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SlimFast Foods Company, Medical Department, West Palm Beach, FL 33410
*
Department of Internal Medicine, Tokai University School 7 Medicine, Boseidai, Isehara 259-1193, Japan
Nippon Lever K.K., 2–22-3 Shibuya, Shibuya-ku, Tokyo 150-8388, Japan
3To whom correspondence should be addressed. E-mail: fntanios{at}slimfast.com.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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5.7 mmol/L)]. Reductions (P < 0.001) in TC and LDL-C due to treatment in the former group were 4.9 and 7.9%, respectively. In the hypercholesterolemic group, the reductions (P < 0.001) were 7.1 and 10.6%, respectively. The decreases did not differ between normal/mildly cholesterolemic and hypercholesterolemic subjects. Plasma apolipoprotein B (apoB) and remnant-like particle (RLP) cholesterol (RLP-C) concentrations were lower when subjects consumed the PS spread (44.3 g/L) than the control spread (49.7 g/L). Plasma ß-carotene concentration was lower (P < 0.001) in subjects consuming the PS spread than in the control. Changes in plasma vitamins A and E levels did not differ after intake of the PS and control spreads. In conclusion, consumption of a PS-enriched spread effectively lowered plasma TC, LDL-C, apoB and RLP-C regardless of baseline plasma TC at an intake of 1.8 g/d of plant sterols.
KEY WORDS: • plant sterols • Japanese diet • cholesterol • lipoprotein • ß-carotene
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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–8
). Normal dietary intake of plant sterols is 
160–360 mg/d, with a typical composition of 65% as ß-sitosterol, 30% as campesterol and 5% as stigmasterol (9
,10
). When consumed at levels 5–10 times higher than the normal intake, plant sterols have been shown to lower blood LDL cholesterol (LDL-C)4 levels. In conjunction with a healthy diet, cholesterol lowering of 10–15% can be achieved (11
,12
). Dietary plant sterols lower blood cholesterol levels by reducing the absorption of dietary and biliary cholesterol from the gut. Possible mechanisms include displacing cholesterol from the micelles, limiting the intestinal solubility of cholesterol or decreasing the hydrolysis of cholesterol esters in the small intestine (3
). Although a series of clinical trials were conducted to study the cholesterol-lowering efficacy of plant sterol-ester (PS)-enriched spreads under a wide range of settings and formulations, none has tested the effect of this new type of spread in Japanese subjects consuming their traditional diets. The objectives of this study were to investigate the efficacy of spreads enriched with PS on blood cholesterol levels in healthy Japanese men and women and to determine whether initial baseline cholesterol levels modulate the efficacy of plant sterols.
One side-effect associated with the consumption of PS-enriched spreads is a small reduction in plasma levels of the most lipophilic carotenoids such as ß-carotene. The effects of this spread on plasma ß-carotene as well as vitamin A and E levels were also assessed. The effects of the PS-enriched spread on plasma levels of the protein moiety of lipoprotein (apoprotein) and those of some arteriosclerosis-promoting factors including plasminogen activator inhibitor (PAI)-1, fibrinogen and remnants of triglyceride (TG)-rich lipoprotein were also investigated.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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This double-blind trial began with a run-in period of 1 wk (ending d 9), followed by two intervention periods of 3 wk in a 2 x 2 crossover (period 1 ending d 30 and period 2 ending d 51) and a post-trial follow up of 3 wk (ending d 71). The lipid levels were measured on two consecutive days (except for the post-trial follow up at d 71) and the mean was used for the statistical analysis. During the two consecutive 3-wk interventions, subjects received 15 g/d of spread (control or containing the equivalent of 1.8 g free sterols). They were instructed to consume half at breakfast and the other half at lunch or dinner with minimum and maximum intervals of 4 and 10 h, respectively. The study design was approved by the Institutional Review Board of Waseda Clinic, Tokyo, Japan.
Calculation of sample size.
Sample size estimation for equal group numbers was calculated using the simple normal method. This calculation is based on the outcome of previous experiments, which demonstrated a 10–13% reduction in LDL-C concentrations and a CV of 8% (5
,7
). On the basis of this variation estimate, 54 subjects were required to detect a difference of 5% in LDL-C levels with a power of 90% (
= 0.05). Subjects were allocated to the two different periods according to sex and baseline total cholesterol (TC) level. After each experimental period of 3 wk, body weight was measured and a blood sample was drawn. Dietary intake during the run-in period was assessed using a food-frequency questionnaire (FFQ). Special attention was paid to intakes of total energy, macronutrients and of fatty acids and cholesterol. Throughout the study, subjects recorded illnesses, medicine use, any important deviations from their normal lifestyle, activity pattern and dietary intake (during the first phase of the study). The total spread consumed was checked by weighing the spread left over in the sachets and by checking the spread compliance forms.
Subjects.
Volunteers were recruited from 80 (37 men; 43 women) respondents. All subjects expressed interest in the study and had answered a personal and lifestyle characteristics questionnaire based on inclusion criteria. Twenty-seven subjects were excluded. A total of 53 subjects were selected and invited to join the experiment. The selected volunteers were between 24 and 67 y of age, with stable body weights and Quetelet Index [body mass index (BMI)] between 19 and 30 kg/m2. They had normal dietary patterns (no reported weight-loss diets, medically prescribed diets, vegan or vegetarian diets). All were assessed as healthy from the personal and lifestyle characteristics questionnaire (no reported current disease or history of metabolic disease, chronic gastrointestinal disorders, cardiovascular disease, high blood pressure or high blood cholesterol, no reported medical treatment, no use of medicine except analgesics or contraceptives, bowel frequency at least once per 48 h). Subjects could not participate in another biomedical trial or donate blood 1 mo (for men) or 2 mo (for women) before the start of the study. Alcohol intake was <1 L/wk. Subjects engaged in <10 h/wk of intense exercise. The women were not lactating or pregnant. All subjects gave their written informed consent before participation and were told that they were free to withdraw at any time during the study. Subjects who completed the study received a financial reward. There were no dropouts.
Spreads.
The test spread was a specially prepared fat spread enriched with PS (Nippon Lever, Tokyo, Japan). The final free plant-sterol concentration was 12 g/100 g for the spread fortified with PS. A nonfortified spread was used as a control with the free plant sterols being replaced with water. The water-oil emulsion in the spread was treated so that subjects could not detect any hedonic difference between the PS-enriched and the nonenriched spreads. Spreads in sachets were refrigerated (5°C) before delivery to the subjects. The spreads were coded A and B and the intervention periods coded 1 and 2. Each individual received a unique personal code that was used by the statistician to allocate each subject to a spread group for each period. Members of the study team who associated with the volunteers or were responsible for the analysis of the blood samples had no knowledge of the type of spreads the subjects received. The spreads were intended for personal use to replace all or part of the subjects’ usual spread or butter. The spreads were provided in 42 labeled sachets for one period (21 d x 2/d) for a target intake of 15 g/d. The subjects were instructed to use a sachet (7.5 g) at breakfast and another sachet (7.5 g) at lunch or dinner, but not to bake or fry with the spread. They were instructed to note on the compliance form the time when the spread was consumed as well as information on dietary intake, sleeping hours, exercise, alcohol intake and health. Unconsumed sachets were returned at the next visit to the clinic. The total amount of spread consumed was checked each period by weighing the spread in the sachets before and after each experimental period, and by checking the compliance forms.
Measurements.
The subjects recorded illnesses, changes in lifestyle and activity pattern and medicine use on a compliance form. After each period, body weight was measured, after voiding, with an analog balance (Eiko Instrument, Tokyo, Japan) with the subjects wearing light indoor clothing and no shoes.
During the run-in period, the dietary intake was assessed in terms of energy, protein, cholesterol, lipid, carbohydrates, Ca, Fe, vitamins A, E, thiamine, riboflavin and C, NaCl and fiber, using the Japanese nutrition database software, BASIC-4 (Kagawa Nutrition University’s Publishing Division, Tokyo, Japan) by Bywanell (Tokyo, Japan). Subjects answered a questionnaire during the run-in period. The answers in the FFQ were checked for completeness in an interview with dieticians. Food diaries were not requested during period 2.
Blood samples from the antecubital vein were collected from fasting subjects in seated positions at the clinic on d 1, 8, 9, 29, 30, 50, 51 and 71. Serum and plasma were stored at 4, -22 or -84°C. No hemolysis was seen in any blood sample. Plasma concentrations of TC and TG were determined with Olympus AU 5232 autoanalyzer (Olympus Optical, Tokyo, Japan) and LDL-C was measured with Olympus –AU600 autoanalyzer (Olympus Optical). Plasma HDL cholesterol (HDL-C) was estimated with dextran sulfate-Ca precipitation method (13
). Plasma apoproteins were measured using a turbidimetric immunoassay (14
). Remnant-like particle cholesterol (RLP-C) was determined with a precipitation method using monoclonal antibodies against human apo(protein) A-I and B-150 (15
,16
). PAI-1 was measured with an ELISA method using a Biopool EIA kit (Ventura, California) (17
). Fibrinogen was analyzed using the test kit, Fibrinogen a "RD" (Roche Diagnostics, Tokyo, Japan). ß-Carotene was analyzed by HPLC (column; Lichrospher 100RP-18) (Hitachi, Tokyo, Japan) (18
). Vitamins A and E were determined by HPLC (Ex 290 nm/Em 325 nm; Ex 325 nm/Em 480 nm, respectively) (JASCO, Tokyo, Japan and Hitachi) (19
). Clinical chemistry (aspartate aminotransferase, alanin aminotransferase, alkaline phosphatase, 
-glutamyl transpeptidase, blood urea nitrogen, creatinin, uric acid and glucose) and hematological variables (hemoglobin, hematocrit, leukocytes, erythrocytes and platelets) were measured by routine clinical techniques (CV < 4%) (Olympus Optical).
Statistical analysis.
Statistical analysis was performed by ANOVA using as factors, gender, subject (normal, mildly and hypercholesterolemic), period and spread. Subjects were also separated into a normal to mildly cholesterolemic group and a hypercholesterolemic group. These groups were tested for significant difference. Differences with P-values < 0.05 were considered significant. SAS version 6.12 (Cary, NC) was used for data analysis.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Most of the spreads were consumed at breakfast, lunch or dinner as intended (breakfast 72%, lunch 39%, dinner 81%, between meals 8%: total 200% (100% x 2 sachets). The customary intake of the spreads reached the target of 15 g/d. None of the subjects changed their eating habits during period 1 of the experiment. The same individuals smoked with no change in daily intake. Nobody reported changes in alcohol intake during the first period, and intake did not exceed the limit (1 L/wk). In both test groups, similar illnesses were reported such as headache, diarrhea, common cold and hay fever (data not shown). Medicine use was limited and related mainly to illnesses listed above or previous illnesses.
Subjects’ characteristics.
Twenty-six men and 27 women completed the study. They ranged in age from 24 to 67 y and their BMI at selection time was between 19 and 30 kg/m2 (Table 1
). Body weight did not differ between the two groups. Twenty-one women were premenopausal (age range 33–53 y) and six were postmenopausal (age range 57–64 y).
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The fatty acid composition of the PS-enriched spread closely resembled that of the control product. Differences, as planned, were in the sterol content. The fatty acid composition and the tocopherol and the ß-carotene contents were similar in the two spreads (Table 2
).
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The fat fraction of the spread was calculated by adding the fatty acids of the sterol esters to total fat concentration. Energy, total fat and dietary cholesterol intakes did not differ between subjects consuming the PS and the control spreads during period 1 of the study. Spread intake contributed slightly <7% to the total energy intake and 15% to total fat intake (Table 3
). Intakes were not assessed during period 2.
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Blood chemistry and liver enzymes did not differ for subjects when consuming the control or the PS-enriched spreads. The spread enriched with PS significantly lowered plasma TC (-5.8%) and LDL-C (-9.1%) concentrations compared with the control spread without any effect on plasma HDL-C and TG levels (Table 4
). When subjects were divided into two groups, those with TC < 5.7 mmol/L (normal cholesterolemic) and those with TC > 5.7 mmol/L (hypercholesterolemic), the reductions in TC, LDL-C and apoB did not differ between the groups (Table 4)
. No changes were observed in apoAI, apoAII, apoCII, apoCIII and apoE concentrations (Table 5
). A periodic effect on the LDL-C level was detected. LDL-C levels for both groups (control and treatment) in period 2 were higher than those in period 1. ApoAI, apoAII, apoE and TG were different in periods 1 and 2. Plasma RLP-C level was lower after intake of the PS spread (44.3 g/L) compared with the control spread (49.7 g/L; 95% confidence interval: -0.97, -0.10). No differences were observed in PAI-1 and fibrinogen levels due to PS and control spreads.
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. After standardization for plasma lipids, the reduction in ß-carotene diminished, but was significant (data not shown). There were no differences in the changes in plasma vitamins A and E when subjects consumed the plant sterol–enriched spread or control spread (Table 5)
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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,5
,7
). This was to account for the lower daily consumption of spreads in the Japanese diet compared with Western diets (15 vs. 20 g/d, respectively). At 15 g spread/d, the sterol intake of 1.8 g was comparable to that of other reported studies and lowered plasma TC and LDL-C regardless of baseline cholesterol levels. This is in agreement with Weststrate and Meijer (5
) and Law (12
). The plasma cholesterol–lowering efficacy of PS was the same in both normal and hypercholesterolemic subjects. Six postmenopausal women were included in the study. Exclusion or inclusion of the postmenopausal women in the statistical analyses did not affect the outcome of the study. Japanese daily intake of plant sterols is 300 mg (2
), which is similar to that of dietary cholesterol reported in this trial. Plant sterol intake was not determined in this study; thus, we could not confirm the values reported by other investigators (2
). Inhibition of intestinal absorption of exogenous (dietary) and endogenous (biliary) cholesterol is the major mechanism of the cholesterol-lowering action of plant sterols (2
,3
,6
), although the exact mechanism of action remains to be fully explained.
The percentage of energy from fats in a typical Japanese diet is close to a Step 1 diet (National Cholesterol Education Program) (20
,21
). Diets low in dietary saturated fatty acids (SFA) and rich in polyunsaturated fatty acids and monounsaturated fatty acids lower blood cholesterol by up to 10% (20
–24
). In Western countries, high intakes of animal fat and oils rich in SFA have been associated with increased blood cholesterol and elevated risk of coronary heart disease (25
–31
). Interestingly, the effect of the PS-enriched spread on LDL-C in Japanese subjects was similar to what was reported earlier in Westerners (5
,7
,32
). This further confirms that background diet does not alter the efficacy of PS in reducing blood cholesterol (33
–35
). Energy from fats was 34% in this study. A national survey by the Japanese Health, Welfare and Labor showed that energy intake from fats was 26% in Japan (20
,21
). Fat intake in subjects in this study was higher than in ordinary Japanese people. Despite the higher fat intake, results from this study parallel those of Hallikainen et al. (11
) in which LDL-C level was reduced by 10.4% in hypercholesterolemic subjects consuming 2 g/d of sterol-esters in conjunction with a Step 1 diet.
Compliance was high. Physical activity and BMI did not change during the study, confirming that the reductions in blood cholesterol levels were probably due to the PS in the spread. However, a periodic effect was observed for LDL-C and TG. Although the respective changes in LDL-C and TG levels were similar in both periods, the means differed. The subjects were their own controls and the crossover design reduced the between-individual variation and the time effect. Dietary records were reported to dieticians for period 1 of the trial only. The data indicated that all subjects had similar dietary backgrounds in period 1. Because the change in LDL-C was similar in periods 1 and 2, all subjects in period 2 had most likely changed their dietary habits. Although spread consumption was very close to the target of 15 g/d and intake occurred mainly at breakfast, lunch or the evening meal, unreported dietary changes may have occurred in period 2 because of the elimination of the dieticians’ follow-up. Subjects may have shifted from a relatively high carbohydrate diet to a lower or more complex carbohydrate diet. This observation is further supported by the fact that TG levels were different in periods 1 and 2 and LDL-C levels increased slightly due to both interventions in period 2. Normal energy intakes in Japanese individuals between 30 and 49 y old are 10.669 MJ/d (men) and 8.368 MJ/d (women) (20
). Energy intakes in this study population were slightly lower than the Japanese average, but intakes did not differ when the two spreads were consumed.
