Reduced-calorie orange juice beverage with plant sterols lowers C-reactive protein concentrations and improves the lipid profile in human ...
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Reduced-calorie orange juice beverage with plant sterols lowers
C-reactive protein concentrations and improves the lipid profile in
human volunteers1–3
Sridevi Devaraj, Bryce C Autret, and Ishwarlal Jialal
ABSTRACT sterols or stanols in reducing LDL-cholesterol concentrations
Background: Dietary plant sterols effectively reduce LDL choles- and possibly reducing the risk of CVD (1, 2). Stanols and sterols,
terol when incorporated into fat matrices. We showed previously found in fat-soluble fractions of plants, are structurally related
that supplementation with orange juice containing plant sterols (2 to cholesterol and originate mainly from the diet because they
g/d) significantly reduced LDL cholesterol. Inflammation is pivotal cannot be synthesized by humans. Plant sterols exert their
in atherosclerosis. High-sensitivity C-reactive protein (hs-CRP), the cholesterol-lowering action presumably by suppressing intesti-
prototypic marker of inflammation, is a cardiovascular disease risk nal absorption and increasing ATP-binding cassette transporter
marker; however, there is a paucity of data on the effect of plant expression, which promotes cholesterol efflux (3–7). Consump-
sterols on CRP concentrations.
tion of plant sterols, in free and esterified form, reduces plasma
Objective: The aim of this study was to examine whether plant
total and LDL-cholesterol concentrtions in human subjects, es-
sterols affect CRP concentrations and the lipoprotein profile when
incorporated into a reduced-calorie (50 calories/240 mL) orange
pecially in fat matrices. Meta-analyses suggest that ingestion of
juice beverage. 2 g plant sterols/d incorporated into dietary fat vehicles such as
Design: Seventy-two healthy subjects were randomly assigned to margarine yields a 10% reduction in LDL-cholesterol concen-
receive a reduced-calorie orange juice beverage either without (Pla- trations in patients with hypercholesterolemia (3, 4). Because of
cebo Bev) or with (1 g/240 mL; Sterol Bev) plant sterols twice a day their cholesterol-lowering effects, plant sterols are now incorpo-
with meals for 8 wk. Fasting blood was obtained at baseline and after rated into many functional foods. We recently reported that in a
8 wk of Placebo Bev or Sterol Bev supplementation. nonfat matrix, ie, orange juice (OJ) with plant sterols (2 g/d)
Results: Sterol Bev supplementation significantly reduced total significantly reduced LDL-cholesterol concentrations in mildly
cholesterol (5%; P 쏝 0.01) and LDL cholesterol (9.4%; P 쏝 0.001) hypercholesterolemic subjects when consumed twice a day with
compared with both baseline and Placebo Bev (P 쏝 0.05). HDL meals (8). However, OJ contains 110 calories and 27 g total
cholesterol increased significantly with Sterol Bev (P 쏝 0.02). No carbohydrate per 240-mL serving. To expand the usefulness of
significant changes in triacylglycerol, glucose, or liver function tests such nonfat moieties in reducing LDL cholesterol, it is desirable
were observed with Sterol Bev. Sterol Bev supplementation resulted to provide an option for those persons interested in reducing
in no significant change in vitamin E and carotenoid concentrations.
caloric intake. Inflammation is pivotal in all stages of atheroscle-
Sterol Bev supplementation resulted in a significant reduction of
rosis, and high concentrations of C-reactive protein (CRP) have
CRP concentrations compared with baseline and Placebo Bev (me-
dian reduction: 12%; P 쏝 0.005). been shown to confer an increased risk of CVD in several pro-
Conclusion: Supplementation with a reduced-calorie orange juice spective studies (9). A paucity of data exists with regard to the
beverage containing plant sterols is effective in reducing CRP and effect of plant sterols on CRP concentrations. The hypotheses we
LDL cholesterol and could be incorporated into the dietary portion tested were that a reduced-calorie beverage with plant sterols
of therapeutic lifestyle changes. Am J Clin Nutr 2006;84: would reduce not only LDL cholesterol but also CRP concen-
756 – 61. trations. Therefore, the main objective of the present study was to
examine the efficacy of supplementation with a reduced-calorie
KEY WORDS Inflammation, C-reactive protein, phytosterol,
1
plant sterol, cholesterol, lipid profile, nonfat beverage, diet From the Laboratory for Atherosclerosis and Metabolic Research and
General Clinical Research Center, University of California Davis Medical
Center, Sacramento, CA.
