AJCN Tufts Nutrition Symposium, Boston & Online Sept 2009
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Klingberg, S.
Right arrow Articles by Winkvist, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Klingberg, S.
Right arrow Articles by Winkvist, A.
Agricola
Right arrow Articles by Klingberg, S.
Right arrow Articles by Winkvist, A.
American Journal of Clinical Nutrition, Vol. 87, No. 4, 993-1001, April 2008
© 2008 American Society for Nutrition

ORIGINAL RESEARCH COMMUNICATION

Inverse relation between dietary intake of naturally occurring plant sterols and serum cholesterol in northern Sweden1,2,3

Sofia Klingberg, Lars Ellegård, Ingegerd Johansson, Göran Hallmans, Lars Weinehall, Henrik Andersson and Anna Winkvist

1 From the Department of Clinical Nutrition, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden (SK, LE, HA, and AW); the Departments of Public Health and Clinical Medicine/Nutritional Research (IJ and GH), Odontology/Cariology (IJ), and Public Health and Clinical Medicine/Epidemiology and Public Health Sciences (LW), University of Umeå, Umeå, Sweden; and the Department of Community Medicine, Västerbotten County Council, Umeå, Sweden (LW)

2 Supported by FORMAS, the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, grant 22.2/2003-0655 and by the Swedish Research Council, grant 521-2003-3826. The plant sterol analyses were supported by a grant from the Swedish government under the LUA agreement and the Swedish Cancer Foundation. The Västerbotten Intervention Program was funded by the Swedish Cancer Society, the Europe Against Cancer Programme, and Västerbotten County Council. The development and maintenance of the dietary database is supported by grants from The Swedish Council for Working Life and Social Research and the Swedish Research Council.

3 Reprints not available. Address correspondence to S Klingberg, the Sahlgrenska Academy at Göteborg University, PO Box 459, SE 405 30 Göteborg, Sweden. E-mail: sofia.klingberg{at}nutrition.gu.se.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background:Plant sterols are bioactive compounds, found in all vegetable foods, which inhibit cholesterol absorption. Little is known about the effect of habitual natural dietary intake of plant sterols.

Objective:We investigated the relation between plant sterol density (in mg/MJ) and serum concentrations of cholesterol in men and women in northern Sweden.

Design:The analysis included 37 150 men and 40 502 women aged 29–61 y, all participants in the Västerbotten Intervention Program.

Results:Higher plant sterol density was associated with lower serum total cholesterol in both sexes and with lower LDL cholesterol in women. After adjustment for age, body mass index (in kg/m2), and (in women) menopausal status, men with high plant sterol density (quintile 5) had 0.15 mmol/L (2.6%) lower total serum cholesterol (P for trend = 0.001) and 0.13 mmol/L (3.1%) lower LDL cholesterol (P = 0.062) than did men with low plant sterol density (quintile 1). The corresponding figures for women were 0.20 mmol/L (3.5%) lower total serum cholesterol (P for trend < 0.001) and 0.13 mmol/L (3.2%) lower LDL cholesterol (P for trend = 0.001).

Conclusions:The present study is the second epidemiologic study to show a significant inverse relation between naturally occurring dietary plant sterols and serum cholesterol. To the extent that the associations found truly mirror plant sterol intake and not merely a diet high in vegetable fat and fiber, it highlights the importance of considering the plant sterol content of foods both in primary prevention of cardiovascular disease and in the dietary advice incorporated into nutritional treatment of patients with hyperlipidemia.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Cardiovascular disease (CVD) caused one-third of all deaths worldwide in 2003 (1). In Sweden, although the incidence of myocardial infarction (MI) has decreased by 1–2% per year during the past decade, MI still affects {approx}40 000 persons per year. Mortality from MI has also decreased during the same time period, but it is still the main cause of death in Sweden (2).

The traditional risk factors for CVD include cigarette smoking, hypertension, and dyslipidemia. Serum cholesterol is affected by dietary intake, and dietary interventions may reduce the incidence of coronary heart disease by 12%, of which 5% is because of lowered cholesterol (3). A 10% reduction of serum cholesterol was estimated to lower the risk of ischemic heart disease by 50% at age 40 y and by 20% at age 70 y (4).

