In this cross-sectional study, ox-LDL concentrations were positively associated with GPx activity and inversely associated with nail selenium levels, both recognized antioxidant markers, in healthy young adults.
GPx is an important antioxidant enzyme, which has been used as oxidative stress marker concerning to an altered antioxidant balance [4, 33]. Previous studies have supported the positive predictive effect of GPx activity on circulating levels of ox-LDL [16, 18]. Experimental studies showed an increase in the activity of this enzyme in endothelial cells or macrophages treated with ox-LDL, as a protective mechanism against the increased generation of reactive oxygen species induced by ox-LDL [17, 18], while other observational study reported also a positive association between GPx activity and ox-LDL in healthy young Spanish adults, despite it was not statistically significant . Thus, our findings are in agreement to the hypothesis that a positive association between GPx activity and ox-LDL might constitute a consequence of the high ox-LDL concentrations, being an adaptive mechanism to prevent further oxidative imbalance.
In turn, our study demonstrated, apparently for the first time, the negative association of nail selenium levels and ox-LDL concentrations, whereas an increase of 1 ng of selenium per g of nail was associated with a decrease of 0.06 U/L in ox-LDL. Selenium is an essential antioxidant mineral, whereas its increased consumption has been inversely associated with pro-inflammatory markers [34, 35] as well as with lower hypercholesterolemia [36, 37] and lower LDL susceptibility to oxidation . In addition, increased nail selenium levels also have been related to lower pro-inflammatory marker concentrations, such as complement C3 factor, asymmetric dimethylarginine, and interleukin-18 in young healthy adults [13, 14, 19]. According to previous and onset findings, it could speculate an inverse relationship between dietary selenium intake and the oxidation of LDL-c. Moreover, our finding reinforces the measurement of this mineral in the nail as a promising alternative to assess the relationship of dietary selenium and pro-inflammatory and oxidative stress markers, since it is a good indicator of dietary selenium intake , which in turn, has a limited assessment by the scarcity of information in the tables of food composition and by influence of several factor on its bioavailability .
Furthermore, ox-LDL was positively associated with other lipid biomarkers, such as total cholesterol and LDL-c, in accordance to previous studies [7, 8, 16, 41, 42]. Interestingly, the participants of this study are young adults predominantly normolipidemic (total cholesterol <200 mg/dL and LDL-c <160 mg/dL represent 92.5 and 97.5% of the sample, respectively). Thus, it is noteworthy that the increase of 1 mg/dL in serum total cholesterol or in LDL-c as well as of one unit in the total cholesterol-to-HDL-c ratio was predictors of an increment of 0.22; 12.21 and 15.78 U/L in ox-LDL concentrations, respectively. Thus, despite the cross-sectional nature of this study, we could speculate that the positive association between lipid profile and ox-LDL - a recognized oxidative stress marker - occurs early and could explain, at least in the part, the time-course dependent relationships between oxidative stress and chronic disorders in middle-aged and older subjects.
Other relevant outcome of this study was the relationship between uric acid and ox-LDL concentrations, independently of gender, age, smoking status, physical activity, whereas the addition of 1 mg/dL in serum uric acid was associated with the increase of plasma ox-LDL in 4.4 U/L. In this sense, hyperuricemia (≥ 7 mg/dL) has been considered a risk factor for cardiovascular diseases [9, 10, 43] and a positive predictor of the occurrence of small and dense LDL-c, more susceptible to oxidation . Moreover, uric acid concentration higher than 4 mg/dL appears to have a pro-oxidant redox effect , in addition to its synthesis can lead to the generation of superoxide anion radicals, hydroxyl and hydrogen peroxide . The results reported by other authors suggest the role of uric acid in the relationship between oxidative stress and cardiovascular diseases, while the finding of this study might establish a new link of uric acid with oxidative conditions. However, the association between uric acid and ox-LDL was attenuated after adjusting for truncal fat and cholesterol total concentrations, indicating that this relation could be conditioned by other oxidative and metabolic-related risk factors, as previously postulated by other authors [11, 43].
Regarding the association of ox-LDL concentrations with anthropometric and body fat distribution data, BMI was significantly higher in those individuals with high ox-LDL, while truncal was significantly positively associated with ox-LDL concentrations. However, both variables were not able to predict to ox-LDL concentrations, which is not in agreement with other studies [6–8]. In fact, the body fat distribution, characterized by central fat accumulation, has been associated with increasing in pro-inflammatory and oxidative stress markers [6, 23, 45]. In this context, the lack of associations between concentrations of ox-LDL and adiposity indicators in this study could be explained by the predominance of normal-weight individuals (BMI <25.0 kg/m2; 85% of the sample) or by relatively small size of sample.
Moreover, ox-LDL was not related to glucose biomarkers in young adults. On one hand, some studies have demonstrated the association of hyperglycemia and hyperinsulinemia with increased circulating levels of ox-LDL [7, 41, 46]. On the other hand, other authors found no significant correlations between circulating levels of ox-LDL and glucose biomarkers [42, 47]. Likely, differences in the study sample, such as gender distribution, age, obesity degree or body fat distribution, might influence the outcomes .
Our study had certain limitations. The cross-sectional design did not clearly elucidate the cause-and-effect on the results. In addition, the residual confounders that may affect the oxidization of lipoproteins, but were not included in our present study (i.e. dietary factors), should also be considered. Finally, further replication in independent and larger samples would be convenient for a future translational application at a population level, although the sample size is adequate from the standpoint of the initial association discovery, with a satisfactory statistical power in the most relevant analyses of this work.