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Original Research Communication |
1 From the Chicago Center for Clinical Research; Tufts University, Boston; Lipton, Englewood Cliffs, NJ; and the Boston VA Medical Center.
2 Supported by Lipton, Englewood Cliffs, NJ. 3 Address reprint requests to KC Maki, Chicago Center for Clinical Research, 515 North State Street, Suite 2700, Chicago, IL 60610. E-mail: kmaki{at}protocare.com.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Objective: This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia.
Design: Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high-sterol group).
Results: Subjects in the low- and high-sterol groups who consumed 
80% of the scheduled servings (per-protocol analyses) had total cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower, and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower, respectively, than values for the control group (P < 0.001 for all). Additionally, triacylglycerol concentrations decreased by 10.4% in the high-sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were generally within reference ranges at baseline and postintervention. Serum plant sterol concentrations increased from baseline (0.48% of total sterol by wt) to 0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05 compared with control).
Conclusion: A reduced-fat spread containing plant sterol esters incorporated into a low-fat diet is a beneficial adjunct in the dietary management of hypercholesterolemia.
Key Words: Dietary management • sterol esters • hypercholesterolemia • lipoproteins • National Cholesterol Education Program Step I diet • table spread • cholesterol • plant sterols
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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30% of total energy from fat (8–10% saturated fatty acids, 10% polyunsaturated fatty acids, and 15% monounsaturated fatty acids), 55% of total energy from carbohydrates, 
15% of total energy from protein, <300 mg cholesterol/d, and total energy to achieve desirable body weight (1). The NCEP Step I diet is typically reported to lower LDL-cholesterol concentrations by 3–10% (1, 8, 9). Because NCEP diets are frequently not sufficient for persons with mild-to-moderate hypercholesterolemia to reach their LDL-cholesterol goal, an adjunct to diet that is safe and well-tolerated would be useful in the nonpharmacologic management of hypercholesterolemia.
Plant sterols (phytosterols) occur naturally and are structurally similar to cholesterol (10). The major plant sterols found in nature are sitosterol, campesterol, and stigmasterol (11). Plant sterols are present in Western diets in amounts similar to those for dietary cholesterol (170–358 mg/d) (12). At usual levels of consumption, plant sterols have little effect on blood cholesterol concentrations. However, because plant sterols share much structural similarity with cholesterol, higher dietary consumption of plant sterols may reduce intestinal and biliary cholesterol absorption and lower circulating blood cholesterol concentrations (13, 14).
More than 40 y of investigation in animals and humans has shown that plant sterols can reduce total and LDL-cholesterol concentrations (14, 15). The cholesterol-lowering activity of vegetable oil–based table spreads enriched in plant sterol esters was reported in 2 investigations of normocholesterolemic to mildly hypercholesterolemic subjects (11, 16). These studies showed that consumption of margarine or spreads enriched with esterified plant sterols effectively lowered plasma total and LDL-cholesterol concentrations (11, 16). However, those trials, like most others conducted to date, incorporated esterified plant sterols in a high-fat product into the subjects' habitual diets. In contrast, the present study evaluated the LDL-cholesterol-lowering effect of reduced-fat spreads containing plant sterol esters consumed as part of an NCEP Step I diet by men and women with mild-to-moderate primary hypercholesterolemia. In addition, changes from baseline in other aspects of the serum lipid profile (total cholesterol, HDL cholesterol, the ratio of total to HDL cholesterol, triacylglycerols, apolipoprotein A-I, and apolipoprotein B) were examined, as were the effects on serum concentrations of fat-soluble vitamins and carotenoids, serum sterol concentrations, clinical chemistry values, and subject-reported side effects.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Screening
Participants were recruited from the Chicago metropolitan area by using the database of the Chicago Center for Clinical Research and through radio and print advertisements. Men and women aged 21–75 y, who were prescreened by telephone, were required to abstain from all hypolipidemic therapy (including lipid-lowering medications and supplements thought to alter lipid metabolism) for 4 wk before reporting to the clinic for screening. At the screening visit, eligibility was further assessed by review of medical history and fasting serum lipid (total, calculated LDL, and HDL cholesterol and triacylglycerols) and apolipoprotein (A-I and B) profiles. For initial eligibility, subjects were required to have an LDL-cholesterol concentration between 3.4 and 5.2 mmol/L (130 and 200 mg/dL) and a triacylglycerol concentration <4.0 mmol/L (<350 mg/dL).
Additional eligibility requirements were assessed by physical examination, electrocardiogram, and clinical laboratory testing (chemistry, hematology, and urinalysis) conducted during the 4-wk diet-stabilization period. Exclusion criteria included a body mass index (in kg/m2) 35.0, cancer other than nonmelanoma skin cancer or basal cell carcinoma within the previous 5 y, and current or recent history (within 6 mo) of significant atherosclerotic, gastrointestinal, pulmonary, hepatic, renal, endocrine, immune, or biliary disease. Persons with poorly controlled or uncontrolled hypertension (systolic blood pressure > 160 mm Hg or diastolic blood pressure > 95 mm Hg) were excluded, as were individuals with type 1 diabetes, insulin-requiring type 2 diabetes, or poorly controlled non-insulin-requiring type 2 diabetes. Individuals receiving drugs for regulating hemostasis, other than stable-dose aspirin or dipyridamole, were also excluded. Women of childbearing potential were required to use an approved mechanical method of contraception during the trial.
Diet instruction
Four weeks before the start of the baseline period, subjects were instructed by a registered dietitian about the NCEP Step I diet. To aid with instruction, subjects were given copies of the American Heart Association educational booklet Step by Step: Eating to Lower Your High Blood Cholesterol (17) and handouts that explained appropriate diet choices based on the NCEP recommendations. Subjects were instructed to follow the NCEP Step I diet throughout the study.
Study products
The nutrient composition and ingredients of the control and plant-sterol-enriched reduced-fat spreads are shown in Table 1
. With the exception of the sterol esters, the product ingredients were common to typical soft, low-fat spreads available in the US market. During the lead-in period, a commercially available, conventional 50%-fat spread (Promise; Lipton, Englewood Cliffs, NJ) with no added plant sterol was consumed. The plant-sterol-ester-enriched reduced-fat spreads (40% fat) were prepared with commercially available plant sterol esters. Plant sterol ester concentrates derived from soybean oil distillates (Archer Daniels Midland Company, Decatur, IL) were blended into the oil phase of the spreads and processed into the test products according to standard procedures on a full-scale margarine processing line. The major plant sterols in the products were, in descending order of predominance, ß-sitosterol, campesterol, and stigmasterol. Concentrations of plant sterols in the plant-sterol-ester-enriched spreads were 8% (low-sterol group) and 16% (high-sterol group). The spread containing 8% plant sterols had a composition identical to a commercially available plant-sterol-ester-enriched spread (Take Control; Lipton). This product has Food and Drug Administration GRAS (generally recognized as safe) status. Control and plant-sterol-ester-enriched products were similar in appearance and sensory quality.
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Lead-in and intervention phases
During the 4-wk diet stabilization (lead-in) period, subjects returned to the clinic at weeks -2, -1, and 0 for measurement of their vital signs, body weight, and serum lipid profile. After completion of the lead-in period, subjects continued to follow the NCEP Step I diet and were randomly assigned to either the control group (n = 92), low-sterol group (n = 92), or high-sterol group (n = 40) for a 5-wk intervention period. Subjects and investigators were blinded to subject randomization status. Subjects returned to the clinic 3 times during the 5-wk double-blind intervention period, at weeks 2, 3.5, and 5, for assessment of their vital signs, body weight, and serum lipid profile. Additionally, apolipoproteins A-I and B were measured at weeks -5, -1, 0, 3.5, and 5. Blood concentrations of carotenoids were measured at weeks -1, 0, 3.5, and 5; in a subgroup of subjects (n = 71), serum fat-soluble vitamin and sterol concentrations were assessed at weeks 0 and 5. Additionally, at the end of the 5-wk intervention period, a physical examination, electrocardiogram, and clinical laboratory tests (including serum chemistry, hematology, and urinalysis) were completed.
Diet records
At the screening visit, a dietitian instructed all subjects how to complete the 3-d diet records. Diet records were dispensed at week -5 (screening), week -1, and week 3.5 with instructions to record dietary intakes for 3 d (2 weekdays and 1 weekend day) during the week before the next clinic visit. Diet records were collected from subjects at weeks -4, 0, and 5 and were analyzed by using the University of Minnesota NUTRITION DATA SYSTEM (NDS) FOR RESEARCH, version 4.0 (1998). Adherence to the NCEP Step I diet recommendations was monitored by review, with the subject, of each completed 3-d diet record.
