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Coenzyme Q10 (PDQ®)     
Last Modified: 12/18/2007
Health Professional Version
Table of Contents

Purpose of This PDQ Summary
Overview
General Information
History
Laboratory/Animal/Preclinical Studies
Human/Clinical Studies
Adverse Effects
Overall Level of Evidence for Coenzyme Q10
Changes to This Summary (12/18/2007)
More Information

Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of coenzyme Q10 as a treatment for cancer. The summary is reviewed regularly and updated as necessary by the PDQ Cancer Complementary and Alternative Medicine Editorial Board 1.

Information about the following is included in this summary:

This summary is intended as a resource to inform and assist clinicians and other health professionals who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level of evidence designation. These designations are intended to help the readers assess the strength of the evidence supporting the use of specific interventions or treatment strategies. The PDQ Cancer Complementary and Alternative Medicine Editorial Board uses a formal evidence ranking system 2 in developing its level of evidence designations. These designations should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version 3, which is written in less technical language.

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 human subjects. 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 summary.

This summary contains the following key information:

  • 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.

Many of the medical and scientific terms used in the summary are hypertext linked (at first use in each section) to the NCI Dictionary 4, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window. All linked terms and their corresponding definitions will appear in a glossary in the printable version of the summary.

Reference citations in some PDQ CAM information summaries may include links to external Web sites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the Web sites or of any treatment or product by the PDQ Cancer CAM Editorial Board or the National Cancer Institute (NCI).

General Information

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. Reviewed in [1-4] Coenzyme Q10 is also used by the body as an endogenous antioxidant. Reviewed in [1,2,4-8] 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).[9,10]

Coenzyme Q10 is present in most tissues, but the highest concentrations are found in the heart, the liver, the kidneys, and the pancreas.[11] The lowest concentration is found in the lungs.[11] Tissue levels of this compound decrease as people age, due to increased requirements, decreased production,[11] 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 normal values ranging from 0.30 to 3.84 µg /mL.[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 explored. 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.[17,28-30] 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 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.[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 U.S. Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. The FDA can, however, remove from the market dietary supplements that it deems unsafe. Because dietary supplements are not formally reviewed for manufacturing consistency, there may be considerable variation from lot to lot. 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.[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 mg/day.

References

  1. Crane FL, Sun IL, Sun EE: The essential functions of coenzyme Q. Clin Investig 71 (8 Suppl): S55-9, 1993.  [PUBMED Abstract]

  2. Pepping J: Coenzyme Q10. Am J Health Syst Pharm 56 (6): 519-21, 1999.  [PUBMED Abstract]

  3. Folkers K, Wolaniuk A: Research on coenzyme Q10 in clinical medicine and in immunomodulation. Drugs Exp Clin Res 11 (8): 539-45, 1985.  [PUBMED Abstract]

  4. Overvad K, Diamant B, Holm L, et al.: Coenzyme Q10 in health and disease. Eur J Clin Nutr 53 (10): 764-70, 1999.  [PUBMED Abstract]

  5. Beyer RE, Nordenbrand K, Ernster L: The role of coenzyme Q as a mitochondrial antioxidant: a short review. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 5. Amsterdam, The Netherlands: Elsevier Science Publishers B V (Biomedical Division), 1986, pp 17-24. 

  6. Gordon M: Dietary antioxidants in disease prevention. Nat Prod Rep 13 (4): 265-73, 1996.  [PUBMED Abstract]

  7. Palazzoni G, Pucello D, Littarru GP, et al.: Coenzyme Q10 and colorectal neoplasms in aged patients. Rays 22 (1 Suppl): 73-6, 1997 Jan-Mar.  [PUBMED Abstract]

  8. Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271 (1): 195-204, 1995.  [PUBMED Abstract]

  9. Yamamoto Y, Yamashita S, Fujisawa A, et al.: Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochem Biophys Res Commun 247 (1): 166-70, 1998.  [PUBMED Abstract]

  10. Yamamoto Y, Yamashita S: Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. Mol Aspects Med 18 (Suppl): S79-84, 1997.  [PUBMED Abstract]

  11. Ernster L, Forsmark-Andrée P: Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig 71 (8 Suppl): S60-5, 1993.  [PUBMED Abstract]