INTRODUCTION 2
Supported by the Beverage Institute for Health & Wellness, The Coca-
Cardiovascular disease (CVD) is the leading cause of morbid- Cola Company, and the National Institutes of Health K-24 AT00596 (to IJ).
3
Address reprint requests to S Devaraj, Laboratory for Atherosclerosis
ity and mortality in the United States. High concentrations of
and Metabolic Research, Department of Pathology, UC Davis Medical Cen-
LDL cholesterol are associated with an increased incidence of
ter, 4635 Second Avenue, Res 1 Building, Room 3000, Sacramento, CA
CVD. Dietary recommendations from the National Cholesterol 95817. E-mail: sridevi.devaraj@ucdmc.ucdavis.edu.
Education Panel (NCEP) and the US Food and Drug Adminis- Received January 31, 2006.
tration have emphasized the utility of supplementation with plant Accepted for publication May 12, 2006.
756 Am J Clin Nutr 2006;84:756 – 61. Printed in USA. © 2006 American Society for NutritionLOW-CALORIE STEROL BEVERAGE LOWERS CRP AND CHOLESTEROL 757
OJ beverage containing added plant sterols (Sterol Bev, 1g ste- TABLE 1
rols/240 mL beverage, 50 calories) on the lipoprotein profile and Composition of the beverages1
CRP concentrations in healthy human volunteers in a parallel, Sterol Bev (240 mL) Placebo Bev (240 mL)
placebo-controlled, double-blind, randomized trial.
Calories 50 50
Total fat (g) 0 0
SUBJECTS AND METHODS Total carbohydrate (g) 12 13
Total protein (g) 0 0
Seventy-seven subjects aged 19 –74 y participated in the Folate (g) 24 24
present placebo-controlled, double-blind, randomized trial. All Vitamin E (IU) 6 —
subjects gave informed consent, and the study was approved by Vitamin B-6 (mg) 0.4 0.08
the Institutional Review Board of the University of California at Vitamin B-12 (g) 1.2 —
Davis Medical Center. Vitamin C (mg) 72 72
Adults with a normal complete blood count, LDL cholesterol Potassium (mg) 450 450
쏜100 mg/dL, normal liver and renal function (normal transami- Thiamine (mg) 0.15 0.15
nases, alkaline phosphatase, and creatinine), no bleeding diathe- Free sterol (g) 1.0 —
sis, and normal thyroid function were included in the study. 1
Table lists the constituents of one dose of beverage (240 mL). Also
Secondary causes of hypercholesterolemia, such as nephrotic contains 9 mg Ca, 0.4 mg niacin, and 400 g -carotene. Vitamin E was
syndrome, cholestasis, and hypothyroidism, were ruled out. added in the form of dl-␣-tocopheryl acetate, and vitamin B-12 was also
The list of exclusion criteria were as follows: participation in added. Sterol Bev, reduced-calorie orange juice beverage with plant sterols;
an active weight-loss program; pregnancy or lactation; smoking; Placebo Bev, placebo beverage.
current use of vitamin supplements or alcohol intake 쏜30 mL/d;
history of CVD or chronic inflammatory diseases (eg, Crohn
was obtained from the subjects at baseline (average of 2 samples,
disease, rheumatoid arthritis, and systemic lupus erythemato-
5–7 d apart) and after 4 and 8 wk of the study (average of 2
ses); recent bacterial infection (쏝2 wk); use of antiinflammatory
samples, 5–7 d apart). The subjects were asked to keep a 3-d diet
steroidal or nonsteroidal medication, hypolipidemic or thyroid
record at the beginning and at the end of the study. The compo-
drugs, oral contraceptives, or anticoagulants; history of sitoste-
sition of the Placebo Bev and Sterol Bev are given in Table 1.
rolemia; gastrointestinal problems; and concurrent or recent
(within 30 d) participation in an intervention study.
