## 4 Discussion  
This controlled nutritional and interventional study was designed to investigate whether the acute consumption of a functional refined olive oil, enhanced with bioactive compounds from orange peel extract, could have a beneficial effect on the postprandial metabolic biomarkers of individuals at cardiometabolic risk. We hypothesized that the ingestion of the novel refined olive oil, enhanced with orange peel polyphenols, parallel with a meal rich in fat and carbohydrates, may lead to milder postprandial lipidemic, glycemic, and oxidative stress responses, rather than the ROO, in cardiometabolic risk participants, based on the existing evidence of the efficacy of polyphenols in the modulation of postprandial lipidemic, glycemic, and oxidative metabolisms [17, 21, 27]. The estimated initial 10-year cardiovascular risk of the participants ranged at similar levels to those predicted in European men and women who live in low-risk countries, according to European Society of Cardiology (ESC) data [26]. The primary finding of the study indicated that the acute intake of the novel refined olive oil, enhanced with 10% \(w/v\) orange peel extract, may lead to modulation of LDL-cholesterol postprandial metabolism, in comparison with the standard ROO, in the context of a high-fat and high-carbohydrate meal. This effect was highlighted by a gradual decrease in LDL-cholesterol levels during the 3-h metabolism. It is well-known that olive oil can modulate postprandial cholesterol metabolism, due to the presence of bioactive components such as unsaturated fatty acids and polyphenols, which are key contributors to the protection against the LDL-cholesterol oxidation, a pathway implicated in the atherosclerosis process [28]. In fact, there is evidence that the polyphenic content of human LDL increases in a dose-dependent manner with the total phenolic content of VOO consumed [2]. The main mechanism, described by [PERSON] et al. for this effect, is the polyphenols' binding, mainly tyrosol and its metabolites, by human LDL. However, the same clinical study showed that after the intake of a ROO, polyphenols were not detected in the blood, due to low concentration of polyphenols in the ROO [29]. This conclusion may explain the non-significantly changed concentrations of LDL-cholesterol, after the administration of the standard ROO rather than the novel refined olive oil, in participants at cardiometabolic risk. The results of a nutritional intervention by [PERSON] et al. indicated that the daily intake of 25 mL ROO for six weeks resulted in increased LDL-cholesterol levels, while the ingestion of the same amount of EVOO decreased this biomarker's concentration, in participants with at least one of the major cardiovascular risk factors [20]. Another clinical study, conducted by [PERSON] et al., demonstrated that the three-week supplementation of the diet with 25 mL/day of low-polyphenyl-content ROO significantly increased the number of total and small LDL particles, while the ingestion of high-polyphenyl-content VOO for the same time period resulted in decreased concentrations [30]. It is worth mentioning that hesperidin, one of the main bioflavonoids found in orange peel, has been reported to present hypolipidemic and anti-inflammatory effects, possibly by the enhancement of the gene encoding the LDL receptor expression [31]. Given the fact that ROO contains a minor polyphenic concentration [20], the LDL-cholesterol modulatory effect could be attributed to the presence of a concentration almost four times higher of polyphenols in the novel refined olive oil, enhanced with orange peel extract. Recent findings from an in vitro study by [PERSON] et al., evaluating the antioxidant capacity and the total polyphenic content of selective fruit by-products, indicated that orange peel may provide 7.16 milligrams of gallic acid per gram of dry mass [32]. However, the present nutritional intervention did not differentially affect the kinetics of postprandial lipids or cholesterol metabolism, in the three-hour postprandial phase.