![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Maastricht University, Department of Human Biology, Maastricht, The Netherlands
2To whom correspondence should be addressed. E-mail: R.Mensink{at}HB.unimaas.nl.
 |
ABSTRACT |
|---|
 TOP ABSTRACT SUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
KEY WORDS: • plant sterol • plant stanol • serum cholesterol • LDL • humans
Plant sterols and stanols, which effectively lower serum LDL cholesterol by reducing the absorption of both dietary and biliary cholesterol (1), are not well absorbed. Using a dual stable isotope method, it was estimated that cholesterol absorption was 30–80% (2), whereas the absorption of campesterol, sitosterol, campestanol and sitostanol was only 1.89, 0.51, 0.16 and 0.04%, respectively (3). Because of this low uptake in combination with rapid biliary elimination (4,5), serum concentrations of campesterol, sitosterol and plant stanols (campestanol and sitostanol) are only 0.3, 0.1 and 
0.01%, respectively, of serum cholesterol concentrations (6–8).
Consumption of plant sterols and stanols at recommended intakes of 2–2.5 g/d doubled their respective serum concentrations; however, they remained much lower than those of cholesterol (6–8). Further, several (6,9–13), but not all (14) studies have suggested that plant stanols not only reduced serum concentrations of cholesterol, but also those of plant sterols. Similarly, plant sterols may lower the serum concentration of plant stanols (15). If plant sterols and stanols indeed influence each other’s serum concentrations, then the increase in serum plant sterol and stanol concentrations may depend on the ratio of plant sterols to stanols in the diet. To examine this, we provided healthy subjects with three different margarines containing either no added plant sterols and stanols (control) or 2 g of plant sterols plus stanols at two different ratios. The effects of these mixtures on serum lipid and lipoprotein concentrations were also studied.
|
SUBJECTS AND METHODS |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Subjects were recruited via posters in the university building, and by advertisements in the weekly journal for employees of the academic hospital Maastricht, in local newspapers and on local television. Ninety-one subjects expressed interest and received an information brochure about the purpose of the study. Fifty subjects, who met our first selection criteria, were willing to participate and were invited for two screening visits. These subjects were between 18 and 65 y of age, had a BMI < 30 kg/m2 and a stable body weight (weight gain or loss of not >3 kg in the past 3 mo); did not use medication or a diet known to affect serum lipid levels, had no history of coronary heart disease, diabetes mellitus or liver disease; were not pregnant or breast-feeding; had not participated in another biochemical trial or donated blood within the previous 30 d; and did not use commercially available products enriched with plant sterol or stanol esters. The screening visit consisted of two blood samples from fasting subjects taken with at least 3 d in between for lipid and lipoprotein analysis, measurement of blood pressure and collection of a urine sample for determination of glucose. All subjects had to fill in a medical questionnaire. Forty-five subjects met our selection criteria and had mean serum total cholesterol concentrations < 8.0 mmol/L, mean serum triacylglycerol concentrations < 4.0 mmol/L and no indication for treatment with cholesterol-lowering drugs according to the Dutch Cholesterol Consensus (16). Further, all subjects had blood pressures < 160 /95 mm Hg, no glucosuria and did not abuse drugs or alcohol.
In the end, 44 subjects, 29 women and 15 men, started the study. During the study two women dropped out, because of illness (n = 1) or for personal reasons (n = 1). Therefore, data of 42 subjects were used for analyses.
The women were 32 ± 14 y of age (mean ± SD) and had a BMI of 23 ± 3 kg/m2. Their mean serum concentration of total cholesterol was 4.69 ± 1.05 mmol/L, of LDL cholesterol 2.69 ± 0.95 mmol/L, of HDL cholesterol 1.36 ± 0.44 mmol/L and of triacylglycerol 1.22 ± 0.57 mmol/L. Four women smoked cigarettes, 16 used oral contraceptives and 4 were menopausal. The men were 37 ± 16 y of age and had a BMI of 24 ± 3 kg/m2. Their mean serum concentration of total cholesterol was 4.64 ± 1.25 mmol/L, of LDL cholesterol 2.93 ± 1.25 mmol/L, of HDL cholesterol 1.16 ± 0.42 mmol/L and of triacylglycerol 1.16 ± 0.54 mmol/L. Two men were smokers.
Diet and design.
