DF: Cardiovascular Disease (2008)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:

To examine the effect of oat bran in comparison to a low-soluble fiber diet (wheat bran) as a supplement to a fat-modified diet  in hypercholesterolemic subjects in three cohorts over approximately 26 weeks.

Inclusion Criteria:
  • Hypercholesterolemic subjects:
    • LDL-cholesterol level between 50th and 95th percentile for age and sex
    • Triglyceride levels less than or equal to 400mg per dL
  • Age from 20 to 70 years.
Exclusion Criteria:
  • History of diabetes
  • Drug or alcohol abuse
  • Use of medications known to affect blood lipid levels
  • Surgical treatment to lower lipid levels
  • Unusually high-fiber intake (greater than 10g of soluble fiber per day)
  • Lactose intolerance
  • Lower intestinal difficulties
  • Pregnancy
  • Weight more than 20% above or below ideal weight for height and sex.
Description of Study Protocol:

Recruitment

  • Community-based cholesterol screening programs
  • Excluded from the analyses: 64 patients dropping out during the study due to:
    • Conflicts with work or family
    • Incovenience
    • Loss of interest in the study
    • Non-related medical problems
  • Of the dropouts leaving the study after randomization:
    • Oat bran group: Five
    • Wheat bran group: 11
    • Diet control group: 15.

Design

Randomized clinical trial for approximately 26 weeks:

  • All free-living subjects were instructed to follow the American Heart Association Step I (AHA-I) diet for six weeks. Instructions were given during a two-hour group session conducted by a registered dietitian and follow-up was done by phone within two to four weeks. Subjects were instructed in diet record-keeping and to use standard measures of food portion visuals for portion sizes.
  • After this first six weeks, subjects were stratified by sex, age, LDL-cholesterol and baseline-estimated fiber intake and were randomized into treatment groups (oat bran and wheat-based cereal) and control (diet only) group
  • Each of the treatment periods were for six weeks, with crossover of cereal groups at the midpoint (period one and period two)
  • The cereal groups received unlabeled, ready-to-eat cold cereal, a measuring cup, two cereal bowls and instructions to measure and they recorded the required servings
  • Subjects recorded the amount and time of daily cereal intake throughout the treatment period, and measured and reported leftover at the end of six weeks
  • Four-day food records, including at least one weekend, were assigned in week five of each study period. A food-frequency questionnaire was used at baseline.

Blinding Used 

Yes.

Intervention

  • Oat bran  and wheat bran: Two ounces per day; oat bran for crossover period one (six weeks) and wheat bran for crossover period two (six weeks)
  • Wheat bran and oat bran: Two ounces per day; wheat bran for crossover period one (six weeks) and oat bran for crossover period two (six weeks)
  • Diet only: AHA-I for both periods, one and two.

Statistical Analysis

  • Repeated analysis of variance
  • Tukey's HSD tests were performed for lipid variables
  • Two-tailed paired T-tests (side effects and palatability were assessed).
Data Collection Summary:

Timing of Measurements

  • Week five of each treatment:
    • Food records
    • Side effects
    • Cereal palatability
    • Compliance
  • Week six of each phase:
    • Blood lipids
    • body weight
  • Beginning and end of the study: Physical activity. 

Dependent Variables

  • Plasma total cholesterol, LDL and HDL: Roche COBAS method
  • Four-day food records and food-frequency: Analyzed by University of Minnesota Nutrition Coordinating Center's Nutrient Data System (NDS)
  • Predicted vs. observed lipid changes: Keys equations used to analyze lipid changes by treatment period
  • Body weight (kg)
  • Side effects rating.

Independent Variables

Oat bran and wheat bran vs. control diet only.

Control Variables

  • Age
  • Sex
  • Baseline lipid
  • Total soluble fiber.
Description of Actual Data Sample:
  • Location: University of Minnesota, Minneapolis
  • Initial N: 209
  • Attrition (final N): 145
  • Age: 20 to 70 years
  • Anthropometrics: Matched at the baseline for age, sex, weight and lipid parameters
  • Location: University of Minnesota, Minneapolis, MN.
Summary of Results:

Key Findings

  • Total cholesterol, LDL and HDL
    • Initial diet period: All groups decreased significantly the total cholesterol and LDL-cholesterol; P<0.05
    • Improvement of LDL-cholesterol throughout the cereal treatment periods in the diet and wheat-cereal group was not sustained. Oat bran decreased significantly total cholesterol and LDL-cholesterol; P<0.01.
    • Oat bran period: The individual range in LDL-C response during oat bran period was from -27.4% to +26.5%
    • No significant change in HDL-cholesterol during all the study. 
Lipids Baseline

Diet Only

(Six Weeks)

Period One

(Six Weeks)

Period Two

(Six Weeks)