  12. Folkers K: The potential of coenzyme Q 10 (NSC-140865) in cancer treatment. Cancer Chemother Rep 2 4 (4): 19-22, 1974.  [PUBMED Abstract]

  13. Folkers K, Osterborg A, Nylander M, et al.: Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 234 (2): 296-9, 1997.  [PUBMED Abstract]

  14. Jolliet P, Simon N, Barré J, et al.: Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. Int J Clin Pharmacol Ther 36 (9): 506-9, 1998.  [PUBMED Abstract]

  15. Baggio E, Gandini R, Plancher AC, et al.: Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med 15 (Suppl): s287-94, 1994.  [PUBMED Abstract]

  16. Cortes EP, Gupta M, Chou C, et al.: Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treat Rep 62 (6): 887-91, 1978.  [PUBMED Abstract]

  17. Folkers K, Brown R, Judy WV, et al.: Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Commun 192 (1): 241-5, 1993.  [PUBMED Abstract]

  18. Iarussi D, Auricchio U, Agretto A, et al.: Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Mol Aspects Med 15 (Suppl): s207-12, 1994.  [PUBMED Abstract]

  19. Folkers K, Shizukuishi S, Takemura K, et al.: Increase in levels of IgG in serum of patients treated with coenzyme Q10. Res Commun Chem Pathol Pharmacol 38 (2): 335-8, 1982.  [PUBMED Abstract]

  20. Complementary treatments highlighted at recent meeting. Oncology (Huntingt) 13 (2): 166, 1999.  [PUBMED Abstract]

  21. Bliznakov E, Casey A, Premuzic E: Coenzymes Q: stimulants of the phagocytic activity in rats and immune response in mice. Experientia 26 (9): 953-4, 1970.  [PUBMED Abstract]

  22. Folkers K, Hanioka T, Xia LJ, et al.: Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex. Biochem Biophys Res Commun 176 (2): 786-91, 1991.  [PUBMED Abstract]

  23. Kawase I, Niitani H, Saijo N, et al.: Enhancing effect of coenzyme, Q10 on immunorestoration with Mycobacterium bovis BCG in tumor-bearing mice. Gann 69 (4): 493-7, 1978.  [PUBMED Abstract]

  24. Bliznakov EG: Effect of stimulation of the host defense system by coenzyme Q 10 on dibenzpyrene-induced tumors and infection with Friend leukemia virus in mice. Proc Natl Acad Sci U S A 70 (2): 390-4, 1973.  [PUBMED Abstract]

  25. Bliznakov EG, Adler AD: Nonlinear response of the reticuloendothelial system upon stimulation. Pathol Microbiol (Basel) 38 (6): 393-410, 1972.  [PUBMED Abstract]

  26. Bliznakov EG: Coenzyme Q in experimental infections and neoplasia. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 1. Amsterdam, The Netherlands: Elsevier/North-Holland Biomedical Press, 1977, pp 73-83. 

  27. Barbieri B, Lund B, Lundström B, et al.: Coenzyme Q10 administration increases antibody titer in hepatitis B vaccinated volunteers--a single blind placebo-controlled and randomized clinical study. Biofactors 9 (2-4): 351-7, 1999.  [PUBMED Abstract]

  28. Lockwood K, Moesgaard S, Hanioka T, et al.: Apparent partial remission of breast cancer in 'high risk' patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Mol Aspects Med 15 (Suppl): s231-40, 1994.  [PUBMED Abstract]

  29. Lockwood K, Moesgaard S, Folkers K: Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Commun 199 (3): 1504-8, 1994.  [PUBMED Abstract]

  30. Lockwood K, Moesgaard S, Yamamoto T, et al.: Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun 212 (1): 172-7, 1995.  [PUBMED Abstract]

  31. Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun 224 (2): 358-61, 1996.  [PUBMED Abstract]

  32. Ren S, Lien EJ: Natural products and their derivatives as cancer chemopreventive agents. Prog Drug Res 48: 147-71, 1997.  [PUBMED Abstract]

  33. Hodges S, Hertz N, Lockwood K, et al.: CoQ10: could it have a role in cancer management? Biofactors 9 (2-4): 365-70, 1999.  [PUBMED Abstract]

