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The effects of coenzyme Q10 on women with breast cancer: a systematic review protocol

Mathews, Megan BA, MBBS, BSc Med

Author Information
JBI Database of Systematic Reviews and Implementation Reports: August 2014 - Volume 12 - Issue 8 - p 127-144
doi: 10.11124/jbisrir-2014-1140
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Inclusion criteria

Types of participants

This review will consider studies that include adult women aged 18 years or older who have been managed with conventional treatment (surgery, radiotherapy and/or chemotherapy including hormonal therapy- either alone or in any combination) regardless of type, stage or grade of breast cancer.

Types of intervention(s) and comparators

The intervention of interest is coenzyme Q10 therapy following or in addition to conventional treatment (surgery, radiotherapy and/or chemotherapy, including hormonal therapy), either alone or in addition to other nutrients or antioxidants. This study will consider supplementation with coenzyme Q10 regardless of the route or dosage and for a minimum of one week administration.

The comparison group is adult women with breast cancer who have had conventional treatment (surgery, radiotherapy and/or chemotherapy, including hormonal therapy). In some study designs there may not be a comparator group and coenzyme Q10 will be considered as an exposure.

Types of outcomes

This review will consider the following parameters that indicate increased survival, reduced recurrence and tumor burden, and cancer cure.

  • Death/survival rate;
  • Blood concentrations of biochemical markers - standard tests (FBC, EUC, LFT); inflammatory markers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)14; tumor markers (CA 15.3, CA 125, CEA)15; and tumor-related markers (such as but not limited to TNF-alpha, IL2, IL6 and IL8);
  • Size of primary tumor assessed by ultrasound (US), mammography, computerized axial tomography (CAT scan), magnetic resonance imaging (MRI), positron emission tomography (PET);
  • Number and size of secondary tumors assessed by ultrasound, chest X-ray, mammography, computerized axial tomography (CAT scan), magnetic resonance imaging (MRI) or positron emission tomography (PET scan);
  • Adverse events resulting from coenzyme Q10;
  • Adherence to conventional therapy;
  • Impact of coenzyme Q10 on conventional treatment. This may be either to inhibit, augment or ameliorate actions or adverse events resulting from conventional treatment; and
  • Effect of coenzyme Q10 on measures of patient quality of life (such as sleep, nausea, vomiting, hair loss, appetite, mobility, lymphedema, pain and patient satisfaction) related to the cancer as well as the cancer treatment-related symptoms.

Types of studies

This review will consider both experimental and epidemiological quantitative studies including randomized control trials, non-randomized control trials, quasi-experimental, case control, cohort case series and case reports which examine the effects of coenzyme Q10 on women with breast cancer.

Search strategy

A three-step search strategy will be used in this systematic review to find both published and unpublished studies between 1961 to the present date (April 2014). This deliberately broad time-frame is designed to capture any early clinical studies on coenzyme Q10. First, a limited search of MEDLINE and CINAHL, followed by analysis of the text words contained in the title and abstract, then the index terms used to describe the articles. Then, a second search will be conducted across all appropriate databases using all identified keywords and index terms. Then, a third search of the reference lists of all identified reports and articles will be done.

Studies published in any language will be considered for inclusion in this review.

Databases and repositories to be searched include PubMed, CINAHL, Scopus, BIOSIS, EMBASE, CancerLit, Science Direct, Web of Science, International Congress on Complementary Medicine Research, American Society of Clinical Oncology, MedNar, Cochrane Central Register of Controlled Trials, WHO register of trials, and Australian National University Digital Theses, Open Access Theses and Dissertations and ProQuest Dissertations and Theses.

The following keywords/terms will be used for the initial search:

cancer/tumour/tumor/neoplasm/carcinoma/malignan*/breast/mammary/breast cancer/breast tumour/breast tumor, AND

coenzyme Q10/co-enzyme Q10/coQ10/CoQ 10/vitamin 10/ubiquinol/ubiquinone/ubiquinone Q10/ubiquinone 50/ubidecarenone/2,3-dimethoxy-5-methyl-6-decaprenylbenzoquinone/Q-ter/ubisemiquinone/ ubisemiquinone radical/Bio-Quinone Q10/coenzyme Q10, isomer/coenzyme Q10, ion (1-), (all E)-isomer

Studies identified by the search will be considered against the inclusion criteria. Those that match the criteria will undergo methodological quality assessment. Those that do not match the inclusion criteria will be excluded.