Analyses
Study design Plasma was separated by centrifugation for 15 min at 4Ҁ12 °C
Blood was drawn from the subjects after an overnight fast. The and 600 ҂ g. All analyses were carried out in the Clinical Pa-
subjects were then randomly assigned in a blinded fashion to thology Laboratory at UC Davis Medical Center, Sacramento,
receive either Sterol Bev or Placebo Bev for the next 8 wk. Both CA. Total cholesterol and total triacylglycerol were analyzed on
the Placebo Bev and Sterol Bev were provided by The Coca-Cola the Beckman Access autoanalyzer (Beckman Instruments, Brea,
Company (Houston, TX). Sterol Bev consisted of plant sterol CA). LDL-cholesterol concentrations were calculated by using
with the targeted particle size distribution suspended in a the Friedewald equation. HDL-cholesterol concentrations were
reduced-calorie OJ beverage (Coca-Cola; patent pending). The analyzed by using the direct HDL-cholesterol assay. Apoli-
beverage plant sterol was derived from vegetable oils, with poprotein (apo) A and B concentrations were measured in the
the 3 major components distributed approximately as 40% Clinical laboratory with the use of the Beckman Array (Beckman
-sitosterol, 25% campesterol, and 20% stigmasterol by weight. Instruments). The inter- and intraassay CVs for cholesterol and
Calories were reduced by reducing the juice content of the bev- triacylglycerol assays were 쏝4%. CRP concentrations were
erage and adding back as much of the nutrients to the original OJ measured by using a high-sensitive assay (Beckman LxPro;
levels, with the exception of folate due to regulations regarding Beckman Instruments), which has an inter- and intraassay CV of
folate fortification in foods. The product was prepared and 쏝5%. Vitamin E and carotenoid concentrations were assayed in
shipped by the supplier 1 wk before disbursement of juice to the plasma by HPLC. Diet analyses were performed with the use of
subjects. The subjects were given enough juice to last 18 d, were the ESHA FOOD PROCESSOR program (version 7.4; ESHA
asked to keep the juice refrigerated, and were instructed to shake Research, Salem, OR).
the contents of the container before measuring their 240 mL
serving. The study investigators were also blinded to protocol Statistical analysis
assignment until the end of the study. Each subject was asked to Data are expressed as means (앐SDs) for parametric data and
consume 240 mL juice twice a day with breakfast and dinner. medians for nonparametric data. Statistical analyses were con-
This corresponded to 2 g sterol/d in the Sterol Bev (50 calories/ ducted with the use of GRAPHPAD PRISM software (version 4;
240 mL); this dose was used because it has been shown to effec- GraphPad Software, San Diego, CA). Between-group and
tively reduce cholesterol concentrations and is the dose recom- within-group differences were analyzed by 2-factor repeated-
mended by the NCEP Adult Treatment Panel III (ATPIII). The measures analysis of variance followed by Student’s t tests for
subjects were asked to refrain from consuming any source of parametric data and Friedman test followed by Wilcoxon signed-
margarines and spreads containing plant sterols, such as Benecol rank tests for nonparametric data. For multiple comparisons,
(MCNeil, Fort Washington, PA) or Take Control (Unilever, Bonferroni correction was performed on the Wilcoxon test. A
Englewood Cliffs, NJ), 4 wk before study entry and during the P 쏝 0.05 was considered significant. Spearman or Pearson cor-
period of the study and were asked to adhere to their usual diet relations were performed to analyze for correlations in changes
and exercise regimen for the duration of the study. Fasting blood in the variables tested.758 DEVARAJ ET AL
TABLE 2 and 4 and 8-wk concentrations of total cholesterol, LDL choles-
Baseline characteristics of the subjects1 terol, non-HDL cholesterol, HDL cholesterol, and total triacyl-
Sterol Bev Placebo Bev glycerol are provided in Table 4. No significant changes in the
(n ҃ 36) (n ҃ 36) lipid profile were observed with the Placebo Bev. A significant
time-by-treatment interaction for total cholesterol and LDL-
Age (y) 44 앐 14 48 앐 15
cholesterol concentrations was observed between the groups and
BMI (kg/m2) 24 앐 6 25 앐 6
between baseline and 8 wk in the Sterol Bev group (5.0% de-
M/F 16/20 15/21
Total cholesterol (mg/dL) 213 앐 41 217 앐 45 crease in total cholesterol and 9.4% decrease in LDL cholesterol,
Total triacylglycerol (mg/dL) 124 앐 74 119 앐 54 P 쏝 0.01, Table 4). As expected, non-HDL-cholesterol concen-
LDL cholesterol (mg/dL) 144 앐 30 145 앐 37 trations were reduced significantly (8.8%; time ҂ treatment in-
HDL cholesterol (mg/dL) 45 앐 11 46 앐 12 teraction, P 쏝0.02) with Sterol Bev compared with baseline and
Non-HDL cholesterol (mg/dL) 164 앐 27 161 앐 24 Placebo Bev. No significant changes in triacylglycerol concen-
Apolipoprotein B (mg/dL) 106 앐 28 104 앐 23 trations were observed. HDL-cholesterol concentrations were
Apolipoprotein A (mg/dL) 96 앐 33 99 앐 29 significantly increased in the Sterol Bev group at 8 wk compared
1
All values are x 앐 SD. No significant differences were observed with baseline (6% increase), but not compared with Placebo Bev
between the groups. Sterol Bev, reduced-calorie orange juice beverage with (time ҂ treatment interaction not significant; Table 4). Further-
plant sterols; Placebo Bev, placebo beverage. more, although there was a significant reduction in apo B con-
centrations after supplementation with Sterol Bev compared
with baseline and Placebo Bev, no significant changes in apo A1
RESULTS concentrations were observed (P ҃ 0.09 for Week 8 compared
Although 77 subjects entered the study, 5 dropped out because with baseline in the Sterol Bev group).
