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Phytosterols Supplementation Reduces Endothelin-1 Plasma Concentration in Moderately Hypercholesterolemic Individuals Independently of Their Cholesterol-Lowering Properties.
Oliveira Godoy Ilha, A, Sutti Nunes, V, Silva Afonso, M, Regina Nakandakare, E, da Silva Ferreira, G, de Paula Assis Bombo, R, Rodrigues Giorgi, R, Marcondes Machado, R, Carlos Rocha Quintão, E, Lottenberg, AM
Nutrients. 2020;(5)
Abstract
Experimental and clinical studies have demonstrated the effect of phytosterols (PS) on reducing plasma levels of cholesterol and LDL-c, but the effects of plant sterols beyond cholesterol-lowering are still questionable. Since inflammation and endothelial dysfunction are involved in the pathogenesis of atherosclerosis, this study aims to evaluate the effect of PS on biomarkers involved in atherosclerosis progression and whether these effects are independent of alterations in plasma LDL-c levels. Thirty-eight moderately hypercholesterolemic volunteers (58 ± 12 years; LDL-c ≥ 130 mg/dL) were randomly assigned to consume 400 mL/day of soy milk or soy milk + PS (1.6 g/day) for 4 weeks in a double-blind, placebo-controlled, cross-over study. Blood samples were collected and lipid profiles and biomarkers for inflammation and endothelial dysfunction determined. The results showed that PS treatment reduced endothelin-1 plasma concentration by 11% (p = 0.02) independently of variations in plasma levels of LDL-c. No alterations were observed regarding fibrinogen, IL-6, hs-CRP, SAA, TNFα, or VCAM-1 between placebo and PS-treated groups. Furthermore, PS reduced total plasma cholesterol concentration (-5,5%, p < 0.001), LDL-c (-6.4%, p < 0.05), triglycerides (-8.3%, p < 0.05), and apo B (-5.3%, p < 0.05), without changing HDL-c concentration (p > 0.05). Therefore, PS supplementation effectively lowers endothelin-1 independently of the reductions in plasma levels of LDL-c, contributing to the comprehension of the effect of plant sterols on endothelial function and prevention of cardiovascular diseases.
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Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia.
Salen, G, von Bergmann, K, Lütjohann, D, Kwiterovich, P, Kane, J, Patel, SB, Musliner, T, Stein, P, Musser, B, ,
Circulation. 2004;(8):966-71
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Abstract
BACKGROUND Sitosterolemia is a recessively inherited disorder that results from mutations in either ABCG5 or G8 proteins, with hyperabsorption of dietary sterols and decreased hepatic excretion of plant sterols and cholesterol. As a consequence of markedly elevated plasma and tissue sitosterol and campesterol levels, premature atherosclerosis develops. METHODS AND RESULTS In this multicenter, double-blind, randomized, placebo-controlled study, we examined whether treatment with ezetimibe, an inhibitor of cholesterol absorption, reduces plant sterol levels in patients with sitosterolemia. After a 3-week placebo run-in, 37 patients were randomized to receive placebo (n=7) or ezetimibe 10 mg/d (n=30) for 8 weeks. Sitosterol concentrations decreased by 21% (P<0.001) in patients treated with ezetimibe compared with a nonsignificant 4% rise in those on placebo (between-group P<0.001). The reduction in sitosterol from baseline was progressive, with further decline observed at each subsequent biweekly visit. Campesterol also progressively declined, with a mean decrease after 8 weeks of 24% with ezetimibe and a mean increase of 3% with placebo treatment (between-group P<0.001). Reductions in plant sterol concentrations were similar irrespective of whether patients were undergoing concomitant treatment with resin or statin. Reductions in total sterols and apolipoprotein B were also observed. Ezetimibe was well tolerated, with no serious treatment-related adverse events or discontinuations due to adverse events being reported. CONCLUSIONS Ezetimibe produced significant and progressive reductions in plasma plant sterol concentrations in patients with sitosterolemia, consistent with the hypothesis that ezetimibe inhibits the intestinal absorption of plant sterols as well as cholesterol, leading to reductions in plasma concentrations.
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Plant sterols and endurance training combine to favorably alter plasma lipid profiles in previously sedentary hypercholesterolemic adults after 8 wk.