Intakes of dietary fiber, total fat, and saturated fat are accepted as dietary components that affect concentrations of serum cholesterol (3). Other dietary components such as soy protein and plant sterols were also suggested to affect concentrations of serum cholesterol (5, 6).

Plant sterols are bioactive compounds found in all vegetable foods at various concentrations. They inhibit the uptake of cholesterol, both dietary and endogenous, by incorporation into mixed micelles in the small bowel; this is the main reason for their hypocholesterolemic effects (7). Since the 1950s, plant sterols have been known to lower concentrations of serum cholesterol when given in pharmacologic doses. Margarine enriched with plant sterols was shown in 1995 to reduce serum cholesterol (8). Commercial products enriched with plant sterols, with a recommended daily dose of 2 g of plant sterols, were shown to reduce LDL-cholesterol concentrations by 10% (9). Much less is known about the effect of a habitual natural intake of plant sterols, but results from 2 clinical trials show that an intake of 300 mg plant sterols reduces cholesterol absorption by 11% in a 3-d trial (10) and by 28% in a test meal trial in which dietary fat content was kept constant and only the content of dietary plant sterols varied (11). In a recent large-scale epidemiologic study of a British population [European Prospective Investigation into Cancer and Nutrition (EPIC)–Norfolk] in collaboration with the Medical Research Council Dunn Clinical Nutrition Centre, Cambridge, and the Institute of Public Health, University of Cambridge, we showed that a high intake of naturally occurring dietary plant sterols was inversely related to serum total and LDL-cholesterol concentrations (12). The aim of the present study was to investigate the relation between plant sterol density and serum concentrations of cholesterol in men and women in a Swedish population.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study population
The Västerbotten Intervention Program, which began in 1985, invites all inhabitants in Västerbotten county in northern Sweden (population {approx}260 000) to a health checkup at their primary health care center in the year they turn 40, 50, or 60 y of age (until 1995, those turning 30 y were also included) (13, 14). During the health checkup, participants answer an extensive diet and lifestyle questionnaire and are asked to donate blood for future research purposes. The program is ongoing. On average, {approx}60% of the invited population has participated each year. No systematic differences were found between those who participated and those who declined (13). The questionnaire was not optically machine-readable until 1992, and so this study only includes data from 1992 to 2005. During those years, 83 013 health checkups (39 885 of men and 43 128 of women) took place. Of those 83 013 visits, the 71 367 first-time visits and 11 640 second-time visits were included in the present study, whereas 6 third-time visits were excluded. First-time visits and second-time visits were treated as separate observations. Further exclusions were made because of wrong age (<29 y or >61 y; n = 95), incomplete dietary data (n = 3771), and missing or unrealistic total cholesterol (<2.5 mmol/L and >20.0 mmol/L n = 708). The Regional Ethical Review Board in Göteborg, Sweden, approved the study (registration number 622-05).

Exclusion of extreme outliers
Basal metabolic rate was estimated from sex, age, and weight according to Schofield (15). The food intake amount was calculated from energy intake divided by basal metabolic rate. All subjects were divided into 1 of 4 groups according to sex and whether they had completed a 64-item or 84-item food-frequency questionnaire (FFQ). In each of the 4 groups, participants with the highest and lowest 0.5% of food intake amount were excluded, in accordance with the method used in the EPIC-Norfolk study (16). This resulted in exclusion of 781 subjects. In total, 77 652 visits (37 150 by men and 40 502 by women) were included in the analyses.

Blood samples and laboratory procedures
Total cholesterol and serum triacylglycerols were measured on fresh capillary plasma with the use of a bench top analyzer (Reflotron; Boehringer Mannheim GmbH Diagnostica, Mannheim, Germany). The tests were taken after a minimum of 4 h of fasting. HDL cholesterol was measured on a subsample with high total cholesterol according to the study protocol. HDL cholesterol was measured after precipitation of the other lipoproteins with sodium phosphowolframate-magnesium chloride. LDL cholesterol was calculated according to Friedewald et al (17).