Interestingly, plasma levels of RLP-C, which is equivalent to the remnant of TG-rich lipoproteins, e.g., VLDL and chylomicrons, were reduced by the ingestion of the PS spread. Although plasma TG and VLDL levels from fasting subjects were similar in both interventions, the postprandial hyperlipidemia that potentially progresses into arteriosclerosis may have been improved by the ingestion of PS spreads. Plasma TG is carried in chylomicrons, which are produced in the intestine from dietary fat, and in VLDL, which are produced in the liver. VLDL but not chylomicrons are present in the plasma of fasting subjects; thus, plasma levels of TG in fasting subjects reflect the amount of VLDL. Remnant-like particles consist of chylomicron remnants and VLDL remnants. Plasma levels of TG were the same after consumption of either spread. Therefore, PS did not affect plasma levels of VLDL-TG. Plasma RLP-C were lower in the subjects when they consumed the PS spread than when they consumed the control spread. This is probably due to the decrease of chylomicron remnant formation by plant sterols. Further work may be required to explain the potential effect of plant sterols on chylomicron formation or fat absorption.
No significant differences in the changes in vitamins A and E were detected in the study, consistent with earlier studies on PS spreads. Plasma ß-carotene level was lower when the PS, rather than the control spread was consumed. The reduction in ß-carotene followed seasonal variation and is in agreement with previous studies in sterol- and stanol-ester–enriched spreads (5
,36
). Recently, Noakes et al. (37
) reported that increasing fruit and vegetable intakes to the American Heart Association recommendation of 5 portions/d returned plasma carotenoid levels to baseline. In addition, Hallikainen et al. (33
,34
,38
) reported minor or no changes in carotenoid levels (lipid standardized) when subjects followed detailed oral and written instructions about healthy, low fat diets, specifying the amount and quality of food by main food groups, including vegetables.
In conclusion, as part of a traditional Japanese diet, a spread enriched with PS reduced plasma cholesterol levels and its efficacy did not depend on baseline plasma cholesterol concentration.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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2 Supported by Unilever Bestfoods and conducted according to Good Clinical Practice at the Waseda Clinic, Tokyo, Japan.
4 Abbreviations used: apoB, apolipoprotein B; BMI, body mass index; FFQ, food-frequency questionnaire; HDL-C, HDL cholesterol; LDL-C, LDL cholesterol; PAI, plasminogen activator inhibitor; PS, plant sterol-esters; RLP-C, remnant-like particle cholesterol; SFA, saturated fatty acids; TC, total cholesterol; TG, triglyceride.
Manuscript received 26 April 2002. Initial review completed 17 May 2002. Revision accepted 27 August 2002.
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LITERATURE CITED |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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1. Moghadasian, M. H. & Frohlich, J. J. (1999) Effects of dietary phytosterols on cholesterol metabolism and atherosclerosis: clinical and experimental evidence. Am. J. Med. 107:588-594.[Medline]
2. Jones, P. J., MacDougall, D. E., Ntanios, F. & Vanstone, C. A. (1997) Dietary phytosterols as cholesterol-lowering agents in humans. Can. J. Physiol. Pharmacol. 75:217-227.[Medline]
3. Ling, W. H. & Jones, P.J.H. (1995) Dietary phytosterols: a review of metabolism, benefits and side effects. Life Sci 57:195-206.[Medline]
4. Pollak, O. J. & Kritchevsky, D. (1981) Sitosterol. Monographs on Atherosclerosis 1981:60-163 Karger Basel, Switzerland.
5. 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]
6. 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.
7. Hendriks, H. F., Weststrate, J. A., van Vliet, T. & Meijer, G. W. (1999) Spreads enriched with three different levels of vegetable oil sterols and the degree of cholesterol lowering in normocholesterolaemic and mildly hypercholesterolaemic subjects. Eur. J. Clin. Nutr. 53:319-327.[Medline]
8. Ntanios, F. Y. (2001) Plant sterol-ester-enriched spreads as an example of a new functional food. Eur. J. Lipid Sci. Technol. 103:102-106.
9. Morton, G. M., Lee, S. M., Buss, D. H. & Lawrence, P. (1995) Intakes and major dietary sources of cholesterol and phytosterols in the British diet. J. Hum. Nutr. Diet. 8:429-440.
10. Cerqueira, M. T., Fry, M. M. & Connor, W. E. (1979) The food and nutrient intakes of the Tarahumara Indians of Mexico. Am. J. Clin. Nutr. 32:905-915.
11. Hallikainen, M. A., Sarkkinen, E. S., Gylling, H., Erkkila, A. T. & Uusitupa, M.I.J. (2000) Comparison of the effects of plant sterol eater and plant stanol ester-enriched margarines in lowering serum cholesterol concentrations in hypercholesterolaemic subjects on a low-fat diet. Eur. J. Clin. Nutr. 54:715-725.[Medline]
12. Law, M. (2000) Plant sterol and stanol margarines and health. Br. Med. J. 320:861-864.
13. Bunrstein, M., Scholnick, H. R. & Morfin, R. (1970) Rapid method for isolation of lipoprotein from the human plasma by precipitation with polyanions. J. Lipid Res. 11:583-595.[Abstract]
14. Noma, A., Hata, Y. & Goto, Y. (1991) Quantification of serum apolipoprotein A-1, A-2, B, C-II, C-III and E in healthy Japanese by the turbidimetric immunoassay, reference values, and age and sex-related differences. Clin. Chim. Acta 199:147-158.[Medline]
15. Nakajima, K., Saito, T., Tamura, A., Suzuki, M., Nakano, T., Adachi, M., Tanaka, A., Tada, N., Nakamura, H. & Campos, E. (1993) Cholesterol in remnant-like lipoproteins in human serum using monoclonal antiapo B-100 and antiapo A-1 immunoaffinity mixed gel. Clin. Chim. Acta 223:53-71.[Medline]
16. Campos, E., Nakajima, K., Tanaka, A. & Havel, R. L. (1992) Properties of an apoprotein E-enriched fraction of triglyceride-rich lipoproteins isolated from human-blood plasma with a monoclonal antibody to apolipoprotein B-100. J. Lipid Res. 33:369-380.[Abstract]
17. Declerck, P. J., Alessi, M.-C., Verstrecken, M., Kruithof, E.K.O., Julia-Vague, I. & Collen, D. (1988) Measurement of plasminogen activator inhibitor-1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay. Blood 71:220-225.
18. Driskell, W. J., Bashor, M. M. & Neese, J. W. (1983) Beta-carotene determined in serum by lipid chromatography with an internal standard. Clin. Chem. 29:1042-1044.
19. Parviainen, M. T. & Koskinen, T. (1983) Vitamin A, D and E status in a Finnish population—a multivitamin study. Hum. Nutr. Clin. Nutr. 37:397-403.[Medline]
20. Nakamura, T., Takebe, K., Tando, Y., Arai, Y., Yamada, N., Ishii, M., Kikuchi, H., Machida, K., Imamura, K. & Tereda, A. (1995) Serum fatty acid composition in normal Japanese and its relationship with dietary fish and vegetable oil contents and blood lipid levels. Ann. Nutr. Metab. 39:261-270.[Medline]
21. Itoh, K., Imai, K., Masuda, T., Abe, S., Nakao, H., Tanaka, M. & Nakamura, M. (1999) Relationship between serum total cholesterol level and nutritional status in Japanese young female. Nutr. Rev. 19:1145-1152.
22. Hegsted, D. M., McGrandy, R. B., Myers, M. L. & Stare, F. J. (1965) Quantitative effects of dietary fat on serum cholesterol in man. Am. J. Clin. Nutr. 17:281-295.[Medline]
23. Mensink, R. P. & Katan, M. B. (1992) Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials.. Arterioscler. Thromb. 12:911-919.
24. Katan, M. B., Zock, P. L. & Mensink, R. P. (1994) Effects of fats and fatty acids on blood lipids in humans: an overview. Am. J. Clin. Nutr. 60:1017S-1022S.
25. Keys, A. (1997) Coronary heart disease in seven countries. Nutrition 13:250-252.[Medline]
26. Keys, A., Aravanis, C., Blackburn, H. W., Van Buchem, F. S., Buzina, R., Djordjevic, B. D., Dontas, A. S., Fidanza, F., Karvonen, M. J., Kimura, N., Lekos, D., Monti, M., Puddu, V. & Taylor, H. L. (1966) Epidemiological studies related to coronary heart disease: characteristics of men aged 40–59 in seven countries. Acta Med. Scand. 460:1-392.