Assessment of methodological quality

Titles and abstracts of studies identified during the search process will be screened by the primary reviewer. Articles selected for retrieval based on title and abstract will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standard critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.

Data collection

Quantitative data will be extracted from papers included in this review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. The information collected will include the following:

  • Methods: study design, methods of allocation, allocation concealment, blinding, dropout rates from studies and reasons for dropping out.
  • Participants: country of origin, setting, sample size, diagnosis, age, ethnicity.
  • Intervention: type, program length, frequency, duration (for experimental and comparator interventions).
  • Outcomes: type of outcomes, assessment instruments, assessment time point and follow-up time point.

Data synthesis

Data will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratios (for categorical or dichotomous data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square and also explored using subgroup analyses based on the different study designs included in this review. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate.

Conflicts of interest



As this systematic review forms partial submission for the degree award of Masters of Clinical Science through the University of Adelaide, a secondary reviewer (Ms Dagmara Riitano) will be used for critical appraisal of literature considered for inclusion in the review.

The primary reviewer wishes to thank the University of Adelaide and the Joanna Briggs Institute for this opportunity to extend her skill-base and do such interesting research. She also wishes to thank Associate Professor Edoardo Aromataris for previous supervision.


1. Australian Government CA. Breast cancer statistics Canberra2013 [cited April 2014]. Available from:
    2. Australian Institute of Health and Welfare & Cancer Australia. Breast cancer in Australia: an overview. In: Australian Institute of Health and Welfare & Cancer Australia, Canberra 2012:0-100.
      3. Edwards B, Howe H, Ries L. Annual report to the nation on the status of cancer, 1973-1999, featuring implications of age and aging on U.S. cancer burden. USA Government; 2002:2766-92.
        4. Nicholson T. Complementary and alternative medicines (including traditional Maori treatments) used by presenters to an emergency department in New Zealand: a survey of prevalence and toxicity. N Z Med J. 2006 May;119 (1233):1954-8.
          5. Parkin D, Bray F, Ferlay J et al. Global Cancer Statistics. Cancer J Clin. 2002;2005(55):74-108.
            6. Westlake S. Cancer incidence and mortality: trends in the United Kingdom and constituent countries, 1993 to 2004. Health Stats Quarterly. 2008 Summer;9380;33-46.
              7. Gatta G, Mallone S, van der Zwan J. Cancer Prevalence in Europe at the beginning of 2000. Ann Oncol. 2013;24(6):1660-6.
              8. Siegel R, Naishadham M, Jemal A. Cancer statistics, 2012. Cancer J Clin 2012;62(1):10-29.
                9. Cheng SH, Wang CJ, Lin J et al. Adherence to quality indicators and survival in patients with breast cancer. Medical care. 2009 Feb;47(2):217-25.
                  10. Falck AK, Ferno M, Bendahl PO et al. St Gallen molecular subtypes in primary breast cancer and matched lymph node metastases - aspects on distribution and prognosis for patients with luminal A tumours: results from a prospective randomised trial. BMC cancer. 2013 Nov 25;13(1):558-62.
                    11. Malhotra GK, Zhao X, Band H et al. Histological, molecular and functional subtypes of breast cancers. Cancer biology & therapy. 2010 Nov 15;10(10):955-60.
                      12. Gannon LM, Cotter MB, Quinn CM. The classification of invasive carcinoma of the breast. Expert review of anticancer therapy. 2013 Aug;13(8):941-54.
                        13. Cadoo KA, Traina TA, King TA. Advances in molecular and clinical subtyping of breast cancer and their implications for therapy. Surgical oncology clinics of North America. 2013 Oct;22(4):823-40.
                          14. Han Y, Mao F, Wu Y. Prognostic role of C-reactive protein in breast cancer: a systematic review and meta-analysis. Int J Biol Markers. 2011;26(4):209-15.
                          15. Lee J, Park S, Park J. Elevated levels of preoperative CA 15-3 and CEA serum levels have independently poor prognostic significance in breast cancer. Ann Oncol. 2013;24(5):1225-31.
                          16. Longo D, Kasper D, Fauci A et al. Harrison's Principles of Internal Medicine (18th ed). New York: McGraw-Hill Med Pub Div; 2012.
                            17. Xue C, Zhang A, Da Costa C et al. Complementary and alternative medicine use in Australia: a national population-based survey. J Altern Complement Med. 2007;13(6):643-50.
