EAL

DLM: Stanols/Sterols (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

"To determine:

1. Dose-response curve for serum total and LDL cholesterol during different doses of plant stanols (0-3.2g) added to margarine

2. Effects of different doses of stanol ester on serum plant sterol concentrations to obtain information on absorption and bioavailability of plant sterols and stanols."

Inclusion Criteria:

Inclusion criteria: T chol 5.0-8.5 mmol/L TG < 3.5 mmol/L Age: 25-65 years Willingness to participate

Exclusion Criteria:

1. Abnormal liver, kidney or thyroid function 2. On lipid lowering meds 3. Unstable CHD 4. Alcohol abuse (>45 g ethanol/d) 5. Irregular eating habits

Description of Study Protocol:

26 subjects recruited from former studies carried out at the Department of Clinical Nutrition, U of Kuopio and from the local society of Finnish Heart Association Study Design: 1. 1 wk trial period, followed by assignment in random order to different levels of plant stanol ester in rapeseed oil-based margarine: 2.4, 3.2, 1.6, 0 (control) or 0.8 g/day each for a 4 wk period. 2. Subjects were instructed to follow a diet 34% fat, 12% saturated fat, 14% MUFA, 8% PUFA.; subjects kept food records (3 days during pretrial and 4 days during each 4 week period). 3. Fasting blood lipid samples, during the pretrial period and at the beginning, middle and end of each study period. Outcome measures: Serum lipids, serum stanols

Data Collection Summary:

Total, LDL, HDL, VLDL cholesterol; Triglycerides; Apolipoprotein A-1 and Apolipoprotein B : measured at baseline and the end of each of the 5 periods
4-day food record (including at least one weekend day) at the end of each dose period and a 3-day food record during the baseline pre-trial period

Description of Actual Data Sample:

22 subjects completed the study (8 men, 14 women)

Summary of Results:

Changes in serum lipids compared to controls on different doses of stanol: Stanol g/d 0.8 1.6 2.4 3.2 T chol (%change ):

Total cholesterol: 2.8 6.8 10.3 11.3 (P value) 0.38 <0.001) <0.001) < 0.001
LDL cholesterol 1.7 5.6 9.7 10.4 (P value) 0.89 < 0.05 <0.001 <0.001
Although the reduction were greater with 2.4 and 3.2 g/d doses of stanol, the differences were not significant (P<0.054 to 0.516)
Apolipoprotein B concentration decreased significantly at 0.8 g/d dose of stanol (P<0.001).
Apolipoprotein E Significant reduction of serum total and LDL cholesterol is reached with 1.6 g stanol/day

Author Conclusion:

"Significant reduction of serum total and LDL cholesterol concentrations is reached with the dose of 1.6 g stanol, and increasing the dose of stanol from 2.4g o 3.2 g does not provide clinically significant additional benefits."

Funding Source:

Industry:

Raisio Benecol Ltd. (Finland)

Food Company:

Reviewer Comments:

Though this study was highly controlled, the data do not entirely support the conclusions. No wash-out period was incorporated into the design, and periods were only 4 weeks in duration. Therefore, carry-over effects can not be ruled out. The order of the doses was the same for all participants, so order effects can not be tested. The order was 2.4,3.2, 16, 0(control), and 0.8g for all participants.

There is a consistent downward trend in Total and LDL cholesterol with each increasing dose. The authors report that since the difference isn't statistically significant between higher doses levels, "increasing the dose from 2.4 to 3.2g dose not provide clinically important additional effect". However, with 22 participants, a power calculation would be useful for determining whether there are sufficient data to support this conclusion.

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)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	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?	N/A
	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?	???
	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?	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?		No
	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?	No
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	???
	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?	No
	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?		No
	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?	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?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
10.	Is bias due to study's funding or sponsorship unlikely?		No
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	No