Increases in plasma plant sterols stabilize within four weeks of plant sterol intake and are independent of cholesterol metabolism.

BACKGROUND AND AIMS: Plant sterols (PS) lower plasma LDL-cholesterol through partial inhibition of intestinal cholesterol absorption. Although PS themselves are poorly absorbed, increased intakes of PS result in elevated plasma concentrations. In this paper, we report time curves of changes in plasma PS during 12 weeks of PS intake. Furthermore, the impact of cholesterol synthesis and absorption on changes in plasma PS is explored. METHODS AND RESULTS: The study was a double-blind, randomized, placebo-controlled, parallel-group study with the main aim to investigate the effects of PS on vascular function (clinicaltrials.gov: NCT01803178). Hypercholesterolemic but otherwise healthy men and women (n = 240) consumed low-fat spreads without or with added PS (3 g/d) for 12 weeks after a 4-week run-in period. Blood sampling was performed at week 0, 4, 8 and 12. Basal cholesterol-standardized concentrations of lathosterol and sitosterol + campesterol were used as markers of cholesterol synthesis and absorption, respectively. In the PS group, plasma sitosterol and campesterol concentrations increased within the first 4 weeks of intervention by 69% (95%CI: 58; 82) starting at 7.2 µmol/L and by 28% (95%CI: 19; 39) starting at 11.4 µmol/L, respectively, and remained stable during the following 8 weeks. Placebo-corrected increases in plasma PS were not significantly different between high and low cholesterol synthesizers (P-values >0.05). Between high and low cholesterol absorbers, no significant differences were observed, except for the cholesterol-standardized sum of four major plasma PS (sitosterol, campesterol, brassicasterol and stigmasterol) showing larger increases in low absorbers (78.3% (95%CI: 51.7; 109.5)) compared to high absorbers (40.8% (95%CI: 19.9; 65.5)). CONCLUSIONS: Increases in plasma PS stabilize within 4 weeks of PS intake and do not seem impacted by basal cholesterol synthesis or absorption efficiency. This study was registered at clinicaltrials.gov (NCT01803178).

Modified Corneosurfametry as a new accelerated high-throughput ex vivo methodology for predicting cleanser effects towards human skin.

BACKGROUND: Corneosurfametry (CSM) was originally developed as a tool to predict irritation potential of cleansers. In this method, surface skin stripped using cyanoacrylate is contacted with surfactants/products, rinsed and stained with toluidine blue and basic fuschin dyes. The intensity of staining increases with increases in irritation potential of surfactant. Our objective was to modify the CSM technique to achieve better control of the tape stripping process. Another objective was to correlate the modified CSM (MCSM) with a traditional in-vivo forearm controlled application test (FCAT) for mildness and to explore its utility to assess the state of corneum after a clinical test. METHODS: Surface skin cells were tape stripped from forearms of volunteers with D-Squame Adhesive Discs. Discs were treated with a 10% solution of the product in a 96-plate well for 10 min, rinsed, dried and treated with basic fuschin-toluidine blue dye solution, rinsed and dried again. Forearm Controlled Application Test (FCAT) was based on a published protocol. Tape strips obtained after product treatment were also analyzed by the MCSM procedure without additional product treatment. RESULTS: Mildness/barrier damage assessed from in-vivo FCAT showed a similar ranking to the MCSM results. MCSM, TEWL and Erythema analysis of between-treatment differences showed a good correlation indicating that barrier damage seen in in-vivo studies can be predicted from ex-vivo MCSM studies. MCSM analysis of tape strips after the FCAT study showed that the damage decreased with increase in tape strip number. A moisturizing body wash (MBW) with mild surfactants showed the least damage in all layers. In contrast, harsh dish washing liquid showed significantly higher damage down to several layers. Another MBW with petrolatum in a harsher base showed damage almost similar to that of the harsh dish washing liquid in the surface layers. Thus, the MCSM was able to show underlying damage which would have been normally masked by the deposited petrolatum. CONCLUSION: The MCSM assay was shown to be a valuable tool for accelerated high throughput evaluation of mildness of surfactants and fully formulated products. MCSM can also be used to assess the state of the corneum after a product treatment.

Effect of a plant sterol-enriched spread on biomarkers of endothelial dysfunction and low-grade inflammation in hypercholesterolaemic subjects.

Plant sterols (PS) lower LDL-cholesterol, an established risk factor for CHD. Endothelial dysfunction and low-grade inflammation are two important features in the development of atherosclerosis. Whether PS affect biomarkers of endothelial function and low-grade inflammation is not well studied. The aim of the present study was to investigate the effect of regular intake of PS on biomarkers of endothelial dysfunction and low-grade inflammation. In a double-blind, randomised, placebo-controlled, parallel-group study, which was primarily designed to investigate the effect of PS intake on vascular function (clinicaltrials.gov: NCT01803178), 240 hypercholesterolaemic but otherwise healthy men and women consumed a low-fat spread with added PS (3 g/d) or a placebo spread for 12 weeks. Endothelial dysfunction biomarkers (both vascular and intracellular adhesion molecules 1 and soluble endothelial-selectin) and low-grade inflammation biomarkers (C-reactive protein, serum amyloid A, IL-6, IL-8, TNF-α and soluble intercellular adhesion molecule-1) were measured using a multi-array detection system based on electrochemiluminescence technology. Biomarkers were combined using z-scores. Differences in changes from baseline between the PS and the placebo groups were assessed. The intake of PS did not significantly change the individual biomarkers of endothelial dysfunction and low-grade inflammation. The z-scores for endothelial dysfunction (-0·02; 95 % CI -0·15, 0·11) and low-grade inflammation (-0·04; 95 % CI -0·16, 0·07) were also not significantly changed after PS intake compared with placebo. In conclusion, biomarkers of endothelial dysfunction and low-grade inflammation were not affected by regular intake of 3 g/d PS for 12 weeks in hypercholesterolaemic men and women.