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 investigate the effects of plant stanol ester-containing spread on plasma levels of lipids, apoproteins, remnant-like particle (RLP-C), cholesteryl ester transfer protein (CETP) and oxidized LDL (Ox-LDL) in Japanese subjects, whose traditional diet is low in fat and cholesterol.

Inclusion Criteria:

Healthy men and healthy non-pregnant women
Age 20 years and older
Plasma total cholesterol levels 5.4 to 7.2mmol per L
Plasma triglyceride levels less than 3.9mmol per L.

Exclusion Criteria:

Women were not pregnant, nor expected to become pregnant during study
Plasma total cholesterol levels had to be between 5.4 and 7.2mmol per L and TG levels had to be below 3.9mmol per L.

Description of Study Protocol:

Baseline Measurements

Fasting plasma lipid levels
Apoproteins
TG-rich lipoproteins
CETP mass and Ox-LDL
a-tocopherol
Two-day diet analysis
Routine labs.

Randomization

Placebo spread (N=35)
Two grams per day plant stanol (3.4g stanol ester, N=34) or 3g per day plant stanol (5.1g stanol ester, N=36).

Timing of Measurements

Week two: Fasting plasma lipid levels
Week four and final week:
- Fasting plasma lipid levels
- Apoproteins
- TG-rich lipoproteins
- CETP mass and Ox-LDL
- a-tocopherol
- Two-day diet analysis
- Routine labs
Week eight: Fasting plasma lipid levels.

Data Collection Summary:

Independent Variables

Fasting blood sampling: TC, TG, HDL-C, LDL-C, apoproteins, cholesterol of remnant-like particle (RLP-C), CETP, Ox-LDL, a-tocopherol
Computerized dietary analysis completed by questionnaire and RD interview
Plasma levels of sitostanol, campestanol, sitosterol, campesterol, retinol and ß-carotene measured in one of three subjects with highest and lowest TC levels
Routine labs included urinalysis, CBC, serum levels of enzymes, total protein, albumin, uric acid, urea N, creatinine, glucose, electrolytes.

Dependent Variables

Placebo group (N=35): One serving of placebo spread contained 8g of low-fat spread
Plant stanols, 2g-PS group (N=34): Consumed one serving of plant stanol ester spread (containing 1g of plant stanols) at breakfast and dinner
Plant stanols, 3g-PS group (N=36): Consumed one serving of plant stanol ester spread (containing 1g of plant stanols) at breakfast, lunch and dinner.

Blinding was used for randomization and measurements until completion.

Description of Actual Data Sample:

Initial N: 105
Final N: 101; Four subjects did not complete the study due to consuming less than 80% of spread or did not come for scheduled blood sampling or was diagnosed with hypothyroidism
Characteristics of participants: No differences in age, sex, body mass index (BMI), blood pressure, plasma lipids, smoking, alcohol status or dietary composition among groups.

Summary of Results:

Plasma levels of TC, LDL-C, apoB, apoE, CETP mass and Ox-LDL were reduced significantly by 6.5% (P=0.0022), 9.6% (P=0.0049), 8.3% (P<0.0001), 4.5% (P=0.0270), 6.1% (P=0.0468) and 20% (P<0.0001), respectively, in the 2g per day plant stanol group.
Plasma levels of TC, LDL-C, apoB, CETP mass and Ox-LDL were reduced significantly by 5.5% (P=0.0068), 7.3% (P=0.0139), 5.6% (P=0.0032), 3.3% (P=0.131) and 19% (P<0.0001), respectively, in the 3g per day plant stanol group.
Plasma levels of plant stanols, plant sterols, retinol, ß-carotene and a-tocopherol did not change in any group, but levels of campestanol increased and a-tocopherol decreased slightly in the sitostanol groups.

Author Conclusion:

Plasma levels of TC and LDL-C were significantly reduced by 6% and 10%, respectively based on ingestion of a plant stanol ester-containing spread
The smaller reduction than in comparable Western studies and the lack of dose-dependency in this study might be due to the different basal diets
Authors concluded that plant stanol ester-containing spread is safe and effective in reducing LDL-C, apoB, CETP and Ox-LDL levels and that 2g per day of plant stanols is sufficient for Japanese people.

Funding Source:

University/Hospital:

Tokai University School of Medicine (Japan), Graduate school of Kyushu University, Keio University School of Medicine, Niiza Shiki Central General Hospital, Prefectural University of Kumamoto (all Japan)

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Large, well-controlled study.

After four weeks of 2.0g sterols:

TC Baseline: 6.08±0.41mmol per L (235.30±15.87mg per dL)
TC Ending: 0.39±0.35mmol per L lower (15.09±13.55mg per dL)
% Change: 6.3±5.5% (P=0.0022)
LDL-C Baseline: 3.96±0.49mmol per L (153.25±18.96mg per dL)
LDL-C Ending: 0.38±0.28mmol per L lower (14.71±10.84mg per dL)
% Change: 9.6±6.9% (P=0.0049)
HDL-C and TG: No statistically significant changes.

After four weeks of 3.0g sterols:

TC Baseline: 6.00±0.41mmol/L (232.20±15.87mg per dL)
TC Ending: 0.34±0.46mmol/L lower (13.16±17.80mg per dL)
% Change: 5.5±7.6% (P=0.0068)
LDL-C Baseline: 3.96±0.44mmol per L (153.25±17.03mg per dL)
LDL-C Ending: 0.30±0.40mmol per L lower (11.61±15.48mg per dL)
% Change: 7.3±9.9% (P=0.0139)
HDL-C and TG: No statistically significant changes.

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