of personal reasons (2 in the Sterol Bev group and 3 in the Placebo Sterol Bev supplementation resulted in a significant reduction
Bev group); therefore, 72 subjects (n ҃ 36 per group) completed (12%) in CRP concentrations (time ҂ treatment interaction, P 쏝
the study. Compliance was high and body weights were un- 0.02; Figure 1A). No significant correlation between reductions
changed during the trial. The subjects in both groups (Placebo in LDL-cholesterol and CRP concentrations were observed (r ҃
Bev and Sterol Bev) were matched for age, sex, ethnicity, and 0.16, P 쏜 0.05). To confirm the results of the present study, we
body mass index. Baseline subject characteristics and baseline also examined the effect of sterols on CRP concentrations in
lipid profiles are reported in Table 2. No significant differences blood samples collected in an earlier study that was conducted
in the baseline lipid profile, ie, total cholesterol, total triacyl- with sterol-fortified OJ (110 calories/240 mL serving). The de-
glycerols, HDL cholesterol, and LDL cholesterol, were observed sign and results of the previous study were reported previously
between the 2 groups. Diet analyses uncovered no significant (8). We also report for the first time that there was a significant
differences in the composition of the diet between the 2 groups reduction in CRP concentrations in the samples obtained from
before and after Sterol Bev and Placebo Bev supplementation the earlier study (23% reduction; time ҂ treatment interaction,
(Table 3). P 쏝0.01) (Figure 1B).
Sterol Bev supplementation resulted in no significant changes We also examined the effects of Sterol Bev supplementation
in body mass index, complete blood count, liver function tests, on plasma vitamin E and carotenoid concentrations. No signifi-
blood glucose concentrations, and renal function. Mean baseline cant differences in the concentrations of both vitamin E and
carotenoids were observed after supplementation compared with
Placebo Bev (Table 5).
TABLE 3
Dietary composition before and after Sterol Bev and Placebo
DISCUSSION
supplementation1
Dietary therapy is the cornerstone of strategies aimed at re-
Macronutrient Baseline Week 8
ducing LDL cholesterol and thereby reducing the risk of CVD
Total fat (%) (1). Incorporating foods fortified with plant sterols in the daily
Sterol Bev (n ҃ 30) 31 앐 7 32 앐 14 diet, in addition to other lifestyle modifications such as exercise,
Placebo Bev (n ҃ 32) 33 앐 11 32 앐 7 will greatly enhance the cholesterol-lowering effect of diet ther-
Saturated fat (%) apy. In the present placebo-controlled double-blind trial, we re-
Sterol Bev (n ҃ 30) 11 앐 4 11 앐 3 ported a significant improvement of the lipid profile in subjects
Placebo Bev (n ҃ 32) 10 앐 2 10 앐 2
who consumed a reduced-calorie beverage (Sterol Bev group), as
Cholesterol (mg/d)
evidenced by a significant reduction of total cholesterol and LDL
Sterol Bev (n ҃ 30) 215 앐 14 219 앐 17
Placebo Bev (n ҃ 32) 221 앐 19 228 앐 21 cholesterol compared with placebo and a significant increase in
Protein (%) HDL cholesterol compared with baseline. Furthermore, the ad-
Sterol Bev (n ҃ 30) 21 앐 5 19 앐 6 dition of plant sterols to OJ or reduced-calorie (Sterol Bev) bev-
Placebo Bev (n ҃ 32) 17 앐 6 18 앐 7 erages resulted in a significant reduction in CRP concentrations.