The study had a multiple crossover design with three experimental margarines and three successive periods of 3 wk (Fig. 1). Subjects were divided into six groups (n = 7–8). Each group received the three margarines in one of the six possible treatment orders and daily consumption was 25 g. During the study, subjects were not allowed to use any other margarine. The control margarine contained natural levels of sterols and stanols, whereas 25 g of the low sterol margarine provided 1 g plant sterols plus 1 g plant stanols per day. The high sterol margarine provided 1.5 g plant sterols plus 0.5 g plant stanols per day. Stanols were produced by hydrogenation of plant sterols; 50% of the plant sterol batch was used for the production of one batch of plant stanols. The free plant sterols and stanols were esterified with rapeseed oil fatty acids and subsequently mixed with the margarine. The fatty acid composition of the three margarines was similar; they contained the same amounts of absorbable fats because sterols and stanols were exchanged for water. Before the start of the study, 30 subjects selected a light margarine with 38% absorbable fats and twelve subjects selected a regular margarine with 62% absorbable fats. Switching between the two types of margarines during the study was not allowed. All margarines were based on sunflower oil and prepared especially for this study. To standardize fatty acid intake as much as possible, subjects were also provided with a sunflower oil–based shortening for baking. This shortening contained 98% absorbable fats and natural levels of plant sterols or plant stanols. The detailed composition of the experimental products is shown in Table 1. All products were prepared, packaged and color-coded by the RAISIO GROUP (Raisio, Finland). Subjects as well as the investigators had no knowledge of treatment assignment.
|
|
200 g of margarine and subjects were instructed to consume one eighth of the tub every day. The tubs of shortening contained 220 g. The new and used tubs of margarine and shortening were weighed. In this way, mean daily intakes of the experimental products could be determined and used to calculate mean daily plant sterol and stanol intake for each subject. To estimate energy and nutrient intakes, subjects were asked to fill in food frequency lists at the end of every dietary period as described elsewhere (17). Subjects were weighed every week to determine whether body weight remained constant. They were asked not to change their habitual diet, level of physical exercise, smoking habits or use of alcohol or oral contraceptives during the study. They were also asked to record illness and use of medication, amount of alcohol consumed, the phase of the menstrual cycle and any deviations from the protocol in a diary. The study protocol was approved by the medical ethical committee of the Maastricht University. All subjects gave their written informed consent before the start of the study.
Blood sampling.
Blood samples were taken after an overnight fast and after abstinence from drinking alcohol the day preceding and smoking on the morning of blood sampling. All blood samples from fasting subjects were taken by venipuncture at the same location and at about the same time of the day.
Blood samples were taken once at the start of the study (d 0) and twice at the end of every dietary period (wk 3, 6 and 9, Fig. 1). The interval between the two blood samples was 3 d. On each occasion, a 10-mL serum tube (Becton Dickinson Vacutainer Systems, Franklin Lakes, NJ) was used. To obtain serum, the tube was left for at least 1 h after venipuncture at room temperature. Then, serum was prepared by centrifuging at 2000 x g for 30 min at 4°C. Serum samples were stored at -80°C until the end of the study. At d 0 and once at the end of every dietary period, blood was also sampled in a 10 mL EDTA tube (Becton Dickinson Vacutainer Systems).
Measurements.
In all serum samples, total cholesterol, HDL cholesterol and triacylglycerol with correction for free glycerol were analyzed enzymatically as described (17). Serum LDL cholesterol levels were calculated using the Friedewald equation (18). Samples from one subject were always analyzed in one run. Within-run CV were 1.4% for total cholesterol, 6.8% for HDL cholesterol and 2.6% for triacylglycerol.
Before analyses of serum sterols and stanols (sitosterol, sitostanol, campesterol and campestanol), and a cholesterol precursor sterol (lathosterol), sera from the two blood samples at the end of every dietary period were pooled. Analyses were performed in duplicate as described elsewhere (8). Values of plant sterols, plant stanols and lathosterol were corrected for serum total cholesterol concentrations.
In serum samples taken at the start of the study and at the end of each dietary period, alanine aminotransferase (ALAT),2 aspartate aminotransferase (ASAT), total bilirubin, 
-glutamyl transpeptidase (-GT), creatinine and C-reactive protein were analyzed using a Beckman Synchron CX7 System (Beckman Instruments, Palo Alto, CA). Hematologic variables (number of white blood cells, number and percentage of lymphocytes, number and percentage of monocytes, number and percentage of granulocytes, number of RBC, hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, number of platelets and mean platelet volume) were analyzed in EDTA-containing blood samples on a Coulter Microdiff 18 (Coulter Corporation, Miami, Fl).
