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MNT: Disorders of Lipid Metabolism (2015)

Citation:

Zazpe I, Sanchez-Tainta A, Estruch R, Lamuela-Raventos RM, Schroder H, Salas-Salvado J, Corella D, Fiol M, Gomez-Gracia E, Aros F, Ros E, Ruiz-Gutierrez V, Iglesias P, Conde-Herrera M, Martinez-Gonzalez MA. A large randomized individual and group intervention conducted by registered dietitians increased adherence to Mediterranean-type diets: The PREDIMED study. J Am Diet Assoc. 2008; 108 (7): 1,134-1,144.

PubMed ID: 18589019
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To evaluate the effectiveness of the 12-month nutrition education and dietary intervention in producing changes in the consumption of key foods and nutrients that are most relevant for the definition of a Mediterranean-style diet.
Inclusion Criteria:
  • Community-dwelling
  • Men aged 55 years to 80 years or women aged 60 years to 80 years
  • Free of CHD
  • Diabetes or at least three CHD risk factors (e.g., current smoker, hypertension, LDL-cholesterol of at least 160mg per dL or treatment with hypolipidemic drugs, HDL no more than 40mg per dL, BMI 25 or higher or family history of premature CHD; if HDL is 60mg per dL or higher, one risk factor is subtracted).
Exclusion Criteria:
  • History of CHD or other cardiovascular diseases
  • Any severe chronic illness
  • Drug or alcohol addiction
  • History of allergy or intolerance to olive oil or nuts
  • Low predicted likelihood of changing dietary habits according to Prochaska stages of change model.
Description of Study Protocol:

Recruitment

Participants were recruited from primary care centers affiliated with 10 teaching hospitals in eight Spanish cities between October 2003 and October 2004.

Design

The PREDIMED study is a multi-center, randomized, controlled, single-blinded four-year clinical trial. Participants were randomly assigned to one of three equally sized groups:

  • Mediterranean Diet Group with Virgin Olive Oil
  • Mediterranean Diet Group with Mixed Nuts
  • Control Group.
Randomization was conducted using a computer-generated random-number sequence. A stratified randomization table was constructed to assign each participant into blocks of 50 participants balanced by center, sex and age group (under 70 years and 70 years and older).

The intervention lasted 12 months.

Blinding Used

Allocation to intervention groups was concealed by using sealed envelopes with correlative numbers by pre-specified sub-groups of sex and age.

Intervention

Mediterranean Diet Groups (olive oil or nuts)

  • Depending on group assignment, participants were given either virgin olive oil (one L per week) or mixed nuts (30g per day, distributed as 15g walnuts, 7.5g almonds and 7.5g hazelnuts)
  • Quarterly individual motivational interview, included a 14-item questionnaire on adherence to a Mediterranean diet and positive recommendations to follow the food pattern. RD personalized the message by adapting it to the participant’s clinical condition, preferences and beliefs.
  • Quarterly group sessions with the Mediterranean diet groups run by the PREDIMED RDs, consisted of informative talks and provision of written material with elaborate descriptions of typical Mediterranean-diet foods and seasonal shopping lists, meal plans and cooking recipes.
Control Group
  • Interview with an RD that included the 14-item questionnaire on adherence to a Mediterranean diet, a leaflet with the recommendations according to the American Heart Association guidelines and brief personal recommendations about how to follow the diet
  • No further visits were scheduled until the 12-month follow-up evaluation.

Statistical Analysis

  • Paired T-tests were conducted for within-group changes
  • ANOVA was conducted for between-group changes
  • All P-values presented are two-tailed. P<0.05 was considered statistically significant unless otherwise specified.
Data Collection Summary:

Timing of Measurements

Baseline and at 12-month follow-up

Dependent Variables

  • Changes in food consumption were assessed for 12 food groups: virgin olive oil, refined-mixed olive oil, total nuts, vegetables, cereals, legumes, fruits, fish or seafood, meat or meat products, pastries, cakes or sweets, dairy products and alcohol. Food consumption was assessed using 2 different questionnaires: a 14-item questionnaire which assessed the degree of adherence to the typical Mediterranean dietary pattern and a 137-item FFQ that assessed dietary habits that has been validated in Spain.