                            18. Wilson K, Dowson C, Mangin D. Prevalence of complementary and alternative medicine use in Christchurch, New Zealand: children attending general practice versus paediatric outpatients. JNZMA. 2007;120:1251-56.
                              19. Richie M. Use of herbal supplements and nutritional supplements in the UK: what do we know about their pattern of usage? Proceedings of the Nutr Soc. 2007;66:479-82.
                                20. Gavin J, Boon H. CAM in Canada: places, practices, research. Complement Ther Clin Pract. 2005;11(1):21-7.
                                21. Su D, Li L. Trends in the use of complementary and alternative medicine in the United States: 2002-2007. Journal of health care for the poor and underserved. 2011 Feb;22(1):296-310.
                                  22. Roberti di Sarsina P, Iseppato I. Looking for a person-centered medicine: non conventional medicine in the conventional European and Italian setting. Evid Based Complement Alternat Med. 2011;2011:382-96.
                                    23. Fisher P, Ward A. Medicine in Europe: Complementary medicine in Europe. Br Med J 1994;309:107-11.
                                    24. Centers for disease control and prevention. National Health Interview Survey 13. USA 2008 [cited April 2014]. Available from:
                                      25. Boon H, Olatunde F, Zick S. Trends in complementary/alternative medicine use by breast cancer survivors: Comparing survey data from 1998 and 2005. BMC Womens Health. 2007;7:4-8.
                                      26. Girgis A, Adams J, Sibbritt D. The Use of Complementary and Alternative Therapies by Patients with Cancer. Oncol Res Featuring Preclinical and Clin Canc Therapeut. 2005;15(5):281-9.
                                        27. Yates JS, Mustian KM, Morrow GR et al. Prevalence of complementary and alternative medicine use in cancer patients during treatment. Supportive care in cancer:. 2005 Oct;13(10):806-11.
                                          28. Henderson JW, Donatelle RJ. Complementary and alternative medicine use by women after completion of allopathic treatment for breast cancer. Altern therap in health and medicine. 2004 Jan-Feb;10(1):52-7.
                                            29. Wanchai A, Armer J, Stewart B. Complementary and alternative medicine use among women with breast cancer: a systematic review. Clin J Oncol Nursing. 2010;14(4):45-54.
                                              30. Health NIo. National Center for Complementary and Alternative Medicine. USA: National Institutes of Health; 2013 [cited April 2014]. Available from:
                                                31. Report of the White House Commission on Complementary and Alternative Medicine Policy: recommendations and actions. Journal of pain & palliative care pharmacotherapy. 2002;16(4):101-4.
                                                32. House of Lords, Sixth Report - Science and Technology, session 1999-2000. British Government; (cited April 2014) Available from:
                                                  34. Goldstein M. The culture of fitness and the growth of CAM. Complementary and Alternative Medicine: Challenge and Change. Canada: Harwood Academic Publishers, 2000.
                                                    33. Berliner H, Salmon J. The holistic alternative to scientific medicine: History and analysis. Internat J Health Services. 1980;10:133-47.
                                                      35. Deyo R. Practice variations, treatment fads, and rising disability. Spine. 1993;18(15):2153-7.
                                                      36. Broom AF, Kirby ER, Sibbritt DW et al. Use of complementary and alternative medicine by mid-age women with back pain: a national cross-sectional survey. BMC complementary and alternative medicine. 2012;12:98.
                                                      37. Pelletier KR, Astin JA. Integration and reimbursement of complementary and alternative medicine by managed care and insurance providers: 2000 update and cohort analysis. Alternative therapies in health and medicine. 2002 Jan-Feb;8(1):38-9.
                                                        38. Wetzel M, Eisenberg D. Courses involving complementary and alternative medicine at US medical schools. JAMA. 1998;280:784-7.
                                                        39. Posadzki P, Alotaibi A, Ernst E. Prevalence of use of complementary and alternative medicine (CAM) by physicians in the UK: a systematic review of surveys. Clin Med. 2012;12(6):505-12.
                                                        40. Standish LJ, Greene K, Greenlee H et al. Complementary and alternative medical treatment of breast cancer: a survey of licensed North American naturopathic physicians. Alternative therapies in health and medicine. 2002 Jul-Aug;8(4):74-6.