  34. Folkers K, Porter TH, Bertino JR, et al.: Inhibition of two human tumor cell lines by antimetabolites of coenzyme Q10. Res Commun Chem Pathol Pharmacol 19 (3): 485-90, 1978.  [PUBMED Abstract]

History

Coenzyme Q10 was first isolated in 1957, Reviewed in [1] and its chemical structure (benzoquinone compound) was determined in 1958. Reviewed in [2] 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.[2] Reviewed in [3,4] A subsequent study showed a statistically significant relationship between the level of plasma coenzyme Q10 deficiency and breast cancer prognosis.[5] 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.[2,6] Reviewed in [7] Furthermore, decreased levels of coenzyme Q10 have been detected in malignant human tissue,[8-12] but increased levels have been reported as well.[8]

A large amount of laboratory and animal data on coenzyme Q10 has accumulated since 1962. Reviewed in [2] 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,[13] greater numbers and/or activities of macrophages and T cells (T lymphocytes),[13,14] and increased resistance to infection.[15-17] 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.[18-20] 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.[21,22] Research subsequently delineated the antioxidant properties of coenzyme Q10.[23,24] Reviewed in[25-27]

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, Reviewed in [1,25,28] and it has been suggested that increased cellular energy leads to increased antibody synthesis in B cells (B lymphocytes).[6,18] As noted previously (General Information section 5), coenzyme Q10 can also behave as an antioxidant. Reviewed in [1,25-27,29-32] 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 [1,25,27,32] Free radical damage to DNA (and possibly to other cellular molecules) may be a factor in cancer development. Reviewed in [11,23,30,33-36]

References

  1. Pepping J: Coenzyme Q10. Am J Health Syst Pharm 56 (6): 519-21, 1999.  [PUBMED Abstract]

  2. Folkers K, Osterborg A, Nylander M, et al.: Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 234 (2): 296-9, 1997.  [PUBMED Abstract]

  3. Lockwood K, Moesgaard S, Yamamoto T, et al.: Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun 212 (1): 172-7, 1995.  [PUBMED Abstract]

  4. Ren S, Lien EJ: Natural products and their derivatives as cancer chemopreventive agents. Prog Drug Res 48: 147-71, 1997.  [PUBMED Abstract]

  5. Jolliet P, Simon N, Barré J, et al.: Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. Int J Clin Pharmacol Ther 36 (9): 506-9, 1998.  [PUBMED Abstract]

  6. Folkers K: The potential of coenzyme Q 10 (NSC-140865) in cancer treatment. Cancer Chemother Rep 2 4 (4): 19-22, 1974.  [PUBMED Abstract]

  7. Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun 224 (2): 358-61, 1996.  [PUBMED Abstract]

  8. Chipperfield B: Ubiquinone concentrations in some tumour-bearing tissues. Ubiquinone concentrations in tumours and some normal tissues in man. Nature 209 (29): 1207-8, 1966.  [PUBMED Abstract]

  9. Eggens I, Elmberger PG, Löw P: Polyisoprenoid, cholesterol and ubiquinone levels in human hepatocellular carcinomas. Br J Exp Pathol 70 (1): 83-92, 1989.  [PUBMED Abstract]

  10. Mano T, Iwase K, Hayashi R, et al.: Vitamin E and coenzyme Q concentrations in the thyroid tissues of patients with various thyroid disorders. Am J Med Sci 315 (4): 230-2, 1998.  [PUBMED Abstract]

  11. Picardo M, Grammatico P, Roccella F, et al.: Imbalance in the antioxidant pool in melanoma cells and normal melanocytes from patients with melanoma. J Invest Dermatol 107 (3): 322-6, 1996.  [PUBMED Abstract]

  12. Portakal O, Ozkaya O, Erden Inal M, et al.: Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 33 (4): 279-84, 2000.  [PUBMED Abstract]

  13. Bliznakov E, Casey A, Premuzic E: Coenzymes Q: stimulants of the phagocytic activity in rats and immune response in mice. Experientia 26 (9): 953-4, 1970.  [PUBMED Abstract]

  14. Kawase I, Niitani H, Saijo N, et al.: Enhancing effect of coenzyme, Q10 on immunorestoration with Mycobacterium bovis BCG in tumor-bearing mice. Gann 69 (4): 493-7, 1978.  [PUBMED Abstract]

