Cardiovascular Disease and Micronutrients

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

To determine whether plasma levels of alpha-tocopherol can be increased by dietary measures (food sources vs. supplements) to reduce cardiovascular risk.

Inclusion Criteria:
  • Aged 18 years or older
  • Total cholesterol less than 7.5mmol per L
  • Triglyceride less than 3.0mmol per L
  • Non-smoking
  • Not taking supplements containing vitamin E
  • Not taking any medications known to affect lipid metabolism
  • No pre-existing serious medical conditions.
Exclusion Criteria:
  • Age less than 18 years
  • Total cholesterol 7.5mmol per L or more
  • Triglycerides 3.0mmol per L or more
  • Current smoker
  • Currently taking supplements containing vitamin E
  • Taking medications known to affect lipid metabolism
  • Serious, pre-existing medical conditions.
Description of Study Protocol:

Recruitment

Advertisements in local newspapers and on local radio.

Design

Randomized controlled trial.

Blinding Used 

Participants assigned to two of the three groups were blinded as well as investigators:

  • Vitamin E supplement group
  • Placebo.

Intervention

  •  One-week run-in period
    • Usual diet
    • Completed food record.
  • Randomized to one of three treatment groups via random numbers
  • Treatment groups
    • Dietary intervention:
      • Goal was to obtain 30mg to 40mg of vitamin E daily from dietary sources
        • Provided with vitamin-E-rich foods; if consumed in suggested amounts, would provide 28mg daily of vitamin E
          • Ground hazelnuts: 70mg daily
          • Canola-based margarine: 30g daily
          • Wheatgerm oil: 5ml daily
        • Increase other vitamin-E-rich foods such as avocado and pumpkin
        • To prevent increase in PUFA intake, participants encouraged to only use supplied fats and to reduce added fats and other high-fat foods
        • Individualized dietary counseling throughout study, recipes
      • Total fat: 30% energy intake
    • Vitamin E supplement: 200 IU RRR-alpha tolcopherol capsule daily plus usual diet
    • Placebo (soy lecithin capsules free of vitamin E): Placebo capsule daily plus usual diet
  • Food records and blood work obtained
  • Duration of study: Eight weeks.

Statistical Analysis

  • Multiple regression analysis was used to determine differences between treatment groups. Adjustments made for baseline values.
  • Two-tailed Pearson correlations were performed to examine the changes in dietary and plasma alpha tocopherol measurements between baseline and week eight.
Data Collection Summary:

Timing of Measurements

  • Blood work was performed at baseline and at two, four, six and eight weeks
  • Food records were collected at baseline and at four and eight weeks.

Dependent Variables

  • Alpha-tocopherol
  • Total cholesterol
  • Triglyceride
  • Lipoproteins
    • LDL
    • HDL
  • Apoprotein B
  • Alpha tocopherol to cholesterol ratio
  • Dietary intake
    • Vitamin E (mg per day)
    • Energy, macronutrients, saturated, monounsaturated and polyunsaturated fats, cholesterol.

Independent Variables

  • Dietary intervention
  • Vitamin E supplement
  • Placebo.

Control Variables

Baseline values:

  • HDL
  • Triglycerides
  • Others not specified.
Description of Actual Data Sample:

Initial N

N=90:

  • Dietary intervention: N=40
  • Vitamin E supplement: N=10
  • Placebo: N=40.

Attrition (Final N)

N=82:

  • Dietary intervention: N=37 (14 males and 23 females)
  • Vitamin E supplement: N=10 (three males and seven females)
  • Placebo: N=35 (seven males and 28 females)
  • Reasons for attrition:
    • Illness, family bereavement, overseas travel: N=5
    • Lost to follow-up during trial: N=3.

Age

48.0 years (mean), range 22 to 72 years.

Other Relevant Demographics

  • Mean plasma alpha tocopherol: 26.9μmol per L (range 16.7 to 45.5)
  • Mean plasma alpha tocopherol to cholesterol ratio: 5.3μmol per mmol (range 3.1 to 9.3)
  • Mean total cholesterol was similar in all groups (mean values not provided)
  • HDL was lower, triglyceride was higher in the dietary intervention group compared to the placebo and vitamin E supplemented group.

Anthropometrics

Mean BMI: 25.9 (range 18.2 to 40.7).

Location

New Zealand.

 

Summary of Results:

 Dietary Intake

  • Vitamin E supplement and placebo groups maintained similar energy and macronutrient intake throughout study
  • At week eight, dietary intervention group consumed more vitamin E (12mg per day) compared to the placebo group (95% CI: eight to 15, reported as significant difference but P value was not reported)
  • Dietary intervention group consumed less saturated fat and more total, monounsaturated and polyunsaturated fats compared to the placebo group (all significant but no P value was reported).
                                                                                   Intervention Baseline Week Eight Difference from Placebo (95% CI)
Percentage fat (kJ) 

Placebo

Diet intervention

31±6

31±6

31±7

37±8

5 (2, 8)
Percentage  saturated fat (kJ)

Placebo

Diet intervention

13±4

13±4

14±4

12±3

-2 (-3, -1)
Percentage monounsaturated fat (kJ)

Placebo 

Diet intervention    

10±2

11±3

10±3

14±4

4 (2, 6)
Percentage polyunsaturated fat (kJ)                            

Placebo

Diet intervention     

5±2

4±1

4±2

7±3

 

3 (2, 4)
Vitamin E to PUFA (mg per g)                                    

Placebo

Diet intervention

1.0±0.3

1.1±0.3

1.1±0.3

1.3±0.3

0.2 (0.1, 0.4)

 

  • Dietary intervention group:
    • Consumed an average of 24g hazelnuts, 12g canola margarine, and 4ml of wheatgerm oil daily
    • Seven of 35 participants met goal of 30mg vitamin E per day
    • Remaining participants (N=28) averaged 18mg per day.

 Vitamin E and Lipids

  Group                    Baseline     Week Eight     95% CI Between Diet Intervention and Placebo Groups at Week Eight                         95% CI Between Vitamin E Supplement and Placebo Groups at Week Eight                           
Plasma alpha tocopherol (μmol per L)                     Dietary intervention 27.3±5.1 28.5±6.9 1.8 (-0.8 to 4.4)              
  Vitamin E 29.8±8.2 44.9±12.7                                 16.0 (12.0 to 20.0)*
  Placebo 25.7±6.5 25.3±6.5                                      
Plasma alpha tocopherol to cholesterol ratio (μmol per mmol) Dietary intervention 5.2±1.2 5.5±1.0 0.5 (0.0 to 1.1)  
  Vitamin E 5.5±0.4 8.5±2.6   3.4 (2.5 to 4.2)*
  Placebo 5.2±1.2 5.0±1.3    
HDL cholesterol (mmol per L) Dietary intervention 1.31±0.36 1.27±0.25 -0.1 (-0.3 to 0.0)*  
  Vitamin E 1.49±0.66 1.69±0.57    
  Placebo 1.5±0.40 1.56±0.45    

 *Significantly different but P-value not provided.

  • Change in dietary vitamin E intake was significantly correlated with change in plasma alpha tocopherol (R=0.28, P=0.027)
  • No significant correlation between change in dietary vitamin E and change in plasma alpha tocopherol
  • No significant changes in other lipids during the study.

Other Findings

BMI remained unchanged throughout the study.

 

Author Conclusion:

Dietary modification is unlikely to appreciably raise plasma alpha tocopherol levels.

Funding Source:
Other: Otago Medical Research Foundation Laurenson Award
Reviewer Comments:
  • Sample size may have been inadequate per authors
  • Reasons for not using supplied foods not indicated.
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? No
  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? ???
  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? No
  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? 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? No
  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)? No
  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? No
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? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes