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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/m2, n = 9, mean 22.6 kg/m2) or overweight/obese (BMI > 25 kg/m2, n = 11, mean 28.4 kg/m2), 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.

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.

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 0.407, P

We measured the percent absorption, turnover, and distribution of campestanol (24-methyl-5 a -cholestan-3 b - ol) in a sitosterolemic homozygote, her obligate heterozygous mother, and three healthy human control subjects. For rea- sons relating to sterol hyperabsorption, the homozygote con- sumed a diet low in plant sterols that contained campestanol at about 2 mg/day. The heterozygote and three control sub- jects were fed a diet supplemented with a spread that con- tained campestanol at 540 mg/day and sitostanol (24-ethyl- 5 a -cholestan-3 b -ol) at 1.9 g/day as fatty acid esters. Plasma campestanol concentrations determined by capillary gas- liquid chromatography were 0.72 6 0.03 mg/dl in the homozygote, 0.09 6 0.04 mg/dl in the heterozygote, and 0.05 6 0.03 mg/dl for the control mean. After simulta- neous pulse labeling with (3 a - 3 H)campestanol intrave- nously and (23- 14 C)campestanol orally, the maximum per- cent 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 6 4.3% as the mean for three control subjects. Turnover (pool size) values esti- mated by mathematical analysis of the specific activity ver- sus time (3 a - 3 H)campestanol decay curves were as follows: 261 mg in the homozygote, 27.3 mg in the heterozygote, and 12.8 6 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 in- take in the homozygote, 2.1 mg/day or 0.3% of intake in the heterozygote, and 0.7 6 0.3 mg/day or 0.1% of intake in the three control subjects. However, the excretion constant from pool A (K A ) was prolonged markedly in the homozy- gote, but was 100 times more rapid in the heterozygote and three control subjects. Thus, campestanol, like other non- cholesterol sterols, is hyperabsorbed and retained in sitoster- olemic 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. Hyperabsorp- tion and retention of campestanol in a sitosterolemic homo- zygote: comparison with her mother and three control sub- jects. J. Lipid Res. 2000. 41: 1883-1889.

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.

International audience; Consumption of phytosterols is a nutritional strategy to reduce cholesterol absorption, but the efficacy of various phytosterol intake modalities remains uncertain. The main objective was to investigate the effects of phytosterol esters (PE) provided either as a spread (dispersed in fat) during a mixed meal or as a minidrink (micro-dispersed in liquid form) after a meal. In a randomized, single-blinded crossover design, 12 healthy intubated volunteers tested three different liquid meal sequences with and without PE. The liquid meal (500 mL, Fortisip) contained an oral dose (80 mg) of deuterium-enriched cholesterol (D7C). The intubation was stopped at 240 min, and the fate of sterols was determined in the different phases of duodenal content samples as function of time. A second solid fat-containing meal without sterols was consumed at 270 min. D7C was quantified in chylomicrons and plasma for 8 h. The conditions tested were as follows: (1) no PE added (control), (2) PE in a spread added into a liquid meal (PE-spread meal) and (3) PE given 30 min after a liquid meal as 100-g yoghurt drink (PE-minidrink meal). Addition of PE decreased the incorporation of cholesterol into the duodenum aqueous phase including micelles. PE added as a spread or as a minidrink significantly and comparably lowered meal cholesterol occurrence in chylomicrons (-40 % for PE-spread and -54 % for PE-minidrink, p < 0.0001) compared with the control meal. PE either dispersed in fat during a meal or micro-dispersed in a liquid form after a meal resulted in a markedly reduced occurrence of meal-derived cholesterol in the circulation at a comparable extent.

International audience; 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

To test for potential estrogenic activity of plant stanols and plant stanol esters, two short-term tests were performed. These were the E-screen test, which measures a substance's ability to induce proliferation of estrogen-responsive human breast adenocarcinoma (MCF-7) cells in culture, and an in vivo test, which measures uterotrophic activity in immature female rats fed the test substance. Four samples of vegetable oil-derived stanols (containing 88-99% stanols) were tested in the E-screen test, and one sample of wood-derived and one of vegetable oil-derived stanol fatty acid esters were tested in the in vivo test. In the E-screen test, the positive control substance, 17beta-estradiol, at 100 pM, produced a statistically significant, 11.6-fold increase in cell proliferation, as measured by sulforhodamine B staining. None of the stanol preparations produced any increase in cell proliferation when tested at 1, 10, and 100 microM. The highest dose of each stanol sample was associated with microscopic evidence of cytotoxicity and crystalline precipitation in the culture dishes. In the in vivo test, the positive control compound, diethylstilbestrol, produced a significant, dose-related increase in absolute and relative uterus weight in young female rats (17 days old at the start of treatment) fed the compound at 5, 10, and 20 ppb in the diet for 4 days. Neither of the two stanol ester preparations caused any significant change in absolute or relative uterus weight when fed at a concentration of 8.3% in the diet for 4 days. Thus, under the conditions of testing used, neither the free stanols nor the stanol fatty acid ester preparations showed evidence of estrogenic or uterotrophic activity.