## 4 Discussion
Total and HDL-cholesterol, as well as plasma triglycerides, seemed to peak at 30 min after the meal intake, following by similar, incremental weakening until the endpoint. These findings are in contrast to the results of previous studies [11]. In particular, there are indications that hesperidin in orange peel may exhibit bioactivity on endothelial function and other pro-inflammatory responses, but this is transient and limited to the postprandial state [12]. Hesperidin and naringenin, present in orange peel, may contribute to thereduction of cholesterol esterification, reducing lipoprotein capacity and allowing a lower degree of cholesterol transport into circulation [33]. Nevertheless, our findings did not show such an acute effect. They may also inhibit the activity and expression of the microsomal triglyceride transfer protein (MTP) [33]. It is worth mentioning that some researchers report that the data on the effect of citrus bioactives on cholesterol levels are limited, while their ineffectiveness has been reported in moderately hypercholesterolemia individuals [33]. Orange peel flavonoids have been extensively mentioned for their antidiabetic activities, mainly due to their ability to increase insulin levels in the blood, affecting the improvement of pancreatic beta cells [34]. Moreover, in the postprandial phase, hesperidin has been suggested to be useful in preventing hyperglycemia, acting as an inhibitor of the intestinal glucose transporter [35]. Nevertheless, these data were not confirmed in the present study, as similar glycemic metabolism were observed, on both refined olive oils tested, in the specified measurements and time frames. Possibly, the polyphenols' concentration, provided by the orange peel extract, and by extension in the novel refined olive oil, was insufficient to exert postprandial bioactivity [19], which could lead to better glycemic response. Regarding plasma antioxidant status responses, total plasma antioxidant capacity showed an increase 30 min after receiving both meals, followed by a similar concentration reduction until 1.5 h after meal consumption. A differential antioxidant metabolism was observed at the last time period until 3 h, highlighted by a 20% rise in antioxidant levels in the functional group, while in the control group, 28.8% lowering levels were noticed. However, these differences were not captured in the overall antioxidant effect between the interventions over time, under the present analysis procedure. Despite the fact that previous findings indicate that polyphenic metabolites may play a key role in the acute induction of antioxidant capacity, mainly 1.5 h after the ingestion [10; 19], the present results are not completely clear and could describe only a trend of improved, postprandial antioxidant status. The presence of cardiometabolic risk factors in the clinical profiles of the participants may play a significant role in the differentiation of antioxidant responses between healthy and non-healthy individuals [36]. Further investigation is needed to clarify the possible beneficial effect. The significant supplementation of a challenge meal with natural antioxidants has been reported to beneficially affect the acute, postprandial metabolic kinetics, and thus the analysis of our findings remains complicated, regarding the cardiometabolic effects [11]. This pilot clinical trial presented some limitations. In this dietary intervention, the total, LDL-, and HDL-cholesterol, as well as the triglyceride levels, were assessed, but the postprandial responses of oxidized LDL-cholesterol (ox-LDL) and the concentration of very low-density lipoprotein (VLDL), which have been reported as key biomarkers when investigating postprandial lipid metabolism with an impact on acute inflammatory pathways, were not determined [29]. Other biomarkers of inflammation and endothelial function (e.g., C-reactive protein, interleukin, etc. ), as well as the insulin determination, could be added to our measurements [37].