Assessment of cholesterol oxidation products in statin-treated subjects after a plant sterol-food supplement intake

Cholesterol oxidation products (COPs) are major contributors to atherosclerosis through endothelium adhesion induction and inflammation [1]. Subjects with elevated levels of plasma cholesterol tend to have higher COPs levels as well. The traditional pharmacologic treatment for reducing plasma cholesterol, statins, fails to prevent COPs formation, though. In this sense, bioactive compounds such as plant sterols (PS) could be an effective alternative due to its hypocholesterolemic and anti-inflammatory effects [2], linked to a potential COPs decreasing activity. The aim of this randomized, double-blind, parallel clinical trial was to examine the impact of consuming a PS supplement (2 g PS/day) on plasma COPs levels in individuals with hypercholesterolemia who were undergoing statin treatment. The potential link between this outcome and lifestyle was also considered. A total of twenty-six participants (fifteen women) were randomly assigned to a PS food supplement group (case) or a placebo group (control). Surveys regarding physical activity (IPAQ-short) and Mediterranean diet adherence (MEDAS) were performed at the beginning of the treatment. Blood samples were collected before (T0) and after a 6-week intervention (T1), and plasma was immediately isolated and stored. Sterols from plasma were extracted with diethyl ether, purified by solid phase extraction (SPE-NH2), and derivatized. Cholesterol and six COPs (α-epoxy-cholesterol, β-epoxy-cholesterol, cholestanetriol, 7α-hydroxy-cholesterol, 7β-hydroxy-cholesterol, and 7-ketocholesterol) were identified and quantified using gas chromatography/mass spectrometry [3]. Both groups presented similar baseline cholesterol levels; however, none of them showed a statistically significant decrease (p > 0.05) after the intervention, even though the case group showed a slight trend to decrease (10.6%, compared to 5.5% decrease in the control group). The same lack of decrease was observed for total and individual COPs levels. The dietary habits of subjects were relatively good, as none of the subjects presented low adherence to the Mediterranean diet. Nevertheless, the level of physical activity was generally low, most subjects being classified as low activity. No association between these lifestyle parameters and COPs levels was found (p > 0.05). The low study population, together with a high variability in the levels of the parameters assessed, may explain these results. For this reason and given the strong evidence supporting the cholesterol-lowering effects of PS, larger studies assessing these parameters would be of uttermost interest to explore more deeply the influence of PS on cardiovascular risk factors. 1 Kulig et al. Chem Phys Lipids, 2016, 199, 144–160. 2 Alvarez-Sala et al. Food Funct, 2018, 9, 5209–5219. 3 Cardenia et al. J Sep Sci, 2012, 35, 424–430.