EAL

DLM: Plant Stanols and Sterols (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the cholesterol-lowering effect and possible side effects of vegetable oil-based spreads fortified with two different doses of microcrystalline plant sterols in hypercholesterolemic Finnish subjects.

Inclusion Criteria:

Serum TC greater than 5.8mmol per L
Serum TG less than 3mmol per L
Aged 25 to 64 years
Willingness to participate
No alcohol abuse
Subjects on stable medication for hypothreosis
Type II DM
HTN
CVD.

Exclusion Criteria:

Diagnosis of Type I DM
MI within past three months
Malignancy
Psychosis
Malabsorption
Chronic liver or renal disease
Homozygous familiar hypercholesterolemia
Receiving lipid-lowering drugs or dietary regimen
Using corticosteroids, oral anticoagulants or immunosuppressants
Pregnant or lactating women
Women not using contraception.

Description of Study Protocol:

Screening

Medical history
Alcohol consumption
Use of drugs
Weight, height recorded
Blood samples for TC and TG concentration
Routine physical exam
Half of subjects kept seven-day food diary.

Six Week Run-in Period

All subjects received rapeseed oil-based control spread, fasting blood samples
Half of subjects kept seven-day food diary.

Randomization into Three Groups

Control group continued to use control spread (N=46)
Two test groups using spreads with either 1.5g per day (N=46) or 3.0g per day (N=43) of added plant sterols, consumed as part of normal diet, eaten twice a day.

Three Months

Fasting blood samples.

Six Months

Fasting blood samples
Half of subjects kept seven-day food diary.

Six Weeks Post-study

Fasting blood samples.

Data Collection Summary:

Serum TC, LDL-C, HDL-C and TG concentrations
Routine blood chemistry (Hgb, WBC, RBC, HCT, platelet count)
TSH
Enzymes
Glucose
Creatinine
Serum concentrations of lipid soluble vitamins (retinol and a-tocopherol) and carotenoids (a- and ß-carotene)
Serum plant sterol and ubiquinol-10 concentrations
Baseline diene conjugation in circulating LDL, antioxidant potential of LDL, serum campesterol and ß-sitosterol concentrations
Body weight, height, blood pressure and resting pulse, compliance and health status, medication and deviations from normal lifestyle, side effects asked through questionnaire.
Double blind study.

Description of Actual Data Sample:

270 volunteers screened; 155 hypercholesterolemic subjects (55 males, 100 females)
21 voluntarily withdrew (seven from control, five from 1.5g per day group and nine from 3g per day group)
There were no statistically significant differences between control and test groups.

Summary of Results:

Estimated daily plant sterol intakes in the two test groups were 1.5±0.2g and 3.0±0.4g
After three months of consuming the test spreads, the serum TC levels were 0.58mmol per L (8.6%) and 0.51mmol per L (7.5%) lower with 1.5 and 3.0g of plant sterols as compared with control group (P=0.003), respectively
After six months of consumption corresponding TC levels were 0.62mmol per L (8.9%) and 0.58mmol per L (8.3%) lower than those of control group (P=0.001), respectively
LDL-C serum levels were 0.46mmol per L (10.5%) and 0.50mmol per L (11.5%) lower than those of control group after three months of consumption (P=0.004) and 0.49mmol per L (11.3%) and 0.46mmol per L (10.6%) lower after six months of consumption (P=0.002), respectively.
Statistically, the TC and LDL-C levels of the two test groups consuming plant sterol-enrichment did not differ significantly. No effect on HDL-C or TG concentrations occurred. The test spreads did not induce any adverse effects in blood clinical chemistry, hematology or decreases in serum concentrations of lipid soluble vitamins.

Author Conclusion:

In conclusion, plant sterols in a microcrystalline form reduced serum cholesterol concentrations significantly when used as part of a normal diet
The daily dose of 1.5g per day was enough to reach the maximum effect
In the test groups consuming plant sterol enrichments either 1.5g or 3.0g per day, the serum ß-sitosterol concentration increased almost twofold during the study
The sterol enrichments did not affect the serum concentrations of lipid soluble vitamins or carotenoids or have any other obvious adverse effects.

Funding Source:

Government:

TEKES

Industry:

Teriaka Ltd (Finland)

Food Company:

Reviewer Comments:

Large, well-controlled study with high compliance over six month study period, but did have 13.5% dropout rate
After six months of 1.5g sterols:
- TC Baseline: 6.66±0.82mmol per L (257.74±31.73mg per dL)
- TC Ending: 0.62mmol per L lower (23.99mg per dL)
- % Change: 8.9% (P=0.001)
- LDL-C Baseline: 4.29±0.75 mmol per L (166.02±29.03mg per dL)
- LDL-C Ending: 0.49mmol per L lower (18.96mg per dL)
- % Change: 11.3% (P=0.002)
- HDL-C: No statistically significant change, data not reported
- TG: No statistically significant change, data not reported

After six months of 3.0g sterols:
- TC Baseline: 6.66±0.82mmol per L (257.74±31.73mg per dL)
- TC Ending: 0.58mmol per L lower (22.45mg per dL)
- % Change: 8.3% (P=0.001)
- LDL-C Baseline: 4.29±0.75mmol per L (166.02±29.03mg per dL)
- LDL-C Ending: 0.46mmol per L lower (17.8mg per dL)
- % Change: 10.6% (P=0.002)
- HDL-C: No statistically significant change, data not reported
- TG: No statistically significant change, data not reported.

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)	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")?	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?	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?	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?	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?	N/A
	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?	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)?	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?	Yes
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