EAL

DLM: Plant Stanols and Sterols (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose was to study the effects of long-term intake of plant sterols and plant sterol esters on mood and neurocognitive areas in subjects who were on statin medications.

Inclusion Criteria:

Subject with stable statin treatment
Age 18 to 70 years
Body mass index ≤32kg/m²
Diastolic blood pressure ≤95mm Hg
Systolic blood pressure ≤200mm Hg.

Exclusion Criteria:

Individuals with proteinuria, glucosuria, clinical manifestations of hepatic disorders, diabetes mellitus, or cardiovascular disease in the six-month period prior to the study.

Description of Study Protocol:

Recruitment

From a larger study that was assessing long-term effects of statin therapy combined with plant stanol/sterol foods

Design

Randomized, double-blind, placebo-controlled dietary intervention trial

Blinding used

Double-blind

Intervention

"Light" margarine with plant stanols and "light" margarine with plant sterols instead of usual margarine spread

Statistical Analysis

Normal probability-probability plots showed skewness of the depression sub-scale of the Symptom Checklist 90 scores, to be corrected by log-transformation
Levene's test for equality of error variances was used to determine homogeneity of variances
Chi-square tests were used to assess differences in the groups in terms of gender and educational level
One-way ANOVA checked for group differences related to age and serum concentrations of plant sterols/stanols at baseline and serum concentration of sitosterol at the end of the intervention
Post-hoc Dunnett's T-tests were used to compare the two intervention groups to the control group
The non-parametric Kruskal-Wallis test was performed to determine group differences in serum campesterol, sitostanol and campestanol at the end of the intervention
Mann-Whitney U-tests were used to compare the intervention and control groups
Non-parametric test were conducted to assess group differences in absolute changes in serum plant sterol concentration
Univariate ANCOVA were performed to determine effects of plant sterol/stanol intake on cognitive performance, subjective cognitive functioning and self-reported mood
The baseline test scores of dependent variables were included as covariates for each analysis
Between-subjects factor "group" was used to evaluate the overall intervention effect
Power calculation for ANCOVA on primary outcome measures with a medium effect size of 0.15 revealed a statistical power of 0.79
Results are presented as means ± SD
Differences were significant at P<0.05
SPSS was used to perform statistical analyses.

Data Collection Summary:

Timing of Measurements

Five-week run-in period in which subjects used a control margarine
85-week intervention period after the run-in period in which subjects were randomized into three groups (margarine with plant stanols, margarine with plant sterols and regular margarine)
At weeks five, 50 and 90, subjects returned the used tubs from the previous eight weeks. The returned tubs were weighed to assess margarine intake.
A food frequency questionnaire was used to assess nutrient intake during the previous four weeks.

Dependent Variables

The Stroop Color-Word Interference test was conducted to assess selective attention
Serum total cholesterol level
Changes in cognition (subjects completed a cognitive assessment and two self-reported questionnaires)
- Dementia, changes in mood and cognitive functioning were measured with the Mini-Mental State Examination. Scores of ≤24 were considered to be at risk for dementia and were excluded from statistical analysis.
- Cognitive function was also measured using the Letter-Digit Substitution test was performed to test the efficiency of operations in working memory
- Two other tests that were used for cognitive function were the Visual Verbal Word Learning Task to assess learning capacity and memory recall and retrieval, and a Concept Shifting test to measure behavioral planning.

Independent Variables

Margarine containing plant sterols or plant stanols

Control Variables

A control margarine product without plant stanols or plant sterols
Serum plant stanols and plant sterols were analyzed GC-MSand was the method used to measure serum values, which, in turn, measured compliance with eating the margarine
Serum plant sterol and stanol concentrations were measured to assess compliance, with venous blood draws done at weeks four, five, 49, 50, 89 and 90.
Mini-Mental State Examination. Scores of ≤24 were considered to be at risk for dementia and were excluded from statistical analysis
Absolute plant stanol and plant sterol serum levels were expressed as µmol/L and cholesterol-standardized serum concentrations as 102 x µmol/mmol cholesterol.

Description of Actual Data Sample:

Initial N

Control, 17
Plant sterol group, 19
Plant stanol group, 21.

Attrition (final N)

54 (22 females, 32 males)

Control, 17
Plant sterol, 18 (lost one)
Plant stanol, 19 (lost two).

Age

43 to 69 years

Control group mean age 60.4±7.4 years
Plant sterol group mean age 59.8±6.2 years
Plant stanol group mean age 59.0±7.1 years.

Ethnicity

Not described

Other relevant demographics

Low level of education

Control group n=5
Plant sterol group n=9
Plant stanol group n=7.

Location

The Netherlands

Summary of Results:

Key Findings

No differences were found between the control and plant sterol and plant stanol margarine groups for the key outcomes of:

Memory (P=0.25)
Subjective cognitive functioning (P=0.84)
Mood (P=0.53).

Changes in serum cholesterol as compared to the control group:

Plant sterol group reduced 5.1% (P=0.09)
Plant stanol group reduced 9.4% (P<0.05).

Changes in serum LDL-cholesterol as compared to the control group:

Plant sterol group reduced 8.7% (P=0.08)
Plant stanol group reduced 13.1% (P<0.05).

Author Conclusion:

Long-term consumption of plant stanol and plant sterol esters does not affect mood and cognitive function and performance. These plant compounds may not affect brain cholesterol levels.

Funding Source:

Government:

The Netherlands Organization for Health Research and Development (Program Nutrition: Health, Safety, and Sustainability

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)	No
	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)	Yes
	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?	N/A
	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)?	???
	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?		N/A
	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