Co-Q10 And Cancer

Coenzyme Q10 in Cancer Therapy

Overview

This complementary and alternative medicine (CAM) information summary provides an overview of the use of coenzyme Q10 in cancer therapy. The summary includes a history of coenzyme Q10 research, a review of laboratory studies, and data from investigations involving humans.

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 CAM summary. A glossary of scientific terms used in the summary appears just before the references. Terms defined in the glossary are marked in the text by hypertext links.
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 United States, dietary supplements are regulated as foods not drugs. Therefore, premarket evaluation and approval by the Food and Drug Administration (FDA) are not required unless health claims are made. Because dietary supplements are not formally reviewed for manufacturing consistency, there may be considerable variation from lot to lot.

To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. Since the existence of an IND application is often highly confidential, it is not known whether one has been submitted or approved for the study of coenzyme Q10 as a treatment for cancer.

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 Denmark followed 32 breast cancer patients for 18 months.[28] The disease in these patients had spread to the axillary lymph nodes, and an unreported number had distant metastases.

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 CAM treatments for cancer, the strength of the evidence (i.e., the "levels of evidence") associated with each type of treatment is provided whenever possible.

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 CAM treatments for cancer, please click on the following link: Levels of Evidence Analysis for Human Studies of Cancer Complementary and Alternative Medicine.

Angstrom Minerals Product And Price List

The information on this page has been extracted from http://www.mercola.com/2000/sep/10/coq10_cancer.htm