Coenzyme Q10, or CoQ10, is a naturally occurring, lipid-soluble antioxidant and an essential electron carrier involved in the mitochondrial respiratory chain. In mitochondria, CoQ10 functions as a coenzyme that assists in the oxidative phosphorylation of nutrients, leading to production of cellular adenosine triphosphate (ATP), or energy.[1–4] It is endogenously synthesized by mammals and plants and is found in virtually all aerobic cells.
The best food sources of CoQ10 are meat and poultry, and the typical US diet provides approximately 5 to 10 mg of CoQ10 per day. The highest levels of dietary CoQ10 are found in red meat products, particularly organ meats (liver and heart), from which this compound was first isolated. After absorption, CoQ10 is circulated to the liver and incorporated into very-low-density lipoproteins.
In the body, more than 90% of CoQ10 is converted to its active form, called CoQH2-10 or ubiquinol. Ubiquinol has strong antioxidant properties. Although humans are capable of producing adequate amounts of CoQ10, certain medications, such as statins, beta-blockers, antidepressants, and antipsychotics, may decrease the body’s natural production of this compound. Conditions that cause oxidative stress, such as liver disease, have been noted to decrease the ratio of ubiquinol to CoQ10, and tissue levels of CoQ10 have also been found to decline with age. Serum concentrations of CoQ10 have been shown to increase after consumption of supplemental CoQ10 and after meals containing CoQ10. It is absorbed well, although rather slowly; peak plasma levels occur 5 to 10 hours after ingestion. Serum levels of CoQ10 have been used to determine the amount of ingested CoQ10 needed to raise endogenous levels of CoQ10. Research suggests that a range of 150 to 300 mg of dietary CoQ10 may be needed to achieve physiologic effects.[7,8]
How Is CoQ10 Currently Used?
While CoQ10 has been used for several decades as a dietary supplement for general health maintenance, the benefits of its administration have been most extensively evaluated in a variety of cardiovascular and neurodegenerative conditions. In patients with congestive heart failure, CoQ10 supplementation in addition to conventional medical therapy may improve quality of life, New York Heart Association classification, and congestive symptoms including dyspnea and edema.[9–13] Similar benefits were seen in a study of patients with hypertrophic cardiomyopathy.
Rosenfeldt et al, in a meta-analysis of 12 published clinical trials, reported that CoQ10 administration decreases systolic and diastolic blood pressure. These cardiovascular changes may be a result of effects of CoQ10 on vascular endothelium, including improvements in the activity of superoxide dismutase, an enzyme thought to protect the vasculature against oxidant-induced damage.[16,17] Equivocal results have been described following efforts to prevent myalgias and myopathy in patients receiving HMG-CoA reductase inhibitors—the “statin” drugs—with CoQ10 supplementation.[18–21]
Some data suggest high-dose CoQ10 administration may slow functional decline in patients with early Parkinson’s disease. Unfortunately, 300 mg CoQ10 twice daily did not improve total functional capacity in 347 patients with early Huntington’s disease. CoQ10 supplementation has been shown to be effective in the uncommon primary CoQ10 deficiency syndromes associated with specific genetic defects in the CoQ10 biosynthesis pathway.[24–26] Placebo-controlled, double-blind, randomized trials have demonstrated efficacy of CoQ10 in men with idiopathic infertility.[27,28] Supplementation led to increased seminal plasma and sperm motility, but it is not clear if these changes lead to increased rates of pregnancy.
In light of its role in mitochondrial energy generation, CoQ10 supplementation has been evaluated in a variety of patient populations with fatigue. It has clearly been demonstrated to improve the symptoms of weakness and fatigue in the rare patient with inherited defects in CoQ10 biosynthesis.[24,25] As described, CoQ10 may have beneficial effects on dyspnea and exercise tolerance—cardiac fatigue—in patients with congestive heart failure and/or cardiomyopathy.[11,29,30] However, conflicting data exist regarding the effect of CoQ10 on fatigue in a normal population. Cooke et al described a trend towards an increased time to exhaustion following 2 weeks of CoQ10 intake. A number of other placebo-controlled studies have failed to demonstrate an improvement in physical functioning in similar trained and untrained populations.[32–36]
What Is the Evidence Related to CoQ10 and Cancer?
During cancer treatment, many patients experience flavor aversions, particularly to meat, and may not be able to consume adequate amounts of dietary CoQ10. In addition, antineoplastic therapy may have a direct impact on CoQ10 synthesis.
Unfortunately, clinical and epidemiologic investigations of CoQ10 in cancer are limited and the few studies that have been reported have involved small numbers of participants. Importantly, the incidence of CoQ10 deficiency has been found to be significantly higher in cancer patients than in healthy controls.CoQ10 deficiency has also been reported in women diagnosed with breast cancer. In a study conducted in 200 women hospitalized for breast cancer surgery, a CoQ10 deficiency was noted in patients with both malignant and nonmalignant breast lesions. In contrast, CoQ10 deficiency at baseline was not observed in a prospective, placebo-controlled trial of CoQ10 administration in women with breast cancer and self-reported fatigue who were receiving adjuvant chemotherapy. Additionally, Folkers et al reported reductions of total CoQ10 levels in patients with myeloma. The importance of potential CoQ10 deficiencies in these patients is unclear, however.
Of some concern is the finding reported from the largest epidemiologic evaluation of CoQ10, in which investigators described a positive association between higher prediagnostic levels of CoQ10 and breast cancer risk in postmenopausal women. In contrast, Rusciani et al reported an association between low CoQ10 levels and metastasis and progression of melanoma, while Palan et al reported an inverse association between cervical intraepithelial neoplasia and cervical cancer with circulating levels of CoQ10.[40,41]
A number of trials have evaluated the ability of CoQ10 supplementation to ameliorate or prevent cardiotoxicity in patients receiving anthracycline chemotherapy. Iarussi et al reported a protective effect for CoQ10 on left ventricular global function during anthracycline therapy in a prospective, randomized, controlled trial in 20 children.
Okuma et al described no changes in QRS voltage or QTc duration in a heterogeneous group of 39 patients receiving CoQ10 along with doxorubicin-containing chemotherapy, whereas decreased QRS voltage and lengthened QTc duration was seen in a 41-patient control group.
Until recently, no published data existed on the effects of CoQ10 on fatigue in patients with cancer. As a result, we performed a prospective, randomized, double-blind, placebo controlled study of Co-Q10 in women with breast cancer and self-reported fatigue while receiving adjuvant chemotherapy. Between 2004 and 2009, a total of 236 women were enrolled.
Treatment arms were well balanced with respect to age, performance status, ethnicity, and planned chemotherapy. At 24 weeks, there were no significant differences between the CoQ10 and placebo arms on the POMS-Fatigue, FACIT-Fatigue, or FACT-Breast subscales despite sustained increases in serum CoQ10 levels in treated patients. No serious adverse events were noted. Therefore, these data provide no support for an effect of CoQ10 supplementation on fatigue in newly diagnosed breast cancer patients.