Carbohydrate (%) Although several trials in different populations have shown
Sterol Bev (n ҃ 30) 48 앐 11 48 앐 9 that plant sterol consumption in fat matrices (margarine, butter,
Placebo Bev (n ҃ 32) 49 앐 10 49 앐 8 or dressing) results in reduced total and LDL-cholesterol con-
1
All values are x 앐 SD. No significant differences were observed centrations (3.4 –11.6% and 5.4 –15.5%, respectively) (3, 4), the
between the groups. Sterol Bev, reduced-calorie orange juice beverage with incorporation of plant sterols in reduced-fat matrices have
plant sterols; Placebo Bev, placebo beverage. yielded variable results. This could be due to a small sample size,LOW-CALORIE STEROL BEVERAGE LOWERS CRP AND CHOLESTEROL 759
TABLE 4
Effect of the reduced-calorie Sterol Bev on the lipoprotein profile1
Baseline Week 4 Week 8 P22
Total cholesterol (mg/dL)3 0.024
Sterol Bev 213 앐 41a 209 앐 37b 208 앐 34b
Placebo Bev 217 앐 45a 217 앐 45a 218 앐 45a,4
Total triacylglycerol (mg/dL) 0.566
Sterol Bev 124 앐 74 124 앐 68 119 앐 76
Placebo Bev 119 앐 54 129 앐 61 129 앐 74
LDL cholesterol (mg/dL)5 0.013
Sterol Bev 144 앐 30a 145 앐 37a 139 앐 32b
Placebo Bev 145 앐 37a 143 앐 36a 145 앐 35a,4
HDL cholesterol (mg/dL) 0.084
Sterol Bev 45 앐 11a 46 앐 11 48 앐 12b
Placebo Bev 46 앐 12 48 앐 13 47 앐 13
Non-HDL Cholesterol (mg/dL)3 0.026
Sterol Bev 164 앐 27a 159 앐 28b 147 앐 25b
Placebo Bev 161 앐 24a 158 앐 40a 158 앐 30a,4
Apolipoprotein B (mg/dL)5 0.009
Sterol Bev 106 앐 28a ND 96 앐 12b
Placebo Bev 104 앐 23a ND 103 앐 19a,4
Apolipoprotein A (mg/dL) 0.097
Sterol Bev 96 앐 33 ND 101 앐 24
Placebo Bev 99 앐 29 ND 97 앐 21
1
All values are x 앐 SD. n ҃ 36 per group. Sterol Bev, reduced-calorie orange juice beverage with plant sterols; Placebo Bev, placebo beverage.
2
P values for interaction (time ҂ treatment effects) tested with ANOVA. Means in a row with different superscript letters are significantly different, P 쏝
0.05 (ANOVA with paired t test, except for triacylglycerols which were compared by Friedman test with Bonferroni-corrected Wilcoxon test).
3,5
Significantly different from baseline and Placebo Bev (ANOVA with paired t test): 3P 쏝 0.01, 5P 쏝 0.001.
4
Significantly different from Sterol Bev group, P 쏝 0.01 (ANOVA with paired t test).
lack of a placebo control, lack of ingestion of the supplement with calories and carbohydrate content that is also effective in im-
meals, or other variables. Maki et al (10) reported that a 50% fat proving the lipoprotein profile be available as an option for a
spread that provided 1.1 and 2.2 g plant sterols/d resulted in a heart-healthy diet. However, the efficacy of plant sterols incor-
respective 7.6% and 8.1% reduction in LDL-cholesterol. How- porated into a different matrix in lowering total and LDL cho-
ever, no difference in cholesterol concentrations was observed in lesterol needed to be assessed, as proposed by Katan et al (4).
