EAL

DLM: Plant Stanols and Sterols (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To study the metabolic impact of plant sterol esters vs. plant stanol esters on healthy subjects and patients with familial hypercholesterolemia receiving statin therapy.

Inclusion Criteria:

Patients in West London center, United Kingdom
Willing to follow the dietary regimen for two months (with a one-month run-in and washout period.

Author' subject description: A total of 139 subjects completed the trial, slightly greater than 50% of whom were patients with familial hypercholesterolemia (FH), nearly all of them receiving statins. The remainder was unaffected subjects, mostly relatives, whose baseline values of total and LDL-cholesterol and triglyceride were slightly lower and HDL-cholesterol values slightly higher than those of the FH patients.

Exclusion Criteria:

The authors did not list specific criteria that would exclude subjects, but it can be assumed that patients would be excluded from participating in the study if they were unwilling or unable to follow the dietary protocol established by the research team.

Description of Study Protocol:

Recruitment

Two centers in West London, United Kingdom

Design

Parallel-group, randomized, double-blind study

Blinding used

Yes, double-blinding

Intervention

Consumption of 1.6 grams per day of plant sterol ester or 1.6 grams per day of plant stanol ester, or 2.6 grams per day of of plant stanol for two months

Statistical Analysis

Mean percent changes ± SEM were reported
Ranges were reported
Percent changes were reported with 95% CI and the corresponding P-value.

Data Collection Summary:

Timing of Measurements

The dietary regimens lasted two months and it was preceded and succeeded by one-month run-in and washout periods using a placebo spread.

Dependent Variables

Blood cholesterol
Plasma plant sterols
Bile acid synthesis
Lipid-soluble antioxidants.

Independent Variables

Plant sterol ester vs. plant stanol ester

Control Variables

Description of Actual Data Sample:

Initial N: Information not provided
Attrition (final N): 139 subjects. The authors did state that the randomization procedure resulted in three well-matched treatment groups regarding numbers, age, ratio of FH to unaffected subjects, baseline serum lipids and distribution of apolipoprotein E phenotypes.
Age: Information not provided
Ethnicity: Residents of United Kingdom
Other relevant demographics: Not provided
Anthropometrics (e.g., were groups same or different on important measures) not provided. The authors did state that body weights remained constant throughout the trial.
Location: The study was conducted at two centers in West London, United Kingdom.

Summary of Results:

Key Findings

Effects on serum cholesterol
- There was no statistical difference in the response to plant sterols or stanols between FH patients taking statins and unaffected subjects. Changes in total cholesterol ranged from 3 to 7.5% and were more marked in the plant sterol group at one month and in the plant stanol groups at two months; no significant difference observed among the three groups.
- Decreases in LDL-cholesterol ranged from 4.8 to 6.6%. The decreases in LDL-cholesterol seemed to be more marked at two months in the plant stanol groups, whereas in the plant sterol group, the decrease at two months was only half as great as at the one-month and was no longer significantly different from baseline.
- Changes in HDL-cholesterol were slight, but there was a tendency for values to decrease by about 3% in each of the groups, returning to baseline values after the washout period.
Effects on plasma plant sterols
- Basal ratios of sitosterol and campesterol were about twice as high in FH patients as in unaffected subjects. Despite these discrepancies, percent changes in serum plant sterol levels during the active phase of the study were similar. Increases in campesterol and sitosterol ratios averaged about 40% and 20%, respectively, on plant sterol, which contrasted with decreases of 25-35% in both ratios on plant stanols.
Effects on bile acid synthesis
- The authors stated that their most important finding was a differential effect on plant sterols vs. plant stanol esters on serum 7α-OHC, a well-validated marker of bile acid synthesis. There was a 27% decrease (P=0.01) in 7α-OHC levels in the subjects fed plant sterols after two months intake, without any changes in either of the plant stanol groups.
Effects on lipid-soluble antioxidants
- Overall, there were no differences between plant sterol and stanol esters. Small, but significant decreases from baseline relative to cholesterol in α-tocopherol, γ-tocopherol, ß-cryptoxanthin, lycopene, α-carotene, β-carotne and alpha and beta-carotene in the three treatment groups.

Other Findings regarding adverse effects

The authors did not report any adverse effects from the sterols or stanol spreads. Analysis of food diaries showed that compliance with ingestion of spreads and cereal bars was equally good within each treatment group.

Author Conclusion:

These findings suggest that absorption of dietary plant sterols down regulates bile acid synthesis, which attenuates their cholesterol-lowering efficacy. They concluded that plant stanol esters are preferable for the long-term management of hypercholesterolemia.

Funding Source:

Industry:

Flora-Pro-Active, Unilever Bestfoods UK Limited

Food Company:

University/Hospital:

Dept. of Metabolic Medicine, Division of Invest. Science, London, UK

Other:

In-Kind support reported by Industry:

Yes

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?	???
	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?	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?	???
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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?	Yes
	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?		No
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	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%.)	???
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	4.4.	Were reasons for withdrawals similar across groups?	???
	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?	Yes
	6.6.	Were extra or unplanned treatments described?	No
	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?	???
	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?	No
	8.2.	Were correct statistical tests used and assumptions of test not violated?	???
	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)?	???
	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