  15. Bliznakov EG: Effect of stimulation of the host defense system by coenzyme Q 10 on dibenzpyrene-induced tumors and infection with Friend leukemia virus in mice. Proc Natl Acad Sci U S A 70 (2): 390-4, 1973.  [PUBMED Abstract]

  16. Bliznakov EG, Adler AD: Nonlinear response of the reticuloendothelial system upon stimulation. Pathol Microbiol (Basel) 38 (6): 393-410, 1972.  [PUBMED Abstract]

  17. Bliznakov EG: Coenzyme Q in experimental infections and neoplasia. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 1. Amsterdam, The Netherlands: Elsevier/North-Holland Biomedical Press, 1977, pp 73-83. 

  18. Folkers K, Shizukuishi S, Takemura K, et al.: Increase in levels of IgG in serum of patients treated with coenzyme Q10. Res Commun Chem Pathol Pharmacol 38 (2): 335-8, 1982.  [PUBMED Abstract]

  19. Folkers K, Hanioka T, Xia LJ, et al.: Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex. Biochem Biophys Res Commun 176 (2): 786-91, 1991.  [PUBMED Abstract]

  20. Barbieri B, Lund B, Lundström B, et al.: Coenzyme Q10 administration increases antibody titer in hepatitis B vaccinated volunteers--a single blind placebo-controlled and randomized clinical study. Biofactors 9 (2-4): 351-7, 1999.  [PUBMED Abstract]

  21. Shaw M, Ray P, Rubenstein M, et al.: Lymphocyte subsets in urologic cancer patients. Urol Res 15 (3): 181-5, 1987.  [PUBMED Abstract]

  22. Tsuyuguchi I, Shiratsuchi H, Fukuoka M: T-lymphocyte subsets in primary lung cancer. Jpn J Clin Oncol 17 (1): 13-7, 1987.  [PUBMED Abstract]

  23. Yamamoto Y, Yamashita S, Fujisawa A, et al.: Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochem Biophys Res Commun 247 (1): 166-70, 1998.  [PUBMED Abstract]

  24. Yamamoto Y, Yamashita S: Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. Mol Aspects Med 18 (Suppl): S79-84, 1997.  [PUBMED Abstract]

  25. Crane FL, Sun IL, Sun EE: The essential functions of coenzyme Q. Clin Investig 71 (8 Suppl): S55-9, 1993.  [PUBMED Abstract]

  26. Overvad K, Diamant B, Holm L, et al.: Coenzyme Q10 in health and disease. Eur J Clin Nutr 53 (10): 764-70, 1999.  [PUBMED Abstract]

  27. Ernster L, Forsmark-Andrée P: Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig 71 (8 Suppl): S60-5, 1993.  [PUBMED Abstract]

  28. Folkers K, Wolaniuk A: Research on coenzyme Q10 in clinical medicine and in immunomodulation. Drugs Exp Clin Res 11 (8): 539-45, 1985.  [PUBMED Abstract]

  29. Beyer RE, Nordenbrand K, Ernster L: The role of coenzyme Q as a mitochondrial antioxidant: a short review. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 5. Amsterdam, The Netherlands: Elsevier Science Publishers B V (Biomedical Division), 1986, pp 17-24. 

  30. Gordon M: Dietary antioxidants in disease prevention. Nat Prod Rep 13 (4): 265-73, 1996.  [PUBMED Abstract]

  31. Palazzoni G, Pucello D, Littarru GP, et al.: Coenzyme Q10 and colorectal neoplasms in aged patients. Rays 22 (1 Suppl): 73-6, 1997 Jan-Mar.  [PUBMED Abstract]

  32. Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271 (1): 195-204, 1995.  [PUBMED Abstract]

  33. Aust AE, Eveleigh JF: Mechanisms of DNA oxidation. Proc Soc Exp Biol Med 222 (3): 246-52, 1999.  [PUBMED Abstract]

  34. Halliwell B: Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat Res 443 (1-2): 37-52, 1999.  [PUBMED Abstract]

  35. Burcham PC: Internal hazards: baseline DNA damage by endogenous products of normal metabolism. Mutat Res 443 (1-2): 11-36, 1999.  [PUBMED Abstract]

