In our current study, supplementation with CoQ10 for 24 weeks not only improved serum levels of glucose, insulin, TG, LDL-c and ApoA-I / ApoB, but also increased serum adiponectin and decreased resistin. In CoQ10 group, change in adiponectin and resistin was correlated with the improvement of glucolipid profile.
As a lipophilic antioxidant, CoQ10 regulated lipid and glucose profile in a series of diseases, such as diabetes and metabolic syndrome. Consistently, our study also concluded that in Chinese dyslipidemia patients, long-term CoQ10 supplementation improved their insulin sensitivity and lipid profile. Though less powerful and cost-effective than clinical medication in lipid lowering and hypoglycemic therapy, CoQ10 has benefits on multiple risk factors of cardiovascular disease, including lowering blood pressure, blood glucose, lipids and HOMA-IR. Moreover, as a natural endogenous compound, supplementation of CoQ10 cause few side effect. Therefore, CoQ10 is quite a good option for those who have moderate dyslipidemia with borderline hypertension and prediabetes.
Adipokines were closely related to lipid and glucose metabolism. Several trials had explored the relation between adipokines and CoQ10 supplementation in various metabolic diseases with conflicting conclusions[18–21]. To our knowledge, this is the first study to examine the effect of supplementation with CoQ10 on serum adipokines in patients with dyslipidemia. Leptin is secreted by adipose tissue and transported through blood brain barrier to acted on neuroendocrine axes, plays an important role in anorexia and energy expenditure. leptin is a reliable marker of percentage of fat mass. Increased circulating leptin was observed in insulin resistance and T2DM and correlated positively with lipids levels. In previous studies, CoQ10 supplementation significantly reduced leptin levels in individuals with non-alcoholic fatty liver disease and type 2 diabetes, which were inconsistent with our study. The conflicting results may come from that the baseline serum level of leptin in the present study (13.17 ng/mL) was much lower than previous two RCTs (26.94 ng/mL in patients with non-alcoholic fatty liver disease and 23.51 ng/mL in patients with type 2 diabetes). Accordingly, participants in our study were much thinner (mean BMI was 25.07 kg/m2) than those two RCTs (mean BMI was 28.96 kg/m2 in patients with non-alcoholic fatty liver disease and 28.99 kg/m2 in patients with type 2 diabetes). Our results also shown that CoQ10 did not cause significant weight loss. Therefore, it was not surprising to observe a less remarkable improvement in leptin in subjects who per se had moderate increased of leptin and BMI. However, we cannot totally rule out the possibility that CoQ10 influence leptin secretion.
Several published RCTs had reported conflicting effect of CoQ10 in adiponectin in various diseases. CoQ10 supplementation at 100 mg/d for 12 weeks increased adiponectin concentration in individuals with non-alcoholic fatty liver disease and mild hypertension. A dose of 200 mg/d CoQ10 supplemented for 8 weeks increased serum adiponectin in individuals with type 2 diabetes. The increase of adiponectin was parallel with the ameliorative effects on lipid peroxidation and glucose control. Results from our present study were coincident with these trials. However, study conducted by Moazen et al found that CoQ10 supplemented at a dose of 100 mg/d in type 2 diabetes for 8 weeks showed no significant difference in adiponectin when compared to the placebo control. In healthy, nonsmoking, sedentary men, CoQ10 supplementation at 100 mg/d for 8 weeks also suggested no improvement of adiponectin. The limited intervention time (less than 12 weeks) and mild illness condition may account for the negative results of adiponectin responded to CoQ10 supplementation.
Adiponectin was thought as a protective adipokine. Extensive evidence have demonstrated anti-atherosclerotic, anti-diabetic, and anti-inflammatory activities that adiponectin possessed. In contract to leptin, serum adiponectin level was inversely correlated with body fat and obesity[30, 31]. Weight loss due to caloric restriction or insulin sensitivity improvement due to pharmacological treatment  would raise adiponectin concentration. The gene expression of adiponectin is tightly controlled by a number of factors. PPAR-γ, which is expressed mainly in adipose tissue, is the major positive regulator of adiponectin gene expression. In contrast, inflammation factors such as tumor necrosis factor-alpha (TNF-α) inhibit adiponectin gene expression. CoQ10 intervention can raise the expression of PPAR-γ in peripheral blood mononuclear cells of subjects with polycystic ovary syndrome. CoQ10 can also partially attenuate the effect of TNF-α on PPAR-γ in HL-1 cardiomyocytes. Then in the present study, we found that CoQ10 could up-regulate adiponectin at the 12th week of intervention, and the effect was more obvious at the 24th week. Remarkable, the increased of adiponectin was related to the improvement of HOMA-IR and lipid profiles. These results further suggested that adiponectin may be an important pathway and target of CoQ10 to improve lipid and glucose metabolic disorders. However, more studies were needed to further confirm them.
Resistin is a signalling molecule that is induced during adipogenesis and secreted mainly by white adipocytes. The concentration of serum resistin increased in genetic and diet-induced obesity. Resistin decreased insulin-stimulated glucose uptake in vitro and impaired glucose tolerance in mice. In human studies, however, resistin is synthesized predominantly by mononuclear cells inside and outside adipose tissues[38, 39]. It can increase the production of the proinflammatory cytokines through the transcription factor NF-κB in mononuclear cells and adipicytes[40, 41]. Plasma resistin levels have been correlated with TNF-α and interleukin-6 (IL-6) in coronary atherosclerosis patients. As we known, chronic inflammation were involved in the pathogenesis of obesity, type 2 diabetes and atherosclerosis. Therefore, resistin has been suggested as an important modulator and predictor of the activity of related diseases.
To our knowledge, this is the first study to investigate the effect of CoQ10 on resistin. Supplementation of CoQ10 for 24 weeks reduced serum resistin. Moreover, change in resistin concentration was positively correlated with the change in HOMA-IR and TG in CoQ10 group, indicating that inflammation signaling pathway modulated by resistin may be involved in the regulation mechanism of CoQ10 on dyslipidemic patients. Interestingly, we did not found significant improvement of high-sensitivity C-reactive protein by CoQ10. Prospective study in atherosclerosis patients showed that resistin was a predictive factor for coronary atherosclerosis in humans, independent of CRP. Other study also suggested that resistin's intracellular signaling pathway was distinct from other common cycotine. Whether the reduction of resistin by CoQ10 was the result from the amelioration of metabolic condition, or suggested a new mechanism need further investigation. Resisitin has been suggested as a marker of the severity of myocardium ischemic injury, the change of resistin by CoQ10 in dyslipidemic patients indicated a decreased risk for them to develop atherosclerosis.