EAL

DLM: Plant Stanols and Sterols (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to investigate the effect of plant sterols mixed with low-fat dairy products (yogurt, hard cheese and fresh cheese) on safety parameters such as serum levels of various plant sterols and fat-soluble vitamins as well as their cholesterol-lowering efficacy in hypercholesterolemic subjects.

Inclusion Criteria:

Adult volunteers
Serum cholesterol between 5.0 and 8.5mmol/l and serum triglycerides of less than 4.0mmol/l during the baseline period.

Exclusion Criteria:

Diabetes mellitus
History of myocardial infarction (within the previous three months)
History of malignancy
Psychosis
Malabsorption
Chronic liver disease or homozygous familiar hypercholesterolemia
Use of hypoglycemic agents
Use of corticosteroids
Oral anti-coagulants
Use of hormone or immunosuppressant treatment.

Description of Study Protocol:

Recruitment

Three different locations in Helsinki, Finland, Tampere-Ilmomantsi and Oulu).

Design

Parallel-group, double-blind design

Blinding used

Yes, double blinded

Intervention

The targeted plant sterol intake was 2 grams per day (added to three dairy products) for six weeks with a three-week run-in period.

Statistical Analysis

Differences in changes in serum lipids before and after the trial period were tested between the experimental and control group using the Student's T-test or with the Wilcoxon test for non-normal variables
The chi-square test was used to test differences between the randomization groups for category variables.

Data Collection Summary:

Timing of Measurements

Serum lipid levels were determined at each study visit:
- Weekly during the three-week run-in phase, and serum lipids were sampled again during week three and six during the experimental phase.

Dependent Variables

Serum cholesterol levels
Fat-soluble vitamin levels
Serum plant sterol values.

Independent Variables

The dietary cheeses (low-fat hard cheese or low-fat fresh cheese) were enriched with about 2 grams of plant sterols and stanols. The yogurt product contained somewhat smaller amounts (1.65 grams) of the plant sterols and stanols.

Control Variables

The energy content, the macronutrient content, and the cholesterol content of the two diets were the same.

Description of Actual Data Sample:

Initial N: 164 (35 males, 129 females)
Attrition: None
Age: 57 years ±9 years
Ethnicity: Northern Europeans (all the sites were in Finland)
Anthropometrics: There were no significant differences in the average BMI, waist-hip ratio, or average weight between the sterol group and the control group
Location: Helsinki, Tampere-Ilomantsi, Oulu.

Summary of Results:

Key Findings

Serum lipids: Serum total cholesterol decreased in the sterol group by 4% among the subjects consuming the yogurt products, 8% among the subjects consuming the hard cheese and by 7% in the fresh cheese group, and by 7% in all the groups combined. LDL-cholesterol decreased by 9% in the yogurt group and by 11% in the hard cheese and fresh cheese groups and by 10% in all the groups combined. There were no significant differences in total cholesterol or LDL-cholesterol responses among the three randomized treatment groups.
- HDL-cholesterol and triglyceride values did not change significantly between the sterol and control groups.
Serum plant sterols: The total concentration of serum plant sterols increased in the sterol group (P=0.0001), but not in the control group. Sitosterol concentration increased significantly in the sterol group, but not in the control group (P=0.0001). Avenasterol concentration decreased in the sterol group and campesterol also showed a decreasing trend. The changes in serum lathosterol did not differ significantly in either group.

Other Findings

Plasma fat-soluble vitamins
- No significant effects on serum concentrations of 25(OH) vitamin D and retinol were observed. Plasma alpha-tocopherol and beta-carotene concentrations decreased significantly in the sterol diet group compared to the control group, but the changes were no longer significant when the alpha-tocopherol and beta-carotene values were adjusted for the reduced serum total concentrations.
Blood pressure
- There was a significant difference between the groups in the change in systolic blood pressure (-4±5 and 0±10mm Hg) in the sterol and control groups, respectively.
LDL oxidation
- No statistical difference was observed between the sterol and the control groups concerning the rate of LDL oxidation, maximal oxidation, lag phase or diene formation.
Adverse effects
- There were no differences in adverse effects between the groups during the study. The subjects did not report any adverse effects.

Author Conclusion:

Yogurt, hard cheese and fresh cheese enriched with plant sterols resulted in total and LDL-cholesterol lowering effects in hypercholesterolemic subjects. The subjects did not report any adverse effects. The results indicated that a daily intake of 2 grams of plant sterol mixture did not influence cholesterol-adjusted vitamin levels and only increased the total plasma sterol level by 7%.

Funding Source:

Industry:

Valio Ltd.

Food Company:

Other:

TEKES, Lalio Ltd and Foundation for Nutrition Research for the study products and for financial support

Reviewer Comments:

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	???
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes