DLM: Plant Stanols and Sterols (2010)
Citation:
Study Design:
Class:
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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: |
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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
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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? | ??? | |