EAL

Vitamins and Antioxidants and the Prevention and Treatment of CVD

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the effect on blood lipid profiles of including 30g of walnuts/day in a modified diet plan compared with the provision of generic low-fat or low-fat/modified-fat dietary advice in patients with type 2 diabetes.

Inclusion Criteria:

age 35-75 years
type 2 diabetes for at least one year
generally well

Exclusion Criteria:

insulin therapy
BMI>35
HbA1c>9%
illiteracy
inadequate conversational English
food habits or allergies that would inhibit the study

Description of Study Protocol:

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.

Data Collection Summary:

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

Description of Actual Data Sample:

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

Summary of Results:

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).

Author Conclusion:

A "whole of diet" approach inclusive of specific advice on walnuts in addition to fish can help to improve the lipid profile of patients with type 2 diabetes.

Funding Source:

Reviewer Comments:

Authors note that lower cholesterol levels in the walnut group at baseline (resulting from randomization) did not create an expected bias.

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?	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