Disorders of Lipid Metabolism and Cholesterol

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

To examine if phytosterols alter the plasma lipoprotein profile when incorporated into nonfat orange juice

Inclusion Criteria:

Normal CBC, LDL-C > 100 mg/dl, normal liver and renal function, no bleeding diathesis, normal thyroid function

Exclusion Criteria:

Pregnancy or lactation, smoking, current use of vitamin supplements, alcohol intake > 1 oz per day, history of CVD or chronic inflammatory diseases, recent bacterial infection, anti-inflammatory steroidal or nonsteroidal meds, hypolipidemic or thyroid drug use, OC or anticoagulant use, history of sitosterolemia, GI problems, and concurrent or recent intervention study participation

Description of Study Protocol:

2 week run-in: all received unfortified OJ

Blinded Randomization to 2 groups:  Sterol OJ (2 g/day) or Placebo OJ (n=36 in both), asked to drink 240 ml of juice with B and D

Baseline:  fasting blood, 3 day diet record

2 Weeks:  fasting blood

10 Weeks:  fasting blood, 3 day diet record

Data Collection Summary:

TC, TG, LDL-C using Friedewald eqn, HDL-C, ApoB, homocysteine, folate, B12. Double blind.

Description of Actual Data Sample:

75 entered study, 3 discontinued due to personal reasons (2 in sterol OJ, 1 in placebo OJ). 72 free-living mildly hypercholesterolemic healthy subjects, aged 20 – 73 years.  Subjects were matched for age, gender and BMI.  There were no significant differences in baseline lipid profile or apoB between the groups.

Summary of Results:

Compliance was high. Body wt was unchanged during trial.  There were no significant differences in the diet composition before and after OJ supplementation. 

With regard to TC and LDL-C, there was a significant reduction in concentrations between groups as well as compared with baseline within the sterol OJ group (7.2% decrease in TC and 12.4% decrease in LDL-C, P < 0.001).  Whereas non-HDL concentrations were unchanged in the placebo group, there was a significant reduction (7.8%, P < 0.01) in non-HDL-C concentrations in the sterol OJ group compared with baseline and compared with the placebo OJ group.  Apolipoprotein B levels were significantly decreased (9.5%, P < 0.01) with sterol OJ.  There were no significant changes in HDL cholesterol or triglycerides with the sterol OJ.  While folate and B12 levels significantly increased due to the OJ fortification, homocysteine levels were unchanged.

Author Conclusion:

This is the first placebo-controlled, double-blind trial to our knowledge to report a significant cholesterol-lowering effect of plant sterols incorporated in a nonfat beverage in normal healthy subjects with mild hypercholesterolemia.   In this study, we show significant lowering of TC (7.2%), LDL-C (12.4%), and non-HDL-C (7.8%) with sterol OJ compared with baseline and with placebo OJ. In conclusion, this study shows a novel LDL-C-lowering effect of plant sterols (2 g/day) in a nonfat beverage.

Funding Source:
Government: NIH
Industry:
Minute Maid-The Coca Cola Company
Food Company:
University/Hospital: University of California Davis Medical Center
In-Kind support reported by Industry: Yes
Reviewer Comments:

Well controlled study. Author notes that cholesterol-lowering effect may be related to fact that juice was consumed with meals, not alone.

After 8 weeks of 2.0 g sterols:

  • TC Baseline:  207 +/- 27 mg/dL
  • TC Ending:  194 +/- 27  mg/dL
  • % Change:  7.2% (p < 0.001)
  • LDL-C Baseline: 137 +/- 21 mg/dL
  • LDL-C Ending: 125 +/- 25 mg/dL
  • % Change:  12.4% (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? 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