another trial that compared the effects between consumption of Also, whereas the concentrations appeared to be trending in the
plant sterols at 3 g/d in a reduced-fat spread, 6 g/d in a 28% fat right direction at 4 wk, we saw no significant change in LDL
dressing, and 9 g/d in reduced-fat spread and dressing (11). Daily cholesterol until after 8 wk supplementation with Sterol Bev
consumption of low-fat (1%) yogurt containing 1g plant sterols compared with placebo. With an increased sample size, benefits
significantly lowered total and LDL-cholesterol concentrations; may have been observed at 4 wk. Although it is hard to speculate
however, the weakness of that study was that the placebo reduced on the exact mechanism by which the Sterol Bev reduces LDL
total and LDL-cholesterol concentrations, albeit nonsignifi- cholesterol, its effects on cholesterol absorption and expression
cantly, and comparisons with a placebo were not made (12). of ATP-binding cassette transporter G5 and 8 will be examined
Mensink et al (13) also showed a 13.7% reduction in LDL cho- in future studies. Note that HDL-cholesterol concentrations in-
lesterol using esterified stanols (3 g/d) in low-fat yogurt. Jones et creased in the Sterol Bev group but not compared with the Pla-
al (14) observed no significant differences in total and LDL cebo Bev group. However, because apo A1 concentrations were
cholesterol between the placebo and the low- or nonfat beverages not significantly different between the Placebo Bev and Sterol
containing free sterols, which were incorporated into a controlled Bev groups, this needs to be confirmed with larger studies in
diet regimen. The diet regimen itself resulted in a 5% reduction patients with low HDL cholesterol.
in the LDL-cholesterol concentration. Clifton et al (15) showed Several lines of evidence provide support for the pivotal role
that the efficacy of plant sterols (1.6 g/d for 3 wk) consumed in of inflammation in atherosclerosis. Numerous prospective stud-
low-fat milk was 3 times that of their consumption in bread and ies have shown that high concentrations of CRP predict increased
cereal. We previously showed that in a nonfat matrix (ie, OJ) cardiovascular events. Statins have been shown to have pleio-
containing 1 g sterols/240 mL consumed twice a day with meals tropic effects in addition to reducing LDL-cholesterol and CRP
lowered total and LDL-cholesterol concentrations (8). In a recent concentrations (17). Also, the cholesterol absorption inhibitor,
study conducted on modestly hypercholesterolemic subjects, ezetimibe, was shown to lower CRP concentrations when ad-
Noakes et al (16) reported a significant reduction in LDL cho- ministered with a statin (18). Furthermore, in a small study, Cater
lesterol (8 –9%) with plant sterol esters (1.8-2 g/d) when incor- et al (19) showed that combined administration of plant stanols
porated in low-fat milk or yogurt. Because of the increase in the with a statin significantly reduced CRP concentrations in patients
incidence of diabetes, metabolic syndrome, and obesity in the with coronary artery disease; however, they found no significant
United States, it is desirable that a nonfat beverage with reduced change in CRP concentrations with plant stanol esters alone.760 DEVARAJ ET AL
TABLE 5
Effect of the reduced-calorie sterol beverage on plasma vitamin E and
carotenoid concentrations1
Week 8
Baseline (n ҃ 36) P22
␣-Tocopherol (mol/L) 0.65
Sterol Bev 31 앐 7 34 앐 9
Placebo Bev 32 앐 14 36 앐 12
␣-Carotene (mol/L) 0.31
Sterol Bev 0.37 앐 0.16 0.41 앐 0.21
Placebo Bev 0.41 앐 0.36 0.44 앐 0.31
-Carotene (mol/L) 0.36
Sterol Bev 0.64 앐 0.30 0.59 앐 0.32
Placebo Bev 0.54 앐 0.37 0.59 앐 0.35
Lycopene (mol/L) 0.61
Sterol Bev 0.35 앐 0.22 0.28 앐 0.24
Placebo Bev 0.36 앐 0.24 0.41 앐 0.29
Lutein (mol/L) 0.78
Sterol Bev 0.16 앐 0.10 0.17 앐 0.12
Placebo Bev 0.16 앐 0.12 0.16 앐 0.10
1
All values are x 앐 SD and were analyzed by Friedman test with
Wilcoxon test. n ҃ 36 for both the Sterol Bev group and the Placebo Bev
group. Sterol Bev, reduced-calorie orange juice beverage with plant sterols;
Placebo Bev, placebo beverage.
2
P values for interaction (time ҂ treatment effects).
mechanisms, this could have major implications with respect to
the prevention of CVD because the concomitant reduction in
LDL cholesterol and CRP with statin therapy was associated with
the greatest benefit in terms of cardiovascular events (22, 23). A
plausible mechanism for the antiinflammatory effect of plant
sterols is the attenuation of the proinflammatory burden in the
liver, which emanates from the gastrointestinal tract.
