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Purpose: Lowering of LDL cholesterol levels by plant sterols and stanols is associated with decreased risk of cardiovascular disease in humans. Plant sterols and stanols also lower triacylglycerol (TG). However, it is not fully understood how reduction in TG is achieved and what the full potential of plant sterols and stanols is on whole-body metabolism. We here hypothesize that high levels of plant sterols and stanols stimulate whole-body energy expenditure, which can be attributed to changes in mitochondrial function of brown adipose tissue (BAT), skeletal muscle and liver. Methods: Phytosterolemic mice were fed chow diets for 32 weeks to examine whole-body weight gain. In vitro, 24-h incubation were performed in adipocytes derived from human BAT, human myotubes or HepG2 human hepatocytes using sitosterol or sitostanol. Following mitochondrial function was assessed using seahorse bioanalyzer. Results: Chow feeding in phytosterolemic mice resulted in diminished increase in body weight compared to control mice. In vitro, sitosterol or sitostanol did not change mitochondrial function in adipocytes derived from human BAT or in cultured human myotubes. Interestingly, maximal mitochondrial function in HepG2 human hepatocytes was decreased following sitosterol or sitostanol incubation, however, only when mitochondrial function was assessed in low glucose-containing medium. Conclusions: Beneficial in vivo effects of plant sterols and stanols on lipid and lipoprotein metabolism are well recognized. Our results indicate that alterations in human mitochondrial function are apparently not involved to explain these beneficial effects. [ABSTRACT FROM AUTHOR]

Phytosterols (plant sterols and stanols) can lower intestinal cholesterol absorption, but the complex dynamics of the lipid digestion process in the presence of phytosterol esters (PEs) are not fully understood. We performed a clinical experiment in intubated healthy subjects to study the time course of changes in the distribution of all lipid moieties present in duodenal phases during 4 h of digestion of meals with 3.2 g PE (PE meal) or without (control meal) PE. In vitro experiments under simulated gastrointestinal conditions were also performed. The addition of PE did not alter triglyceride (TG) hydrolysis in the duodenum or subsequent chylomicron TG occurrence in the circulation. In contrast, cholesterol accumulation in the duodenum aqueous phase was markedly reduced in the presence of PE (−32%, P < 0.10). In vitro experiments confirmed that PE reduces cholesterol transfer into the aqueous phase. The addition of PE resulted in a markedly reduced presence of meal-derived hepta-deuterated cholesterol in the circulation, i.e., in chylomicrons (−43%, PE meal vs. control; P < 0.0001) and plasma (−54%, PE meal vs. control; P < 0.0001). The present data show that addition of PE to a meal does not alter TG hydrolysis but displaces cholesterol from the intestinal aqueous phase and lowers chylomicron cholesterol occurrence in humans.

We measured the percent absorption, turnover, and distribution of campestanol (24-methyl-5α-cholestan-3β-ol) in a sitosterolemic homozygote, her obligate heterozygous mother, and three healthy human control subjects. For reasons relating to sterol hyperabsorption, the homozygote consumed a diet low in plant sterols that contained campestanol at about 2 mg/day. The heterozygote and three control subjects were fed a diet supplemented with a spread that contained campestanol at 540 mg/day and sitostanol (24-ethyl-5α-cholestan-3β-ol) at 1.9 g/day as fatty acid esters. Plasma campestanol concentrations determined by capillary gasliquid chromatography were 0.72 ± 0.03 mg/dl in the homozygote, 0.09 ± 0.04 mg/dl in the heterozygote, and 0.05 ± 0.03 mg/dl for the control mean. After simultaneous pulse labeling with [3α-3H]campestanol intravenously and [23-14C]campestanol orally, the maximum percent absorption measured by the plasma dual-isotope ratio method as a single time point was 80% in the homozygote, 14.3% in the heterozygote, and 5.5 ± 4.3% as the mean for three control subjects. Turnover (pool size) values estimated by mathematical analysis of the specific activity versus time [3α-3H]campestanol decay curves were as follows: 261 mg in the homozygote, 27.3 mg in the heterozygote, and 12.8 ± 7.6 mg in the three control subjects (homogygote vs. controls, P < 0.001). The calculated production rate (mg/24 h) equivalent to actual absorption in the presence of dietary sterols and stanols was 0.67 mg/day or 31% of intake in the homozygote, 2.1 mg/day or 0.3% of intake in the heterozygote, and 0.7 ± 0.3 mg/day or 0.1% of intake in the three control subjects. However, the excretion constant from pool A (KA) was prolonged markedly in the homozygote, but was 100 times more rapid in the heterozygote and three control subjects. Thus, campestanol, like other noncholesterol sterols, is hyperabsorbed and retained in sitosterolemic homozygotes. However, campestanol absorption was only slightly increased in the sitosterolemic heterozygote and removal was as rapid as in control subjects.—Salen, G., G. Xu, G. S. Tint, A. K. Batta, and S. Shefer. Hyperabsorption and retention of campestanol in a sitosterolemic homozygote: comparison with her mother and three control subjects. J. Lipid Res. 2000. 41: 1883–1889.