  36. Dreher D, Junod AF: Role of oxygen free radicals in cancer development. Eur J Cancer 32A (1): 30-8, 1996.  [PUBMED Abstract]

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 [1,2] and to viral and chemically induced neoplasia.[1-3] Reviewed in [4] Early studies of coenzyme Q10 showed increased hematopoiesis (the formation of new blood cells) in monkeys, Reviewed in [4,5] rabbits,[6] and poultry. Reviewed in [5] Coenzyme Q10 demonstrated a protective effect on the heart muscle of mice, rats, and rabbits given the anthracycline anticancer drug doxorubicin.[7-12] 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.[13] Researchers in one study sounded a cautionary note when they found that coadministration of coenzyme Q10 and radiation therapy decreased the effectiveness of the radiation therapy.[14] 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 were treated with radiation therapy 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 5), there is some evidence from laboratory and animal studies that analogs of coenzyme Q10 may have direct anticancer activity.[15,16]

References

  1. Bliznakov EG, Adler AD: Nonlinear response of the reticuloendothelial system upon stimulation. Pathol Microbiol (Basel) 38 (6): 393-410, 1972.  [PUBMED Abstract]

  2. Bliznakov EG: Coenzyme Q in experimental infections and neoplasia. In: Folkers K, Yamamura Y, eds.: Biomedical and Clinical Aspects of Coenzyme Q. Vol 1. Amsterdam, The Netherlands: Elsevier/North-Holland Biomedical Press, 1977, pp 73-83. 

  3. Bliznakov EG: Effect of stimulation of the host defense system by coenzyme Q 10 on dibenzpyrene-induced tumors and infection with Friend leukemia virus in mice. Proc Natl Acad Sci U S A 70 (2): 390-4, 1973.  [PUBMED Abstract]

  4. Folkers K, Osterborg A, Nylander M, et al.: Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 234 (2): 296-9, 1997.  [PUBMED Abstract]

  5. Folkers K, Brown R, Judy WV, et al.: Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Commun 192 (1): 241-5, 1993.  [PUBMED Abstract]

  6. Ludwig FC, Elashoff RM, Smith JL, et al.: Response of the bone marrow of the vitamin E-deficient rabbit to coenzyme Q and vitamin E. Scand J Haematol 4 (4): 292-300, 1967.  [PUBMED Abstract]

  7. Choe JY, Combs AB, Folkers K: Prevention by coenzyme Q10 of the electrocardiographic changes induced by adriamycin in rats. Res Commun Chem Pathol Pharmacol 23 (1): 199-202, 1979.  [PUBMED Abstract]

  8. Combs AB, Choe JY, Truong DH, et al.: Reduction by coenzyme Q10 of the acute toxicity of adriamycin in mice. Res Commun Chem Pathol Pharmacol 18 (3): 565-8, 1977.  [PUBMED Abstract]

  9. Folkers K, Choe JY, Combs AB: Rescue by coenzyme Q10 from electrocardiographic abnormalities caused by the toxicity of adriamycin in the rat. Proc Natl Acad Sci U S A 75 (10): 5178-80, 1978.  [PUBMED Abstract]

  10. Lubawy WC, Dallam RA, Hurley LH: Protection against anthramycin-induced toxicity in mice by coenzyme Q10. J Natl Cancer Inst 64 (1): 105-9, 1980.  [PUBMED Abstract]

  11. Shinozawa S, Gomita Y, Araki Y: Protective effects of various drugs on adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice and rats. Biol Pharm Bull 16 (11): 1114-7, 1993.  [PUBMED Abstract]

  12. Usui T, Ishikura H, Izumi Y, et al.: Possible prevention from the progression of cardiotoxicity in adriamycin-treated rabbits by coenzyme Q10. Toxicol Lett 12 (1): 75-82, 1982.  [PUBMED Abstract]

  13. Shaeffer J, El-Mahdi AM, Nichols RK: Coenzyme Q10 and adriamycin toxicity in mice. Res Commun Chem Pathol Pharmacol 29 (2): 309-15, 1980.  [PUBMED Abstract]

