No 'Go' with CoQ10 for Treatment-Related Fatigue

Abstract & Commentary

This article originally appeared in the July 2012 issue of Integrative Medicine Alert.

Synopsis: Results of this well-done trial strongly suggest that CoQ10 administration over 24 weeks' time does not help relieve the treatment-related fatigue experienced by a significant proportion of women with newly diagnosed breast cancer.

Source: Lesser GJ, et al. A randomized, double-blind, placebo-controlled study of oral coenzyme Q10 to relieve self-reported treatment-related fatigue in newly diagnosed patients with breast cancer. J Support Oncol doi.org/10.1016/j.suponc.2012.03.003.

The majority of people receiving treatment for cancer experience a degree of fatigue that severely impairs their quality of life, and very few generally effective treatments exist to address the condition. The authors designed this randomized, double-blind, placebo-controlled study of coenzyme Q10 (CoQ10) in women with newly diagnosed breast cancer beginning adjuvant chemotherapy to evaluate CoQ10 supplementation's effect on treatment-induced fatigue, overall quality of life (QOL), and depression. Together with other eligibility criteria, subjects had to have an Eastern Cooperative Oncology Group (ECOG) performance status < 2 (at least able to walk and manage self-care) and not have lost more than 5% of their total body weight in the prior 3 months. Participants were stratified by chemotherapy type (anthracycline vs no anthracycline) and whether they received radiation therapy, and were then randomized to receive either 300 mg CoQ10 (Soft Gel Technologies, Los Angeles, California) or placebo daily, each combined with 300 IU vitamin E (to facilitate absorption, also from Soft Gel Technologies, Los Angeles, California), in divided doses three times a day with food for 24 weeks. Interventions were begun no later than 4 days after treatment with chemotherapy had started. Adherence to study protocol was assessed through serial determinations of serum CoQ10 and vitamin E levels at baseline and following 8, 16, and 24 weeks of treatment. Various QOL tools were employed to capture information on the primary outcome of fatigue, as well as the secondary endpoints of overall QOL, depression, and social support, and included the POMS-F, the FACIT-F, a self-reported LASA-Fatigue score, the FACT-B, CES-D, and the Medical Outcomes Study Social Support Survey (all of which are well-described by the study authors). Assessments were made at baseline and then after 8, 16, and 24 weeks of therapy.

A total of 236 women participated in the study (age range 28-85 years, median = 51 years; 87% non-Hispanic whites). The vast majority (84%) were receiving anthracycline chemotherapy, and more than half (61%) also received radiation therapy. Subjects generally reported low levels of fatigue at baseline, while 44% had serum CoQ10 levels deemed lower than normal (< 0.64 µg/ mL). By 8 weeks' time, CoQ10 levels had tripled in the intervention group from a mean (SD) of 0.7 (0.4) µg/mL at baseline to 2.2 (1.2) µg/mL; however, average post-treatment CoQ10 levels were lower than baseline in 12% of participants in the CoQ10 arm. Vitamin E levels almost doubled from 13.8 (8.7) µg/mL at baseline to 24.1 (15.1) µg/mL at 8 weeks, but again average post-treatment vitamin E levels were lower than baseline for 11% of subjects. Fatigue increased significantly in both groups once chemotherapy was initiated (P < 0.001) and gradually lessened thereafter, never returning to pretreatment levels. Models of treatment effect failed to show any benefit from CoQ10 supplementation compared with placebo for the relief of treatment-related fatigue regardless of baseline and subsequent serum CoQ10 concentration at any time during the study, including at trial's end (24 weeks). Subjects in both treatment groups experienced an overall decrease in QOL (P < 0.001); this was not significantly ameliorated by CoQ10 administration. Likewise, the non-significant increase in depressive symptoms detected following the start of adjuvant chemotherapy was not impacted by the use of CoQ10 when compared with placebo. Adverse effects experienced by participants were not significantly different between the two groups. The researchers conclude that their results show there is no benefit to supplementation with "standard-dose" CoQ10 for the management of treatment-related fatigue in women newly diagnosed to have breast cancer.

Commentary

A review of the therapeutic approach to cancer-related fatigue published last year reported that 50-90% of people being treated for cancer, especially those receiving different modalities, experience distressing fatigue that dramatically impairs QOL and often impacts their ability to complete their course of treatment.1 The National Comprehensive Cancer Network defines cancer-related fatigue as "a persistent subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that significantly interferes with usual functioning."2 Notably, it is not usually relieved with rest alone.

Regular screening for fatigue throughout treatment is now recommended; however, available treatment options remain largely ineffective. Such was the genesis of the current study, especially in light of the fact that CoQ10 is known to play an important role in energy production within mitochondria and has been shown to benefit exercise capacity in some people with mild-to-moderate left heart failure at doses as low as 100 mg per day. How disappointing then that, even with significant increases in CoQ10 levels in the majority of subjects receiving active therapy at a dose of 300 mg daily, no meaningful benefit was experienced with respect to perceived energy levels and activity. The finding that slightly more than 10% of participants did not achieve significant increases in serum levels of CoQ10 and vitamin E is interesting, but is little more than a footnote in relation to the central findings, and does not weaken the argument against CoQ10's use for the management of treatment-related fatigue.

The authors rightly point out that attrition was very high (97 subjects withdrew prior to their final assessments), but this is not uncommon with the study population at hand. Reasons for withdrawal were in line with those common to almost all studies addressing cancer patients and were heavy on treatment toxicity, including inability to tolerate oral medications.

The search for interventions that offer meaningful relief from treatment-related fatigue for people with cancer is far from over. Non-pharmacological means that show promise include regular exercise and cognitive behavioral therapy, but there is little or no reason to further pursue the potential benefit of CoQ10 in this setting — it is not indicated.

References

1. Campos MP, et al. Ann Oncol 2011;22:1273-1279.

2. Mock V, et al. Oncology 2000;14:151-161.