Cholesterol (mg per dL)
Wheat cereal-oat bran 237±29.8  239±25.1  231±30.5  225±32.1 
Diet 238±28.6  236±30.2  236±30.2  242±33.6 
*Oat bran-wheat cereal 239±25.1  224±26.7  224±26.7  239±27.8 
LDL-cholesterol (mg per dL)    
Wheat cereal-oat bran 164±21.3  159±28.2  158±23.6  152±23.2 
Diet 165±24.7  156±25.1  162±27.5  166±29.4 
Oat bran-wheat cereal 162±25.1  159±24.6 148±26.7  160±26.3 
HDL-cholesterol (mg per dL)    
Wheat cereal-oat bran 49.1±10.4  48.0±9.3  48.3±9.3  49.1±10.1 
Diet 48.3±11.6  48.3±17.4  48.7±11.6  49.5±12.4 
Oat bran-wheat cereal 47.2±12.0  47.6±11.6  47.2±12.0  48.3±12.8 

 

Values are mean±SD.

*Subjects ingested oat bran for crossover period one and wheat cereal for crossover period two.

  • Nutritional variables: 
    • Baseline dietary variables were the same for all groups
    • The overall group had a pre-study consumption of 32.8% of their calories from fat; 11.2% came from saturated fat; 12% from monounsaturated fat; 6.8% from polyunsaturated fat and the daily cholesterol intake was 271mg
    • Total soluble fiber was 6.4g per day in the initial diet period
      • Oat bran groups increased the soluble fiber intake to 2.8g in period one and 2.9g in period two
      • Diet group decreased the consumption progressively
    • All groups demonstrated a slight weight loss over the course of the study.
Nutritional Variable Baseline

Diet Only

(Six Weeks)

Period One

(Six Weeks)

Period Two

(Six Weeks)

Total kcal     
Oat cereal-wheat bran  2281±764  1858±527  1759±426  1878±439 
Diet  1981±589  1898±661  1836±580  1814±595 
Wheat bran-oat cereal 2198±715  1684±577  1810±566  1762±459 
Dietary cholesterol (mg    
Oat cereal-wheat bran   320±153  193±86  176±92  199±92 
Diet  240±99  218±211  179±92  190±100 
Wheat bran-oat cereal 276±127  173±80  197±106  182±86 
Dietary soluble fiber (g)
Oat cereal-wheat bran  6.4  6.7.0±1.9  7.7±2.4  6.1±2.1 
Diet  5.8  6.8±3.3  6.2±2.2  6.0±2.1
Wheat bran-oat cereal  6.4  5.8±2.5  6.0±1.9  7.4±1.9 
Mean body weight (kg)     
Oat cereal-wheat bran   75.6±11.9  75.0±11.2  74.6±11.6  74.4±12.3 
Diet 73.5±11.7  73.3±11.3  72.9±11.3  72.0±11.6 
Wheat bran-oat cereal 76.7±10.6  75.8±11.1  75.5±11.2 75.5±11.0 

Values are mean±SD.

  • Predicted vs. observed changes in plasma cholesterol: Oat-bran groups demonstrated further reductions in total cholesterol and LDL-cholesterol beyond those predicted by the Keys formulas.

Other Findings

  • Oat bran treatment: A significant correlation with the reduction in LDL-cholesterol and total fiber intake from oat bran treatment was found only in women with more than 50 years and men with less than 50 years; P<0.01. The older women demonstrated the higher change in LDL-cholesterol level due oat bran treatment (-14.3±17.0) when compared with young women (+6.6±18.6), old men (-3.1±14.3) and young men (-9.3±15.5).
  • Side effects: Intestinal gas and looser stools were significantly higher frequency in the oat bran treatment periods, P<05; and constipation was significantly greater in the wheat-cereal periods, P<0.005. Compliance with the cereal doses was 90.6% for the wheat cereal and 92.1% for the oat bran.
Author Conclusion:

The study demonstrated significant lipid improvements in oat bran-treated subjects and support the use of oat bran as a beneficial supplement in a heart-healthy eating plan for most persons with hypercholesterolemia. However, this study raises the possibility that younger women and older men may be less likely to benefit than younger men and older women.

Funding Source:
Reviewer Comments:
  • The Keys equations used to predict lipid changes were developed using only male subjects in a controlled metabolic ward setting, which make them with limited application to study free-living subjects
  • Quantity of supplemental fiber consumed by group was not described
  • Lacking information about the numbers of males and females in each group
  • Tables and figures are not complete as far as statistical treatment, missing the significance that makes it difficult to interpret the data by only looking at the tables and figures
  •  This study was supported by a grant from the Quaker Oats Company, which could be a potential conflict of interest.


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? 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? Yes
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? 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? 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? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  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? 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? Yes
  6.6. Were extra or unplanned treatments described? No
  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)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  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? N/A
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? Yes
  10.2. Was the study free from apparent conflict of interest? No