EAL

DLM: Plant Stanols and Sterols (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Analysis of the serum plant sterol, fat-soluble vitamin and sex hormone concentrations in blood samples in order to evaluate whether enrichment of foods with plant sterols is associated with:

Enhanced intestinal absorption of these substances
Reduced intestinal absorption of fat soluble substances, such as vitamins, occurs
Alterations in sex hormone balance.

Inclusion Criteria:

Mild to moderate hypercholesterolemia (6-8mmol/liter)

Exclusion Criteria:

"Severe diseases". This criteria was not described in any detail
Taking drugs with serum lipid-modifying effects.

Description of Study Protocol:

Recruitment

78 subjects with mild to moderate hypercholesterolemia

Design

Randomized; randomization scheme not described

Blinding used

Double-blind

Intervention

A four week run-in/stabilization period was followed by randomization into sterol or control group for the 15-week study period
Sterol group food items were enriched with mineral nutrients as well as with three levels of sterols (1.25 grams during first five weeks, 2.5 grams during second five-week study period and 5.0 grams per day provided during the third five-week study period
Sterol powder was used to enrich bread, yogurt with jam and meat products: 79% sitosterol, 11% sitostanol, 7.5% campesterol and small amounts of campestanol, cycloartenol and D-7-avenasterol
The control group received corresponding non-enriched food items
Three-day food diaries were completed, using a validated portion size picture book, five times during the study period: Baseline, placebo run-in and three times during the dietary treatment period
Laboratory analysis four times during the study period: Serum or plasma samples for plant sterol, (subset of 12 and eight subjects in the sterol and placebo groups, respectively) fat-soluble vitamins and sex hormones.

Statistical Analysis

Intention to treat analysis
Non-parametric Wilcoxon rank-sum test used for variables not normally distributed
P<0.05.

Data Collection Summary:

Timing of Measurements

Plant Sterols: Baseline, five weeks, 10 weeks, 15 weeks
Sex-hormones and vitamins: Baseline, 15 weeks.

Dependent Variables

Serum levels of:
- Plant sterols: Capmesterol, sitosterol, stigmasterol, D5-avenasterol
- Hormones: Testosterone, estradial, sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone, prolactin
- Vitamins: Plasma retinol, alpha-tocopherol, beta-carotene.

Independent Variables

Sterol content of diet (1.25, 2.5 or 5.0 grams per day of plant sterols during the first, second and third five-week periods) or to placebo group receiving similar food items without plant sterols.

Description of Actual Data Sample:

Initial N

78 (52 women, 19 men)

Attrition

73; 36 in sterol diet group, 37 in the control group

Age

27 to 74 years old

Ethnicity

Not described

Anthropometrics

BMI and total cholesterol were similar between groups (data not shown)

Location

Helsinki, Finland

Summary of Results:

Key Findings

Change in Serum Values
Variables	Baseline Measures and confidence intervals	Week 15 Measures and confidence intervals	Statistical Significance of Group Difference Change from baseline to 15 weeks
Sitosterol in treatment group n=12	2.84±0.93	5.35±1.12
Sitosterol in placebo group n=8	5.35±1.12	3.04±2.01	P=0.0042 treatment vs. placebo*

	Sterol Group at 15 weeks n=36	Control Group at 15 weeks n=35	Statistical Significance of Group Difference
Alpha-tocopherol	-3.64±4.36	0.30±3.77	P=0.0002**

*Total plant sterols did not differ between treatment groups after 15 weeks

**After adjusting for the change in LDL-cholesterol (carrier) this difference is no longer significant (P=0.79)

Other Findings

Intake of plant sterols was less than expected: 0.91, 1.86, and 4.17 grams per day during the three five-week intervals. These values are in comparison to the planned 1.25, 2.5 and 5.0 grams per day.

There was no significant difference in serum sex hormones between the treatment group in either gender. Differences in progesterone between pre- and post-menopausal women were attributed to cyclic variation of progesterone levels.

Author Conclusion:

A 15-week consumption of natural non-esterified plant sterol-enriched food items did not result in adverse effects of clinical importance. Serum alpha-tocopherol levels were somewhat reduced in the sterol group and corresponded to the fall in their carrier protein LDL.

Funding Source:

Government:

TEKES, Finland

Reviewer Comments:

It is unclear why only sub-samples of intervention and control groups were assayed for the serum plant concentration assay. The authors identified that the sub-sample was randomly chosen but did not state how or why this approach was taken in the study. Placebo n=8; Plant sterols group n=12. The sample sizes for the serum vitamin assay were adequate (placebo n=35 and Sterols n=36).

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?		No
	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?	No
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	???
	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")?	Yes
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?	No
	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?	N/A
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
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?		???
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	No