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 effects of plant stanol esters emulsified into low-fat yoghurt (0.7% fat) on fasting concentrations of plasma lipids and lipid soluble antioxidants, which may also change by plant stanol consumption.

Inclusion Criteria:

Aged 18 – 65 years, mean fasting serum TC concentration < 6.5 mmol/L (251 mg/dL), mean fasting TG concentration < 3.0 mmol/L (266 mg/dL), BMI < 30, DBP < 95 mm Hg, SBP < 160 mm Hg

Exclusion Criteria:

No presence of glucosuria, use of medication or diet known to affect serum lipids, no drug or alcohol abuse, no known dairy allergy or indigestion, no signs of illness, no history of CHD. Not allowed to consume plant stanol esters-enriched margarines, donate blood, or participate in another study 1 month prior or during. No pregnant or lactating women.

Description of Study Protocol:

Start: fasting blood sample

3 week run-in period: 3 daily cups (150 ml) of placebo yoghurt and margarine with low erucic acid rapeseed oil to standardize fatty acid intake, FFQ, 2 fasting blood samples on weeks 2 and 3

Randomization to 2 groups: control group (n=30) continued to use placebo yoghurt, experimental group (n=30) received similar yoghurt with added plant stanol ester mixture, with targeted daily consumption of 3 g/day

Week 4: fasting blood sample

Week 5: fasting blood sample

Week 6: fasting blood sample

Week 7: fasting blood sample, FFQ

Data Collection Summary:

Serum lipids, lipoproteins, plant sterols and stanols, cholesterol precursors, liver and kidney function parameters, C-reactive protein concentrations, hematological analysis (WBC, lymphocytes, monocytes, granulocytes, RBC, HGB, HCT, MCV, MCH, platelets, MPV), antioxidants, VLDL, IDL, LDL, HDL₁ plus Lp [a], HDL₂, HDL₃and a bottom fraction, total cholesterol, HDL-C, TG concentrations. LDL-C calculated using Freidewald equation. Plasma concentrations of tocopherols (a-tocopherol, d-tocopherol, and ß+?-tocopherol), hydrocarbon carotenoids (a-carotene, ß-carotene, and lycopene), oxygenated carotenoids (lutein / zeaxanthin and ß-cryptoxanthin), phytofluene and retinol. Double blind.

Description of Actual Data Sample:

86 subjects screened, 72 met criteria. Study was only designed for 60 people. 16 men and 44 women selected at random, all completed study. No dropouts

Summary of Results:

Energy intake and proportions of energy from fat, fatty acids, carbohydrates and protein, as well as cholesterol and fiber intake were essentially similar in the 2 groups during both the run-in and experimental periods.

TC concentrations increased from 4.76 to 4.83 mmol/L in the control group, but decreased from 4.98 to 4.62 mmol/L in the experimental group. The difference in changes between the 2 groups of 0.43 mmol or 8.7% was highly significant (P < 0.001 for the difference in absolute changes, 95% CI –0.29 to -0.57 mmol/L). LDL-C (mean +/- SD) increased by 0.06 +/- 0.21 mmol/L in the placebo group, but decreased by –0.34 +/- 0.30 mmol/L in the experimental group. The difference in changes between the 2 groups of 0.40 mmol or 13.7% was highly significant (P < 0.001, 95% CI for the difference, -0.26 to –0.53 mmol/L). Effects were already maximal after 1 week. HDL-C and TG concentrations did not change. Plasma cholesterol-standardized sitostanol (P < 0.001) and campestanol (P = 0.035) concentrations increased. To compensate for the decrease in intestinal cholesterol absorption, endogenous cholesterol synthesis, as indicated by the increase in plasma cholesterol-standardized lathosterol concentrations, increased (P = 0.017). Total tocopherol levels increased by 1.43 µmol/mmol LDL-C (14.0%, P=0.015). ß-carotene levels, however, decreased by –0.02 µmol/mmol LDL-C (-14.4%, P = 0.038). Decreases in absolute ß-carotene concentrations were found in all apoB-containing lipoproteins. LDL-C standardized phytofluene levels decreased by 21.4 +/- 25.7% (P < 0.001), while other plasma carotenoid (lutein/zeaxanthin, ß-cryptoxanthin, lycopene and a-carotene) levels did not change significantly.

Author Conclusion:

This double-blind study in 60 healthy volunteers showed that a low-fat yoghurt enriched with plant stanol esters lowered serum cholesterol concentrations by nearly 14%. To summarize, our findings suggest that within 1 week a low-fat yoghurt enriched with plant stanol esters lowers LDL-C concentrations to the same extent as oil-based products. The reduction in absolute plasma tocopherol concentrations, as found in many other studies, was not observed in this study. In fact, our results suggested he LDL particle became enriched in tocopherols. The frequently reported decrease in carotenoids, and especially of the hydrocarbon carotenoids, has been confirmed in this study and appears not to be limited to the LDL fraction.

Funding Source:

University/Hospital:

Maastricht University (Netherlands), Wageningen University (Netherlands),

Reviewer Comments:

Well controlled study with high compliance confirmed by serum plant sterols and low dropout rate.

After 4 weeks of 3.0 g sterols:

TC Baseline: 4.98 +/- 0.81 mmol/L (192.73 +/- 31.35 mg/dL)

TC Ending: 4.62 +/- 0.78 mmol/L (178.79 +/- 30.19 mg/dL)

% Change: -8.7% (p < 0.001)

LDL-C Baseline: 2.92 +/- 0.87 mmol/L (113.00 +/- 33.67 mg/dL)

LDL-C Ending: 2.68 +/- 0.74 mmol/L (103.72 +/- 28.64 mg/dL)

% Change: 13.7% (p < 0.001)

Total:HDL-C Baseline: 3.67 +/- 1.12

Total:HDL-C Ending: 3.39 +/- 0.97

Change: -0.28 +/- 0.26 (p < 0.001)

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
	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
	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
	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
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	Yes
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	N/A
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	N/A
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	N/A
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	N/A
	1.3.	Were the target population and setting specified?	N/A
	1.3.	Were the target population and setting specified?	N/A
	2.	Was the selection of study subjects/patients free from bias?	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?	N/A
	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?	N/A
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	N/A
	2.4.	Were the subjects/patients a representative sample of the relevant population?	N/A
	2.4.	Were the subjects/patients a representative sample of the relevant population?	N/A
	3.	Were study groups comparable?	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)	N/A
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	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.)	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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
	3.4.	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
	3.5.	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
	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.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	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%.)	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	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
	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.	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?	N/A
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	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.)	N/A
	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.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	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
	5.4.	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
	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.	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?	N/A
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	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?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.6.	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
	6.7.	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?	N/A
	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.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	N/A
	7.1.	Were primary and secondary endpoints described and relevant to the question?	N/A
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	N/A
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	N/A
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	N/A
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	N/A
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	N/A
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	N/A
	7.5.	Was the measurement of effect at an appropriate level of precision?	N/A
	7.5.	Was the measurement of effect at an appropriate level of precision?	N/A
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	N/A
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	N/A
	7.7.	Were the measurements conducted consistently across groups?	N/A
	7.7.	Were the measurements conducted consistently across groups?	N/A
	8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?	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?	N/A
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	N/A
	8.2.	Were correct statistical tests used and assumptions of test not violated?	N/A
	8.2.	Were correct statistical tests used and assumptions of test not violated?	N/A
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	N/A
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	N/A
	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)?	N/A
	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)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	N/A
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
	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.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	N/A
	9.1.	Is there a discussion of findings?	N/A
	9.2.	Are biases and study limitations identified and discussed?	N/A
	9.2.	Are biases and study limitations identified and discussed?	N/A
	10.	Is bias due to study's funding or sponsorship unlikely?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	N/A
	10.1.	Were sources of funding and investigators' affiliations described?	N/A
	10.2.	Was the study free from apparent conflict of interest?	N/A
	10.2.	Was the study free from apparent conflict of interest?	N/A