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 subunits 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, mitochondria produce energy for cell growth and maintenance.[1-4] Coenzyme Q10 is also used by the body as an endogenous antioxidant.[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.[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. 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.[2,4,13,14]
Given the importance of coenzyme Q10 in optimizing 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.[2,4,15] 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.[19,20] 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.[17,20,28-33]
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 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 (gel bead 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.[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.
- Crane FL, Sun IL, Sun EE: The essential functions of coenzyme Q. Clin Investig 71 (8 Suppl): S55-9, 1993. [PUBMED Abstract]
- Pepping J: Coenzyme Q10. Am J Health Syst Pharm 56 (6): 519-21, 1999. [PUBMED Abstract]
- 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]
- 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]
- 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.
- Gordon M: Dietary antioxidants in disease prevention. Nat Prod Rep 13 (4): 265-73, 1996. [PUBMED Abstract]
- 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]
- Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271 (1): 195-204, 1995. [PUBMED Abstract]
- 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]
- 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]
- Ernster L, Forsmark-Andrée P: Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig 71 (8 Suppl): S60-5, 1993. [PUBMED Abstract]
- Folkers K: The potential of coenzyme Q 10 (NSC-140865) in cancer treatment. Cancer Chemother Rep 2 4 (4): 19-22, 1974. [PUBMED Abstract]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Complementary treatments highlighted at recent meeting. Oncology (Huntingt) 13 (2): 166, 1999. [PUBMED Abstract]
- 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]
- 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]
- 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]
- 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]
- Bliznakov EG, Adler AD: Nonlinear response of the reticuloendothelial system upon stimulation. Pathol Microbiol (Basel) 38 (6): 393-410, 1972. [PUBMED Abstract]
- 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.
- 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]
- 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]
- 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]
- 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]
- 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]
- Ren S, Lien EJ: Natural products and their derivatives as cancer chemopreventive agents. Prog Drug Res 48: 147-71, 1997. [PUBMED Abstract]
- 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]
- 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]