Summary Background & aims Consumption of plant stanols and plant sterols decreases LDL cholesterol level and increases serum concentrations of plant stanols/sterols, but it is practically unexplored whether also their tissue concentrations increase. Thus, the aim of this study was to assess whether consuming plant stanols/sterols increases their concentrations in stenotic aortic valves and affect the valvular structure (collagen and elastin) or inflammation (macrophages and mast cells). Methods In a randomized, double-blind controlled intervention patients with severe aortic stenosis consumed margarine without (n = 11) or with 2 g of plant stanols (n = 12) or sterols (n = 13) until valve replacement surgery (2.6 months, on average). The effects of sitostanol and sitosterol on the expression and secretion of proinflammatory cytokines by cultured aortic valve myofibroblasts were also assessed. Results Control-related LDL-cholesterol was diminished by 16% (p < 0.05) by plant stanol and by 11% (NS) by plant sterol consumption, respectively. In the resected valves, cholesterol, plant stanol and sterol levels were similar in all groups. Consumed plant stanols or sterols had no effect on valvular structure or mast cell or macrophage numbers in valves. Incubation of cultured myofibroblasts derived from stenotic valves with sitostanol or sitosterol decreased mRNA expression of the monocyte chemotactic protein-1 (p < 0.05) and interleukin-1 beta (p < 0.05). Conclusions In this study, plant stanol/sterol consumption did not affect cholesterol, plant stanol or sterol levels in stenotic aortic valves; neither did they influence the structure or the inflammatory status of the valves. However, these findings need to be confirmed in a larger-scale intervention. ClinicalTrials.govRegister # NCT00738933 . [ABSTRACT FROM AUTHOR]

We investigated the changes of cholesterol and non-cholesterol sterol metabolism during plant stanol ester margarine feeding in 153 hypercholesterolemic subjects. Rapeseed oil (canola oil) margarine without (n = 51) and with (n = 102) stanol (2 or 3 g/day) ester was used for 1 year. Serum sterols were analyzed with gas–liquid chromatography. The latter showed a small increase in sitostanol peak during stanol ester margarine eating. Cholestanol, campesterol, and sitosterol proportions to cholesterol were significantly reduced by 5–39% (P < 0.05 or less for all) by stanol esters; the higher their baseline proportions the higher were their reductions. The precursor sterol proportions were significantly increased by 10–46%, and their high baseline levels predicted low reduction of serum cholesterol. The decrease of the scheduled stanol dose from 3 to 2 g/day after 6-month feeding increased serum cholesterol by 5% (P < 0.001) and serum plant sterol proportions by 8–13% (P < 0.001), but had no consistent effect on precursor sterols. In twelve subjects, the 12-month level of LDL cholesterol exceeded that of baseline; the non-cholesterol sterol proportions suggested that stimulated synthesis with relatively weak absorption inhibition contributed to the non-responsiveness of these subjects. In conclusion, plant stanol ester feeding lowers serum cholesterol in about 88% of subjects, decreases the non-cholesterol sterols that reflect cholesterol absorption, increases the sterols that reflect cholesterol synthesis, but also slightly increases serum plant stanols. Low synthesis and high absorption efficiency of cholesterol results in the greatest benefit from stanol ester consumption.—Gylling, H., P. Puska, E. Vartiainen, and T. A. Miettinen. Serum sterols during stanol ester feeding in a mildly hypercholesterolemic population. J. Lipid Res. 1999. 40: 593–600.

Purpose: Chronic inhibition of cholesterol absorption with large doses of plant stanol esters (staest) alters profoundly cholesterol metabolism, but it is unknown how an acute inhibition with a large staest dose alters the postprandial serum and lipoprotein cholesterol precursor, plant sterol, and sitostanol contents. Methods: Hypercholesterolemic subjects, randomly and double-blind divided into control ( n = 18) and intervention groups ( n = 20), consumed experimental diet without and with staest (plant stanols 8.8 g/day) for 10 weeks. Next morning after a fasting blood sample (0 h), the subjects had a breakfast without or with staest (4.5 g of plant stanols). Blood sampling was repeated 4 h later. Lipoproteins were separated with ultracentrifugation, and sterols were measured with gas-liquid chromatography. Results: In 0-h chylomicrons and VLDL, plant sterols were lower in staest than in controls. Postprandially, cholestenol (cholesterol synthesis marker) was reduced in chylomicrons in staest compared with controls (−0.13 ± 0.04 μg/dL vs. 0.01 ± 0.08 μg/dL, P < 0.05). Staest decreased postprandially avenasterol in chylomicrons ( P < 0.05 from 0 h). Sitostanol was high at 0 h by chronic staest in serum and VLDL but not in chylomicrons. Postprandial sitostanol was increased by staest in VLDL only. Conclusions: Chronic cholesterol absorption inhibition with large amount of plant stanol esters decreases plant sterols in triglyceride-rich lipoproteins. Acute plant stanol ester consumption increases sitostanol content in triglyceride-rich lipoproteins but suggests to decrease the risk of plant sterol and plant stanol accumulation into vascular wall by chylomicrons. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aims: It is not known whether dietary intake of plant stanols or sterols changes the composition of arterial sterols. Therefore, we compared serum and carotid artery cholesterol and non-cholesterol sterols after plant stanol (staest) or sterol (steest) ester feeding in endarterectomized patients. Methods and Results: Elderly statin-treated asymptomatic patients undergoing carotid endarterectomy were randomized double-blind to consume staest (n =11) or steest (n =11) spread (2g of stanol or sterol/day) for four weeks preoperatively. Non-cholesterol sterols from serum and carotid artery tissue were analysed with gas-liquid chromatography. Staest spread lowered serum total (17.2%), VLDL, and LDL cholesterol and serum triglycerides, while steest spread lowered serum total (13.8%) and LDL cholesterol levels from baseline (p <0.05 for all). Serum cholestanol and avenasterol were decreased in both groups, but campesterol and sitosterol were decreased by staest and increased by steest from baseline (p <0.05 from baseline and between the groups). Serum sitostanol to cholesterol ratio was increased by staest, but in arterial tissue this ratio was similar in both groups. On staest, lathosterol, campesterol, and sitosterol, and on steest sitosterol and avenasterol correlated significantly between serum and arterial tissue. Cholesterol metabolism, eg. lathosterol/campesterol, suggested that plant sterols were reduced in serum and in arterial tissue during staest. Conclusion: The novel observations were that plant stanol ester consumption, in contrast to plant sterols, tended to reduce carotid artery plant sterols in statin-treated patients. Furthermore, despite increased serum sitostanol contents during plant stanol ester consumption, their arterial levels were unchanged suggesting that sitostanol is not taken up into the arterial wall. [Copyright &y& Elsevier]