Anthropometric measurements
Height was measured without shoes to the nearest centimeter. Weight was measured in light clothing without shoes to the nearest kilogram. Body mass index (BMI; in kg/m2) was calculated.

Lifestyle variables and medication
Participants were classified as smokers if they were smoking at least 1 cigarette/d. Estimation of high physical activity was made from a combination of physical activity at work, physical activity in spare time, and mode of travel to work. Participants were classified as users of cholesterol-lowering medication if they had used cholesterol-lowering medication in the past 14 days. Women were classed as menopausal if >51.8 y of age according to the median age of menopause in Sweden.

Plant sterol analysis
Analyses of the food items were performed at the Department of Clinical Nutrition, Göteborg University, Sweden, with the use of a gas-liquid chromatography procedure modified after Jonker et al (18) and validated with gas chromatography–mass spectrometry (19). In short, the method comprised acid hydrolysis (6 mol/L HCl), alkaline saponification (96% ethanolic potassium hydroxide), lipid extraction with toluene, and a final washing in deionized water to neutral pH. Internal standard, containing 5{alpha}-cholestane, was added to all samples before saponification to quantify the sterols. Samples were dehydrated with sodium sulphate, filtered, and evaporated under vacuum at 50 °C. The residue was dissolved in chloroform and stored at –20 °C. Silylation of sterols to trimethylsilyl ether derivatives was performed before analysis by gas-liquid chromatography. The limit of detection was set to 0.01 mg/100 g fresh material of the tested product. The concentrations of the 5 most frequently occurring plant sterols were measured: the unsaturated plant sterols campesterol (24{alpha}-methyl-5-cholesten-3β-ol), stigmasterol (5,22-cholestadien-24{alpha}-ethyl-3β-ol), and β-sitosterol (24{alpha}-ethylcholest-5-en-3β-ol), and the saturated plant stanols campestanol (24{alpha}-methyl-5{alpha}-cholestan-3β-ol) and β-sitostanol (24{alpha}-ethyl-5{alpha}-cholestan-3β-ol). The sum of these 5 plant sterols is described hereafter as "total plant sterols." All foods were analyzed in duplicate. All fruit and vegetables were bought in 1996, cereals in 1997, and fatty foods in 1997 and 2001 in 2 shops in the Gothenburg area. Fruit and vegetables were analyzed as a mix of 2 different samples, and cereals and fatty foods were analyzed as a mix of 2–7 samples. Seasonal variation in fruit and vegetables was not taken into account.

Plant sterol database
Analyses of >330 food items were collected in a plant sterol database, and this database was used to estimate plant sterol intake. The database included vegetables, fruit, cereals, bread, fats, nuts, confectionery, and beverages. Food items from this database were matched with the food items present in the FFQ. The plant sterol data on vegetables, fruit, cereals, and fatty foods were published elsewhere (20–22).

Dietary assessment
Dietary assessments were obtained by a semiquantitative FFQ, containing either 84 or 64 questions. The 84-question FFQ has been validated and calibrated with 24-h diet recalls, and it was concluded to have a validity similar to other FFQs used in prospective cohort studies (23). The design of the FFQ with 84 questions was described previously, as well as criteria for exclusions (23). In the 64-question FFQ, some questions were merged to cover the same foods as the 84-question FFQ but with fewer questions.

Assignment of plant sterol values for each question in the FFQ
Each FFQ question could represent a single food item, an aggregate of items (eg, tomato and cucumber), or a food group (eg, berries). In the cases of aggregates and groups, data from a single 24-h recall from 3000 persons in the calibration study (24) or from 10 repeated 24-h recalls from 195 persons from the validation study (23) were used to estimate intake distribution in the population for each of the foods in the aggregate or group. The plant sterol content was estimated by multiplying the reported intake frequency by age- and sex-defined portion sizes or standard sizes, such as for an apple, with additional weighting for intake distribution for questions representing food aggregates or food groups.

