EAL

DLM: Plant Stanols and Sterols (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the effect of three stanol ester spreads with different fatty acid composition on serum lipids and endothelial function in mildly hypercholesterolemic individuals.

Inclusion Criteria:

Age 20 to 50 years
Healthy
Mild hypercholesterolemia (total cholesterol >5mmol/l and triglycerides <2.5mmol/l)
Non-smoker for at least five years
Not taking cholesterol-lowering medication
Not using plant stanol/sterol on a regular basis.

Exclusion Criteria:

Severe obesity (BMI >35kg/m²
Diabetes
Cardiovascular disease
Pregnant
Alcohol or drug abuse.

Description of Study Protocol:

Recruitment

Occupational health service clinic in Turku, Finland
Information also sent to several places of employment to distribute among employees
Newspaper advertisement in local paper.

Design

Randomized control trial

Blinding used

Individual reading ultrasound studies to evaluate carotid artery elasticity and brachial artery test was blinded to treatment group
Double blind per authors.

Intervention

Randomized to one of four treatment groups
- Group 1: Camelina oil spread with plant stanol esters (2 grams per day) transesterified with rapeseed oil fatty acids
- Group 2: Rapeseed oil spread with plant stanol esters (2 grams per day) transesterifed with rapeseed oil fatty acids
- Group 3: Sunflower oil spread with plant stanol esters (2 grams per day) transesterified with rapeseed oil fatty acids
- Group 4 (control): Sunflower oil spread without added plant stanol esters
Recommended dose of spread: 25 grams per day
Composition of stanol ester blend
- 50-51% absorbable fat
  - Saturated fat: 12-15 grams per 100-gram product
  - MUFA
    - Camelina oil: 18 grams per 100-gram product
    - Rapeseed oil: 27 grams per 100-gram product
    - Sunflower oil: 15 grams per 100-gram product
  - PUFA
    - Camelina oil: 19 grams per 100-gram product
    - Rapeseed oil: 12 grams per 100-gram product
    - Sunflower oil: 22-24 grams per 100-gram product
  - Trans-fatty acids: 0.1-0.3 grams per 100-gram product
- Phytosterols
  - Sitostanol: 88.1%
  - Campestanol: 8.6%
  - Sitosterol: 1.6%
  - Other sterols: 0.7%
Follow habitual diet except to reduce usual fat intake by approximately 23 grams
Duration of study was months.

Statistical Analysis

For comparisons between study groups: ANOVA with Bonferroni correction, two-sided T-test and paired T-test
Correlation coefficients were determined with Spearman rank correlations
Statistical significance: P<0.05
Stanol-treated groups were combined into a single group
- Treatment effect similar among the different spreads indicating cholesterol-lowering was similar despite varying fatty acid composition
Active treatment groups (groups one to three) were matched with controls for age, LDL-cholesterol level, carotid artery elasticity and flow mediated dilatation.

Data Collection Summary:

Timing of Measurements

Baseline and end of study (three months)
- Lipids
- Sterols
- Anthropometric measurements
  - Height
  - Weight
  - Waist circumference
- Blood pressure
- Ultrasound measurements
  - Carotid artery elasticity
  - Brachial artery test.

Dependent Variables

Serum lipids
- Total cholesterol
- HDL-cholesterol
- LDL-cholesterol
Sterols
- Serum cholesterol
- Squalene
- Markers of cholesterol synthesis
  - Cholestenol
  - Desmosterol
  - Lathosterol
- Markers of cholesterol absorption
  - Cholestanol
  - Campesterol
  - Sitosterol
  - Avenasterol
Carotid arterial compliance (CAC)
- Carotid artery elasticity is a marker for CAC (ability of the arteries to expand in response to pulse pressure caused by cardiac contraction/relaxation)
Endothelial function
- Flow mediated dilatation (FMD) of the brachial artery is a marker for endothelial function. Maximal percent increase in arterial diameter during hyperemia compared to rest.

Independent Variables

Stanol ester spread

Description of Actual Data Sample:

Initial N

N=200

Stanol ester group: N=150
Control group: N=50.

Attrition

Stanol ester group: N=143 (68 males/75 females) for 95% study completion
Control group: N=47 (32 males/15 females) for 94% study completion
Reasons for dropping out were unrelated to study.

Age (means±SE)

Stanol ester: 42.5±0.5 years
Control: 42.4±0.8 years.

