiotoxicity, the studies that have been published consist of anecdotal reports, case reports, case series, and uncontrolled clinical studies.[3,16,17,28-30, reviewed in 20,31-33]
In view of the promising results from animal studies, coenzyme Q10 was tested as a protective agent against the cardiac toxicity observed in cancer patients treated with the anthracycline drug doxorubicin.
It has been postulated that doxorubicin interferes with energy generating biochemical reactions involving coenzyme Q10 in heart muscle mitochondria and that this interference can be overcome by coenzyme Q10 supplementation.[16,51,54] Studies with adults and children, including the aforementioned randomized trial, have confirmed the decrease in cardiac toxicity observed in animal studies.[3,16-18]
The potential of coenzyme Q10 as an adjuvant therapy for cancer has also been explored. In view of observations that blood levels of coenzyme Q10 are frequently reduced in cancer patients,[12,13, reviewed in 30-32] supplementation with this compound has been tested in patients undergoing conventional treatment.
An open-label (nonblinded), uncontrolled clinical study in
The patients received antioxidant supplementation (vitamin C, vitamin E, and beta-carotene), other vitamins and trace minerals, essential fatty acids, and coenzyme Q10 (at a dose of 90 milligrams per day), in addition to standard therapy (surgery, radiation therapy, and chemotherapy, with or without tamoxifen). The patients were seen every 3 months to monitor disease status (progressive disease or recurrence), and, if there was a suspicion of recurrence, mammography, bone scan, x-ray, or biopsy was performed.
The survival rate for the study period was one hundred percent (four deaths were expected). Six patients were reported to show some evidence of remission; however, incomplete clinical data were provided, and information suggestive of remission was presented for only three of the six patients.
None of the six patients had evidence of further metastases. For all 32 patients, decreased use of painkillers, improved quality of life, and an absence of weight loss were reported. Whether painkiller use and quality of life were measured objectively (e.g., from pharmacy records and validated questionnaires, respectively) or subjectively (from patient self-reports) was not specified.
In a follow-up study, one of the six patients with a reported remission and a new patient were treated for several months with higher doses of coenzyme Q10 (390 and 300 milligrams per day, respectively).[29] Surgical removal of the primary breast tumor in both patients had been incomplete.
After 3 to 4 months of high-level coenzyme Q10 supplementation, both patients appeared to experience complete regression of their residual breast tumors (assessed by clinical examination and mammography). It should be noted that a different patient identifier was used in the follow-up study for the patient who had participated in the original study.
Therefore, it is impossible to determine which of the six patients with a reported remission took part in the follow-up study. In the follow-up study report, the researchers noted that all 32 patients from the original study remained alive at 24 months of observation, whereas six deaths had been expected.[29]
In another report by the same investigators, three breast cancer patients were followed for a total of 3 to 5 years on high-dose coenzyme Q10 (390 milligrams per day).[30] One patient had complete remission of liver metastases (assessed by clinical examination and ultrasonography [echogram]), another had remission of a tumor that had spread to the chest wall (assessed by clinical examination and chest X-ray), and the third had no microscopic evidence of remaining tumor after a mastectomy (assessed by biopsy of the tumor bed).
All three of the above-mentioned human studies [28-30] had important design flaws that could have influenced their outcome. Study weaknesses include the absence of a control group (i.e., all patients received coenzyme Q10), possible selection bias in the follow-up investigations, and multiple confounding variables (i.e., the patients received a variety of supplements in addition to coenzyme Q10, and they received standard therapy either during or immediately before supplementation with coenzyme Q10).
Thus, it is impossible to determine whether any of the beneficial results was directly related to coenzyme Q10 therapy.
Anecdotal reports of coenzyme Q10 lengthening the survival of patients with pancreatic, lung, rectal, laryngeal, colon, and prostate cancers also exist in the peer-reviewed, scientific literature.[17] The patients described in these reports also received therapies other than coenzyme Q10, including chemotherapy, radiation therapy, and surgery.