84-Question FFQ
Aggregates of foods were calculated for 31 questions, in 28 cases from the calibration data and in 3 from the validation data. Foods from 28 questions were assumed to have zero plant sterol content, mostly because of pure animal origin. The plant sterol content of foods from a further 40 questions was based on direct analysis of the food or the foods representing the question. Calculations of standard recipes with analyzed ingredients were used for 13 questions, the proportion of an analyzed food item was used for 1 question, and a combination of direct analysis and recipe calculations was used for 2 questions.

64-Question FFQ
Aggregates of foods were calculated for 25 questions, in 22 cases from the calibration data, and in 3 from the validation data. Foods from 20 questions were assumed to have zero plant sterol content because of pure animal origin. The plant sterol content of foods from a further 33 questions was based on direct analysis of the food or the foods representing the questions. Calculations of standard recipes with analyzed ingredients were used for 7 questions, and a combination of direct analysis and recipe calculations or proportions was used for 4 questions.

Statistical analysis
Statistical calculations were performed with the use of SPSS 14.0 for WINDOWS (SPSS Inc, Chicago, IL). Data from men and women were analyzed separately. Division into quintiles of plant sterol density was done by ranking according to total plant sterol density defined as milligram plant sterols per megajoule. Multivariate linear regression with plant sterol quintile as main predictor was used for the analyses. Linear trends were evaluated by fitting quintile group membership (1–5) as a variable in a linear regression. The following variables were evaluated for potential confounding effects: age, BMI, menopausal status, saturated fat intake (in percent of energy), unsaturated fat intake (in percent of energy), dietary fiber intake (in g/MJ), alcohol intake (in percent of energy), high physical activity, smoking, and use of cholesterol-lowering medication. Unsaturated fat intake was not available from the dietary data but was calculated from the difference of total fat intake and saturated fat intake. Because intakes of saturated fat, unsaturated fat, and fiber were strongly correlated with each other (correlations between –0.41 and 0.59), these 3 covariates were combined into a new categorical variable. First, each variable was recoded into high and low. For this the cutoff for saturated fat was set to 10% of energy, unsaturated fat to 15% of energy, and fiber intake to 3 g/MJ according to the Nordic Nutrition Recommendations 2004 (25). Hence, the new variable took 8 values. The correlation between saturated fat and cholesterol was 0.68 for both men and women; hence, it was decided not to include the latter as a covariate in addition to the former because these 2 nutrients basically capture the same foods.

Because energy and nutrient intakes were not normally distributed, the results are presented both as means (±SD) and medians (25th and 75th percentiles). Differences among categorical variables were evaluated with the chi-square test.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Men had a mean plant sterol intake of 252 ± 95 mg/d, which was significantly higher than the intake of women, 212 ± 74 mg/d (P < 0.001). The intake of plant sterols in relation to energy intake (plant sterol density, in mg/MJ) differed between men (28.8 ± 6.6 mg/MJ) and women (31.6 ± 6.9 mg/MJ; P < 0.001).

A significant interaction was observed between sex and quintile of plant sterol density in their effect on total cholesterol (P = 0.042); hence, all results are presented separately for men and women. For both men (Table 1Go) and women (Table 2Go), a higher plant sterol density (in mg/MJ) was associated with higher intake of plant sterols (in mg/d), unsaturated fatty acids (in g/d and percent of energy), and fiber (in g/d and g/MJ) and with lower values for energy intake, intake of saturated fatty acids (in g/d and percent of energy), alcohol (in g/d and percent of energy), and cholesterol (in mg/d and mg/MJ) (all P < 0.001). The women with a higher plant sterol density (in mg/MJ) had a lower energy intake from total fat (percent of energy), whereas the opposite relation was seen in men (all P < 0.001). Intake of total fat (in g/d) was lower in women with higher plant sterol density, whereas it did not differ for men.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Intake of plant sterols, energy, total fat, saturated fat, unsaturated fat, alcohol, cholesterol, and fiber by quintile (Q) of plant sterol density in men aged 29–61 y from the Västerbotten Intervention Program, 1991–2005

 

View this table:
[in this window]
[in a new window]

  		TABLE 2. Intake of plant sterols, energy, total fat, saturated fat, unsaturated fat, alcohol, cholesterol, and fiber by quintile (Q) of plant sterol density in women aged 29–61 y from the Västerbotten Intervention Program, 1991–2005

 
Cardiovascular risk factors and serum lipids by quintiles of plant sterol density are shown in Table 3Go (men) and Table 4Go (women). Higher plant sterol density was associated with lower serum total cholesterol in both men and women and with lower LDL cholesterol in women. After adjustment for age and BMI, the men with high plant sterol density (quintile 5) had 0.15 mmol/L (2.6%) lower total serum cholesterol (P < 0.001) and 0.13 mmol/L (3.1%) lower LDL cholesterol (P = 0.062) than did the men with low plant sterol density (quintile 1). The corresponding figures for the women, after adjustment for age, BMI, and menopausal status, were 0.20 mmol/L (3.5%) lower total serum cholesterol (P < 0.001) and 0.13 mmol/L (3.2%) lower LDL cholesterol (P < 0.001). Further adjustments for intakes of saturated fatty acids, unsaturated fatty acids, dietary fiber, and alcohol; high physical activity; smoking; and cholesterol-lowering medication did not essentially alter total serum cholesterol in the 5 quintiles for either sex. The same adjustments did not affect LDL cholesterol for women, but the linear trend for men changed from borderline significance to P = 0.337.


View this table:
[in this window]
[in a new window]

  		TABLE 3. Cardiovascular risk factors and serum lipids by quintile (Q) of plant sterol density in men aged 29–61 y from the Västerbotten Intervention Program, 1991–2005

 

View this table:
[in this window]
[in a new window]

  		TABLE 4. Cardiovascular risk factors and serum lipids by quintile (Q) of plant sterol density in women aged 29–61 y from the Västerbotten Intervention Program, 1991–2005

 
A multiple linear regression with plant sterol density as a continuous variable was also performed with adjustment for age; BMI; intakes of saturated fatty acids, unsaturated fatty acids, dietary fiber, and alcohol; high physical activity; smoking; cholesterol-lowering medication; and for women also menopausal status. The β coefficient corresponding to an increase in plant sterol density of 20 mg/MJ was –0.06 (P = 0.002) for total cholesterol in men and –0.22 (P < 0.001) in women. The corresponding β coefficients for LDL cholesterol were –0.06 (P = 0.144) and –0.12 (P < 0.001) for men and women, respectively.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The cholesterol-lowering effect of plant sterols is well established, but a similar effect of natural dietary plant sterol intake has been questioned because the average amount consumed is relatively low. In the current study of a large Swedish population, a high plant sterol density was inversely related to serum total cholesterol in both men and women and to LDL cholesterol in women, which confirms the associations seen in our recent study of a large British population (12).

Comparing the present study with our previous British EPIC-Norfolk cohort study, the effect of plant sterol density and plant sterol intake on serum total and LDL cholesterol was similar among both men and women (12). In the British study, total and LDL cholesterol decreased by 0.25 mmol/L (4.1%) and 0.14 mmol/L (3.5%), respectively, in men and by 0.15 mmol/L (2.4%) and 0.12 mmol/L (3.0%), respectively, in women after adjustment for age, BMI, energy intake, and (in women) menopausal status. Because of the different quintile classifications, ie, by plant sterol density (in mg/MJ) in the present study and by plant sterol intake (in mg/d) in the EPIC-Norfolk study, the results are not fully comparable.

