Cardiovascular Disease and Micronutrients
To investigate the effect of vitamin E on lipids and peroxidation during statin treatment.
- Diagnosis of type 1 diabetes
- Total cholesterol higher than 4.9mmol per L
- LDL-cholesterol higher than 3.0mmol per L
- Triglycerides less than 4.5mmol per L
- Normal blood levels of thyroxin and TSH.
Did not meet inclusion criteria.
Recruitment
Patients with history of high cholesterol recruited from outpatient diabetes clinic of Antwerp University hospital.
Design
- RCT
- Patients randomized in blocks of four, matched for age and sex
- Divided into two groups.
Blinding Used
Patients blinded to treatment.
Intervention
After a lipid-lowering free washout period of four to six weeks, patients were randomized to receive 20mg Atorvastatin daily with either:
- 250 IU (168mg) d-alpha-tocopherol three times daily
- Placebo of 280mg soybean oil with 0.25mg tocopherol per capsule that was identical in appearance and taste to treatment capsule.
Statistical Analysis
- Results expressed as means ±SD
- Two-tailed P-values of 0.05 were considered significant
- Between-group comparisons by T-test or Mann-Whitney test for non-Gaussian variables
- Effect of medication versus placebo during the course of three visits analyzed by ANOVA
- Data analyzed for change over time within the groups and for differences in the two groups.
Timing of Measurements
Lipids measured after four to six washout period without cholesterol-lowering medicine (baseline), after three months and after six months of treatment.
Dependent Variables
- Blood lipids by standard hospital laboratory:
- Total cholesterol
- HDL-cholesterol
- Triglycerides
- LDL-cholesterol (calculated according to Friedewald equation).
- Glycated hemoglobin (HPLC cation exchange column)
- Oxidant-antioxidant balance (measured concentrations of vitamins E and A in serum using HPLC)
- Susceptibility of LDL and VLDL to copper-catalyzed oxidation (measured by fluorescence method)
- Composition of non-HDL fraction
- Composition of LDL fraction.
Independent Variables
- 20mg Atorvastatin and 250 IU d-alpha-tocopherol (three capsules daily)
- 20mg Atorvastatin plus 280mg soybean oil (three capsules daily).
Control Variables
Standard diet for diabetes (7.5 to 8.5mJ per kg per day) with nutrient distribution as 50% carbohydrate, 20% protein, 30% fat.
Initial N
24.
Attrition (Final N)
22:
- 10 males and one female in Experimental Group
- 10 males and two females in Placebo Group.
Age
- Experimental Group: Median, 43 (range, 21 to 69)
- Placebo Group: Median, 59 (range, 23 to 66).
Anthropometrics
No significant differences between groups at baseline for BMI (25.2 vs. 26.0kg/m2), blood lipid levels, HbA1C, insulin dosage, median years duration of diabetes or blood pressure.
Location
Antwerp, Belgium.
Between-group comparison of the change in serum lipids was not significant. Atorvastain treatment decreased serum lipids the same amount for both groups:
- Cholesterol by 29%: From 6.08±0.68mmol before treatment to 4.34±0.77mmol after three months of treatment and 4.41±0.71mmol after six months of treatment; P<0.0001
- LDL-cholesterol by 41%: From 3.91±0.52mmol before treatment to 2.32±0.58mmol after three months and 2.33±0.56mmol after six months on the drug; P<0.0001
- Triglycerides decreased by 21%: From 1.17±0.57 to 0.93±0.39mmol per L after three months and 0.93±0.43mmol per L after six months; P=0.005.
There were no significant changes in HgA1C or HDL in either group.
Variables |
Atorvastatin + Vitamin E
|
Atorvastatin + Placebo
|
Statistical Significance of Group Difference |
Total Thiobarbituric Reactive Substances (TBARS) |
4,654±1,110 |
6,527±1,696 |
P=0.020 |
Composition Non-HDL Fraction Content in Alpha-Tocopherol (mmol per L) |
24.8±12.6 |
16.6±5.8 |
P=0.022 |
Vitamin E does not affect lowering of plasma lipids achieved by Atovastatin. However, the antioxidant effect of vitamin E is attenuated when given with the statin.
Other: | Omega-Pharma NV furnished alpha tocopherol and placebo |
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? | 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? | 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? | Yes | |
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? | N/A | |
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)? | No | |
8.5. | Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? | No | |
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? | Yes | |
10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
10.2. | Was the study free from apparent conflict of interest? | Yes | |