Statistics.
For lipids and lipoproteins, results of the two serum samples taken at the end of each period were averaged before statistical analyses. Effects of the experimental products were evaluated by ANOVA. If these effects were significant, the Tukey method was used to compare the three treatments pairwise. For ANOVA, a model that included margarine, period, carry-over effects and subject number as independent variables was used. Because period and carry-over effects were not significant, they were excluded from the model. The 95% CI for the differences in effects between the margarines was corrected for multiple comparisons. Serum total cholesterol–standardized sterol and stanol concentrations as well as liver, kidney and inflammatory variables were not normally distributed, and differences among the dietary periods were therefore analyzed using the Friedman test. If there were differences between the three dietary periods, the Wilcoxon test was used to compare two interventions pairwise. Differences were considered significant at P 0.017. Statistical analyses were performed using SAS version 5 (SAS Institute, Cary, NC) and SPSS for Macintosh 6.1 (SPSS, Chicago, IL). All values are means ± SD.
|
RESULTS |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Daily intakes of energy, and the percentages of energy from fat, saturated fatty acids, monounsaturated fatty acids, PUFA, linoleic acid, 
-linolenic acid, protein and carbohydrates as well as daily intake of cholesterol, fiber and alcohol, did not differ during the three dietary periods (data not shown). Mean daily intake of the control margarine was 25.7 ± 4.1 g, of the low sterol margarine 23.4 ± 3.9 g, and of the high sterol margarine 24.2 ± 3.5 g. Consequently, daily intakes of plant stanols and sterols were close to the targeted intakes (Table 2).
|
The diets did not affect the hematological variables, ALAT, ASAT, total bilirubin, -GT, creatinine and C-reactive protein. Inspection of the diaries revealed no serious deviations from the protocol.
Serum lipids and lipoproteins.
Compared with the control period, serum total cholesterol was 0.15 mmol/L (-3.4%) lower during the low sterol period (P = 0.014, 95% CI for the difference between the dietary periods -0.30 to -0.01 mmol/L) and 0.12 mmol/L (-2.7%) lower during the high sterol period (P = 0.037, 95% CI for the difference -0.27 to 0.02 mmol/L, Table 3). The low and high sterol periods did not differ in serum total cholesterol concentrations (P = 0.705, 95% CI for the difference -0.12 to 0.17 mmol/L).
|
The three margarines did not change serum concentrations of HDL cholesterol (P = 0.714) and triacylglycerol (P = 0.068). However, triacylglycerol concentrations tended to be higher at the end of the high sterol period compared with the control period (P = 0.024). The total to HDL cholesterol ratio was 3.78 ± 1.22 during the control period, 3.61 ± 1.16 during the low sterol period (P = 0.074 vs. control) and 3.60 ± 1.02 during the high sterol period (P = 0.054 vs. control). The LDL to HDL cholesterol ratio was 2.43 ± 1.08 at the end of the control period, 2.24 ± 0.92 at the end of the low sterol period (P = 0.017 vs. control) and 2.21 ± 0.85 at the end of the high sterol period (P = 0.007 vs. control). There were no differences in effect between the low and high fat margarines on any serum lipid or lipoprotein concentrations (data not shown).
Serum plant sterol and stanol concentrations.
Consumption of the low and high sterol margarine increased serum cholesterol–standardized concentrations of campesterol and sitosterol compared with the control margarine (Table 4). Serum cholesterol–standardized campesterol concentrations increased by 58 x 102 µmol/mmol cholesterol (20%) during consumption of the low sterol margarine (P < 0.001) and by 84 x 102 µmol/mmol cholesterol (33%) during consumption of the high sterol margarine (P < 0.001). The serum cholesterol–standardized campesterol concentrations between the low and high sterol period tended to be different (P = 0.020). Serum cholesterol–standardized sitosterol concentrations increased by 9 x 102 µmol/mmol cholesterol (11%) during consumption of the low sterol margarine (P = 0.001) and by 23 x 102 µmol/mmol cholesterol (19%) during consumption of the high sterol margarine (P = 0.002). Serum cholesterol–standardized sitosterol concentrations at the end of the low sterol period did not differ from those of the high sterol period (P = 0.069). The increase in serum cholesterol–standardized sterol concentrations were proportional to intakes; when expressed per gram of daily plant sterol intake, they did not differ during the low sterol (20% for serum campesterol, 11% for serum sitosterol) and high sterol (22% for serum campesterol, 13% for serum sitosterol) periods. To compare the increases in serum cholesterol–standardized plant sterol concentrations from the present study with those from previous studies, we plotted the intakes of campesterol and sitosterol (Fig. 2) against the relative changes in serum cholesterol–standardized plant sterol concentrations in the present study and other studies. In the other studies, products enriched with only plant sterol esters were provided. Only studies that lasted at least 2 wk were included. As can be seen, the relative changes in cholesterol-standardized serum concentrations of campesterol and sitosterol from the present study did not deviate from those of other studies.