Adjustment for intakes of saturated fat, unsaturated fat, and dietary fiber was complicated by the problem of collinearity. However, the issue was dealt with by combining information from the intake of these 3 nutrients into one categorical variable. Adjustment for this categorical fat-fiber variable plus smoking, high physical activity, and cholesterol-lowering medication did not essentially affect the trend of serum total and LDL cholesterol in the quintiles, but for LDL cholesterol in men the linear trend changed from being borderline significant to insignificant. Another complication is that products high in vegetable fats and dietary fiber are main sources also of plant sterols in the diet (26, 27). Hence, the effects of these dietary components are impossible to totally separate from the effects of plant sterols in analyses of epidemiologic data. We believe that our categorical fat-fiber variable handled this complication in the best way possible. In addition, a true effect of naturally occurring dietary plant sterols seen in the present study is supported because a carefully controlled study has shown that plant sterols do affect cholesterol absorption when given in relatively small doses of 150–300 mg (11) and because cholesterol absorption decreases in relation to increasing plant sterol excretion (28). The effect of naturally occurring plant sterols on serum cholesterol seen in the present study is higher than what could be expected from clinical trials with enriched products. It is also known that the relation between plant sterol intake and serum cholesterol is curvilinear rather than linear (9), which supports the higher effect of natural dietary intake. Comparison can also be made with the effect of dietary intake of cholesterol on serum cholesterol, which is known to decline with increasing intake (29). The effect of plant sterol intake on serum cholesterol could, if any, be underestimated in the present analyses because of a diluted effect resulting from measurement errors in the dietary data. Food intake amount was negatively correlated to BMI in both men and women, and the fact that persons with a higher BMI report a lower energy intake could result in that their plant sterol density becomes falsely high. At the same time their serum cholesterol is higher than in persons with a normal BMI and a more reliable energy intake.

An important consideration is that data about LDL cholesterol were only available for a quarter of all participants. These participants were not selected randomly, but because of high total cholesterol, for which a full lipid status was performed according to the study test protocol. The men with available data about LDL cholesterol were slightly older (48.5 y compared with 47.7 y; P < 0.001), had a higher total cholesterol concentration (6.0 mmol/L compared with 5.5 mmol/L; P < 0.001), and had a slightly higher BMI (26.8 compared with 26.1; P < 0.001). The same relation was seen in women with available data about LDL cholesterol who were older (49.5 y compared with 47.6 y; P < 0.001), had a higher total cholesterol (6.0 mmol/L compared with 5.4 mmol/L; P < 0.001), and had a higher BMI (26.2 compared with 25.3; P < 0.001). The fact that the sample is smaller and that it was not randomly selected could explain why the statistical significance was erased in men when the effect of plant sterol intake on LDL cholesterol instead of total cholesterol was studied, although women were not affected. Concentration of HDL cholesterol did decrease marginally from quintile 1 to quintile 5 in both men and women, but this was only statistically significant in the unadjusted model in men and women and for women also in the fully adjusted model. The marginal effect of plant sterols on HDL cholesterol seen in this epidemiologic study is in accordance with a clinical trial (30).

The mean plant sterol intake in the present population was somewhat lower than that reported from other European populations (12, 26, 31, 32), in which the plant sterol intake was reported to be between 240 and 260 mg/d for women and {approx}300 mg/d for men. This was also evident for the plant sterol density that was reported to be {approx}36 mg/MJ for women and 33 mg/MJ for men (27, 31). The lower intake of plant sterols could partly be explained by the lower plant sterol density and partly by a lower reported energy intake. The mean energy intake for men in the present study was 8.8 MJ, compared with 9.6 MJ in the Finnish study by Valsta et al (31) and 9.2 MJ in the British study by Klingberg et al (27). The women in the present study had a mean energy intake of 6.7 MJ, compared with 6.8 MJ in the study by Valsta et al (31) and 8.1 MJ in the study by Klingberg et al (27).

Dietary assessments are frequently biased, resulting in under- and overreporting of energy and nutrient intake (33). This problem is likely to have occurred in the present dietary assessment and is one of the limitations of the study. Extreme outliers, eg, the top and bottom 0.5% of food intake amount, were excluded. Even so, the reported energy intake was low. This should not be a serious problem, because we studied the ranking of participants according to energy-adjusted intake of plant sterols. Further, because energy intake was relatively constant across the quintiles of plant sterol density, the absolute intake of plant sterols increased across the quintiles.

FFQs are generally considered a poor measure of absolute dietary intake. In the present study the method was used to rank participants according to their intake of plant sterol density, and the focus was on the dietary quality rather than the absolute intake. Another limitation of the present study is that the FFQ was not designed specifically to measure plant sterol intake. The Spearman's correlation coefficient between food intake frequencies as assessed by the FFQ and the repeated 24-h recalls was between 0.47 and 0.68 for food groups containing plant sterols, except for potato, rice, and pasta that had lower correlation coefficients (23). Cross-classification of both food intake frequencies and intake of energy and nutrients showed a low incidence of extreme misclassification (23). It is therefore likely that the FFQ was able to capture plant sterol intake and that the classification of participants into quintiles of plant sterol intake truly did distinguish participants with differing plant sterol intake.