                                                          41. Crane FL. The evolution of coenzyme Q. BioFactors. 2008;32(1-4):5-11.
                                                          42. Aberg F, Appelkvist E, Dallner G et al. Distribution and redox state of ubiquinones in rat and human tissues. Arch biochem and biophys. 1992;295(2):230-4.
                                                          43. Nohl H, Gille L, Staniek K. The biochemical, pathophysiological, and medical aspects of ubiquinone function. Ann N Y Acad Sci. 1998;854:394-409.
                                                          44. Choi J, Ryu Y, Seo J. Biotechnological production and applications of coenzyme Q10. App Microbiol Biotech. 2005;68(1):9-15.
                                                            45. Seyfried T. Cancer as a metabolic disease: on the origin, management and prevention of cancer. New Jersey:John Wiley and Sons;2012.
                                                              46. Dreher D, Junod A. Role of oxygen free radicals in cancer development. Europ J Ca. 1996;32A(1):30-8.
                                                                47. Tas F, Hansel H, Belce A. Oxidative stress in breast cancer. Med Oncol. 2005;22(1):11-5.
                                                                48. Portakal O, Ozkaya O, Erden Inal M et al. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clinical biochemistry. 2000 Jun;33(4):279-84.
                                                                  49. Bessler H. Bergman M. Blumberger A et al. Coenzyme Q10 decreases TNF-alpha and IL-2 secretion by human peripheral blood mononuclear cells. J Nutr Sci Vitaminol. 2010;56(1):77-81.
                                                                  50. Folkers K. Hanioka T. Xia Li-Jun 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. 1991;176(2):786-791.
                                                                  51. Groneberg DA, Kindermann B, Althammer M et al. Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells. The international journal of biochemistry & cell biology. 2005 Jun;37(6):1208-18.
                                                                    52. 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. 1996 Jul 16;224(2):358-61.
                                                                      53. Bahar M, Khaghani S, Pasalar P et al. Exogenous coenzyme Q10 modulates MMP-2 activity in MCF-7 cell line as a breast cancer cellular model. Nutrition journal. 2010;9:62.
                                                                      54. Littarru GP, Tiano L. Clinical aspects of coenzyme Q10: an update. Nutrition. 2010 Mar;26(3):250-4.
                                                                        55. Tiwari A. Antioxidants:New-generation therapeutic base for treatment of polygenic disorders. Current science. 2004;86(6):1092-102.
                                                                        56. Rosenfeldt FL, Haas SJ, Krum H et al. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. Journal of human hypertension. 2007 Apr;21(4):297-306.
                                                                          57. Bujan N, Arias A, Montero R et al. Characterization of CoQ biosynthesis in fibroblasts of patients with primary and secondary CoQ deficiency. Journal of inherited metabolic disease. 2013 Jun;18:79-82.
                                                                            58. Ye CQ, Folkers K, Tamagawa H et al. A modified determination of coenzyme Q10 in human blood and CoQ10 blood levels in diverse patients with allergies. BioFactors. 1988 Dec;1(4):303-6.
                                                                              59. Folkers K, Langsjoen P, Nara Y et al. Biochemical deficiencies of coenzyme Q10 in HIV-infection and exploratory treatment. Biochem Biophys Res Commun. 1988 Jun 16;153(2):888-96.
                                                                                60. Tiano L, Padella L, Santoro L et al. Prolonged coenzyme Q10 treatment in Down syndrome patients: effect on DNA oxidation. Neurobiology of aging. 2012 Mar;33(3):626-8.
                                                                                  61. Lance J, McCabe S, Clancy RL et al. Coenzyme Q10—a therapeutic agent. Medsurg nursing. 2012 Nov-Dec;21(6):367-71.
                                                                                    62. 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. 1997 May 19;234(2):296-9.
                                                                                      63. Folkers K, Brown R, Judy W et al. Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Commun. 1993;192(1):241-5.