Today, consumers meet abundant supply of functional foods with plant stanol increments for serum cholesterol lowering purposes. However, efficacy and safety of plant stanols intake beyond 4 g/day have remained unexplored. We evaluated the effects of very high daily intake of plant stanols (8.8 g/day) as esters on cholesterol metabolism, and serum levels of plant sterols and stanols. In a randomized, double-blind, parallel study of 49 hypercholesterolemic subjects (mean age 62 years, range 41–73) consumed a test diet without (control, n = 24), and with added plant stanol esters (staest, n = 25) over 10 weeks followed by 4 weeks on home diet. Serum lipids, lipoprotein lipids, and non-cholesterol sterols were determined at baseline, during intervention, and 4 weeks afterwards. Cholesterol precursor sterol lathosterol reflected cholesterol synthesis, and serum plant sterols and cholestanol mirrored cholesterol absorption. When compared with controls, 8.8 g/day of plant stanols reduced serum and LDL cholesterol by 12 and 17% ( P < 0.01 for both). Synthesis marker lathosterol was increased by 30%, while absorption markers decreased up to 62% when compared with controls ( P < 0.001 for both). Serum plant stanols increased slightly, but significantly compared with controls (serum sitostanol during intervention, controls: 16 ± 1 μg/dL, staest: 37 ± 2 μg/dL, serum campestanol during intervention, controls: 0.5 ± 0 μg/dL, staest: 9 ± 1 μg/dL, P < 0.001 for both). Changes in serum cholesterol, non-cholesterol sterols, and plant stanols were normalized during post-treatment weeks. Serum plant stanol levels remained at comparable low levels as in studies with daily intake of 2–3 g, and were normalized in 4 weeks suggesting that daily intake of 8.8 g of plant stanols might not increase systemic availability of plant stanols, but reduces effectively serum cholesterol and plant sterol levels. [ABSTRACT FROM AUTHOR]

Oxidative degradation of cholesterol has been extensively researched, however, not all products formed have been established. When a phytosterols standard was heated at 60, 120 and 180 °C for different period of time the following groups of components were detected: oxidized phytosterols, fragmented phytosterol molecules, volatile compounds and oligomers. Taking into account all the components formed, we were able to balance the amounts of disappearing sterols with components formed. We established that the amount and type of products formed during thermo-oxidative degradation is affected by temperature and time. The amount of intact phytosterols decreased when temperature and time increase. The amount of oxidized phytosterols was at the highest level when a temperature of 120 °C was applied, whereas the lowest amounts were observed when a temperature of 60 °C was used. At a temperature of 180 °C the amount of oxidized sterols was lower than at 120 °C and it decreased when the heating time was increased. This indicates that oxidized sterols were the main precursors involved in the formation of other components during thermo-oxidative degradation. The amount and type of volatile compounds formed increased when time and temperature increased. We observed diversified groups of volatile compounds formed and most of them are defined as off-flavor compounds for rancid oils. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the difference between the molecular structures of plant sterols and stanols that affect the solubilization of cholesterol in bile salt micelles (in vitro study). First, the aqueous solubility of β-sitosterol, β-sitostanol, and campesterol was determined by considering the specific radioactivity by using a fairly small quantity of each radiolabeled compound. The order of their aqueous solubilities was as follows: cholesterol>campesterol>β-sitostanol>β-sitosterol. The maximum solubility of cholesterol and the abovementioned sterol/stanol in sodium taurodeoxycholate and sodium taurocholate solutions (single solubilizate system) was measured. Moreover, the preferential solubilization of cholesterol in bile salt solutions was systematically studied by using different types of plant sterols/stanols. The solubilization results showed that the cholesterol-lowering effect was similar for sterols and stanol. Thermodynamic analysis was applied to these experimental results. The Gibbs energy change (ΔG°) for the solubilization of plant sterols/stanols showed a negative value larger than that for cholesterol. [Copyright &y& Elsevier]

Abstract: Objective: The aim of this study was to investigate the cholesterol-lowering mechanisms of corn fiber oil (CFO), ferulate phytostanyl esters (FPEs) and parent compounds of FPE, including sitostanol and ferulic acid, in hamsters. Method: Seventy male Golden Syrian hamsters were randomly assigned to six experimental diets for 4 weeks: (1) cornstarch–casein–sucrose-based control diet (control); and (2) control diet plus 0.1% (wt/wt) cholesterol (cholesterol–control). The remaining four groups were given cholesterol–control diet with: (3) 10% (wt/wt) CFO; (4) 0.5% (wt/wt) sitostanol; (5) 0.23% (wt/wt) ferulic acid; and (6) 0.73% (wt/wt) FPE. At the end of dietary intervention, total plasma cholesterol, high-density lipoprotein cholesterol and triglyceride concentrations were determined. Parameters of cholesterol kinetics, including cholesterol absorption and synthesis, as well as mRNA expression of sterol transporters such as Niemann–Pick C1 like 1 (NPC1L1), ATP-binding cassette G5 (ABCG5) and ABCG8, were assessed. Results: Supplementation with CFO decreased (P<.0001) plasma total cholesterol levels by 29% as compared with the cholesterol–control group, while FPE and sitostanol reduced (P<.02) cholesterolemia by 15% and 14%, respectively. CFO and sitostanol decreased (P<.05) cholesterol absorption by 24% compared to the cholesterol–control group. Dietary intervention did not alter the intestinal gene expression of ABCG5, ABCG8 and NPC1L1. Conclusion: The present results show that the CFO-induced and sitostanol-induced decrease in cholesterol absorption is independent of intestinal enterocyte sterol transporters such as ABCG5, ABCG8 and NPC1L1 in hamsters. [Copyright &y& Elsevier]

Esterification of dietary phytosterols and glycerols may affect intestinal absorption of cholesterol and non-cholesterol sterols. We infused plant stanol esters in triacylglycerol (TAG) (F1) and diacylglycerol (DG) (F2) oils, and free plant stanols in F1 and F2 (F3) to the duodenum of healthy human subjects and sampled the contents from the proximal jejunum (PJ). Free and ester sterols were analysed from the infusates, and intestinal contents before and after ultracentrifuge separation of oil, micelle and sediment phases. During the 60-cm intestinal passage, over 40% of plant stanol esters were hydrolysed ( P < 0.05) but around 30% of the infused free plant stanols ( P < 0.05) and up to 40% of cholesterol ( P < 0.05) were esterified in PJ after infusions. TAG in F1 favoured accumulation of plant stanol esters in the oil phase of the PJ aspirates as compared with respective values of F2 and F3 ( P < 0.05 for both). About one third of free plant stanols of F3 had been esterified ( P < 0.05) and 17% precipitated mainly in free form in the PJ aspirates ( P < 0.05 compared with F1 and F2). In conclusion, DG- and TAG-oils had no profound superiority over each other as intestinal carriers regarding hydrolysis/esterification of administered plant stanol esters and cholesterol and their partition in oil, micellar and sediment phases in the PJ. The unesterified plant stanols experienced partial esterification and sedimentation during their intestinal passage, which might influence their biochemical properties in that segment of the gut where cholesterol is absorbed. [ABSTRACT FROM AUTHOR]

ATP binding cassette transporter G5 (ABCG5) and ATP binding cassette transporter G8 (ABCG8) have been suggested to transport absorbed plant sterols and cholesterol from enterocytes to the intestinal lumen and from hepatocytes to bile. It has been thought that mutations of ABCG5 or ABCG8 cause the deposition of plant sterols in the body. In the present study, lymphatic absorption of various plant sterols and their deposition in various tissues was investigated in stroke-prone spontaneously hypertensive rats (SHRSP), having a mutation in Abcg5 and depositing plant sterols in the body. The order of lymphatic 24-h recovery of plant sterols was as follows: campesterol > sitosterol > brassicasterol > stigmasterol = sitostanol. When SHRSP were fed a diet containing one of the plant sterols, the depositions of campesterol and sitosterol were comparatively higher than those of brassicasterol, stigmasterol and sitostanol. Highly positive correlations were obtained between lymphatic recovery of plant sterols and their levels in plasma, liver, adipose tissue and heart. The tendency of differential absorption of plant sterols to the lymph in SHRSP was similar to that in normal Wistar rats previously reported by us (Hamada et al. Lipids 41:551–556, 2006). These observations suggest that differential absorption of various plant sterols is kept in SHRSP in spite of a mutation in Abcg5. [ABSTRACT FROM AUTHOR]

Abstract: Background and aim: Nutritional products containing fat-soluble phytosterol esters for serum cholesterol lowering have traditionally been oil-based. Their cholesterol-lowering efficacy when provided by low-fat vehicles with a diet of normal fat content is questionable. The aims of the present study were to find out whether 1-week consumption of plant stanol esters in pastilles alters absorption percentage of labeled esterified and free cholesterol and fecal elimination of sterols, including phytosterols (n =9), and to define the impact of dietary fat on intestinal sterol ester hydrolysis (n =8) in colectomized human subjects. Methods and results: Levels of lipoprotein cholesterol and triacylglycerols, non-cholesterol sterols and squalene in serum, neutral sterols, non-cholesterol sterols, fat and bile acids in feces, cholesterol absorption efficiency and cholesterol synthesis were analyzed at baseline and at the end of the treatment period. Analyses of esterified and free cholesterol and phytosterols were performed during diets with normal and low-fat content. Serum levels of total and low-density lipoprotein cholesterol decreased by 9% and 14%, respectively (P <0.01 for both), and absorption of 3H-esterified and 14C-free cholesterol decreased in proportion to baseline values (r =−0.58, P <0.05) by over 40% (P <0.01) in colectomized patients with stanol ester pastilles. Fecal elimination of cholesterol was increased by about 35% and almost 60% of campestanol and sitostanol esters were hydrolyzed during their transit in gastrointestinal tract when consumed with a normal fat diet (mean daily fat 93±13g) for 1 week. The hydrolysis of plant stanol esters was more pronounced with a normal than with a low-fat diet (70% versus 40%, P <0.001). Conclusions: We conclude that plant stanol esters provided in fat free milieu exert favourable effects on serum lipid profile by decreasing absorption of cholesterol in colectomized human subjects, even though the intestinal hydrolysis of plant stanol esters is weaker on low than normal fat diet. [Copyright &y& Elsevier]

Plant sterol and stanol esters have been introduced as an additional dietary means to lower serum total and LDL cholesterol concentration. In short-term studies they lower LDL cholesterol by 10%, and according to a meta-analysis by Malcolm Law the incidence of coronary heart disease is considered to be reduced by over 20% in long-term use of these products. Plant stanol and sterol esters are not identical sterols; they have different metabolic effects and their long-term efficacy seems to be different. The present review deals with the differences of the sterols and discusses what is known of their role in preventing the cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Objective: Plant sterol/stanol margarines are recommended as a lipid-lowering dietary supplement in the treatment of hypercholesterolemia. Parameters predicting the individual cholesterol-lowering effect have not been elucidated so far. There fore, we investigated the responsiveness to sitostanol-supplemented margarine in a specially selected population. Methods and results: From a total number of 137 male subjects with hypercholesterolemia, eight subjects with the lowest and eight subjects with the highest ratios of lathosterol to campesterol in serum were included in the study. They received 1 g sitostanol-supplemented margarine b.i.d. for four weeks. Serum lipoproteins, the cholesterol precursor lathosterol, the plant sterols campesterol and sitosterol were measured. Subjects with a low ratio of lathosterol to campesterol had a significant decrease of serum total cholesterol (-14.2%; p <0.01) and LDL cholesterol (-13.8%; p < 0.01; responder). In subjects with a high ratio there was no significant change in total cholesterol and LDL cholesterol (2.2 and 4.3%; non-responder). Conclusion: The ratio of serum lathosterol to campesterol predicts the reduction of total cholesterol and LDL cholesterol during administration of sitostanol-supplemented margarine in patients with mild hypercholesterolemia. [ABSTRACT FROM AUTHOR]

A new GC--MS method for characterization and quantification of phytosterol oxidation products was developed. Applicability of this method was tested by characterizing sitostanol oxides formed in bulk and then quantifying selected oxides in purified rapeseed oil and tripalmitin matrices in which the complex matrix made oxide analysis difficult. In bulk, nine different sitostanol oxides were characterized, including epimers of 7- and 15-hydroxysitostanol and 6- and 7-ketositostanol. In both lipid matrices, the amounts of sitostanol oxides generated in thermo-oxidation were very low. According to statistical analyses, depending on the oxide, the GC--MS results were the same or slightly higher than those quantified by the more common GC--FID method. Thus, GC--MS provides a powerful alternative for characterization and quantification of phytostanol oxides found in low amounts in complex matrices and is a promising method for future phytosterol oxide studies. [ABSTRACT FROM AUTHOR]

Plant sterols and their hydrogenated forms, stanols, have attracted much attention because of their benefits to human health in reducing serum and LDL cholesterol levels, with vegetable oil processing being their major source in several food products currently sold. The predominant forms of plant sterol end products are sitosterol, stigmasterol, campesterol and brassicasterol (in brassica). In this study, 3-hydroxysteroid oxidase from Streptomyces hygroscopicus was utilized to engineer oilseeds from rapeseed (Brassica napus) and soybean (Glycine max), respectively, to modify the relative amounts of specific sterols to stanols. Each of the major phytosterols had its C-5 double bond selectively reduced to the corresponding phytostanol without affecting other functionalities, such as the C-22 double bond of stigmasterol in soybean seed and of brassicasterol in rapeseed. Additionaly, several novel phytostanols were obtained that are not produced by chemical hydrogenation of phytosterols normally present in plants. [Copyright &y& Elsevier]

