Vitamins and Antioxidants and the Prevention and Treatment of CVD
- age 35-75 years
- type 2 diabetes for at least one year
- generally well
- insulin therapy
- BMI>35
- HbA1c>9%
- illiteracy
- inadequate conversational English
- food habits or allergies that would inhibit the study
Recruitment: recruited through advertisements in the local media and university and technical colllege email networks; news clip on television; letters to general medical practitioners.
Design
- subjects randomized into one of three treatment groups
- each group given advice on the number of servings of CHO-rich food, the type of protein-rich foods (low fat) and oils/spreads (MUFA or PUFA rich) and to include two fish meals per week.
- groups followed for 6 months
Blinding used (if applicable): two sites were used to prevent interaction between groups
Intervention (if applicable): three study groups, all based on 30% of energy from fat:
- conventional advice (low-fat diet)
- modified low-fat diet (using exchange lists inclusive of fatty acid considerations)
- modified low-fat diet + 30g walnuts/day (included as one exchange)
Statistical Analysis
- non-Gaussian data were log transformed before analysis
- differences between groups were assessed with one-way ANOVA woth post hoc analysis performed using Tukey's test
- non-parametric analysis was conducted using the Kruskal-Wallis test
- changes in clinical outcomes were analyzed with an intention-to-treat model using repeated-measures ANOVA
- for baseline, dietary data assumptions of normality were made; differences between groups assessed by ANOVA
- effects of treatment over time were assessed by repeated-measures ANOVA based on data from those completing the trial.
- Spearman's correlation coefficient was determined to assess the realtionship between reported changes in dietary PUFA and erythrocyte cell membrane levels in subjects.
Timing of Measurements
- measurements at 0, 3, and 6 months
Dependent Variables
- total plasma antioxidant capacity by Randox assay kit
- erythrocyte fatty acid composition by gas chromatography
- total cholesterol, LDL, HDL, HDL
- total chol ratio
- triglycerides
- HbA1c
Independent Variables
- dietary intake, by validated diet history method and a 3-day food record; analyzed by Foodworks nutrient analysis software.
- body fat and percent body fat assessed by bioelectrical impedance using Tanita TBF-622
Control Variables
Initial N: 58; 24 women, 34 men
Attrition (final N): 55; one dropped out from each study group
Age: 60.48±8.06
Ethnicity: not specified
Other relevant demographics: total cholesterol was significantly different among groups at baseline, with the mean of 4.79±0.82 mmol/l; other measures were not different between groups
Anthropometrics BMI 29.22±2.6; % body fat 31.23±8.05
Location: Australia
Variables |
Control Group, baseline |
Control Group, 6 months |
Modified-fat Group, baseline |
Modified-fat Group, 6 months |
Walnut Group, baseline |
Walnut Group, 6 months | P-value, time* |
P-value, group |
P-value, Time x Group |
Weight |
81.87±11.19 | 82.27±1.67 | 84.55±4.31 | 84.36±14.07 | 87.61±12.83 | 86.33±13.07 | 0.570 | 0.493 | 0.248 |
BMI |
29.22±2.60 |
29.42±2.80 |
30.16±4.51 |
30.05±4.23 |
30.72±3.85 |
30.26±3.84 | 0.264 | 0.599 | 0.229 |
% body fat |
31.23±8.05 |
32.39±8.21 |
35.13±10.16 |
35.51±9.95 |
34.48±9.12 |
34.00±8.97 | 0.374 | 0.379 | 0.057 |
HbA1c, % | 6.56±0.80 | 6.75±0.88 | 6.82±0.88 | 6.97±0.95 | 6.94±1.22 | 6.89±0.82 | 0.000 | 0.489 | 0.380 |
Total Cholesterol mmol/l | 4.79±0.82 | 4.90±1.08 | 4.58±0.88 | 4.83±0.99 | 4.11±0.81** | 4.02±0.77 | 0.037 | 0.021 | 0.434 |
LDL, mmol/l | 2.70±1.56 | 2.69±1.49 | 2.58±1.30 | 2.73±1.20 | 2.17±1.31 | 1.95±0.75 | 0.634 | 0.032 | 0.316 |
HDL, mmol/l | 1.11±0.22 | 1.25±0.27 | 1.11±0.24 | 1.34±0.21 | 1.10±0.24 | 1.30±0.62 | 0.000 | 0.766 | 0.046 |
HDL:cholesterol ratio | 0.24±0.06 | 0.26±0.06 | 0.25±0.07 | 0.29±0.07 | 0.27±0.08 | 0.33±0.10 | 0.000 | 0.109 | 0.049 |
Triglycerides, mmol/l | 2.18±0.82 | 2.13±0.71 | 1.76±0.82 | 1.55±0.73 | 1.90±0.74 | 1.70±0.68 | 0.006 | 0.208 | 0.174 |
Total antioxidant status, mmol/l | 1.08±0.25 | 1.14±0.18 | 1.08±0.14 | 1.13±0.18 | 1.14±0.17 | 1.21±0.14 | 0.000 | 0.341 | 0.975 |
*reflects inclusion of values from 3 months, not shown in this table
**significantly different at baseline
Lipids
The walnut group achieved a significantly greater increase in HDL cholesterol (P=0.046), as well as a significant reduction in total cholesterol (P=0.021) and LDL cholesterol (P=0.032) than the two other treatment groups.
The change in body fat in the walnut group was significantly different compared to the control group (P < 0.04).
The total cholesterol levels of the walnut group remained lower than the other two groups at each time point (P=0.021).
In univariate analysis, the walnut group LDL levels decreased significantly over time (P=0.036).
HDL levels increased significantly in all three groups, producing a time effect (P<0.001).
Changes in HDL:total cholesterol for the modified fat groups were significant for the first 3 months (P= 0.006) and the second 3 months (P=0.048) but this effect was much stronger in the walnut group.
No significant differences were found between groups for changes in triglyceride levels.
Glycemic Control
HbA1c levels decreased at 3 months then increased, leaving a time effect for overall increase in HbA1c (P<0.001) but there were no significant differences between groups.
Total antioxidant status increased significantly in all groups (P=0.000), with no significant difference between groups.
Dietary Intake
Except for changes in fatty acids, reported intakes for macronutrients remained constant, with no time or group differences in energy intake.
The walnut group consumed more PUFA, had a higher dietary P:S ratio, and reported significantly higher ALA intakes (P<0.001).
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? | 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? | No | |
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? | No | |
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? | ??? | |
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? | 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? | 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? | 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? | No | |