4. Discussion
±, LDL-C reduction, ASCVD
SECONDARY, ASCVD, CHOLESTEROLEMIA
During the last two decades, a large and compelling body of evidence has accumulated in support of the use of lipid-lowering dietary supplements in patients at low ASCVD risk, for whom pharmacological treatment is not recommended [Plant sterols impair cholesterol absorption from the bowel via different mechanisms: by competing with dietary and biliary cholesterol for micellar solubilization in the intestinal lumen, impairing intestinal cholesterol absorption, altering the conversion of bile acids into secondary bile acids, and lowering the bile acid hydrophobic/hydrophilic ratio [In the DESCO study, we tested a new ready-to-drink dietary supplement containing 2.5 g of plant sterols to evaluate its LDL-C-lowering effect, as well as the interaction between plant sterols and the quality of the diet on the lipid profile. At 3-week follow-up, supplementation with phytosterols, as expected, was associated with significant improvement in plasma TC, LDL-C, and Apo B-100 compared to baseline and as an adjunct to their standard diet. TC and LDL-C reduction were also significantly reduced when compared to placebo. The dietary supplement was well tolerated and compliance with the treatment was high. The LDL-C reduction we observed was higher than that obtained with plant sterol-enriched foods such as bread, biscuits, and cereals, but lower than that registered with plant sterol-enriched foods such as butter, margarine, and spreads [Interestingly, in our study, greater adherence to the Mediterranean diet significantly correlated with a more relevant clinical improvement in LDL-C (−9.2 ± 11.8%) and TC (−12.3 ± 8.6%), thereby suggesting a potential synergy between phytosterol and other active components of the Mediterranean diet. A possible explanation of this observation might be the larger quantity of polyphenols usually found in the Mediterranean diet [Despite its many strengths, we acknowledge that our study has some limitations. For instance, the washout period was short, so it could be argued that our outcome was affected by a carry-over effect. On the other hand, it must be considered that phytosterols, as previously mentioned, mediate their blood cholesterol-lowering effect via selectively inhibiting the absorption of cholesterol by the small intestine, without enzymatically interfering with its synthesis in the liver. For this reason, a carry-over effect is unlikely, especially because the active treatment period was short. Of course, the short duration of the supplementation could have partially reduced the observed treatment-dependent lipid-lowering effect. However, our purpose was to evaluate whether the tested treatment was able to exert a significant effect on LDL-C in the short term, i.e., the three weeks that the European regulation indicates is the useful time for obtaining a cholesterol-lowering effect. Crossover after washout and the subsequent re-evaluation of study endpoints strengthened the trial.Of course, it is critically important that further longer-term clinical studies also investigate biomarkers for intestinal cholesterol absorption to ensure a more precise interpretation of the results. In effect, it is well known that there is a great interindividual variability in response to plant sterol supplementation [Overall, once our data are confirmed on larger trials, the tested product could be an effective and safe treatment option to improve cholesterolemia in the population and, consequently, a possible ethical business opportunity for food companies. 