Disorders of Lipid Metabolism and Cholesterol

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

To examine the effect of supplementation with unesterified plant sterols and stanols on plasma lipid and phytosterol concentration and cholesterol absorption, synthesis and turnover.

Inclusion Criteria:

Plasma TC of 5.2 – 9 mmol/L, TG concentration < 3.5 mmol/L. Females were postmenopausal or had undergone hysterectomy.

Exclusion Criteria:

No chronic illness, including hepatic, renal, thyroid and cardiac dysfunction, no drug therapy to be used during study.

Description of Study Protocol:

Baseline: medical history, physical exam

Blind Randomization to 4 groups:  1.8 g/day sterols (NS), 1.8 g/day stanols (SS), 50:50 mixture of sterols and stanols (NSS) or cornstarch (controls) blended into butter, food was provided

21 day feeding:  urine, fasting blood samples on day 1 and 21

Washout:  4 weeks

21 day feeding:  urine, fasting blood samples on day 1 and 21

Washout:  4 weeks

21 day feeding:  urine, fasting blood samples on day 1 and 21

Washout:  4 weeks

21 day feeding:  fasting blood samples on day 1 and 21

 

Data Collection Summary:

Plasma TC, HDL-C, TG. LDL-C by Friedewald eqn.  Cholesterol absorption, biosynthesis and turnover, plasma phytosterol concentrations.  Double blind

Description of Actual Data Sample:

10 male, 6 female otherwise healthy free-living volunteers with primary familial hyperlipidemia, aged 35 – 58 years. 15 completed the trial.  

Summary of Results:

Plasma TC concentrations were 7.8%, 11.9%, and 13.1% lower (P < 0.01) in the NS, SS and NSS groups, respectively, than in the control group. LDL-C concentrations were 11.3%, 13.4% and 16.0% lower (P < 0.03) in the NS, SS and NSS groups, respectively, than in the control group.  Plasma TG and HDL-C concentrations did not differ significantly across diets.

Cholesterol absorption efficiency was 56.0%, 34.4% and 48.9% lower (P < 0.001) in the NS, SS and NSS groups, respectively, than in the control group.  The fractional synthesis rate was higher by 45.5% (P < 0.003) in the NSS group than in the control group.  Plasma campesterol and sitosterol concentrations were higher (P < 0.01) in the NS group and sitosterol concentrations were lower (P < 0.01) in the SS group than in the control group.

Author Conclusion:

The major novel finding of the present study is the demonstration that unsaturated, saturated, and an equal mixture of unsaturated and saturated phytosterols, in their unesterified form, significantly and equally reduce both plasma total and LDL-C concentrations. In summary, the results of the present study showed that in free form, sterol and stanol feeding results in equivalent reductions in TC and LDL-C concentrations.  Cholesterol absorption was reduced in response to sterol and stanol feeding and varied directly with reductions in LDL-C concentration.  Cholesterol synthesis was increased, but not to an extent that prevented cholesterol lowering.  Both unesterified plant sterols and stanols favorably lower LDL-C, independent of their degree of hydrogenation, in hypercholesterolemic individuals.

Funding Source:
Industry:
Dairy Farmers of Canada, Forbes Medi-Tech Inc (Canada)
Commodity Group:
Other:
University/Hospital: McGill University (Quebec)
Reviewer Comments:

Small sample size. Crossover study reduces between-individual variation. Plasma plant sterol concentrations used as indicators of compliance.  Provision of foods minimizes dietary confounders.

After 21 days  of 1.8 g stanols:

  • TC Baseline:  6.23 +/- 0.26 mmol/L (241.10 +/- 10.06 mg/dL)
  • TC Ending:  5.57 +/- 0.22 mmol/L (215.56 +/- 8.51 mg/dL)
  • % Change:  -10.4 +/- 2.3% (p < 0.01)
  • % Change from Control: -11.9%
  • LDL-C Baseline:  4.11 +/- 0.18 mmol/L (159.06 +/- 6.97 mg/dL)
  • LDL-C Ending: 3.59 +/- 0.18 mmol/L (138.93 +/- 6.97 mg/dL)
  • % Change:  -11.2 +/- 3.0% (p < 0.01)
  • % Change from Control:  -13.4%

After 21 days of 1.8 g sterols:

  • TC Baseline:  5.97 +/- 0.26 mmol/L (231.04 +/- 10.06 mg/dL)
  • TC Ending:  5.54 +/- 0.22 mmol/L (214.40 +/- 8.51 mg/dL)
  • % Change:  -6.3 +/- 2.9% (p < 0.01)
  • % Change from Control: -7.8%
  • LDL-C Baseline:  4.0 +/- 0.20 mmol/L (154.8 +/- 7.74 mg/dL)
  • LDL-C Ending: 3.6 +/- 0.17 mmol/L (139.32 +/- 6.58 mg/dL)
  • % Change:  -9.1 +/- 2.9% (p < 0.01)
  • % Change from Control: -11.3%

After 21 days of 1.8 g stanols and sterols:

  • TC Baseline:  6.40 +/- 0.31 mmol/L (247.68 +/- 12.00 mg/dL)
  • TC Ending:  5.59 +/- 0.26 mmol/L (216.33 +/- 10.06 mg dL)
  • % Change:  -11.6 +/- 3.2% (p < 0.01)
  • % Change from Control: -13.1%
  • LDL-C Baseline:  4.18 +/- 0.23 mmol/L (161.77 +/- 8.90 mg/dL)
  • LDL-C Ending: 3.55 +/- 0.17 mmol/L (137.39 +/- 6.58 mg/dL)
  • % Change:  -13.8 +/- 3.2% (p < 0.01)
  • % Change from Control:  -16.0%
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? 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
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
  2.2. Were criteria applied equally to all study groups? N/A
  2.3. Were health, demographics, and other characteristics of subjects described? N/A
  2.4. Were the subjects/patients a representative sample of the relevant population? N/A
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
  3.2. 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
  3.4. 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")? N/A
4. Was method of handling withdrawals described? Yes
  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
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. 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
  5.1. 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
  5.3. 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? 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
  6.4. 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
  6.6. 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? 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? 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
  7.4. 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
  7.6. Were other factors accounted for (measured) that could affect outcomes? 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
  8.1. 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
  8.3. 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
  8.5. 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
  8.7. 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
  9.1. Is there a discussion of findings? 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
  10.1. Were sources of funding and investigators' affiliations described? N/A
  10.2. Was the study free from apparent conflict of interest? N/A