DLM: Plant Stanols and Sterols (2010)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To investigate whether different initial baseline cholesterol levels modulate the efficacy of a spread enriched with plant sterol-esters in lowering blood cholesterol in a Japanese population consuming their usual diet.

Inclusion Criteria:
  • Healthy Japanese adults
  • Mean age of 45 years 
  • Alcohol intake less than 1L per week
  • Engaged in less than 10 hours per week intense exercise
  • Mean plasma total cholesterol (TC) level of 6.5mmol per L.
Exclusion Criteria:
  • No reported weight loss, medically-prescribed, vegan or vegetarian diets
  • No reported current disease or history of metabolic disease, chronic GI disorders, CVD, HTN or high blood cholesterol
  • No reported medical treatment
  • No use of medicine other than analgesics or contraceptives
  • Bowel frequency at least once per 48 hours
  • No participation in another biomedical trial
  • No blood donations
  • Not lactating or pregnant.
Description of Study Protocol:

Randomization

  • Allocated to start control spread or 1.8g free sterol spread according to sex and baseline TC level in 2 x 2 crossover design
  • Half of spread to be used at breakfast, other half at lunch or dinner
  • Run-in period (Day 8,9):  FFQ, two consecutive days of fasting blood samples averaged
  • Three week intervention (Day 29, 30): Body weight, two fasting blood samples averaged
  • Three week intervention (Day 50, 51): Body weight, two fasting blood samples averaged
  • Three week post-trial follow-up (Day 71): One fasting blood sample.

 

Data Collection Summary:
  • Subjects weighed with analog balance
  • FFQ compared to dietitian interviews and nutritionally analyzed
  • Fasting blood samples analyzed for:
    • TC, TG, HDL-C, apoproteins, RLP-C, fibrinogen
    • ß-carotene, vitamins A and E
    • Clinical chemistry (enzymes, urea N, creatinine, uric acid and glucose)
    • Hematological variables (hemoglobin, hematocrit, leukocytes, erythrocytes, platelets)
  • Double-blind trial.
Description of Actual Data Sample:
  • Volunteers recruited from 80 respondents
  • N: 53 were selected (26 men; 27 women) 
  • Age: 24 to 67 years old
  • Body weights: Stable
  • BMI: 19 to 30kg per m2
  • There were no dropouts.
Summary of Results:
  • 54 subjects were required to detect a difference of 5% in LDL-C levels with a power of 90% (a=0.05)
  • The customary intake of the spreads reached the target of 15g per day
  • Plasma TC and LDL-C concentrations were 5.8 and 9.1% lower, respectively, when subjects consumed the plant sterol ester-containing spread than when they consumed the control spread (P<0.001), without any effect on plasma HDL-C and TG levels. When subjects were divided into two groups [normal and mildly cholesterolemic (TC less than 5.7mmol per L) and hypercholesterolemic (TC greater than 5.7mmol per L)], reductions in TC, LDL-C and apoB did not differ between the groups. Reductions (P<0.001) in TC and LDL-C due to treatment in the normal / mildly cholesterolemic group were 4.9 and 7.9%, respectively.  
Blood Lipid Levels of Subjects After Consuming a Control Spread and a Spread Enriched with Plant Sterol Esters for Three Weeks Each1
 
N Control Enriched Difference 95% Confidence Interval
   mmol/L  %
All subjects N=53      
Total cholesterol
5.51±0.75
5.19±0.67*
-5.8
-0.46-0.19
LDL-cholesterol
3.07±0.67
 
 
 
