DLM: Plant Stanols and Sterols (2010)
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.
- 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.
Individuals with proteinuria, glucosuria, clinical manifestations of hepatic disorders, diabetes mellitus, or cardiovascular disease in the six-month period prior to the study.
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.
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.
Initial N
57
- 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
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).
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.
Government: | The Netherlands Organization for Health Research and Development (Program Nutrition: Health, Safety, and Sustainability |
Quality Criteria Checklist: Primary Research
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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 | |