Compliance
Compliance with study product consumption was evaluated by interviewing subjects and by counting the unopened product packages returned to the clinic at weeks -2, -1, 0, 2, 3.5, and 5. Compliance was recorded as the percentage of the scheduled servings consumed. Noncompliance was defined as consumption of <80% of the scheduled servings during the study period.
Analyses
Serum lipids and apolipoproteins
Serum total cholesterol, HDL cholesterol, and triacylglycerols were measured by the methods of Myers et al (18) in accordance with the Centers for Disease Control and Prevention lipid measurement standardization program (Covance Central Laboratory Services, Indianapolis). LDL cholesterol in mg/dL was calculated by using the Friedewald equation (LDL cholesterol = total cholesterol - HDL cholesterol - triacylglycerols/5) (19). Because this equation is not valid when the triacylglycerol concentration is >4.5 mmol/L (400 mg/dL), no LDL-cholesterol concentrations were calculated under these circumstances. LDL cholesterol was converted from mg/dL to mmol/L by applying a conversion factor of 0.0259 (20).
Vitamin, sterol, and carotenoid profiles
Samples for vitamin, carotenoid, and sterol analyses were frozen at -80°C and all measures for each subject were completed in the same run (Lipid Metabolism Laboratory, Tufts University, Boston). Vitamin analyses (retinol, tocopherol, dihydroxyvitamin D, and phylloquinone) were conducted according to previously described HPLC procedures (21–23). After lipid extraction, saponification, and reextraction, serum total sterols, total plant sterols, sitosterol, and campesterol were separated from fatty acids and quantified by HPLC (24). Blood concentrations of carotenoids (
-carotene, trans-ß-carotene, lycopene, lutein, zeaxanthin, and cryptoxanthin) were measured by an HPLC procedure (25) with a C30 carotenoid column (Gastrointestinal Nutrition Laboratory, Tufts University). To prevent photodegradation of carotenoids, all serum handling, standard preparation, and HPLC procedures were performed under dim red light.
Statistical analyses
Statistical analyses were conducted by using the STATVIEW 5.0 and SAS version 6.12 statistical analysis packages (SAS Institute, Cary, NC). Two-tailed levels of 0.05 were used to designate statistical significance for pairwise comparisons. Comparability of groups for baseline demographic, anthropometric, and lipid values was assessed by analysis of variance (ANOVA), Kruskal-Wallis tests, and chi-square tests as appropriate. A per-protocol approach, which included all subjects 80% compliant with study product consumption, was used for all analyses. Additionally, an intent-to-treat analysis that included all randomly assigned subjects was performed. The intent-to-treat results were only slightly different from the per-protocol results and the differences were not clinically significant. Therefore, only the intent-to-treat results are presented, unless noted otherwise.
ANOVA was used to compare responses to the intervention (percentage change from baseline to the end of the study) for total cholesterol, calculated LDL cholesterol, HDL cholesterol, the ratio of total to HDL cholesterol, and apolipoproteins A-I and B. For the lipid variables, screening refers to the average of values obtained at weeks -5 and -4; baseline to the average of values obtained at weeks -2, -1, and 0; and end of the study to the average of values obtained at weeks 3.5 and 5. For apolipoprotein variables, screening refers to week -5, baseline to the average of values obtained at weeks -1 and 0, and end of the study to the average of values obtained at weeks 3.5 and 5. If a subject ended the study early, values from the last blood draw obtained were carried forward. In cases for which lipid testing was repeated, these values were added in the average. Pairwise comparisons of lipid responses between groups were conducted with Scheffe's test. Triacylglycerol responses were not normally distributed; therefore, nonparametric Kruskal-Wallis and Mann-Whitney U tests were performed. Separate ANOVA models were generated to assess potential interactions between the intervention and selected variables, including sex, age, baseline LDL cholesterol, and study product compliance.
The percentage change from baseline LDL-cholesterol concentration was determined a priori to be the primary outcome variable. This study was designed to have a power of 85% to detect a 5% difference between the control and plant sterol groups in LDL-cholesterol response. Because 2 doses were studied, a two-tailed level of 0.025 ( = 0.05/2) was used in the sample size calculations to account for the 2 primary comparisons (low-sterol group compared with control group and high-sterol group compared with control group). A pooled SD of 10% for the change from baseline LDL cholesterol was assumed for this calculation. The sample size required for the low-sterol group was larger than that for the high-sterol group because a smaller response was anticipated. To protect the actual analyses from type I errors due to multiple comparisons, standard ANOVA and pairwise comparison testing with Scheffe's procedure were used.
Statistical comparisons among groups for vitamin, carotenoid, and sterol responses were conducted with the Kruskal-Wallis test. Pairwise comparisons were made with Scheffe's test on ranked values. Differences in the incidence of adverse events and laboratory value shifts were assessed with Fisher's exact test. Dietary intakes at screening, baseline, and at the end of the study were compared by using ANOVA and Kruskal-Wallis tests, with pairwise comparisons done with Scheffe's procedure.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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2%). Mean compliance with study product consumption exceeded 90% in all study groups, and there were no significant differences in compliance between the control and intervention groups.
Baseline demographic and anthropometric characteristics of the subjects are shown in Table 2. The groups did not differ in mean or median age, sex, body mass index, race, smoking status, number of alcoholic drinks consumed per week, systolic blood pressure, or diastolic blood pressure. Subjects were predominantly nonsmokers with a mean age of 60 y and a mean body mass index (in kg/m2) of 27. Men and women were evenly distributed in both the low- and high-sterol groups, whereas the control group was 61% female. Race distribution among the 3 groups was similar to that reported in the general US population (26).
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. In general, nutrient intakes were not significantly different among the 3 groups at screening (week -4), at baseline (week 0), and at the end of the study (week 5). However, polyunsaturated fatty acid intake at screening was slightly higher in the low-sterol group (6.2% of energy) than in the high-sterol group (5.3% of energy). Median vitamin K intake at baseline was also significantly higher in the low-sterol group (96 µg/d) than in the high-sterol group (67 µg/d). After the intervention period, total and saturated fatty acid intakes were within NCEP Step I diet recommendations (30% and 10% of energy, respectively).
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. At screening and at baseline, lipid and apolipoprotein concentrations were not significantly different among the 3 groups. Mean baseline total and LDL-cholesterol concentrations were 6.2 mmol/L (240 mg/dL) and 4.1 mmol/L (160 mg/dL), respectively.
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After 5 wk of intervention, total and LDL-cholesterol concentrations, the ratio of total to HDL cholesterol, and apolipoprotein B concentrations were all significantly lower in the plant sterol groups than in the control group. No significant differences were present between the plant sterol groups. The changes from baseline in LDL-cholesterol and apolipoprotein B concentrations are shown in Figures 1 and 2, respectively. Compared with values in the control group, total cholesterol was 5.2% lower in the low-sterol group and 6.6% lower in the high-sterol group. LDL cholesterol was 7.6% and 8.1% lower in the low- and high-sterol groups, respectively, than in the control group. The ratio of total to HDL cholesterol was 5.9% and 8.1% lower in the low- and high-sterol groups, respectively, than in the control group. Apolipoprotein B concentrations were 6.2% and 8.4% lower in the low- and high-sterol groups, respectively, than in the control group. Triacylglycerol concentrations were reduced by 10.4% in the high-sterol group, but were not significantly different between the low-sterol group and the control group. Apolipoprotein A-I and HDL-cholesterol responses did not differ significantly among the 3 groups.
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60 y), sex, and baseline LDL-cholesterol concentration [< or 4.1 mmol/L (160 mg/dL)] indicated no significant interactions. The treatment effect x compliance interaction, however, was significant (P < 0.05). In the intent-to-treat subjects, total and LDL cholesterol, the ratio of total to HDL cholesterol, and apolipoprotein B were a mean of 3.9% and 5.6%, 5.9% and 6.9%, 5.5% and 7.3%, and 5.1% and 6.4% lower in the low-sterol and high-sterol groups, respectively, than in the control group (all P < 0.01).
Clinical chemistry indexes and adverse events
There were no significant differences among groups in the number of shifts from low-normal to high or high-normal to low clinical chemistry, hematology, or urinalysis values. The total number of subjects reporting adverse events was also not significantly different among groups, nor did the number of reports in each body system category differ. Sixty-three (69%) subjects in the control group reported adverse events compared with 54 (59%) and 24 (60%) subjects in the low- and high-sterol groups, respectively. Complaints fell predominantly into the respiratory disorder category. Most of these adverse events were due to cold and flulike symptoms and were deemed by the investigator to be unrelated to the study product. There were 2 serious adverse events during the study. One subject underwent coronary artery bypass graft surgery and was dropped from the study and another subject experienced complications (rectal bleeding) after the removal of colon polyps discovered during a routine colonoscopy. Both of the serious adverse events were deemed by the investigator to be unrelated to study product consumption.
Vitamins and sterols
Fat-soluble vitamin status at baseline and at the end of the study and the percentage change from baseline in a subset of subjects is shown in Table 5. Fat-soluble vitamin concentrations in serum were within reference ranges at baseline and after treatment and were unaffected by plant sterol consumption.
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. These analyses indicated significant, although quantitatively small, dose responses in the change from baseline for campesterol concentrations and the ratio of plant to total sterols. Campesterol concentrations increased by 20.7% and 43.0% in the low- and high-sterol groups, respectively, compared with a decrease of 2.4% in the control group. The ratio of plant to total sterols (% by wt) increased by 0.165% and 0.282% in the low- and high-sterol groups. At the end of the study, sitosterol concentrations increased significantly in the low- and high-sterol groups (17.8% and 28.8%, respectively, compared with 3.4% in the control group), but there was no significant difference between plant sterol groups.
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. In general, blood carotenoid concentrations at baseline and after the 5-wk intervention period were within the reference ranges reported in the third National Health and Nutrition Examination Survey (27). At the end of the study, the median lycopene concentration in the high-sterol group was 0.10 µmol/L, slightly outside the reference range of 0.13–0.82 µmol/L. Although all other carotenoid values remained within reference ranges, there were significant reductions in trans-ß-carotene concentrations of 20.4% and 26.0% in the low- and high-sterol groups. Lycopene and -carotene concentrations were also significantly reduced in the high-sterol group (by 16.3% and 23.6%, respectively), and the lutein response was significantly different in the low-sterol group (-9.4%) than in the control group (5.7%). To determine whether the effects on carotenoid status were related to reductions in total cholesterol concentration, carotenoid concentrations were corrected for total cholesterol concentration. The response persisted for trans-ß-carotene (reductions of 16.8% and 23.5% in low- and high-sterol groups); however, previously significant reductions in -carotene, lutein, and lycopene were no longer evident.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Consistent with an observation made by Weststrate and Meijer (11), we observed no interaction between baseline LDL-cholesterol concentrations and lipid responses to plant sterol ester intervention, suggesting the cholesterol-lowering efficacy of plant sterol esters in persons with even very mildly elevated LDL cholesterol (3.4 mmol/L, or 130 mg/dL). The fact that apolipoprotein B concentrations were also reduced by 6–8% indicates that plant sterol esters do not solely reduce the cholesterol content of LDL particles, but also reduce the total number of circulating atherogenic particles.
Although plant sterols are naturally occurring, their formulation into effective and palatable products has been limited (29). A recent comparison study conducted in the Netherlands reported that the lipid responses to intakes of 3 g esterified plant sterols/d from soybean oil were comparable with responses to plant stanol esters administered in margarine (11). Serum cholesterol concentrations were reduced by 13% compared with concentrations after consumption of a control spread with a similar fatty acid content and composition, but unenriched with sterols or stanols (11). Hendriks et al (16) reported similar LDL-cholesterol responses: -6.7% to -9.9% after plant sterol ester intakes ranging from 0.83 to 3.24 g/d. As in our study, there was no apparent linear dose response over the range tested. ß-Sitosterol, campesterol, and stigmasterol are considered to be equally effective in reducing blood cholesterol concentrations. Additionally, oleate esters of these sterols, individually or in a mixture, were shown to be similar in their ability to decrease cholesterol absorption in rats (30).
Plant sterol ester is proposed to reduce serum cholesterol by competing with cholesterol for solubilization into the bile micellar phase within the intestinal milieu. Thus, it is reasonable to assume that this physiochemical property may also decrease the absorption of lipophilic nutrients such as fat-soluble vitamins and carotenoids (31). In the current study, however, serum vitamin and carotenoid concentrations generally remained within reference ranges. Furthermore, none of the fat-soluble vitamins assessed were significantly altered by plant sterol consumption. Carotenoid concentrations were reduced by intervention with low-dose or high-dose plant sterol esters. As expected, the largest changes were detected among the lipophilic carotenoids (-carotene, ß-carotene, and lycopene) known to associate primarily with LDL (32). The 20–26% reductions in trans-ß-carotene (17–24% after cholesterol correction) and 13–16% reductions in lycopene (8–14% after cholesterol correction) were similar to effects reported previously (16). Plant stanol esters have also been reported to reduce serum ß-carotene concentrations by 30% (20% after cholesterol correction) (31, 33). Although standardization with either total cholesterol or total lipid generally minimizes this effect, decreased carotenoid concentrations typically persist, but to a lesser degree, when corrected for lipid changes (11, 16, 33).
In epidemiologic studies, higher carotenoid intakes and tissue concentrations have been linked with a lower risk of cardiovascular disease and cancer. Results from clinical trials, however, do not support carotenoid supplementation, specifically ß-carotene, as a strategy to reduce risk (32). Although serum carotenoid concentrations were reduced from baseline in the current investigation, with the exception of lycopene in the high-sterol group, all remained within reference ranges. Individuals consuming increased amounts of plant-sterol-ester-enriched products and concerned about the potential effects of such products on blood carotenoids might opt to increase their intakes of carotenoid-rich foods, such as apricots, cantaloupe, broccoli, and spinach.
Plant sterols are themselves absorbed only minimally (34). Blood plant sterol concentrations reflect dietary intakes and the rate of intestinal absorption and excretion by the liver. The rate of intestinal absorption is inversely related to the length of the side chain (35). Sitosterol is absorbed by the intestine to a much lower extent than is campesterol, and both are absorbed to much lesser extents than is cholesterol. As expected, campesterol concentrations were affected dose dependently in our study. von Bergmann and Lütjohann (36) recommended that serum concentrations of plant sterols be expressed as a fraction of total sterol. In the current study, the ratios of plant to total sterols (% by wt) at the end of the study were 0.46%, 0.64%, and 0.71% for the control, low-sterol, and high-sterol groups, respectively, compared with a baseline value of 0.48% for all groups, representing increases of 50% in the plant sterol groups. On the basis of literature examining the relation between circulating plant sterol concentrations and atherosclerotic risk, these small elevations most likely have no clinical relevance (37–39).
Previous studies primarily evaluated the lipid-altering effects of sterols incorporated into subjects' habitual diets. It was suggested that plant sterols and stanols may be most effective for lowering lipids when the exogenous supply of intestinal cholesterol is high. To date, we are aware of only 2 other published studies that examined the effects of plant sterols or stanols as part of a low-fat or low-cholesterol diet (40, 41). Possibly because of the low solubility of unesterified sitostanol, Denke (40) observed no reduction in the plasma cholesterol concentration in subjects consuming 3 g sitostanol/d as part of a diet containing <200 mg cholesterol/d. A recent study conducted by Hallikainen and Uusitupa (41) reported that stanol-ester-enriched margarines incorporated into a low-fat, low-cholesterol diet (NCEP Step II diet) were effective in lowering lipids to a greater extent than diet alone. In the present study, according to 3-d diet records collected after the intervention period, incorporation of plant-sterol-ester-enriched reduced-fat spreads into the NCEP Step I diet was successful. All groups had mean total fat intakes of 29–30% and saturated fatty acid intakes of 9%. To our knowledge, this is the first report of the effects of esterified plant sterols administered as part of a low-fat, low-cholesterol diet. The results of this study, together with other recent investigations of sterol esters, outlined in the recently approved health claim for sterol and stanol products (42), provide evidence that plant sterol esters are a well-tolerated and efficacious adjunct to a lipid-lowering diet, capable of producing clinically significant reductions in LDL cholesterol in persons with mild-to-moderate primary hypercholesterolemia.
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ACKNOWLEDGMENTS |
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) from baseline to week 2, and the percentage change from baseline to the end of the study, according to group assignment1