Varady, KA, Ebine, N, Vanstone, CA, Parsons, WE, Jones, PJ
The American journal of clinical nutrition. 2004;(5):1159-66
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BACKGROUND Plant sterol supplementation was shown to reduce total and LDL-cholesterol concentrations, whereas endurance training was shown to increase HDL-cholesterol concentrations and decrease triacylglycerol concentrations. OBJECTIVE The objective was to examine the effect of plant sterols, endurance training, and the combination of plant sterols and endurance training on plasma lipid and lipoprotein cholesterol concentrations, sterol concentrations, and cholesterol precursor concentrations in previously sedentary hypercholesterolemic adults. DESIGN In an 8-wk, placebo-controlled, parallel-arm clinical trial, 84 subjects were randomly assigned to receive 1 of 4 interventions: 1) combination of sterols and exercise, 2) exercise, 3) sterols, or 4) control treatment. RESULTS Sterol supplementation significantly (P < 0.01) decreased total cholesterol concentrations by 8.2% from baseline. In addition, sterols significantly (P < 0.01) lowered absolute LDL-cholesterol concentrations after treatment but had no effect on the percentage change from the beginning to the end of the trial. Exercise significantly (P < 0.01) increased HDL-cholesterol concentrations by 7.5% and decreased triacylglycerol concentrations by 13.3% from baseline. Moreover, sterol supplementation significantly (P < 0.05) increased lathosterol, campesterol, and beta-sitosterol concentrations after treatment. Exercise significantly (P < 0.01) decreased percentage of body fat by 3.9% from the beginning to the end of the trial. CONCLUSIONS In comparison with plant sterols or exercise alone, the combination of plant sterols and exercise yields the most beneficial alterations in lipid profiles. Implementation of such a combination therapy could improve lipid profiles in those at risk of coronary artery disease.
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Effects of phytosterol ester-enriched vegetable oil on plasma lipoproteins in healthy men.
Seki, S, Hidaka, I, Kojima, K, Yoshino, H, Aoyama, T, Okazaki, M, Kondo, K
Asia Pacific journal of clinical nutrition. 2003;(3):282-91
Abstract
It has been reported that phytosterol esters reduce cholesterol absorption and lower serum cholesterol concentration. There have been very few studies published on the effect of dose of phytosterol esters less than 1.0 g/day on plasma cholesterol levels in healthy subjects using commonly consumed foods. In this study, we evaluated the effect of 0.45 g/day (as free sterol) phytosterol ester-enriched dissolved in vegetable oil on plasma lipoproteins in sixty healthy males with slightly elevated total cholesterol concentration. This study was conducted in a randomized, double-blind, placebo-controlled, and arm parallel study. A total of 14 g/day of phytosterol ester-enriched vegetable oil containing 0.45 g phytosterol (as the major free sterol) was compared with a control vegetable oil containing 0.04 g phytosterol (as the major free sterol). All subjects did not change their usual dietary habit and consumed foods that included about 360 mg/day cholesterol for 12 weeks. In subjects with higher total cholesterol concentrations (>200mg/dL), the phytosterol enriched-vegetable oil significantly reduced total cholesterol (10.3%, P<0.05), very low density (VLDL) lipoprotein cholesterol (22.5%, P<0.05), and remnant-like lipoprotein (RLP) cholesterol (24.7%, P<0.01) compared with the control vegetable oil. A reduction in low density lipoprotein (LDL) cholesterol concentration was also observed. In particular, the improvement in serum lipoprotein was more pronounced in subjects with higher total cholesterol concentrations. Triglycerides and high density lipoprotein (HDL) cholesterol did not change significantly. Plasma concentration of fat-soluble vitamins (tocopherol and retinol) and beta-carotene were not statistically significantly affected by phytosterol ester-enriched vegetable oil. These findings indicate that a daily consumption of phytosterol ester as low as 0.45 g/day (as free sterol) is effective in lowering blood total cholesterol concentration and RLP cholesterol concentration. Lower total cholesterol, VLDL cholesterol and RLP cholesterol due to consumption of the phytosterol ester-enriched vegetable oil may be helpful in reducing the risk of CHD in the population.
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[Food phytosterol ester efficiency on the plasma lipid reduction in moderate hypercholesterolemic subjects].