Ethnicity

Not described

Anthropometrics (e.g., were groups same or different on important measures)

Both BMI and waist circumference were significantly different higher in the control as compared to the the stanol ester group(P<0.05)
BMI (means±SE)
- Stanol ester: 25.4±0.3
- Control: 27.0±0.3
Waist circumference (means±SE)
- Stanol ester: 88±1 cm
- Control: 92±1 cm.

Location

Norway

Summary of Results:

Lipids (means±SE)

Plant sterol ester consumption decreased LDL-cholesterol levels by 6% (P<0.001)
Treatment effect was similar among the three active treatment groups (P=0.14)
No significant changes were noted in HDL-cholesterol or triglyceride levels.

Variable	Control Group (baseline)	Percentage Change	Treatment Group (baseline)	Percentage Change	P-value (compared to baseline treatment group)	P-value (compared to control group)
LDL-cholesterol (mmol/l)	3.8±0.14	3.62±2.32	3.47±0.06	5.66±1.42	<0.05	<0.05
Cholestenol (102 mmol/mol cholesterol)	20.3±1.0	-0.5±3.7	19±0.06	18.8±2.1	<0.05	<0.05
Lathosterol (102 mmol/mol cholesterol)	136.6±7.0	2.7±3.4	131.7±4.2	21.3±2.5	<0.05	<0.05
Campesterol (102 mmol/mol cholesterol)	286.9±15.7	2.3±3.3	274.3±9.1	-26.3±1.3	<0.05	<0.05
Sitosterol (102 mmol/mol cholesterol)	137.5±6.8	5.4±2.7	129.2±4.9	-26.7±1.3	<0.05	<0.05

Arterial Elasticity and Endothelial Function

No significant changes were observed in carotid arterial compliance or brachial artery flow mediated endothelial dependent vasodilatation (FMD)
Post hoc hypothesis investigated whether participants with below median arterial elasticity or endothelial function values might respond differently to treatment compared to participants with above median values.

Subjects with low carotid artery compliance [(N=95), means±SE]

Variable	Control Group (N=26)	Percentage Change	Stanol Ester Group (N=69)	Percentage Change	P-values (compared with controls)
Cholestenol (10² mmol/mol cholesterol	21±1	-4±6	19±1	22±3	<0.05
Lathosterol (10² mmol/mol cholesterol)	136±8	-0.4±5	133±6	24±4	<0.05
Campesterol (10² mmol/mol cholesterol)	277±21	4±5	281±14	-28±2	<0.05
Sitosterol (10² mmol/mol cholesterol)	138±9	5±4	135±8	-28±2	<0.05
Avenasterol (10² mmol/mol cholesterol)	46±2	4±4	46±2	-18±2	<0.05

Subjects with high carotid arterial compliance [(N=95), Means±SE]

Variable	Control Group (N=21)	Percentage Change	Stanol Ester Group (N=74)	Percentage Change	P-value (compared to control group)
Cholesterol (mmol/l)	5.7±0.2	6.4±2.8	5.7±0.1	-3.9±1.3	<0.05
LDL-Cholesterol (mmol/l)	3.6±0.2	8.7±4.2	3.5±0.1	-6.9±1.8	<0.05
Squalene (10² mmol/mol cholesterol)	18±2	-3±7	16±1	19±6	<0.05
Cholestenol (10² mmol/mol cholesterol)	20±1	4±4	19±1	16±3	<0.05
Lathoosterol (10² mmol/mol cholesterol)	138±13	6±4	130±6	19±3	<0.05
Campesterol (10² mmol/mol cholesterol)	299±25	-02±3	268±12	-25±2	<0.05
Sitosterol (10² mmol/mol cholesterol)	137±11	6±3	124±6	-26±2	<0.05
Avenasterol (10² mmol/mol cholesterol)	47±3	5±4	44±1	-16±2	<0.05
Cholestanol (10² mmol/mol cholesterol)	150±6	-1±1	145±3	-6±1	<0.05

Other Findings

Compliance (means±SE)
- Stanol ester spread: 96±0.01%
- Control spread: 97±0.01%
Body weight: Unchanged for all groups.

Author Conclusion:

Endothelial function was not affected in individuals consuming stanol ester spreads for three months despite significantly lowered LDL-cholesterol levels
In a post hoc analysis, plant stanols may improve arterial elasticity and endothelial reactivity in individuals with sub-optimal vascular function.

Funding Source:

Industry:

Raisio Benecol Ltd, Finland

Food Company:

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?	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?	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?	No
	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?	???
	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)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	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?		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