|
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Our results are supported by the findings of a recent study in 15 hypercholesterolemic subjects. In that study, a mixture that provided 0.9 g/d nonesterified plant sterols (0.4 g sitosterol, 0.3 g stigmasterol and 0.2 g campesterol) plus 0.9 g/d stanols (0.6 g sitostanol and 0.3 g campestanol) increased serum cholesterol–standardized concentrations of campesterol by 55% and of sitosterol by 16%. It should be noted, however, that these increases were not significant, which may be due to the relatively small number of subjects (23). Three other studies also examined the effects on serum plant sterol concentrations of a mixture containing 20% free sitostanol and 80% free plant sterols (16% campesterol and 62% sitosterol). Results were not consistent. In hypercholesterolemic subjects, an intake of 1.6 g/d increased serum cholesterol–standardized campesterol concentrations by 47% (not significant) (24), whereas significant increases of 70 and 12% at intakes of 1.8 and 1.9 g/d, respectively, were observed (25,26). In normocholesterolemic subjects, serum cholesterol–standardized campesterol concentrations decreased by 32% at an intake of 1.6 g/d (24). Effects on cholesterol-standardized sitosterol levels were also variable. In hypercholesterolemic subjects, no changes were observed in two studies (24,25), whereas a significant increase of 82% was seen in a third study (26). In normocholesterolemic subjects, a nonsignificant increase of 31% in serum cholesterol–standardized sitosterol concentrations was observed (24). For comparison, we found significant increases in serum cholesterol–standardized concentrations of campesterol (20%) and sitosterol (11%) during consumption of 2 g/d of a mixture containing equal amounts of plant sterols and stanols. The main difference between our study and the four studies mentioned above (23–26) is that we used mixtures of esterified plant sterols and stanols instead of free plant sterols and stanols. However, because plant sterol and stanol esters are almost completely hydrolyzed in the intestinal lumen (4) and have a similar cholesterol-lowering effect, it is not likely that their effects on intestinal metabolism are very different.
Relative changes in serum cholesterol–standardized campestanol concentrations, although not significant, were comparable to those in other studies (8,27,28) that used products enriched with only plant stanols (Fig. 3). Serum cholesterol–standardized sitostanol concentrations did not change. This could be due to the relatively low daily intakes of sitostanol, which were 0.4 and 0.7 g for the high and low sterol margarine, respectively. Indeed, other studies reported significant changes in cholesterol-standardized sitostanol concentrations when sitostanol intake exceeded 1 g/d (Fig. 3) (7,8,27–29). Taken together, these results do not suggest that the absorption of plant stanols was lowered due to the simultaneous consumption of plant sterol esters. It should be noted, however, that in one (15), but not all studies (7,20), consumption of products enriched with only plant sterols lowered serum cholesterol–standardized plant stanol concentrations.
The mechanism underlying plant sterol absorption is still not completely understood, but studies in sitosterolemic patients have shown that ATP-binding cassette (ABC)G5 and ABCG8 are involved (30–32). These intestinal sterol transporters pump plant sterols and stanols out of the enterocyte back into the intestinal lumen (30,33–35). We showed recently that sitostanol increases ABCA1 expression (36). Because ABCA1, ABCG5 and ABCG8 are regulated by the same transcriptional pathway (34,37), it is expected that plant stanols also increase ABCG5 and ABCG8 expression. From the present study, we concluded that plant sterols do not affect serum plant stanol concentrations to any great extent and vice versa, suggesting that both plant sterols and plant stanols are equally potent ABCG5 and ABCG8 activators; this must be confirmed in future studies.
Various studies demonstrated that plant stanol esters and sterol esters reduce cholesterol absorption and serum LDL cholesterol concentrations to the same extent (6,7,13,14,38). This agrees with our finding that the plant sterol to stanol ratio does not change its LDL cholesterol-lowering efficacy. However, in other studies using 2.0–2.2 g/d of either plant sterols or plant stanols (7,9,21), reductions in serum LDL cholesterol of 8–16% were found, which are higher than the reductions of 6–7% in the present study. One could speculate that this smaller reduction was caused by a decrease in the cholesterol-lowering effectiveness of mixtures of plant sterol and plant stanol esters. However, in other studies with mixtures of free plant sterols and stanols, even greater reductions in serum LDL cholesterol (8.9–16%) were found at lower intakes (1.6–1.9 g/d) (23–26). Compared with these latter studies, however, subjects in the present study had lower baseline LDL cholesterol concentrations. When we grouped our subjects into tertiles on the basis of serum LDL cholesterol concentrations during the control period, the first tertile (serum LDL cholesterol 2.26 mmol/L, 4 men and 10 women) showed a decrease in serum LDL cholesterol of 1.9% during the low and an increase of 1.8% during the high sterol period. For the second tertile (serum LDL cholesterol 2.27 to 3.36 mmol/L, 5 men and 9 women), the decreases were 5.6 and 5.7%, respectively, and for the third tertile (serum LDL cholesterol 
3.36 mmol/L, 6 men and 8 women), 6.8 and 8.7%, respectively. These changes were not different among the tertiles, possibly due to the fact that our study was not specifically designed to test this hypothesis. These findings do indicate, however, that contrary to previous observations (6,21), relative changes in serum LDL cholesterol concentrations depend on initial serum LDL cholesterol concentrations.
In conclusion, our study suggests that changes in serum plant sterol and stanol concentrations are not greatly affected by the simultaneous consumption of plant sterols and plant stanols, but are proportional to intakes. Furthermore, both mixtures of plant sterol and stanol esters were equally effective in lowering serum LDL cholesterol concentrations.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
3 Abbreviations used: ABC, ATP- binding cassette; ALAT, alanine aminotransferase; ASAT, aspartate aminotransferase; -GT, -glutamyl transpeptidase.
Manuscript received 22 May 2003. Initial review completed 28 May 2003. Revision accepted 20 June 2003.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. Ostlund, R. E., Jr (2002) Phytosterols in human nutrition. Annu. Rev. Nutr. 22:533-549.[Medline]
2. Bosner, M. S., Lange, L. G., Stenson, W. F. & Ostlund, R. E., Jr (1999) Percent cholesterol absorption in normal women and men quantified with dual stable isotopic tracers and negative ion mass spectrometry. J. Lipid Res. 40:302-308.
3. Ostlund, R. E., Jr, McGill, J. B., Zeng, C. M., Covey, D. F., Stearns, J., Stenson, W. F. & Spilburg, C. A. (2002) Gastrointestinal absorption and plasma kinetics of soy Delta(5)- phytosterols and phytostanols in humans. Am. J. Physiol. 282:E911-E916.
4. Miettinen, T. A., Vuoristo, M., Nissinen, M., Jarvinen, H. J. & Gylling, H. (2000) Serum, biliary, and fecal cholesterol and plant sterols in colectomized patients before and during consumption of stanol ester margarine. Am. J. Clin. Nutr. 71:1095-1102.
5. Salen, G., Ahrens, E. H. & Grundy, S. M. (1970) Metabolism of beta-sitosterol in Man. J. Clin. Investig. 49:952-967.
6. Weststrate, J. A. & Meijer, G. W. (1998) Plant sterol-enriched margarines and reduction of plasma total- and LDL-cholesterol concentrations in normocholesterolaemic and mildly hypercholesterolaemic subjects. Eur. J. Clin. Nutr. 52:334-343.[Medline]
7. Hallikainen, M. A., Sarkkinen, E. S., Gylling, H., Erkkila, A. T. & Uusitupa, M. I. J. (2000) Comparison of the effects of plant sterol ester and plant stanol esters-enriched margarines in lowering serum cholesterol concentrations in hypercholesterolaemic subjects on a low-fat diet. Eur. J. Clin. Nutr. 54:715-725.[Medline]
8. Plat, J. & Mensink, R. P. (2001) Effects of diets enriched with two different plant stanol ester mixtures on plasma ubiquinol-10 and fat-soluble antioxidant concentrations. Metabolism 50:520-529.[Medline]
9. Vanhanen, H. T., Kajander, J., Lehtovirta, H. & Miettinen, T. A. (1994) Serum levels, absorption efficiency, faecal elimination and synthesis of cholesterol during increasing doses of dietary sitostanol esters in hypercholesterolaemic subjects. Clin. Sci. (Lond.) 87:61-67.[Medline]
10. Gylling, H., Radhakrishnan, R. & Miettinen, T. A. (1997) Reduction of serum cholesterol in postmenopausal women with previous myocardial infarction and cholesterol malabsorption induced by dietary sitostanol ester margarine: women and dietary sitostanol. Circulation 96:4226-4231.
11. Miettinen, T. A., Puska, P., Gylling, H., Vanhanen, H. & Vartiainen, E. (1995) Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N. Engl. J. Med. 333:1308-1312.
12. Vanhanen, H. T., Blomqvist, S., Ehnholm, C., Hyvonen, M., Jauhiainen, M., Torstila, I. & Miettinen, T. A. (1993) Serum cholesterol, cholesterol precursors, and plant sterols in hypercholesterolemic subjects with different apoE phenotypes during dietary sitostanol ester treatment. J. Lipid Res. 34:1535-1544.[Abstract]
13. Nestel, P., Cehun, M., Pomeroy, S., Abbey, M. & Weldon, G. (2001) Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods. Eur. J. Clin. Nutr. 55:1084-1090.[Medline]
14. Normen, L., Dutta, P., Lia, A. & Andersson, H. (2000) Soy sterol esters and beta-sitostanol ester as inhibitors of cholesterol absorption in human small bowel. Am. J. Clin. Nutr. 71:908-913.
15. Neil, H. A., Meijer, G. W. & Roe, L. S. (2001) Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread. Atherosclerosis 156:329-337.[Medline]
16. Centraal Begeleidingsorgaan voor de Intercollegiale Toetsing (1998) Syllabus Behandeling en Preventie van Coronaire Hartziekten Door Verlaging van de Plasmacholesterolconcentratie 1998 Centraal Begeleidingsorgaan voor de Intercollegiale Toetsing Utrecht, the Netherlands.
17. Plat, J. & Mensink, R. P. (2000) Vegetable oil based versus wood based stanol ester mixtures: effects on serum lipids and hemostatic factors in non-hypercholesterolemic subjects. Atherosclerosis 148:101-112.[Medline]
18. Friedewald, W. T., Levy, R. I. & Fredrickson, D. S. (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 18:499-502.[Abstract]
19. Jones, P. J., Raeini-Sarjaz, M., Ntanios, F. Y., Vanstone, C. A., Feng, J. Y. & Parsons, W. E. (2000) Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. J. Lipid Res. 41:697-705.
20. Mussner, M. J., Parhofer, K. G., Von Bergmann, K., Schwandt, P., Broedl, U. & Otto, C. (2002) Effects of phytosterol ester-enriched margarine on plasma lipoproteins in mild to moderate hypercholesterolemia are related to basal cholesterol and fat intake. Metabolism 51:189-194.[Medline]
21. Maki, K. C., Davidson, M. H., Umporowicz, D. M., Schaefer, E. J., Dicklin, M. R., Ingram, K. A., Chen, S., McNamara, J. R., Gebhart, B. W., Ribaya-Mercado, J. D., Perrone, G., Robins, S. J. & Franke, W. C. (2001) Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet. Am. J. Clin. Nutr. 74:33-43.
22. Vanhanen, H. T. & Miettinen, T. A. (1992) Effects of unsaturated and saturated dietary plant sterols on their serum contents. Clin. Chim. Acta 205:97-107.[Medline]
23. Vanstone, C., Raeini-Sarjaz, M., Parsons, W. & Jones, P. (2002) Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons. Am. J. Clin. Nutr. 76:1272-1278.
24. Jones, P. J., Howell, T., MacDougall, D. E., Feng, J. Y. & Parsons, W. (1998) Short-term administration of tall oil phytosterols improves plasma lipid profiles in subjects with different cholesterol levels. Metabolism 47:751-756.[Medline]
25. Jones, P. J., Ntanios, F. Y., Raeini Sarjaz, M. & Vanstone, C. A. (1999) Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. Am. J. Clin. Nutr. 69:1144-1150.
