In this clinical trial, we have demonstrated that coenzyme Q10 at the dose of 300 mg/d for 12 weeks increases the antioxidant enzymes activities (SOD, CAT, and GPx) and decreases inflammation in patients with CAD during statins therapy. Tiano et al.  administered coenzyme Q10 (300 mg/d) to patients with ischemic heart disease for 1 month, and they observed that those patients’ extracellular superoxide dismutase activity and endothelium-dependent vasodilatation were improved after supplementation. Antioxidant enzymes such as SOD, CAT, and GPx are the first line of defense against reactive oxygen species , and a decrease in their activities contributes to the elevated oxidative stress in CAD patients . Our previous results showed that coenzyme Q10 at a dose of 150 mg/d increased the activity of SOD by 22.2% and of CAT by 4.5%, but had no effect on that of GPx . In the present study, coenzyme Q10 supplementation at 300 mg/d increased the activity of SOD by 48.5%, CAT by 9.1%, and GPx by 4.3%, and the antioxidant enzymes activities were all positively correlated with the level of coenzyme Q10 after 12 weeks of supplementation (Table 3). It appears that the 300 mg dose of coenzyme Q10 has better antioxidation than 150 mg/d.
Both groups of statins-treated CAD patients in this study had a low level of coenzyme Q10 at baseline (Figure 2), and the level of coenzyme Q10 was significantly increased by approximately 5-fold after 4 weeks of coenzyme Q10 supplementation (data not shown; the median level of coenzyme Q10 was 0.4 to 2.0 μmol/L), which rapidly adjusted their low coenzyme Q10 level to normal values (0.5 – 1.7 μmol/L) . In addition, coenzyme Q10 had a synergic effect with vitamin E [30–33]. In this study, we observed that the level of vitamin E was significantly higher in the Q10-300 group (Figure 2) and was positively correlated with the level of coenzyme Q10 after 12 weeks of supplementation (Table 3). Coenzyme Q10 not only protects vitamin E against superoxide-driven oxidation but also regenerates vitamin E during antioxidation processes [32, 33].
CAD is considered to be a chronic inflammation status . In the present study, the level of TNF-α (Figure 4) and the changed levels of TNF-α and IL-6 were significantly decreased after coenzyme Q10 supplementation (Table 2). The level of coenzyme Q10 was significantly negatively correlated with inflammatory markers (TNF-α and IL-6) (Table 3). Schmelzer et al. [34, 35] demonstrated that coenzyme Q10 could exert anti-inflammation effects via the reduction of nuclear factor-κB (NF-κB) dependent gene expression. NF-κB can be activated by the reactive oxygen species and can then up-regulate pro-inflammatory cytokines expression. However, this NF-κB -activating cascade could be inhibited by antioxidants, such as coenzyme Q10 . Our previous results  showed that coenzyme Q10 at a dose of 150 mg/d decreased the level of IL-6 by 0.40 pg/mL. In the present study, coenzyme Q10 supplementation at 300 mg/d decreased the levels of TNF-α by 0.30 pg/mL and IL-6 by 0.52 pg/mL. However, coenzyme Q10 supplementation had no effect on the level of CRP. As we previously reported, proinflammatory cytokines (TNF-α and IL-6) reflect the status of inflammatory reactions with more sensitivity (easily changed) than CRP, which is a product of hepatic stimulation . A higher level of adiponectin is associated with a lower risk of CAD [20, 37], but coenzyme Q10 supplementation had no effect on the level of adiponectin in the present study. Nakamura et al.  reported that the concentration of plasma adiponectin was not significantly different between stable angina pectoris and control subjects. The subjects who had CAD in this study had not experienced acute myocardial infarction within the previous 6 months and thus were stable angina pectoris patients, which might be the reason why we did not find an effect of coenzyme Q10 on adiponectin.
Regarding the safety of statins therapy and its combination with placebo or coenzyme Q10 in the present study, there were no clinically significant changes in the subjects’ vital signs, serum chemical values, or hematological values, and there were no serious adverse events, no complaints of myalgia or muscle weakness, and no withdrawals due to adverse events. Thus, coenzyme Q10 at a dose of 300 mg/d is safe for co-administration with statins therapy.
Two limitations of the present study should be mentioned. First, the number of participants was small, although we did recruit more subjects than expected. Second, a few of the subjects had higher inflammation in the present study. Only 10% of the subjects had a high inflammation according to the level of CRP (≥ 3.0 mg/L), and this finding might have contributed to observing the null effect on CRP after the supplementation. Large studies are needed to establish the beneficial effect of coenzyme Q10 supplementation on inflammation, especially in subjects who have high inflammation status.