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DLM: Almonds (2009)

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

The purpose of the study was to directly compare the effect of statin treatment with a combination of cholesterol-lowering foods combined in a portfolio-type diet on LDL-cholesterol particle size.

Inclusion Criteria:
  • Hypercholesterolemic adults 
  • Absence of history of CVD, untreated hypertension, liver or renal disease
  • Not taking medications known to influence serum lipid concentrations.
Exclusion Criteria:

 

 

  • Medications known to influence serum lipid concentrations
  • History of CVD
  • Untreated hypertension
  • Liver disease
  • Renal disease.

     

     

     

     

     

 

Description of Study Protocol:

Recruitment

Subjects were recruited from the Risk Factor Modification Center at St. Michaels' Hospital in Toronto and by newspaper advertisement.

Design

Randomized crossover intervention trial in which subjects completed three experimental protocols: Control diet plus placebo, control diet plus statin drugs and portfolio-type diet for four weeks each presented in random order.

Blinding used   

  • Blinding by placebo for statin
  • Diet not blindable.

Intervention  

  • Subjects completed a control diet: Very low saturated fat from dairy and whole wheat products, control diet plus statins, portfolio diet (high in fiber, plant sterol esters, soy protein and almonds) for four weeks each with a washout period between treatments. 
  • All foods except fresh fruits and vegetables were provided 
  • Blood samples were obtained after 12-hour overnight fasts every two weeks
  • Weighed diet histories were obtained for one week before the one-month treatment period
  • Body weight was measured weekly.

 Statistical Analysis 

  • To test differences between treatments and baseline levels of LDL-cholesterol particle size: Least Square Means for repeated measures with Tukey's adjustment for multiple comparisons were used.
  • To examine associations between changes in inflammatory markers (CRP, IL-6 and fibrinogen) and frequency of nut consumption: Nut consumption was divided into three categories of < one time per week, one to four times per week and ≥ five times per week, and analyzed using Spearman Rank correlational analysis. 
  • Differences in nutritional intakes among groups were analyzed using Least Square Means for paired comparisons with Tukey's adjustment for multiple comparisons after establishment of a significant F test by ANOVA
  • For CRP subgroup analysis, values of LDL-cholesterol <25.5nm and CRP >10mg/L were excluded
  • Significance was set at the P<0.05 level of acceptance.
Data Collection Summary:

Timing of Measurements

 Blood samples were obtained after 12-hour overnight fasts every two weeks

  • Weighed diet histories were obtained for one week before the one-month treatment period
  • Body weight was measured weekly.

Dependent Variables

  • Variable 1: LDL-cholesterol particle size measured by non-denaturing polyacrylamide gel electrophoresis 
  • Variable 2: Blood lipids (LDL-cholesterol, total cholesterol, HDL-cholesterol, TAG) measured as previously described and reported
  • Variable 3: CRP-measured as previously described and reported.

Independent Variables

  • Portfolio Diet with high fiber, plant sterol, soy protein and almonds 
  • Statin Treatment.

Control Variables

 

 

Description of Actual Data Sample:

 

Initial N

N=34, 20 males and 14 females

Attrition (final N)

As above

Age

Mean age 58±8.6 years

Ethnicity

29 of 34 participants were of European descent, Chinese (N=1), Indian (N=2), Black (N=1) and Hispanic (N=1)

Other relevant demographics

Anthropometrics

BMI mean 27.3±3.4kg/m2

Location

Toronto, Canada

 

Summary of Results:

 

 

 

Variables Control Diet
Week Zero
(Mean±sem)		 Control Diet
Week Four
(Mean±sem)		 Portfolio Diet
Week Zero
(Mean±sem)		 Portfolio Diet
Week Four
(Mean±sem)		 Statin/Control Diet
Week Zero
(Mean±sem)		 Statin/Control Diet
Week Four
( Mean±sem)		 P-value
For Interactions
 
LDL-C 25.5-26 (mmol/l)
  
1.11
0.05
  
0.97a
0.05
  
1.10
0.06
  
0.74b
0.03
  
1.05
0.06
  
0.76b
0.07
  
0.001
 
LDL-C 
(mmol/l)
  
4.56
0.14
  
4.13a
0.13
  
4.51
0.12
  
3.17b
0.09
  
4.49
0.12
  
2.91b
0.10
  
<0.001
 
Total-C
(mmol/l)
  
6.79
0.16
  
6.23a
0.15
  
6.76
0.15
  
5.25b
0.12
  
6.84
0.15
  
4.97b
0.17
  
<0.001
APO-B
(g/l)		  

1.45

0.04

  

1.34

0.03

  

1.43

0.04

  

1.09b

0.03

  

1.46

0.03

  

1.02b

0.04

  0.001
 
LDL-particle diameter
(Ao)
  
253.0
0.4
  
252.8
0.4
  
253.0
0.4
  
253.0
0.4
  
252.7
0.5
  
253.0
0.5
  
0.42
 
Integrated size (Ao)
  
254.0
0.4
  
253.8
0.4
  
253.0
0.4
  
253.6
0.3
  
253.5
0.4
  
254.0
0.4
  
0.24
LDL >26nm
(%)		  
21.8
1.4
  
20.7
1.3
  
21.2
1.2
  
20.5
1.3
  
19.6
1.5
  
20.4
1.3
  
0.65
 
LDL 25.5-26nm (%)
  
24.4
0.9
  
23.5
0.9
  
24.3
1.1
  
23.3
1.0
  
23.2
1.0
  
25.7
2.1
  
0.10
 
LDL <25.5nm
 (%)
  
53.8
2.1
  
55.7
2.1
  
54.6
1.1
  
56.1
2.0
  
57.2
2.1
  
54.0
2.7
  
0.11

 Values with differing superscripts are significantly different

Other Findings

  • CRP and TAG were not significantly affected by diet or statin at week four. At week two, there were significant differences between treatments (data not shown)
  • Sub-group analysis for CRP showed that on the portfolio diet, subjects with the lowest CRP levels at baseline (<3mg/l) showed significant reduction in LDL-c <25.5nm but no significant differences were seen in the sub-group with baseline CRP levels >3mg/l.
  • CRP did not predict response to control diet or statin.

 

Author Conclusion:
  • Portfolio diet equal to the effect of statin drugs in lowering the level of small LDL cholesterol particles
  • Neither the diet nor the statin affected the percentage of LDL-particle size distribution
  • Portfolio diet equal to the effect of statin drugs in lowering total cholesterol, LDL cholesterol.
Funding Source:
Government: Federal Gov. of Canada, Canadian Natural Sciences and Research Council,
Industry:
Loblaw Brands, Unilever, Almond Board of California, Haine Celestial Group, Kraft Food, Procter & Gamble, Pepsico, Nestle Canada, Barlett Farms, Barwell Food Sales, Burnbrea Farms
Food Company:
Pharmaceutical/Dietary Supplement Company:
Commodity Group:
Reviewer Comments:

It was unclear whether or not the portfolio diet group received placebo.

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
  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
  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
  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
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
  1. Was the research question clearly stated? Yes
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.1. 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
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
  1.3. Were the target population and setting specified? Yes
  2. Was the selection of study subjects/patients free from bias? 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
  2.1. 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
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? 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
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
  3. Were study groups comparable? 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
  3.1. 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
  3.2. 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
  3.3. 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
  3.4. 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
  3.5. 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
  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? N/A
4. Was method of handling withdrawals described? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
  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. 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
  5.1. 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
  5.2. 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
  5.3. 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
  5.4. 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
  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? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? 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
  6.2. 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
  6.3. 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
  6.4. 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
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments 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
  6.7. 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
  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. 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
  7.1. 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
  7.2. 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
  7.3. 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
  7.4. 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
  7.5. 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
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? 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. 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
  8.1. 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
  8.2. 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
  8.3. 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
  8.4. 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
  8.5. 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
  8.6. 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
  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. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? 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. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes
  10.2. Was the study free from apparent conflict of interest? Yes