27. Keys, A., Menotti, A., Aravanis, C., Blackburn, H., Djordevic, B. S., Buzina, R., Dontas, A. S., Fidanza, F., Karvonen, M. J. & Kimura, N. (1984) The Seven Countries Study: 2,289 deaths in 15 years. Prev. Med. 13:141-154.[Medline]
28. Keys, A., Menotti, A., Karvonen, M. J., Aravanis, C., Blackburn, H., Buzina, R., Djordjevic, B. S., Dontas, A. S., Fidanza, F. & Keys, M. H. (1986) The diet and 15-year death rate in the Seven Countries Study. Am. J. Epidemiol. 124:903-915.
29. Kromhout, D., Menotti, A., Bloemberg, B., Aravanis, C., Blackburn, H., Buzina, R., Dontas, A. S., Fidanza, F., Giampaoli, S. & Jansen, A. (1995) Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: the Seven Countries Study. Prev. Med. 24:308-315.[Medline]
30. Kjelsberg, M. O., Cutler, J. A. & Dolecek, T. A. (1997) Brief description of the Multiple Risk Factor Intervention Trial. Am. J. Clin. Nutr. 65:191S-195S.
31. Cutler, J. A., Neaton, J. D., Hulley, S. B., Kuller, L., Paul, O. & Stamler, J. (1985) Coronary heart disease and all-causes mortality in the Multiple Risk Factor Intervention Trial: subgroup findings and comparisons with other trials. Prev. Med. 14:293-311.[Medline]
32. Maki, K. C., Davidson, M. H., Umporowicz, D., Schaefer, E. J., Dicklin, M. R., Ingram, K. A., Chen, S., Gebhart, B. & Franke, W. C. (2000) Lipid responses to plant sterol-enriched reduced-fat spreads incorporated into a Step 1 diet. Am. J. Clin. Nutr. 74:33-43.
33. Hallikainen, M. A. & Uusitupa, M. I. (1999) Effects of 2 low-fat stanol ester-containing margarines on serum cholesterol concentrations as part of a low-fat diet in hypercholesterolemic subjects. Am. J. Clin. Nutr. 69:403-410.
34. Hallikainen, M. A., Sarkkinen, E. S. & Uusitupa, M.I.J. (1999) Effects of low-fat stanol ester enriched margarines on concentrations of serum carotenoids in subjects with elevated serum cholesterol concentrations. Eur. J. Clin. Nutr. 53:966-969.[Medline]
35. Judd, J. T., Chen, S., Clevedence, B., Muering, R., Chen, S. & Meijer, G. W. (2001) Dietary fat and fatty acids and plasma lipid modifying effects of plant sterol esters. FASEB J 15:A397(abs.).
36. Gylling, H. & Miettinen, T. A. (1999) Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism 48:575-580.[Medline]
37. Noakes, M., Clifton, P. M., Ntanios, F. Y., Schrapnel, W., Record, I. & McInerney, J. (2002) An increase in dietary carotenoids when consuming plant sterols or stanols is effective in maintaining plasma carotenoid levels. Am. J. Clin. Nutr 75:79-86.
38. 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]
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 S. S. AbuMweis, C. A. Vanstone, N. Ebine, A. Kassis, L. M. Ausman, P. J. H. Jones, and A. H. Lichtenstein Intake of a Single Morning Dose of Standard and Novel Plant Sterol Preparations for 4 Weeks Does Not Dramatically Affect Plasma Lipid Concentrations in Humans J. Nutr., April 1, 2006; 136(4): 1012 - 1016. [Abstract] [Full Text] [PDF]
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 American Heart Association, S. S. Gidding, B. A. Dennison, L. L. Birch, S. R. Daniels, M. W. Gilman, A. H. Lichtenstein, K. T. Rattay, J. Steinberger, N. Stettler, et al. Dietary Recommendations for Children and Adolescents: A Guide for Practitioners Pediatrics, February 1, 2006; 117(2): 544 - 559. [Abstract] [Full Text] [PDF]
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 Endorsed by the American Academy of Pediatrics, S. S. Gidding, B. A. Dennison, L. L. Birch, S. R. Daniels, M. W. Gilman, A. H. Lichtenstein, K. T. Rattay, J. Steinberger, N. Stettler, et al. Dietary Recommendations for Children and Adolescents: A Guide for Practitioners: Consensus Statement From the American Heart Association Circulation, September 27, 2005; 112(13): 2061 - 2075. [Abstract] [Full Text] [PDF]
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