  14. Lund EL, Quistorff B, Spang-Thomsen M, et al.: Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake. Folia Microbiol (Praha) 43 (5): 505-6, 1998.  [PUBMED Abstract]

  15. Folkers K: The potential of coenzyme Q 10 (NSC-140865) in cancer treatment. Cancer Chemother Rep 2 4 (4): 19-22, 1974.  [PUBMED Abstract]

  16. Folkers K, Porter TH, Bertino JR, et al.: Inhibition of two human tumor cell lines by antimetabolites of coenzyme Q10. Res Commun Chem Pathol Pharmacol 19 (3): 485-90, 1978.  [PUBMED Abstract]

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,[1] 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.[2-7] Reviewed in [8-11]

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.[3,12,13] Studies with adults and children, including the aforementioned randomized trial, have confirmed the decrease in cardiac toxicity observed in animal studies.[1-4]

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,[14,15] Reviewed in [7,9,10] 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.[5] 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).[6] 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).[7] 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 [5-7] 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.

Refer to the NCI Web site 6 for a list of active clinical trials evaluating the use of coenzyme Q10 in cancer patients.

References

  1. Iarussi D, Auricchio U, Agretto A, et al.: Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Mol Aspects Med 15 (Suppl): s207-12, 1994.  [PUBMED Abstract]

  2. Folkers K, Wolaniuk A: Research on coenzyme Q10 in clinical medicine and in immunomodulation. Drugs Exp Clin Res 11 (8): 539-45, 1985.  [PUBMED Abstract]

  3. Cortes EP, Gupta M, Chou C, et al.: Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treat Rep 62 (6): 887-91, 1978.  [PUBMED Abstract]

  4. Folkers K, Brown R, Judy WV, et al.: Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Commun 192 (1): 241-5, 1993.  [PUBMED Abstract]

  5. Lockwood K, Moesgaard S, Hanioka T, et al.: Apparent partial remission of breast cancer in 'high risk' patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Mol Aspects Med 15 (Suppl): s231-40, 1994.  [PUBMED Abstract]

  6. Lockwood K, Moesgaard S, Folkers K: Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Commun 199 (3): 1504-8, 1994.  [PUBMED Abstract]

  7. Lockwood K, Moesgaard S, Yamamoto T, et al.: Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun 212 (1): 172-7, 1995.  [PUBMED Abstract]

  8. Complementary treatments highlighted at recent meeting. Oncology (Huntingt) 13 (2): 166, 1999.  [PUBMED Abstract]

  9. Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun 224 (2): 358-61, 1996.  [PUBMED Abstract]

  10. Ren S, Lien EJ: Natural products and their derivatives as cancer chemopreventive agents. Prog Drug Res 48: 147-71, 1997.  [PUBMED Abstract]

  11. Hodges S, Hertz N, Lockwood K, et al.: CoQ10: could it have a role in cancer management? Biofactors 9 (2-4): 365-70, 1999.  [PUBMED Abstract]

  12. Usui T, Ishikura H, Izumi Y, et al.: Possible prevention from the progression of cardiotoxicity in adriamycin-treated rabbits by coenzyme Q10. Toxicol Lett 12 (1): 75-82, 1982.  [PUBMED Abstract]

  13. Iwamoto Y, Hansen IL, Porter TH, et al.: Inhibition of coenzyme Q10-enzymes, succinoxidase and NADH-oxidase, by adriamycin and other quinones having antitumor activity. Biochem Biophys Res Commun 58 (3): 633-8, 1974.  [PUBMED Abstract]

  14. Folkers K: The potential of coenzyme Q 10 (NSC-140865) in cancer treatment. Cancer Chemother Rep 2 4 (4): 19-22, 1974.  [PUBMED Abstract]

  15. Folkers K, Osterborg A, Nylander M, et al.: Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 234 (2): 296-9, 1997.  [PUBMED Abstract]

Adverse Effects

No serious toxicity associated with the use of coenzyme Q10 has been reported. Reviewed in [1-4] Doses of 100 mg /day or higher have caused mild insomnia in some individuals. Reviewed in [1] 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. Reviewed in [1] 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.[5] Other reported side effects have included dizziness, photophobia (abnormal visual sensitivity to light), irritability,[5] headache, heartburn, and fatigue.[6]

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