Coenzyme Q10 and cancer

Summary of key points

• Coenzyme Q10 is made naturally by the human body.
• Coenzyme Q10 helps cells to produce energy, and it acts as an antioxidant.
• Coenzyme Q10 has shown an ability to stimulate the immune system and to protect the heart from damage caused by certain chemotherapy drugs.
• Low blood levels of coenzyme Q10 have been detected in patients with some types of cancer.
• No report of a randomized clinical trial of coenzyme Q10 as a treatment for cancer has been published in a peer-reviewed, scientific journal.
• Coenzyme Q10 is marketed in the United States as a dietary supplement.

Properties of Co-Q10

Coenzyme Q10 (also known as CoQ10, Q10, vitamin Q10, ubiquinone, and ubidecarenone) is a benzoquinone compound synthesized naturally by 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. Coenzyme Q10 is also used by the body as an endogenous antioxidant. 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 components 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).

Coenzyme Q10 is present in most tissues, but the highest concentrations are found in the heart, the liver, the kidneys, and the pancreas. The lowest concentration is found in the lungs. Tissue levels of this compound decrease as people age, due to increased requirements, decreased production, or insufficient intake of the chemical precursors needed for synthesis. In humans, normal blood levels of coenzyme Q10 have been defined variably, with reported normal values ranging from 0.30 to 3.84 µg/mL.

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 explored. Most of these investigations have focused on coenzyme Q10 as a treatment for cardiovascular disease. 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 and to stimulate the immune system. Stimulation of the immune system by this compound has also been observed in animal studies and in humans without cancer.In part because of its immunostimulatory potential, coenzyme Q10 has been used as an adjuvant therapy in patients with various types of cancer.

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 can 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.

Several companies distribute coenzyme Q10 as a dietary supplement. In the United States, dietary supplements are regulated as foods, not drugs. It should be noted that the FDA has not approved coenzyme Q10 for the treatment of cancer or any other medical condition.

To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. The IND application process is highly confidential, and IND information can be disclosed only by the applicants. To date, no investigators have announced that they have applied for an IND to study 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. Coenzyme Q10 is absorbed best with fat; therefore, lipid preparations are better absorbed than the purified compound. In human studies, supplementation doses and administration schedules have varied, but usually have been in the range of 90 to 390 mg/day.

History of Co-Q10

Coenzyme Q10 was first isolated in 1957, and its chemical structure (benzoquinone compound) was determined in 1958. 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. A subsequent study showed a statistically significant relationship between the level of plasma coenzyme Q10 deficiency and breast cancer prognosis. 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. Reviewed in Furthermore, decreased levels of coenzyme Q10 have been detected in malignant human tissue, but increased levels have been reported as well.

A large amount of laboratory and animal data on coenzyme Q10 has accumulated since 1962. Research into cellular energy-producing mechanisms that involve 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, greater numbers and/or activities of macrophages and T cells (T lymphocytes),and increased resistance to infection. 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. 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. Research subsequently delineated the antioxidant properties of coenzyme Q10.

How co-Q10 works with cancer

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 (which may both be related), as well as its role as an antioxidant. Coenzyme Q10 is essential to aerobic energy production, and it has been suggested that increased cellular energy leads to increased antibody synthesis in B cells (B lymphocytes).As noted previously (above section), coenzyme Q10 can also behave as an antioxidant. 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. ree radical damage to DNA (and possibly to other cellular molecules) may be a factor in cancer development.

Human/Clinical Studies

The use of coenzyme Q10 as a treatment for cancer in humans has been investigated in only a limited manner. With the exception of a single randomized trial, which involved 20 patients and tested the ability of coenzyme Q10 to reduce the cardiotoxicity caused by anthracycline drugs, the studies that have been published consist of anecdotal reports, case reports, case series, and uncontrolled clinical studies.

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 that involve coenzyme Q10 in heart muscle mitochondria and that this interference can be overcome by coenzyme Q10 supplementation. Studies with adults and children, including the aforementioned randomized trial, have confirmed the decrease in cardiac toxicity observed in animal studies.

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, 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.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 mg/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 100% (4 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 3 of the 6 patients. None of the 6 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, 1 of the 6 patients with a reported remission and a new patient were treated for several months with higher doses of coenzyme Q10 (390 and 300 mg/day, respectively).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 6 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 6 deaths had been expected.[6]

In another report by the same investigators, 3 breast cancer patients were followed for a total of 3 to 5 years on high-dose coenzyme Q10 (390 mg/day).One patient had complete remission of liver metastases (determined by clinical examination and ultrasonography), another had remission of a tumor that had spread to the chest wall (determined by clinical examination and chest x-ray), and the third patient had no microscopic evidence of remaining tumor after a mastectomy (determined by biopsy of the tumor bed).

All 3 of the above-mentioned human studies 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.[4] The patients described in these reports also received therapies other than coenzyme Q10, including chemotherapy, radiation therapy, and surgery.

Adverse Effects of co-Q10

No serious toxicity associated with the use of coenzyme Q10 has been reported.Doses of 100 mg/day or higher have caused mild insomnia in some individuals.Liver enzyme elevation has been detected in patients taking doses of 300 mg/day for extended periods of time, but no liver toxicity has been reported. 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. Other reported side effects have included dizziness, photophobia (abnormal visual sensitivity to light), irritability, headache, heartburn, and fatigue.

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. Beta-blockers (drugs that slow the heart rate and lower blood pressure) can inhibit coenzyme Q10-dependent enzyme reactions. The contractile force of the heart in patients with high blood pressure can be increased by coenzyme Q10 administration. Coenzyme Q10 can reduce the body’s response to the anticoagulant drug warfarin. Finally, coenzyme Q10 can decrease insulin requirements in individuals with diabetes.

References

For a specific list of references to this article and for the full back up data on this study, refer to full article [1]

More Information

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).