In conclusion, the present study is the second to show a significant inverse relation between natural-occurring dietary plant sterols and serum concentrations of total and LDL cholesterol. It highlights the importance of considering the plant sterol content of foods both in primary prevention of CVD and in the dietary advices incorporated into nutritional treatment of patients with hyperlipidemia.


   ACKNOWLEDGMENTS
 
The author's responsibilities were as follows—GH and LW: were principal investigators in the Västerbotten Intervention Program (VIP) study; IJ and AW: were responsible for the dietary data of VIP; LE, HA, and SK: developed the plant sterol database; IJ and SK: prepared the plant sterol data set in the VIP cohort; SK (principal investigator): wrote the paper with contributions from coauthors. None of the authors had a personal or financial conflict of interest.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Global strategy on diet, physical activity and health. Cardiovascular disease: prevention and control. Geneva, Switzerland: World Health Organization, 2007.
  2. The National Board of Health and Welfare. Myocardial infarction in Sweden. Stockholm, Sweden: The National Board of Health and Welfare, 2007:1987–2004.
  3. Brunner EJ, Thorogood M, Rees K, Hewitt G. Dietary advice for reducing cardiovascular risk. Cochrane Database Syst Rev 2005;(4):CD002128.[Medline]
  4. Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994;308:367–72.[Abstract/Free Full Text]
  5. Nicolosi RJ, Wilson TA, Lawton C, Handelman GJ. Dietary effects on cardiovascular disease risk factors: beyond saturated fatty acids and cholesterol. J Am Coll Nutr 2001;20(suppl):421S–7S; discussion 440S–2S.[Abstract/Free Full Text]
  6. Fraser GE. Diet and coronary heart disease: beyond dietary fats and low-density-lipoprotein cholesterol. Am J Clin Nutr 1994;59(suppl):1117S–23S.[Medline]
  7. Plat J, Mensink RP. Plant stanol and sterol esters in the control of blood cholesterol levels: mechanism and safety aspects. Am J Cardiol 2005;96:15D–22D.[Medline]
  8. Miettinen TA, Puska P, Gylling H, Vanhanen H, Vartiainen E. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med 1995;333:1308–12.[Abstract/Free Full Text]
  9. Katan MB, Grundy SM, Jones P, Law M, Miettinen T, Paoletti R. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 2003;78:965–78.[Abstract/Free Full Text]
  10. Ellegard L, Andersson H, Bosaeus I. Rapeseed oil, olive oil, plant sterols, and cholesterol metabolism: an ileostomy study. Eur J Clin Nutr 2005;59:1374–8.[Medline]
  11. Ostlund RE Jr, Racette SB, Okeke A, Stenson WF. Phytosterols that are naturally present in commercial corn oil significantly reduce cholesterol absorption in humans. Am J Clin Nutr 2002;75:1000–4.[Abstract/Free Full Text]
  12. Andersson SW, Skinner J, Ellegard L, et al. Intake of dietary plant sterols is inversely related to serum cholesterol concentration in men and women in the EPIC Norfolk population: a cross-sectional study. Eur J Clin Nutr 2004;58:1378–85.[Medline]
  13. Weinehall L, Hallgren CG, Westman G, Janlert U, Wall S. Reduction of selection bias in primary prevention of cardiovascular disease through involvement of primary health care. Scand J Prim Health Care 1998;16:171–6.[Medline]
  14. Pukkala E, Andersen A, Berglund G, et al. Nordic biological specimen banks as basis for studies of cancer causes and control–more than 2 million sample donors, 25 million person years and 100,000 prospective cancers. Acta Oncol 2007;46:286–307.[Medline]
  15. Schofield WN. Predicting basal metabolic rate, new standards and review of previous work. Hum Nutr Clin Nutr 1985;39(suppl 1):5–41.