The concern with plant sterol supplementation is that it may
FIGURE 1. Effect of a reduced-calorie orange juice beverage with plant not only reduce LDL-cholesterol concentrations by inhibiting
sterols (Sterol Bev) on high-sensitivity C-reactive protein (hs-CRP) concen- cholesterol absorption but may also reduce other lipophilic com-
trations in the present study (A) and in an earlier study (B) with sterol- pounds such as carotenoids and vitamin E at the same time (24).
containing orange juice (sterol OJ) (8). Fasting blood samples were obtained
Lipid standardized concentrations of plasma ␣-tocopherol,
at baseline and after 8 wk of supplementation with a placebo beverage
(Placebo Bev) or Sterol Bev or as described in the previous study. All -carotene, and lycopene have been shown to be reduced after
analyses were carried out as described in Methods. Data are presented as consumption of plant stanols or sterols in some studies but not in
medians (25th and 75th percentiles). Two-factor nonparametric analyses others. In our study, we observed no significant differences in
(Friedman test) resulted in a significant time ҂ treatment interaction. Sig- concentrations of the different fat-soluble vitamins with Sterol
nificantly different from placebo: *P ҃ 0.02, **P 쏝 0.03.
Bev supplementation. This is probably due to the incorporation
of these fat-soluble vitamins into the formulation in the free form.
Although statins produce greater reductions in CRP and LDL Previously, Richelle et al (24) showed that free sterols were less
cholesterol, they are not tolerated by all persons. We showed for effective than sterol esters in reducing the bioavailability of vi-
the first time that plant sterols added to a reduced-calorie OJ tamin E and -carotene.
beverage as well as in regular OJ (from the previous study) In conclusion, the present study showed that a reduced-calorie
effectively lower CRP concentrations in healthy human volun- nonfat OJ beverage significantly improved the lipid profile with-
teers and could thus be added to the list of agents that can mod- out compromising carotenoid and vitamin E status. In addition,
ulate CRP concentrations and possibly be considered antiinflam- it concomitantly reduced CRP concentrations, thus offering an
matory. This is particularly important because it has been attractive strategy to incorporate in the therapeutic lifestyle di-
previously shown that glucose intake increases oxidative stress etary regimen recommended by the NCEP/ATP III guidelines.
and glucose infusion induces inflammatory responses (20, 21); Previously, Jenkins et al (25), using a portfolio diet high in plant
however, the reduced-calorie Sterol Bev resulted in a significant sterols, soy protein, viscous fiber, and almonds, reported a sig-
reduction in both LDL-cholesterol and CRP concentrations with- nificant reduction in LDL cholesterol and CRP. Although they
out affecting blood glucose concentrations. Although more stud- could not ascribe the benefit to a particular dietary component,
ies are needed to confirm the CRP-lowering action of plant ste- the study showed that diversifying cholesterol-lowering compo-
rols in different populations and examine the underlying nents in the same dietary portfolio increased the effectiveness ofLOW-CALORIE STEROL BEVERAGE LOWERS CRP AND CHOLESTEROL 761
the diet in treating hypercholesterolemia and in attenuating inflam- of esterified phytosterols administered in reduced-fat spread and
mation. Such dietary therapies will go a long way in reducing car- salad dressing to healthy adult men and women. J Am Coll Nutr
2001;20:307–19.
diovascular burden, especially in subjects who are at an increased 12. Volpe R, Niittynen L, Korpela R, et al. Effects of yoghurt enriched with
risk for the metabolic syndrome, diabetes, and CVD. plant sterols on serum lipids in patients with moderate hypercholester-
olaemia. Br J Nutr 2001;86:233–9.
We thank Carolyn Moore for discussions with regard to the beverage and 13. Mensink RP, Ebbing S, Lindhout M, Plat J, van Heugten MM. Effects of
for review of the manuscript. plant stanol esters supplied in low-fat yoghurt on serum lipids and li-
SD conducted the study. BCA provided technical assistance. IJ provided poproteins, non-cholesterol sterols and fat soluble antioxidant concen-
overall supervision and the follow-up of the volunteers in the study. All trations. Atherosclerosis 2002;160:205–13.
authors approved the final version of the manuscript. None of the authors had 14. Jones PJH, Vanstone CA, Sarjaz MR, St-Onge MP. Phytosterols in low
any personal or financial conflict of interest. and non-fat beverages as part of a controlled diet fail to lower plasma
lipid levels. J Lipid Res 2003;44:713–9.
15. Clifton PM, Noakes M, Sullivan D, et al. Cholesterol-lowering effects of
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