EAL

DLM: Plant Stanols and Sterols (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate both efficacy and safety in humans of long-term consumption of spreads containing plant sterol esters.

Inclusion Criteria:

Healthy men and women volunteers.

Exclusion Criteria:

TC higher than 8.0mM, using medicine, history of medical or surgical events (chronic GI problems, HTN or CVD), unexplained weight loss or gain of more than 7kg in past two years, dieting, pregnant, lactating, or planning pregnancy, physical activity exceeding 10 hours per week, not using spreads, drinking more than 21 (women) or 28 (men) alcoholic beverages per week.

Description of Study Protocol:

Screening: Health questionnaire, physical exam, fasting venous blood analysis, urinalysis
Randomization: To daily consumption of 20g spread containing 1.6g plant sterols as fatty acid esters or a control spread, using serum cholesterol concentration, gender and age. Instructed to consume spreads according to normal habits.
13 weeks: FFQ, fasting venous blood analysis, urinalysis
26 weeks: Subjects instructed to consume 10g spread at breakfast, 10g at lunch or dinner, FFQ, fasting venous blood analysis, urinalysis
39 weeks: Consumption moment of spreads evaluated, FFQ, fasting venous blood analysis, urinalysis
One year: Consumption moment of spreads evaluated, FFQ, fasting venous blood analysis, urinalysis.

Data Collection Summary:

Fasting venous blood analysis: TC, HDL-C, LDL-C, TG, serum lipoprotein (a), carotenoids (a-carotene, ß-carotene, lycopene, lutein, ß-cryptoxanthine, zeaxanthine; CVs 4% to 15%), retinol (CV less than 3%), a-tocopherol (CV less than 3%), vitamin K₁(CV=8%), vitamins D (25-OH-vitamin D), B₁₂ and folic acid, clinical chemical parameters (AST, ALT, ALP, GGT, LDH, total protein, albumin, total bilirubin, creatinine, urea, glucose, Fe, Na, K, Cl), hematological parameters (HGB, HCT, leukocytes, erythrocytes, MCV, MCH, MCHC, PTT and platelets), RBC morphology, serum plant sterols, hormones, urinalysis and adverse effects. Double blind study.

Description of Actual Data Sample:

353 healthy volunteers screened, 196 randomized. Eight subjects dropped out, 10 more included at 13 weeks, 13 more dropped out or were excluded.
185 subjects completed the study: 46 men and 50 women controls and 44 men and 45 women receiving plant sterol ester-containing spread.
Average age was 48 years (range 35 to 64 years).
There were no significant differences between treatment groups.

Summary of Results:

Overall, yearly compliance was high, namely 98.9%±1.8% for controls and 98.9%±2.1% for plant sterol esters users (P=0.99). Individual percentage of compliance ranged between 90.4% and 100.8% for subjects consuming control spread and 87.9% to 105.6% for subjects consuming plant sterol esters-enriched spread.
Consumption of the plant sterol ester-enriched spread consistently lowered TC and LDL-C during the one-year period on average by 4% and 6%, respectively (0.01 to 0.05). However, carotenoid concentrations changed over time.
Plant sterols intake reduced lipid adjusted a- and ß-carotene concentrations by only 15% to 25% after one year, relative to control. Lipid-adjusted fat-soluble vitamin concentrations remained unchanged. Plant sterol concentrations in serum were increased from 2.76 to 5.31 (µmol per mmol TC) for ß-sitosterol (P<0.0001).
The increase in total plant sterol concentration in RBC (5.29 to 9.62µg per g) did not affect RBC deformability. Hormone levels in males (free and total testosterone) and females (LH, FSH, ß-estradiol and progesterone) as well as all clinical chemical and hematological parameters were unaffected.
Adverse effects reported were not different between subjects consuming control spread and subjects consuming plant sterol esters-enriched spread.

Author Conclusion:

A sustained cholesterol-lowering effect of daily consumption of about 20g spread enriched with 1.6g plant sterols was observed in this double-blind, placebo-controlled trial during one year in apparently healthy normocholesterolemic and mildly hypercholesterolemic male and female volunteers. The cholesterol-lowering effect was consistent throughout the study, namely, TC was reduced on average by about 4% and LDL-C on average by about 6%. Despite consumption of spread at two meals, cholesterol-lowering efficacy was not significantly affected, demonstrating that frequency of plant stanol esters-enriched spread intake was not significant. This study indicates that daily consumption of 1.6g plant sterol in the long-term, consistently lowers blood cholesterol levels and does not appear to have any adverse health effects.

Funding Source:

Industry:

Unilever

Food Company:

Reviewer Comments:

Large, well controlled study with high adherence rates considering study length of one year.

After one year of 1.6g sterols:

TC baseline: 5.90±0.98mmol per L (228.33±37.93mg per dL)
TC ending: Not reported
Percent change: 4% lower on average (0.01<P<0.05)
LDL-C baseline: Not reported
LDL-C ending: Not reported
Percent Change: 6% lower on average (0.01<P<0.05)
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?	???
	2.2.	Were criteria applied equally to all study groups?	???
	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?	???
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?	???
	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?	???
	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.)	???
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	???
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?	???
	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?	???
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?	???
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	???
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	???
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?	???
	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?	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)?	???
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	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?	???
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?	???