26. De Graaf, J., De Sauvage Nolting, P. R., Van Dam, M., Belsey, E. M., Kastelein, J.J.P., Haydn Pritchard, P. & Stalenhoef, A.F.H. (2002) Consumption of tall oil-derived phytosterols in a chocolate matrix significantly decreases plasma total and low-density lipoprotein- cholesterol levels. Br. J. Nutr. 88:479-488.[Medline]
27. Mensink, R. P., Ebbing, S., Lindhout, M., Plat, J. & van Heugten, M. M. (2002) Effects of plant stanol esters supplied in low-fat yoghurt on serum lipids and lipoproteins, non-cholesterol sterols and fat soluble antioxidant concentrations. Atherosclerosis 160:205-213.[Medline]
28. Gylling, H. & Miettinen, T. A. (1999) Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism 48:575-580.[Medline]
29. Nguyen, T. T., Dale, L. C., von Bergmann, K. & Croghan, I. T. (1999) Cholesterol-lowering effect of stanol ester in a US population of mildly hypercholesterolemic men and women: a randomized controlled trial. Mayo Clin. Proc. 74:1198-1206.[Abstract]
30. Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R. & Hobbs, H. (2000) Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science (Washington, DC) 290:1771-1775.
31. Lee, M. H., Lu, K., Hazard, S., Yu, H., Shulenin, S., Hidaka, H., Kojima, H., Allikmets, R. & Sakuma, N. et al. (2001) Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat. Genet. 27:79-83.[Medline]
32. Hubacek, J. A., Berge, K. E., Cohen, J. C. & Hobbs, H. H. (2001) Mutations in ATP-cassette binding proteins G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia. Hum. Mutat. 18:359-360.[Medline]
33. Berge, K. E., von Bergmann, K., Lutjohann, D., Guerra, R., Grundy, S. M., Hobbs, H. H. & Cohen, J. C. (2002) Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8. J. Lipid Res. 43:486-494.
34. Fitzgerald, M. L., Moore, K. J. & Freeman, M. W. (2002) Nuclear hormone receptors and cholesterol trafficking: the orphans find a new home. J. Mol. Med. 80:271-281.[Medline]
35. Chen, H. C. (2001) Molecular mechanisms of sterol absorption. J. Nutr. 131:2603-2605.
36. Plat, J. & Mensink, R. P. (2002) Increased intestinal ABCA1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption. FASEB J. 16:1248-1253.
37. Schmitz, G., Langmann, T. & Heimerl, S. (2001) Role of ABCG1 and other ABCG family members in lipid metabolism. J. Lipid Res. 42:1513-1520.
38. Noakes, M., Clifton, P., Ntanios, F., Shrapnel, W., Record, I. & McInerney, J. (2002) An increase in dietary carotenoids when consuming plant sterols or stanols is effective in maintaining plasma carotenoid concentrations. Am. J. Clin. Nutr. 75:79-86.
This article has been cited by other articles:
|
|
 |
|
  I. Demonty, R. T. Ras, H. C. M. van der Knaap, G. S. M. J. E. Duchateau, L. Meijer, P. L. Zock, J. M. Geleijnse, and E. A. Trautwein Continuous Dose-Response Relationship of the LDL-Cholesterol-Lowering Effect of Phytosterol Intake J. Nutr., February 1, 2009; 139(2): 271 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Naumann, J. Plat, A. D.M. Kester, and R. P. Mensink The Baseline Serum Lipoprotein Profile Is Related to Plant Stanol Induced Changes in Serum Lipoprotein Cholesterol and Triacylglycerol Concentrations J. Am. Coll. Nutr., February 1, 2008; 27(1): 117 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Fransen, N. de Jong, M. Wolfs, H. Verhagen, W.M. M. Verschuren, D. Lutjohann, K. von Bergmann, J. Plat, and R. P. Mensink Customary Use of Plant Sterol and Plant Stanol Enriched Margarine Is Associated with Changes in Serum Plant Sterol and Stanol Concentrations in Humans J. Nutr., May 1, 2007; 137(5): 1301 - 1306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Plat, I. Beugels, M. J. J. Gijbels, M. P. J. de Winther, and R. P. Mensink Plant sterol or stanol esters retard lesion formation in LDL receptor-deficient mice independent of changes in serum plant sterols J. Lipid Res., December 1, 2006; 47(12): 2762 - 2771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Plat, M. C. E. Bragt, and R. P. Mensink Common sequence variations in ABCG8 are related to plant sterol metabolism in healthy volunteers J. Lipid Res., January 1, 2005; 46(1): 68 - 75. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
