EAL

DLM: Plant Stanols and Sterols (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to determine if a low-fat plant sterol ester (PSE)-enriched spread consumed in conjunction with a National Cholesterol Education Program (NCEP) Step 1 diet to increase fruit and vegetable intake could improve plasma lipoprotein concentrations without adverse effects on carotenoid concentrations.

Inclusion Criteria:

Males and females from the general population
With moderately raised plasma cholesterol levels (more than 5.2mmol per L) and without other biochemical abnormalities
Without previous serious illnesses
Body mass index (BMI) no more than 30kg/m²
Not taking lipid-lowering medications
Not taking vitamin supplements.

Exclusion Criteria:

Previous critical medical history (serious illness)
BMI higher than 30kg/m²
Taking lipid-lowering medication
Taking vitamin supplements
Biochemical abnormalities other than moderately raised plasma cholesterol levels.

Description of Study Protocol:

Recruitment

Recruited from seven different large Irish companies, using posters in the workplace, work e-mail, and so on.

Design

Placebo-controlled crossover trial
Individuals randomly assigned to consume placebo spread or test spread for three weeks followed by three-week washout crossover period.

Blinding Used

Double-blind.

Intervention

Each group was given 21g portions of low-fat spread (test spread or placebo spread) for daily consumption for three weeks (in crossover design with a three-week washout period)
Both spreads were 35% fat with similar fatty acid profiles
The test spread contained 8.3% plant sterols
The placebo spread contained 0.1% plant sterols
All participants completed an initial dietary assessment, at which time they received individualized dietary advice to adhere to a low-fat (10% energy from fat) NCEP Step 1 diet and increased fruit and vegetable intake to five portions per day.

Statistical Analysis

Two-way ANOVA was used to compare significant difference in plasma lipids and carotenoids according to spread taken and time of consumption
Paired T-tests to determine differences in dietary intake pre- and post-intervention.

Data Collection Summary:

Timing of Measurements

Three-day food diaries completed at baseline and during the last week of each dietary intervention period
Fasting blood samples drawn at weeks zero, three, six and nine for plasma lipoprotein and carotenoid analyses.

Dependent Variables

Dietary intake of the following nutrients measured by entering data from three-day food diaries into a computerized dietary analysis program:
- Energy
- Carbohydrate
- Protein
- Total fat
- Percent of energy from fat
- Saturated fatty acids
- Monounsaturated fatty acids
- Polyunsaturated fatty acids
- Alcohol
- Cholesterol
- Vitamin C
- Folate

Daily intake of β-carotene was assessed using a validated food frequency questionnaire specifically designed for measuring dietary carotenoid intake.

Plasma lipids and carotenoids were measured according to accepted standards:
- Total cholesterol
- Triacylglycerol (TAG)
- Glucose
- Apolipoprotein B
- Apolipoprotein A
- Low-density lipoprotein (LDL) cholesterol
- High-density lipoprotein (HDL) cholesterol
- Retinol
- β-Carotene
- α-Carotene
- γ-Tocopherol
- α-Tocopherol
- Lutein
- Zeaxanthin
- β-Crypyoxanthin
- Lycopene

Independent Variables

Type of spread (plant sterol or placebo).

Description of Actual Data Sample:

Initial N: 51 total (males and females)
Attrition (final N): 48 (27 males; 21 females)
Age: Males, 44.1±7.6 years; females, 48.5±9.8 years.

Anthropometrics

Weight (average):
- Males: 90.22±8.65kg
- Females: 65.49±7.9kg
BMI (average):
- Males: 27.3±2.7kg/m²
- Females: 4.6±3.1kg/m²

Location

Ireland.

Summary of Results:

Key Findings

Variables	Placebo Spread		Plant Sterol Spread
	Pre-trial (Mean ± Standard Deviation)	Post-trial (Mean ± Standard Deviation)	Pre-trial (Mean ± Standard Deviation)	Post-trial (Mean ± Standard Deviation)
Total cholesterol (mmol per L)	6.19±0.63	6.08±0.61	6.18±0.69	5.90±0.78*
Apolipoprotein B (mmol per L)	1.26±0.19	1.23±0.17*	1.25±0.20	1.18±0.22**
LDL cholesterol (mmol per L)	3.91±0.70	3.77±0.65	3.94±0.83	3.66±1.01*
β-Carotene (nmol per L)	690.8±459.1	726.4±437.0	671.4±418.6	584.8±356.7*

Significant difference between treatments compared with pre-trial values are *P<0.05; **P≤0.0005.

Plasma total cholesterol, LDL-cholesterol, and apolipoprotein B concentrations were significantly lower following consumption of the plantsterol spread. A significant increase was observed in the HDL:LDL cholesterol ratio following the plant sterol intervention (P<0.05). Other plasma lipoprotein concentrations did not differ significantly following treatment. Plasma β-carotene concentration was significantly reduced following consumption of the plant sterol spread.
When plasma β-carotene concentrations were standardized according to LDL cholesterol concentrations, there was no significant effect of plant sterol-enriched spread consumption on lipid standardized β-carotene levels. Other plasma carotenoid concentrations did not differ significantly following treatment.

	Pre-trial (Mean ± Standard Deviation)	Plant Sterol Spread (Mean ± Standard Deviation)	Placebo Spread (Mean ± Standard Deviation)
Total fat (g per day)	88.9±26.9	78.5±23.9*	75.50±22.6*
Fat intake (% energy)	37.3±7.6	34.1±5.8*	32.4±6.1**
Saturated fatty acid (g per day)	1.26±0.19	1.23±0.17*	1.25±0.20
Monounsaturated fatty acid (g per day)	26.2±8.9	22.8±7.8*	22.6±8.4*
Cholesterol (mg per day)	281.1±124.0	252.0±108.7	232.4±94.3*
Vitamin C (mg per day)	91.1±66.4	128.1±106.7*	128.4±89.8*

Significant difference compared with week zero. *P<0.05; **P<0.005.

Participants consumed statistically significantly (P<0.02) more placebo spread than PSE-enriched spread. Actual plant sterol ester intake was 1.3g per day. Consistent with following the NCEP Step 1 diet, participants showed significant reduction in daily fat intake, percent of fat from energy, saturated fatty acids and monounsaturated fatty acids when consuming the placebo or PSE-enriched spreads. Consistent with increasing fruit and vegetable intake, statistically significantly more vitamin C was consumed, and non-statistically significantly more folate and β-carotene were consumed when consuming the placebo or PSE-enriched spreads.

Author Conclusion:

Incorporation of PSE-enriched reduced-fat spreads into a reduced fat diet, whereas encouraging a specific increase in fruit and vegetables, was successful in lowering both plasma total and LDL cholesterol concentrations. This was associated with a small reduction in total plasma β-carotene concentrations but no effect on lipid standardized β-carotene levels. In moderately hypercholesterolemic subjects, the combination of cholesterol-lowering dietary therapy plus PSE-enriched foods may reduce the need for cholesterol-lowering drug therapy.

Funding Source:

University/Hospital:

Unit of Nutrition, Dept of Clinical Medicine, Trinity Health Sciences Centre, St. James's Hosp.

Reviewer Comments:

Appears to be a well-designed study, although the authors suggest that a more robust study design would have determined the individual and combined effects of the NCEP Step 1 diet, increased fruit and vegetable intake and increased PSE consumption.

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?	No
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%.)	No
	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?	???
	6.6.	Were extra or unplanned treatments described?	???
	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?	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?		???
	10.1.	Were sources of funding and investigators' affiliations described?	???
	10.2.	Was the study free from apparent conflict of interest?	Yes