Independent Variables

Mediterranean diet groups or control

Control Variables

  • Registered Dietitians were trained and certified to deliver the PREDIMED intervention protocol.
  • Throughout the study, all participants had free and continuous access to their center’s RD for advice and consultation.
  • Biomarkers of compliance: Urinary tyrosol and hydroxytyrosol (as markers of virgin olive oil intake) and the proportion of oleic acid and alpha-linolenic acid (a marker of walnut intake) in whole plasma were determined at baseline and 12-month follow-up in random subsamples of participants in each intervention group.
Description of Actual Data Sample:

Initial N

1,766 participants were randomized (943 female, 823 male).

Attrition (Final N)

1,551 participants were included in analysis (12% drop-out rate)
  • 533 in the Mediterranean Diet Plus Olive Oil Group
  • 533 in the Mediterranean Diet Plus Mixed Nuts Group
  • 485 in the Control Group.

Age

Mean age of initial sample: 67.4 years.

Ethnicity

Spanish.

Other Relevant Demographics

?The three groups were balanced with respect to demographic characteristics, occupational status and educational level.

Anthropometrics

?The three groups were balanced with respect to cardiovascular risk.

Location

?Pamploma, Spain.
Summary of Results:

Key Findings

  • Participants in both Mediterranean diets increased their intake of virgin olive oil, nuts, vegetables, legumes and fruits
  • Fiber, MUFA and PUFA, linoleic acid, alpha-linolenic acid and marine n-3 fatty acid intake increased in both Mediterranean diet groups.

Significant Between-Group Changes
Differences vs. Control

  Mediterranean Diet with Olive Oil vs. Control Group Mediterranean Diet with Mixed Nuts vs. Control Group
Mean (95% CI) P-value Mean (95% CI) P-value
Virgin Olive Oil (10g) (servings/day) 3.14 (2.78, 3.51) <0.001 0.43 (0.08, 0.79) 0.01
Total Nuts (25g) (servings/day) 0.20 (0.12, 0.30) <0.001 0.98 (0.86, 1.08) <0.001
Vegetables (125g) (servings/day) 0.26 (0.10, 0.42) <0.001 0.16 (0.00, 0.32) 0.04
Legumes (40g) (servings/day) 0.12 (0.03, 0.15) <0.001 0.11 (0.06, 0.14) <0.001
Fruits (125g) (servings/day) 0.30 (0.06, 0.55) 0.01 0.25 (0.00, 0.49) 0.04
Mediterranean Diet Score 1.40 (1.10, 1.70) <0.001 1.80 (1.50, 2.10) <0.001
Fiber (g/day) 2.7 (1.6, 3.9) <0.001 3.6 (2.5, 4.7) <0.001
MUFA (% energy) 2.4 (1.7, 3.1) <0.001 1.9 (1.2, 2.6) <0.001
PUFA (% energy) 0.4 (0.1, 0.8) 0.01 2.1 (1.7, 2.4) <0.001
Linoleic Acid (g/day) 1.49 (0.54, 2.44) <0.001 5.10 (4.09, 6.10) <0.001
Alpha-Linolenic Acid (g/day) 0.24 (0.12, 0.65) <0.001 0.72 (0.60, 0.84) <0.001
Marine n-3 Fatty Acids (g/day) 0.07 (0.01, 0.14) 0.03 0.07 (0.00, 0.14) 0.03
Author Conclusion:
  • Individual motivational interventions together with group sessions and the free provision of high-fat and palatable key foods customary in a Mediterranean diet were effective in improving the dietary habits of participants in this trial who already followed a Mediterranean-type diet in part
  • Dietary changes achieved after an intervention for 12 months were similar to those observed at three months, which led to substantial improvements in various surrogate markers of cardiovascular risk in the Mediterranean Diet Groups, compared with the Control Group.
Funding Source:
Government: Spanish Ministry of Health, CIBEROBN, Navarra government, Generalitat Valenciana
In-Kind support reported by Industry: Yes
Reviewer Comments:
Strengths

Large RCT.

Limitations

  • Provided healthful foods but subjects continue after the study ended and provisions stopped
  • Dietary counseling for control was less frequent and intense
  • Potential measurement error with FFQ (as opposed to dietary record).
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? 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? 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? N/A
  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? ???
  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)? 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
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