2.79±0.52**
-9.1
-0.39-0.17
HDL-cholesterol
1.64±0.41
1.62±0.41
-0.06-0.02
Triglycerides
1.14±0.59
1.15±0.60
-0.07-0.10
Subjects with TC<5.7mmol per L N=33
Total cholesterol
5.12±0.43
4.87±0.46*
-4.9
-0.40-0.10
LDL-cholesterol
2.80±0.51
2.58±0.43**
-7.9
-0.34-0.11
HDL-cholesterol
1.62±0.42
1.60±0.42
-0.08-0.02
Triglyceride
0.98±0.46
1.00±0.53
-0.07-0.11
Subjects with TC>5.7mmol/L
N=20
Total cholesterol
6.15±0.72
5.71±0.64*
-7.1
-0.68-0.19
LDL-cholesterol
3.50±0.69
3.13±0.46*
-0.58-0.16
HDL-cholesterol
1.67±0.41
1.65±0.40
-10.6
-0.090.05
Triglyceride
1.39±0.71
1.41±0.63
-0.16-0.2
 
1 Values are means ±SD. Asterisks indicate different from control.
* * P<0.01
** P<0.001
  • In the hypercholesterolemic group, the reductions (P<0.0001) were 7.1% and 10.6%, respectively
  • Plasma apoB and remnant-like particle (RLP) cholesterol (RLP-C) concentrations were lower when subjects consumed the plant sterol ester-containing spread (44.3g per L) than the control spread (49.7g per L)
  • Plasma ß-carotene concentration was lower (P<0.001) in subjects consuming the PS spread than in the control
  • Changes in plasma vitamins A and E levels did not differ after intake of the plant sterol ester-containing and control spreads
  • Blood chemistry and liver enzymes did not differ for subjects. 
Blood Apolipoproteins, Fibrinogen, ß-carotene and Vitamins A and E in Men and Women After Consuming a Control Spread and a Low Fat Spread Enriched with Plant Sterol Esters for Three Weeks Each1
  Control Enriched 95% Confidence Interval
ApoAI, g/L
1.64±0.23
1.63±0.25
-0.05-0.03
ApoAII, mg/L
315±43
317±45
-3.78-8.16
ApoB, g/L
1.04±0.19
 0.98±0.18*
-0.08 to-0.02
ApoCII, mg/L
41.2±14
39.8±14
-3.71-0.94
ApoCIII, mg/L
94.3±26
102±84
-15.1-30.48
ApoE, mg/L
41.8±8.3
40.9±8.2
-2.00-0.27
Fibrinogen, g/L
2.82±0.60
2.93±0.83
-0.06-0.29
ß-carotene, nmol/L
572±400
453±362*
-164 to 73.1
Change from d 51–71, µmol/L
     
Vitamin A
-0.77±0.35
-0.42±0.60
-1.02-1.72
Vitamin E
0.3±0.29
1.2±0.41
-0.1-1.9
 
 

 

Author Conclusion:

In conclusion, as part of a traditional Japanese diet, consumption of a plant sterol ester-enriched spread effectively lowered plasma TC, LDL-C, apoB and RLP-C regardless of baseline plasma TC at an intake of 1.8g per day of plant sterols. Its efficacy did not depend on baseline plasma cholesterol concentration.

Funding Source:
Industry:
Unilever Bestfoods
Food Company:
University/Hospital: Waseda Clinic (Japan)
Reviewer Comments:
  • Well-controlled study with high rates of compliance
  • No dropouts
  • Crossover design reduced between-individual variation
  • After three weeks of 1.8g sterols:
    • TC Control: 5.51±0.75mmol per L (213.24±29.03mg per dL) 
    • TC Sterols: 5.19±0.67mmol per L (200.85±25.93mg per dL) 
    • % Change: -5.8% (P<0.001) 
    • LDL-C Control: 3.07±0.67mmol per L (118.81±25.93mg per dL) 
    • LDL-C Sterols: 2.79±0.52mmol per L (107.97±20.12mg per dL)  
    • % Change: -9.1% (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
  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? ???
  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? ???
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? ???
  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? ???
  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%.) ???
  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? ???
5. Was blinding used to prevent introduction of bias? ???
  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)? ???
  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? ???
10. Is bias due to study's funding or sponsorship unlikely? ???
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? ???