Adverse Effects
No serious toxicity associated with the use of coenzyme Q10 has been reported.[reviewed in 2,4,33,55] Doses of 100 milligrams per day or higher have caused mild insomnia in some individuals. [reviewed in 2] Liver enzyme elevation has been detected in patients taking doses of 300 milligrams per day for extended periods of time, but no liver toxicity has been reported.[reviewed in 2]
Researchers in one cardiovascular study reported that coenzyme Q10 caused rashes, nausea, and epigastric (upper abdominal) pain that required withdrawal of a small number of patients from the study.[15] Other reported side effects have included dizziness, photophobia (abnormal visual sensitivity to light), irritability,[15] headache, heartburn, and fatigue.[56]
Certain lipid-lowering drugs, such as the “statins” (lovastatin, pravastatin, and simvastatin) and gemfibrozil, as well as oral agents that lower blood sugar, such as glyburide and tolazamide, cause a decrease in serum levels of coenzyme Q10 and reduce the effects of coenzyme Q10 supplementation.[57,58, reviewed in 2,59] Beta-blockers (drugs that slow the heart rate and lower blood pressure) can inhibit coenzyme Q10-dependent enzyme reactions.[reviewed in 2]
The contractile force of the heart in patients with high blood pressure can be increased by coenzyme Q10 administration.[reviewed in 2] Coenzyme Q10 can reduce the body’s response to the anticoagulant drug warfarin.[reviewed in 59] Finally, coenzyme Q10 can decrease insulin requirements in individuals with diabetes.[reviewed in 59]
Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine
To assist readers in evaluating the results of human studies of
To qualify for a levels of evidence analysis, a study must 1) be published in a peer-reviewed, scientific journal; 2) report on a therapeutic outcome(s), such as tumor response, improvement in survival, or measured improvement in quality of life; and 3) describe clinical findings in sufficient detail that a meaningful evaluation can be made.
Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score.
A table showing the levels of evidence scores for qualifying human studies cited in this summary is presented below. For an explanation of the scores and additional information about levels of evidence analysis of
Glossary of Terms
adjuvant therapy: Treatment given following the primary treatment to enhance the effectiveness of the primary treatment. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy.
aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present.
aerobic metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration.
aerobic respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism.
analog: In chemistry, a substance that is similar, but not identical, to another.
anecdotal report: An incomplete description of the medical and treatment history of one or more patients. Anecdotal reports may be published in places other than peer-reviewed, scientific journals.
animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models.
anthracycline: A member of a family of anticancer drugs that are also antibiotics.
antibody: A type of protein produced by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies disable antigens directly. Others make the antigen more vulnerable to destruction by white blood cells.
anticoagulant: A drug that helps prevent blood clots from forming. Also called blood thinners.
antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction.
antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation.
axillary: Pertaining to the armpit.
biopsy: The removal of cells or tissues for examination under a microscope. When only a sample of tissue is removed, the procedure is called an incisional biopsy or core biopsy. When an entire tumor or lesion is removed, the procedure is called and excisional biopsy. When a sample of tissue or fluid is removed with a needle, the procedure is called a needle biopsy or fine-needle aspiration.
bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream. It collects in bones and is detected by a scanner.
B cells: White blood cells that develop from bone marrow and produce antibodies. Also called B lymphocytes.
cardiac: Having to do with the heart.
cardiotoxicity: Toxicity that affects the heart.
cardiovascular: Having to do with the heart and blood vessels.
case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin).
case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment.
catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made.
cell respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, aerobic metabolism, or aerobic respiration.
chemotherapy: Treatment with anticancer drugs.
complementary and alternative medicine:
cytotoxic T cells: A type of white blood cell that can directly destroy specific cells. T cells can be separated from other blood cells and grown in the laboratory and then given to the person to destroy tumor cells. Certain cytokines can also be given to people to assist in the formation of cytotoxic T cells within the person’s body.
endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production.
enzyme: A protein that speeds up the rate at which chemical reactions take place in the body.
epigastric: Having to do with the upper middle area of the abdomen.
free radicals: Highly reactive chemicals that often contain oxygen and are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. Free radicals can damage important cellular molecules such as DNA or lipids or other parts of the cell.
hematopoiesis: The forming of new blood cells.
immunoglobulin: A protein that functions as an antibody.
in vitro: In the laboratory (outside the body). The opposite of in vivo (in the body).
infusion: The introduction of a fluid, including drugs, into the bloodstream. Also called intravenous infusion.
insomnia: Inability to obtain adequate sleep.
intramuscular: IM. Within or into muscle.
intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs).
intravenous: IV. Into a vein.
laryngeal: Refers to the larynx.
lipids: Fats.
lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and they contain many lymphocytes, which filter the lymphatic fluid (lymph).
lymphocytes: White blood cells. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases.
macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells.
mammography: An x-ray study of the breast.
mastectomy: Surgery to remove the breast (or as much of the breast tissue as possible).
metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called “secondary tumors,” and contain cells that are like those in the original (primary) tumor. The plural is metastases.
mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place.
molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms.
nasal: By or having to do with the nose.
neoplasia: Abnormal and uncontrolled cell growth.
nonblinded: Describes a clinical trial or other experiment in which the researchers know what treatments are being given to each study subject or experimental group. If human subjects are involved, they know what treatments they are receiving.
oral: By or having to do with the mouth.
oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism.
oxidative stress: A condition in which antioxidant levels are lower than normal. Antioxidant levels are usually measured in blood plasma.
pancreas: A glandular organ located in the abdomen. It makes pancreatic juices, which contain enzymes that aid in digestion, and it produces several hormones, including insulin. The pancreas is surrounded by the stomach, intestines, and other organs.
pancreatic: Having to do with the pancreas.
photophobia: A condition in which the eyes are more sensitive to light than normal.
plasma: The clear, yellowish, fluid portion of the blood in which blood cells are suspended. The proteins that form blood clots are present in plasma.
prognosis: The likely outcome or course of a disease; the chance of recovery.
progressive disease: Cancer that is increasing in scope or severity.
protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope.
ptosis: Drooping of the upper eyelid.
radiation therapy: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials (radioisotopes) that produce radiation that are placed in or near a tumor or in the area where cancer cells are found (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy involves giving a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy.
randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments. Neither the researcher nor the participant can choose the group. Using chance to assign people means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it not known which of the treatments is best. It is the patient’s choice to be in a randomized trial or not.
rectal: By or having to do with the rectum, which is the last 8 to 10 inches of the large intestine ending at the anus.
recurrence: The return of cancer, at the same site as the original (primary) tumor or in another location, after it had disappeared.
regression: A decrease in the extent or size of cancer.
remission: Disappearance of the signs and symptoms of cancer. When this happens, the disease is said to be “in remission.” A remission may be temporary or permanent.
selection bias: An error in choosing the individuals or groups to take part in a study. Ideally, the subjects in a study should be very similar to one another and to the larger population (for example, all individuals with the same disease or condition) from which they are drawn. If there are important differences, the results of the study may not be valid.
serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed.
small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer.
subcutaneous: Beneath the skin.
tamoxifen: An anticancer drug that belongs to the family of drugs called antiestrogens. Tamoxifen blocks the effects of the hormone estrogen in the body. It is used to prevent or delay the return of breast cancer or to control its spread.
T cell: One type of white blood cell that attacks virus-infected cells, foreign cells, and cancer cells. They also produce a number of substances that regulate the immune response.
ultrasonography: A study in which sound waves (called ultrasound) are bounced off tissues and the echoes are converted into a picture (sonogram).
uncontrolled clinical study: A clinical study that lacks a comparison (i.e., control) group.
xenograft: The cells of one species transplanted to another species.
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For more information on complementary and alternative therapies, contact the NIH National Center for Complementary and Alternative Medicine (NCCAM):
NCCAM Clearinghouse
Post Office Box 8218
Silver Spring, MD 20907-8218
TTY/TDY: 1-888-644-6226 (toll free)
Additional information is available in the NCI Cancer Facts sheet Questions and Answers About Complementary and Alternative Medicine in Cancer Treatment.
Date Last Modified: 06/2000
Important: This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
This report can be found at: http://cancernet.nci.nih.gov/cam/Q10.htm