EAL

DLM: Almonds (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare the effect of the portfolio diet with a statin in reducing C-reactive protein (CRP) levels in healthy hyperlipidemic men and post-menopausal women.

Inclusion Criteria:

Healthy men and post-menopausal women
Hyperlipidemia (increased LDL-C levels).

Exclusion Criteria:

Cardiovascular disease
Untreated hypertension
Liver or renal disease
Lipid-reducing medication use (except for three women on stable doses of thyroxine and one of these on ERT).

Description of Study Protocol:

Recruitment

Participants recruited from hyperlipidemic patients attending the Clinical Nutrition and Risk Factor Modification Center at St. Michael's Hospital and from newspaper advertisements

Design

Randomized cross-over with three one-month treatments and separated by two six-week washout periods

Blinding used

Double-blinding used for randomization of identical placebo versus statin tablets
Laboratory staff responsible for analyses were blinded to treatment (received samples labeled with name codes and dates)
Dietitians not blinded to the diets since they were responsible for packing diets and checking diet records.

Intervention

Very low saturated fat dairy and whole wheat cereal diet (control group)
Very low saturated fat dairy and whole wheat cereal diet plus 20mg lovastatin (statin group)
Low saturated fat diet with viscous fibers, plant sterols, soy foods and almonds (portfolio diet group).

Statistical Analysis

Results reported as means and SDs
Treatment differences assessed by least squares means
- Tukey-Kramer adjustment for multiple comparisons
ANOVA model
ANCOVA model
Box-Cox transformations used to obtain more normal sample distribution
Wilcoxon signed rank test used to assess significance of change
Non-parametric sign test used to determine significant difference of diets in completers and intention to treat analysis
Spearman correlation used to assess association between CRP and anthropometric data
Bonferroni adjustment used to assess significance of comparisons.

Data Collection Summary:

Timing of Measurements

Fasting body weights checked weekly
Fasting blood samples at baseline, two weeks and four weeks (for CRP measurement)
Seven day diet histories for week prior to one-month treatment periods
Menu checklists returned at weekly intervals during one month diet periods; weekly exercise also logged.

Dependent Variables

CRP levels measured by fasting blood draw at zero, two and four weeks.

Independent Variables

Portfolio Diet
Statin.

Control Variables

Gender
Age
Race
Body weight and BMI
Exercise.

Description of Actual Data Sample:

Initial N

(55 participants randomized (34 completed all three treatment phases: 20 males, 14 post-menopausal females)

Attrition (final N)

Age

58.4±8.6 years (36-71 years)

Ethnicity

Canadian

Other relevant demographics

None given

Anthropometrics

BMI 27.3±3.3kg/m² (20.5-35.5)

Location

Toronto, Ontario, Canada

Summary of Results:

CRP Levels

No significant treatment differences when all data points used
When analysis restricted to CRP less than 3.5mg/L for completers, the absolute reduction from baseline at four weeks was significant for statin (-3.2±0.12mg/L, N=23, P=0.006) and portfolio (-0.41±0.11mg/L, N=25, P=0.001) but not for control (-0.05±0.14mg/L, N=28, P=0.397)
- As a percentage of the baseline value, changes were -16.3±6.7% (P=0.013) for statin, -23.8±6.9% (P=0.0001) for portfolio and 15.3±13.6% (P=0.907) for control
- Using week four compared to week zero data, portfolio treatment was significantly more effective (P=0.033) than the control diet in reducing CRP
  - 54% of controls showed negative value for change vs. 80% of portfolio vs. 78% of statin
  - Portfolio and Statin treatments were similarly effective (P=0.500).
  - Addition of non-completers gave similar results
When non-completers were included, absolute changes from baseline for statin was-0.33+0.10mg/L (P=0.001), for portfolio was -0.34+0.10mg/L (P=0.001) and for control was -0.06+0.13mg/L (P=0.366)
- As a percentage of the baseline value, changes were -17.4±5.6% (P=0.002) for statin, -21.1±6.4% (P=0.012) for portfolio and 14.3±12.0% (P=0.863) for control
Absolute reduction and percentage reduction were significantly greater on portfolio than control (P=0.043 and P=0.004, respectively)
Difference between statin and control did not reach statistical significance (absolute reduction: P=0.388, percentage change: P=0.194), although statin and portfolio treatments were similar (absolute reduction: P=0.595, percentage change: P=0.349).
After Boniferroni adjustment, there was a significantly greater percentage reduction from baseline in CRP on the portfolio diet compared to control using data with CRP ≤3.5mg/L (P=0.004).
There was a significant interaction effect of sex and treatment, with the absolute reduction in CRP significantly greater for women on the portfolio diet than control (P=0.034) and non-significant for statin vs. control (P=0.824)
There were no significant differences in men between control and portfolio (P=0.958) or statin (P=0.378).

Other Findings

At baseline, CRP was significantly associated with BMI among completers (r=0.40, P=0.018)
- Excluding CRP greater than 3.5mg/L provided similar results (r=0.45, P=0.019)
There were no other significant associations with CRP
There were no associations between change in CRP and change in BMI.

Author Conclusion:

The portfolio diet, which combines a variety of cholesterol-lowering foods was shown to lower CRP levels to a similar extent as a statin. If lowering CRP levels is proven to decrease CHD risk independently, the CRP-lowering effect is another reason why this diet may reduce CHD risk.

Funding Source:

Government:

Canada Research Chair Endowment of the Federal Government of Canada; Canadian Natural Sciences and Engineering Research Council of Canada

Industry:

Reviewer Comments:

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?	N/A
	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?	No
	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?	No
	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?	No
	6.6.	Were extra or unplanned treatments described?	Yes
	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?	No
	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