Aim: To evaluate the effects of gender, apolipoprotein E phenotype and cholesterol absorption and synthesis (estimated as serum plant sterol and cholesterol precursor sterol concentrations) on the cholesterol-lowering effect of plant stanol esters in children.Methods: Eighty-one healthy, normocholesterolaemic 6-y-old children (45 boys) were recruited from the Special Turku Coronary Risk Factor Intervention Project (STRIP), a randomized prospective trial aiming at atherosclerosis prevention in childhood. This placebo-controlled, double-blind, cross-over study comprised two 3-mo study periods and a 6-wk wash-out period. During the study periods, 20 g of the children's daily dietary fat intake was replaced with plant stanol ester margarine or control margarine.Results: In boys, plant stanol esters reduced serum total and low-density lipoprotein cholesterol concentrations by 6% (0.09 to 0.42 mmol/L) and 9% (0.09 to 0.36 mmol/L), respectively (p < 0.01 for both). In girls, the decreases in concentrations were 4% (0.03 to 0.38 mmol/L) and 6% (0.02 to 0.32 mmol/l) (p < 0.05 for both). The response rate did not differ between the genders. Serum total and low-density lipoprotein cholesterol concentrations decreased by 6% and 8% (p < 0.01 for both), respectively, in both children with the apolipoprotein E 3/4 or 4/4 (apoE4+) phenotype and the apolipoprotein E 2/3 or 3/3 (apoE4-) phenotype. Cholesterol absorption decreased both in the apoE4+ children and in the apoE4- children, but cholesterol synthesis consistently increased in the apoE4+ children only.Conclusion: Plant stanol esters reduce serum cholesterol concentration in healthy children irrespective of their gender or apoE4 phenotype. [ABSTRACT FROM AUTHOR]

Abstract Background Differences in genetic constitution may affect cholesterol metabolism and responses to diet. Identification of common variations in genes related to dietary responsiveness is therefore an attractive goal to be able to prescribe individually tailored diets for the treatment of dyslipidaemia. Materials and methods We have examined relationships between serum lipids and lipoproteins, cholesterol-standardized campesterol and lathosterol concentrations with genetic variation, and the presence of a gene–diet interaction between plant stanol ester consumption. Candidate genes were apolipoprotein A-IV (apoA-IV), scavenger receptor-BI (SR-BI), cholesterol ester transfer protein (CETP), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and apolipoprotein E (apoE). These relations were examined in 112 nonhypercholesterolaemic subjects, of whom 70 consumed 3·8–4·0 g plant stanol esters a day for 8 weeks. Results At baseline, high-density lipoprotein (HDL) concentrations of 1·56 ± 0·36 mmol L-1 in SR-BI-2 allele carriers tended to be lower compared to the 1·72 ± 0·42 mmol L-1 in SR-BI-1/1 subjects (P = 0·069). Cholesterol standardized lathosterol concentrations were also lower in the SR-BI-2 allele carriers (P = 0·002). Furthermore, low-density lipoprotein (LDL) cholesterol concentrations in apoE2 subjects, were lower compared to the LDL cholesterol concentration in apoE3 group (P = 0·002) and apoE4 subjects (P < 0·001). No significant differences between the polymorphisms and dietary responsiveness to plant stanol ester consumption could be found, which indicates that it is unlikely that one of the single polymorphisms analysed in this study is a major factor in explaining the variation in serum LDL cholesterol responses. Conclusion These findings suggest that all subjects who want to lower their cholesterol concentration, will benefit from plant... [ABSTRACT FROM AUTHOR]

To evaluate some of the mechanisms involved in the plasma cholesterol lowering of sitostanol (SI), male Hartley guinea pigs were fed diets containing cholesterol (0.25 g/100 g) and four doses of SI: either 0 (control), 0.75, 1.5 or 2.25 g/100 g. In addition a negative control (-C) group with dietary cholesterol (0.04 g/100 g) was included. Corn oil was used as the source of fat and the contribution of fat energy was 35 %. Plasma total cholesterol was 43, 49 and 53 % (P<0.0001) lower after SI intake compared to the control. Plasma LDL concentrations were 47, 53 and 61 % lower with increasing doses of SI. In addition, intake of SI resulted in 26???42 % lower hepatic total cholesterol. Hepatic esterified cholesterol and triacylglycerols were 32???60 % and 55???61 % lower after SI intake. SI intake resulted in favourable plasma and hepatic cholesterol concentrations similar to those in guinea pigs fed low levels of dietary cholesterol (-C). The LDL obtained from the control group had a higher number of molecules of free and esterified cholesterol than the SI groups. SI intake resulted in 69???71 % higher cholesterol excretion compared to the control. SI treatment enhanced the total faecal neutral sterol excretion by 54???58 % compared to control and by 70???76 % compared to the (-C) group. These results suggest that SI might have its hypocholesterolaemic effect by reducing cholesterol absorption, which results in lower concentration of cholesterol in liver. This reduction in hepatic cholesterol might possibly alter hepatic cholesterol metabolism and affect lipoprotein concentration and composition. [ABSTRACT FROM PUBLISHER]

Serum cholesterol values were insufficiently reduced by pravastatin in two different patient populations. Therefore, we studied whether further cholesterol reduction could be achieved by inhibiting both cholesterol synthesis (by pravastatin) and absorption (by neomycin or sitostanol ester). Thus, we measured serum cholesterol, cholesterol precursors (reflecting cholesterol synthesis), cholestanol and plant sterols (reflecting cholesterol absorption and biliary secretion) for up to 6 weeks in pravastatin-treated patients with familial hypercholesterolaemia (FH, n=13) and with and without ileal bypass during addition of neomycin (1.5 g per day) and in another patient population of non-FH ( n=14) subjects during addition of sitostanol ester (1.5 g per day). Addition of neomycin lowered serum total, LDL and HDL cholesterol by a further 20 %, and increased the pravastatin-lowered precursor:cholesterol ratios by 20 % (irrespective of ileal bypass). It also reduced by 20 % the plant sterol:cholesterol ratio (irrespective of ileal bypass) which was markedly increased by pravastatin alone. Pravastatin and neomycin in combination lowered total, LDL and HDL cholesterol by 45 %, 53 % and 17 %, respectively. This combined regimen reduced the serum lathosterol:cholesterol ratio to about half of the reduction caused by pravastatin, while the elevation of the plant sterols:cholesterol ratio was less with the combination than with pravastatin alone. Changes in serum cholesterol precursor:cholesterol and plant sterol:cholesterol ratios during the combined treatment were smaller in the subgroup with ileal bypass. Addition of sitostanol ester did not lower serum total or LDL cholesterol nor the precursor:cholesterol ratios significantly, while the reduction observed in the plant sterols:cholesterol ratios was similar to that achieved with neomycin addition. These findings suggest that simultaneous inhibition of cholesterol synthesis and absorption very effectively reduced serum cholesterol levels and that the addition of neomycin or sitostanol ester reduced cholesterol absorption, while the addition of sitostanol ester reduced serum cholesterol and, compensatorily, increased cholesterol synthesis less consistently than neomycin. [ABSTRACT FROM AUTHOR]

Cholesterol absorption and metabolism and LDL and HDL kinetics were investigated in 11 hypercholesterolaemic non-insulin-dependent diabetic men off and on a hypolipidaemic treatment with sitostanol ester, (3 g sitostanol daily) dissolved in rapeseed oil margarine, by a double-blind crossover study design. Serum total, VLDL and LDL cholesterol and apoprotein B fell significantly by 6±2, 12±6, 9±3 and 6±2%, mean ±SEM, and HDL cholesterol was increased by 11±4% ( p<0.05) by sitostanol ester. LDL cholesterol and apoprotein B were significantly decreased in the dense (1.037-1.055 g/ml), but not light, LDL subfraction due to a significantly diminished transport rate for LDL apoprotein B, while the fractional catabolic rate was unchanged. HDL kinetics, measured with autologous apoprotein AI, was unaffected by sitostanol ester. Cholesterol absorption efficiency was markedly reduced from 25±2 to 9±2% ( p<0.001) during sitostanol ester followed by proportionately decreased serum plant sterol proportions. Cholesterol precursor sterol proportions in serum, fecal neutral sterol excretion, and cholesterol synthesis, cholesterol transport, and biliary secretion were all significantly increased by sitostanol ester. We conclude that the sitostanol ester-induced decrease in cholesterol absorption compensatorily stimulated cholesterol synthesis, had no effect on fractional catabolic rate, but decreased transport rate for LDL apoprotein B so that serum total, VLDL and LDL cholesterol levels were decreased. Dietary rapeseed oil margarine rich in sitostanol ester was well tolerated, appears to be safe from the nutritional point of view and effective for lowering VLDL and LDL cholesterol and increasing HDL cholesterol in hypercholesterolaemic non-insulin-dependent diabetic subjects. [ABSTRACT FROM AUTHOR]

Dietary modifications including plant stanol ester consumption are recommended measures to control serum and low-density lipoprotein (LDL)-cholesterol concentrations, but obesity can affect their responses. We investigated whether body mass index (BMI) affects serum cholesterol levels during plant stanol (mainly sitostanol) ester consumption. This ad hoc analysis was based on earlier results of a cross-over, randomized controlled trial of postmenopausal women consuming rapeseed oil-based margarine without or with plant stanol ester (3 g plant stanols/day) for seven weeks. We classified the subjects as normal-weight (BMI ≤ 25 kg/m 2 , n = 9, mean 22.6 kg/m 2 ) or overweight/obese (BMI > 25 kg/m 2 , n = 11, mean 28.4 kg/m 2 ), and recalculated the results, focusing on cholesterol absorption, cholesterol synthesis, and fecal steroid outputs. Serum cholesterol levels were similar in the groups during the control diet. Plant stanol ester reduced serum cholesterol by 0.63 ± 0.19 mmol/L (11%) in normal-weight and by 0.75 ± 0.13 mmol/L (12%) in overweight/obese subjects ( p < 0.05 for both), and cholesterol absorption was reduced in both groups. However, relative and dietary cholesterol absorption were more effectively reduced in normal-weight subjects. In conclusion, overweight/obesity did not interfere with the serum cholesterol response to plant stanol ester consumption despite substantial differences in cholesterol metabolism between the groups.

Objectives: To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE).Study Design: Eight patients with sitosterolemia (16-56 years of age) were studied during 14 weeks off EZE therapy and 14 weeks on EZE (10 mg/day). Serum thyroid biomarkers (free triiodothyronine [FT3], free thyroxine [FT4], FT3/FT4 ratio, thyroid-stimulating hormone), 5α-stanols (sitostanol and cholestanol), and cholestanol precursors (total cholesterol and its synthesis marker lathosterol, and 7α-hydroxy-4-cholesten-3-one cholestenol) were measured at baseline and during the 14 weeks off EZE and on EZE.Results: EZE increased FT3/FT4 (10% ± 4%; P = .02). EZE reduced plasma and red blood cells sitostanol (-38% ± 6% and -20% ± 4%; all P < .05) and cholestanol (-18% ± 6% and -13% ± 3%; all P < .05). The change in plasma cholestanol level on EZE inversely correlated with the change in FT3/FT4 (r = -0.86; P = .01). EZE lowered total cholesterol (P < .0001) and did not affect 7α-hydroxy-4-cholesten-3-one cholestanol. EZE increased (P < .0001) lathosterol initially, but the level was not sustained, resulting in similar levels at week 14 off EZE and on EZE.Conclusion: In patients with STSL, 5α-stanols levels might be associated with thyroid function. EZE reduces circulating 5α-stanols while increasing FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status.Trial Registration: ClinicalTrials.govNCT01584206. [ABSTRACT FROM AUTHOR]

Phytosterol measurement has gained a lot of interest during the last two decades after foods and supplements with added 4-desmethyl phytosterols were recognized and used as effective and safe non-pharmacologic hypocholesterolemic agents, and also after the mechanisms of intestinal absorption and hepatic excretion of sterols were unraveled. In addition, the wide use of serum phytosterols as biomarkers of cholesterol absorption has increased the interest in their measurement. In this review, the basic methods are discussed without going into details of the practical operations. The analysis includes first lipid extraction and saponification from various biologic matrices such as serum/plasma, feces, or tissues, after which the individual sterols are separated by adsorption chromatography (gas-liquid or liquid or high performance liquid chromatography) based on the polarity of the various sterols. We also deal with some specific aspects of phytosterol measurements in biological samples such as the need of harmonization of their analysis in biological samples, the discrepancies in the results of sitosterol and campesterol concentrations between different studies, and what is known about their biological day-to-day fluctuation. Phytosterols have a remarkable role in human health, so that their complicated and time consuming measurements call attention to routine ways of standardization between the sterol research laboratories., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and aims : Non-alcoholic fatty liver disease (NAFLD) associates with low levels of serum plant sterols in cross-sectional studies. In addition, it has been suggested that the hepatic sterol transport mechanisms are altered in NAFLD. Therefore, we investigated the association between serum, liver and bile plant sterols and sitostanol with NAFLD. Methods : Out of the 138 individuals (age: 46.3 ± 8.9, body mass index: 43.3 ± 6.9 kg/m², 28% men and 72% women), 44 could be histologically categorized to have normal liver, and 94 to have NAFLD. Within the NAFLD group, 28 had simple steatosis and 27 had non-alcoholic steatohepatitis. Plant sterols and sitostanol were measured from serum ( n =138), liver ( n =38), and bile ( n =41). The mRNA expression of genes regulating liver sterol metabolism and inflammation was measured ( n =102). Results : Liver and bile sitostanol ratios to cholesterol were higher in those with NAFLD compared to those with histologically normal liver (all P <0.022). Furthermore, liver sitostanol to cholesterol ratio correlated positively with histological steatosis and lobular inflammation ( r s > 0.407, P <0.01 for both). In contrast, liver sitosterol to cholesterol ratio correlated negatively with steatosis ( r s = -0.392, P =0.015) and lobular inflammation ( r : Our study showed that liver and bile sitostanol ratios to cholesterol associated positively and liver sitosterol ratio to cholesterol associated negatively with liver steatosis and inflammation in obese individuals with NAFLD..s = -0.395, P =0.014). Transcriptomics analysis revealed suggestive correlations between serum plant sterol levels and mRNA expression. Conclusion : Our study showed that liver and bile sitostanol ratios to cholesterol associated positively and liver sitosterol ratio to cholesterol associated negatively with liver steatosis and inflammation in obese individuals with NAFLD.., (© 2018 The Author(s).)

Trace sterols in the seeds of foxtail millet (Setaria italica Beauv.) were investigated by GC-MS. Eleven of these trace sterols, i.e., brassicasterol, episterol, 24-methyllathosterol, 24-ethyllathosterol, avenasterol, 24-methylenecholesterol, fucosterol, isofucosterol, 24-methyl-5α-cholest-24(28)-en-3β-ol, 24-ethyl-5α-cholest-24(28)Z-en-3β-ol, and 24-ethyldesmosterol, were identified, suggesting that the previously reported high content of sitostanol was possibly contaminated with a small amount of isofucosterol.