Lottenberg, AM, Nunes, VS, Nakandakare, ER, Neves, M, Bernik, M, Santos, JE, Quintao, EC
Arquivos brasileiros de cardiologia. 2002;(2):139-42
Abstract
OBJECTIVE This study aimed at relating the pattern of response to dietary plant sterol ester (PSE) treatment of plasma lipids concentrations and apo E polymorphisms. METHODS Patients (20-60y old: 50 women; 10 men) with primary moderate hypercholesterolemia were fed margarine (20g/d), received no treatment (placebo), and were fed PSE (2.8g/d = 1.68 phytosterols), during 3 periods of 4 weeks each, in a crossover, double-blind study. DNA was extracted from white blood cells for the apo E polymorphisms. RESULTS PSE treatment significantly lowered TC and LDL-C 10% and 12%, respectively, in relation to the baseline, and 6% and 8% in relation to the placebo phase, but HDL-C and TG levels were not modified. In regard to the apo E genotyping, no significant difference occurred between apo E 3/3 and apo E (3/4). CONCLUSION Dietary plant sterol ester (PSE) treatment reduced cholesterolemia, and the reduction of LDL-C in absolute values was more pronounced when the initial LDL - C concentration were elevated.
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Serum plant sterols and biliary cholesterol secretion in humans: studies with ursodeoxycholic acid.
Lindenthal, B, Sudhop, T, Schiedermaier, P, Agnan, M, Sauerbruch, T, von Bergmann, K
Journal of lipid research. 2002;(7):1072-7
Abstract
Ratios of cholestanol, campesterol, and sitosterol to cholesterol in serum are known to reflect cholesterol absorption efficiency. Here, a possible link between these ratios and biliary secretion rates of cholesterol was investigated. Biliary lipid secretion rates and serum sterols were determined in 13 patients with gallstones. Seven were treated with ursodeoxycholic acid (UDCA) (1,000 mg/d). Serum cholesterol and non-cholesterol sterols were also measured in a cross over study in 20 healthy volunteers, who received either placebo or UDCA (750 mg/d). Biliary cholesterol secretion was significantly lower, whereas the non-cholesterol sterols and their ratio to cholesterol were higher in patients with gallstones treated with UDCA. A highly significant negative linear correlation between the ratios of non-cholesterol sterols to cholesterol and biliary cholesterol secretion was observed. In volunteers, administration of UDCA for 4 weeks was followed by a significant increase in non-cholesterol sterols and their ratios. Even 4 weeks after discontinuing UDCA administration, campesterol and sitosterol were still significantly higher than pretreatment levels, which was also true for the campesterol-cholesterol ratio after 8 weeks. The results suggest that the ratios of cholestanol, campesterol, and sitosterol to cholesterol can be used as indicators of changes in biliary cholesterol secretion rates.
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Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion.
Nissinen, M, Gylling, H, Vuoristo, M, Miettinen, TA
American journal of physiology. Gastrointestinal and liver physiology. 2002;(6):G1009-15
Abstract
Properties of the intestinal digestion of the dietary phytosterols, cholesterol and cholestanol, and the mechanisms by which phytosterols inhibit the intestinal absorption of cholesterol in healthy human subjects are poorly known. We have studied the hydrolysis of dietary plant sterol and stanol esters and their subsequent micellar solubilization by determining their concentrations in micellar and oil phases of the jejunal contents. Two liquid formulas with low (formula 1) and high (formula 2) plant stanol concentrations were infused via a nasogastric tube to the descending duodenum of 8 healthy human subjects, and intestinal contents were sampled for gas-liquid chromatographic sterol analysis 60 cm more distally. During the duodenal transit, phytosterol esters were hydrolyzed. This was especially profound for sitostanol, as its esterified fraction per milligram of sitosterol decreased 80% (P < 0.001) in formula 1 and 61% (P < 0.001) in formula 2. Contrary to that, esterified fraction of cholesterol per milligram of sitosterol was increased fourfold (P < 0.001) in formula 1 and almost sixfold (P < 0.001) in formula 2, whereas that of cholestanol remained unchanged. Percentages of esterified sterols and stanols in total intestinal fluid samples were higher after the administration of formula 2 than of formula 1. Esterified cholesterol and stanols accumulated in the oil phase, and free stanols replaced cholesterol in the micellar phase. At high intestinal plant stanol concentrations, cholesterol looses its micellar solubility possibly by replacement of its free fraction in the micellar phase by hydrolyzed plant stanols, which leads to a decreased intestinal absorption of cholesterol.