                                                                                      64. Chai W, Cooney RV, Franke AA et al. Plasma coenzyme Q10 levels and postmenopausal breast cancer risk: the multiethnic cohort study. Cancer epidemiology, biomarkers & prevention. 2010 Sep;19(9):2351-6.
                                                                                        65. Jolliet P, Simon N, Barre J et al. Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. International journal of clinical pharmacology and therapeutics. 1998 Sep;36(9):506-9.
                                                                                          66. Cooney RV, Dai Q, Gao YT et al. Low plasma coenzyme Q(10) levels and breast cancer risk in Chinese women. Cancer epidemiology, biomarkers & prevention. 2011 Jun;20(6):1124-30.
                                                                                            67. 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. 1994 Mar 30;199(3):1504-8.
                                                                                              68. Lockwood K, Moesgaard S, Yamamoto T, Folkers K. Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun. 1995 Jul 6;212(1):172-7.
                                                                                                69. Hodges S, Hertz N, Lockwood K et al. CoQ10: could it have a role in cancer management? BioFactors. 1999;9(2-4):365-70.
                                                                                                70. Hertz N, Lister RE. Improved survival in patients with end-stage cancer treated with coenzyme Q(10) and other antioxidants: a pilot study. The Journal of international medical research. 2009 Nov-Dec;37(6):1961-71.
                                                                                                  71. Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in ‘high risk’ patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Molecular aspects of medicine. 1994;15 Suppl:s231-40.
                                                                                                    72. Lesperance ML, Olivotto IA, Forde N et al. Mega-dose vitamins and minerals in the treatment of non-metastatic breast cancer: an historical cohort study. Breast cancer research and treatment. 2002 Nov;76(2):137-43.
                                                                                                      73. Sachdanandam P. Antiangiogenic and hypolipidemic activity of coenzyme Q10 supplementation to breast cancer patients undergoing Tamoxifen therapy. BioFactors. 2008;32(1-4):151-9.
                                                                                                      74. Premkumar VG, Yuvaraj S, Sathish S et al. Anti-angiogenic potential of CoenzymeQ10, riboflavin and niacin in breast cancer patients undergoing tamoxifen therapy. Vascular pharmacology. 2008 Apr-Jun;48(4-6):191-201.
                                                                                                        75. Premkumar VG, Yuvaraj S, Vijayasarathy K et al. Serum cytokine levels of interleukin-1beta, -6, -8, tumour necrosis factor-alpha and vascular endothelial growth factor in breast cancer patients treated with tamoxifen and supplemented with co-enzyme Q(10), riboflavin and niacin. Basic & clinical pharmacology & toxicology. 2007 Jun;100(6):387-91.
                                                                                                          76. Yuvaraj S, Premkumar VG, Vijayasarathy K et al. Augmented antioxidant status in Tamoxifen treated postmenopausal women with breast cancer on co-administration with Coenzyme Q10, Niacin and Riboflavin. Cancer chemotherapy and pharmacology. 2008 May;61(6):933-41.
                                                                                                            77. Hathcock J. N. Shao A. Risk assessment for coenzyme Q10 (Ubiquinone). Regul Toxicol Pharmacol. 2006 July:45(3):282-8.
                                                                                                              78. Hidaka T. Fujii K. Funahashi I et al. Safety assessment of coenzyme Q10 (CoQ10). Biofactors. 2008 Dec;32(1-4):199-208.

                                                                                                                Appendix I - Critical Appraisal instruments

                                                                                                                MAStARI appraisal instruments

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                                                                                                                Appendix II: Data extraction instruments

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                                                                                                                Complementary; adjunct; CoQ10; ubiquinone; ubiquinol; mammary carcinoma

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