  16. Welch AA, Luben R, Khaw KT, Bingham SA. The CAFE computer program for nutritional analysis of the EPIC-Norfolk food frequency questionnaire and identification of extreme nutrient values. J Hum Nutr Diet 2005;18:99–116.[Medline]
  17. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499–502.[Abstract]
  18. Jonker D, Van der Hoek G, Glatz JFC. Combined determination of free, esterified and glycosilated plant sterols in foods. Nutr Rep Int 1985;32:943–51.
  19. Dutta PC, Normén L. Capillary column gas-liquid chromatographic separation of {Delta}5-unsaturated and saturated phytosterols. J Chromatogr A 1998;816:177–84.
  20. Normen L, Johnsson M, Andersson H, van Gameren Y, Dutta P. Plant sterols in vegetables and fruits commonly consumed in Sweden. Eur J Nutr 1999;38:84–9.[Medline]
  21. Normén L, Bryngelsson S, Johnsson M, et al. The phytosterol content of some cereal foods commonly consumed in Sweden and in the Netherlands. J Food Compost Anal 2002;15:693–704.
  22. Normen L, Ellegard L, Brants H, Dutta P, Andersson H. A phytosterol database: fatty foods consumed in Sweden and the Netherlands. J Food Compost Anal 2007;20:193–201.
  23. Johansson I, Hallmans G, Wikman A, Biessy C, Riboli E, Kaaks R. Validation and calibration of food-frequency questionnaire measurements in the Northern Sweden Health and Disease cohort. Public Health Nutr 2002;5:487–96.[Medline]
  24. Slimani N, Kaaks R, Ferrari P, et al. European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study: rationale, design and population characteristics. Public Health Nutr 2002;5:1125–45.[Medline]
  25. Nordic nutrition recommendations 2004. 4th ed. Copenhagen, Denmark: Nordic Council of Ministers, 2004.
  26. Normen AL, Brants HA, Voorrips LE, Andersson HA, van den Brandt PA, Goldbohm RA. Plant sterol intakes and colorectal cancer risk in the Netherlands Cohort Study on Diet and Cancer. Am J Clin Nutr 2001;74:141–8.[Abstract/Free Full Text]
  27. Klingberg S, Andersson H, Mulligan A, et al. Food sources of plant sterols in the EPIC Norfolk population. Eur J Clin Nutr 2007; 18 April (Epub ahead of print; DOI: 10.1038/sj.ejcn.1602765).
  28. Ellegard L, Bosaeus I, Andersson H. Will recommended changes in fat and fibre intake affect cholesterol absorption and sterol excretion? An ileostomy study. Eur J Clin Nutr 2000;54:306–13.[Medline]
  29. Keys A, Anderson JT, Grande F. Serum cholesterol response to changes in the diet: II. The effect of cholesterol in the diet. Metabolism 1965;14:759–65.[Medline]
  30. Hendriks HF, Weststrate JA, van Vliet T, Meijer GW. 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 1999;53:319–27.[Medline]
  31. Valsta LM, Lemstrom A, Ovaskainen ML, et al. Estimation of plant sterol and cholesterol intake in Finland: quality of new values and their effect on intake. Br J Nutr 2004;92:671–8.[Medline]
  32. Jimenez-Escrig A, Santos-Hidalgo AB, Saura-Calixto F. Common sources and estimated intake of plant sterols in the Spanish diet. J Agric Food Chem 2006;54:3462–71.[Medline]
  33. Black AE, Goldberg GR, Jebb SA, Livingstone MB, Cole TJ, Prentice AM. Critical evaluation of energy intake data using fundamental principles of energy physiology: 2. Evaluating the results of published surveys. Eur J Clin Nutr 1991;45:583–99.[Medline]
Received for publication July 14, 2007. Accepted for publication November 9, 2007.





This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Klingberg, S.
Right arrow Articles by Winkvist, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Klingberg, S.
Right arrow Articles by Winkvist, A.
Agricola
Right arrow Articles by Klingberg, S.
Right arrow Articles by Winkvist, A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS