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Citation:

Estruch R, Martínez-González MA, Corella D, Salas-Salvadó J, Ruiz-Gutiérrez V, Covas MI, Fiol M, Gómez-Gracia E, López-Sabater MC, Vinyoles E, Arós F, Conde M, Lahoz C, Lapetra J, Sáez G, Ros E; PREDIMED Study Investigators. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006; 145(1): 1-11.


PubMed ID: 16818923
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
POSITIVE: See Research Design and Implementation Criteria Checklist below.
Research Purpose:

To compare the short-term effects of two Mediterranean diets vs. those of a low-fat diet on intermediate markers of cardiovascular risk.

Inclusion Criteria:

Community-dwelling men 55 to 80 years of age and women 60 to 80 years of age who fulfilled at least one of two criteria:

  • Type 2 diabetes
  • Three or more CHD risk factors:
    • Current smoking
    • Hypertension (blood pressure higher than 140/90mm Hg or treatment with anti-hypertensive drugs)
    • Low density lipoprotein (LDL) cholesterol level of 4.14mmol per L or higher (160mg per dL or more) or treatment with hypolipidemic drugs
    • High density lipoprotein (HDL) cholesterol level 1.04mmol per L or lower (40mg per dL or lower)
    • Body mass index (BMI) 25kg/m2 or higher
    • Family history of premature CHD.
Exclusion Criteria:
  • History of cardiovascular disease
  • 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 the stages-of-change model.
Description of Study Protocol:

Study Description

  • Sub-study of a multi-center, randomized, primary prevention trial of cardiovascular disease (Prevencio´n con Dieta Mediterra´nea [PREDIMED] Study)  
  • 772 asymptomatic persons 55 to 80 years of age at high cardiovascular risk who were recruited from October 2003 to March 2004
  • Participants were assigned to a low-fat diet (N=257) or to one of two Mediterranean diets. Those allocated to Mediterranean diets received nutritional education and either free virgin olive oil, 1L per week (N=257) or free nuts, 30g per day (N=258)
  • Body weight, blood pressure, lipid profile, glucose levels, and inflammatory molecules were measured at baseline and endpoint.

Study Duration

Three months.

Location

Spain.

Data Collection Summary:

Dietary Assessment Method

The baseline examination included the administration of a 14-item questionnaire that assessed the degree of adherence to the traditional Mediterranean diet. Also administered was a 137-item validated food frequency questionnaire (FFQ).

Dietary Index/Score Used

Score of zero or one for adherence to the traditional Mediterranean diet.

Index/Score Components

Consumption (amount and frequency) of:

  •  Mediterranean foods:
    • Olive oil
    • Vegetables
    • Fruits
    • Wine
    • Shellfish
    • Nuts
    • Legumes
    • Tomato sauce
  •  Non-Mediterranean foods:
    • Red meats
    • Butter
    • Carbonated beverages
    • Pastries.

Outcomes Measured

  • Body weight
  • Blood pressure
  • Lipid profile
  • Glucose levels
  • Inflammatory molecules.

Methods of Outcome Assessment

  • Trained personnel measured:
    • Weight and height by using calibrated scales and a wall-mounted stadiometer, respectively
    • Waist circumference (WC) midway between the lowest rib and the iliac crest by using an anthropometric tape
    • Blood pressure in triplicate with a validated semiautomatic oscillometer
  • Samples of serum, EDTA plasma, and urine were coded, then shipped to central laboratories. The clinical investigators and laboratory technicians were blinded to the interventions.
  • Analytes determined for each participant in frozen samples of whole serum or plasma as appropriate were:
    • Blood glucose level by the glucose–oxidase method
    • Serum insulin level by radioimmunoassay
    • Cholesterol and triglyceride levels by enzymatic procedures
    • HDL-cholesterol level after precipitation with phosphotungstic acid and magnesium chloride
    • Apolipoproteins A1 and B levels by using turbidimetry
    • Soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and interleukin-6 levels by standard enzyme-linked immunosorbent assays
    • High-sensitivity C-reactive protein (CRP) level by particle-enhanced immunonephelometry
  • In participants without diabetes, insulin resistance was measured by using the homeostasis model assessment method
  • In a random sample of 273 participants (35%), urinary tyrosol and hydroxytyrosol levels were measured by gas chromatography–mass spectrometry as markers of adherence to virgin olive oil intake and the alpha-linolenic acid plasma content was measured by gas chromatography as a measure of adherence to nut (walnut) intake.
Description of Actual Data Sample:
  • Sample size:
    • 930 assessed
    • 158 excluded
    • N=772 randomized
    • N=3 (less than 0.1%) withdrew
    • Final N=769
    • Excluded from food, energy, nutrient calculations due to unrealistic energy intakes:
      • 21 in the Mediterranean diet plus olive oil group
      • 19 in the Mediterranean diet plus nuts group
      • Eight in the low-fat diet group.

  • Age: 50 to 80 years
  • Gender: For three diet groups:
    • Mediterranean diet plus olive oil group: 60% female
    • Mediterranean diet plus nuts group: 50% female
    • Low-fat diet group: 58% female
  • Race/Ethnicity:
    • 697 of 772: Europeans of Spanish descent
    • 75 of 772: Hispanic from Central and South America
  • Socioeconomic status:
    • Occupation:
      • 23% unskilled
      • Approximately 37% manual skilled
      • 23% non-manual skilled
      • Approximately 17% directive and professional
  • Education:
    • 73% primary
    • 16% first-degree high school
    • 12% high school or university
  • Baseline weight status: 90% overweight or obese (BMI 25kg/m2 or higher)
  • Baseline distribution of dietary patterns:
    • Mean changes and 95% CI (month three minus baseline Mediterranean Diet Score) within groups listed:
      • Mediterranean diet plus olive oil group: 2.2 (1.9 to 2.4)
      • Mediterranean diet plus nuts group: 2.8 (2.6 to 3.1)
      • Low-fat diet group: -0.1 (-0.3 to 0.2).
Summary of Results:

Findings: 

Results Related to Change in Systolic Blood Pressure (SBP)

Significant difference between diet groups (both Mediterranean diets vs. low-fat diet, P<0.001). Mean mm Hg change (95% CI):

  • Mediterranean diet and olive oil: –4.8 (–6.7 to –2.7)
  • Mediterranean diet and nuts: –6.5 (–8.7 to –4.3)
  • Low-fat diet: 0.64 (–1.30 to 2.30).

Results Related to Change in Diastolic Blood Pressure (DBP)

Significant difference between diet groups (both Mediterranean diets vs. low-fat diet, P<0.05). Mean mm Hg change (95% CI):

  • Mediterranean diet and olive oil: –2.5 (–3.5 to –1.5)
  • Mediterranean diet and nuts: –3.6 (–4.7 to –2.5)
  • Low-fat diet: –0.85 (–1.79 to 0.09).

Results Related to Change in Fasting Blood Glucose

Significant difference between diet groups (both Mediterranean diets vs. low-fat diet, P<0.05). Mean mg per dL change (95% CI):

  • Mediterranean diet and olive oil: –3.8 (–7.4 to –0.2)
  • Mediterranean diet and nuts: –2.5 (–5.5 to 0.5)
  • Low-fat diet: 3.5 (–1.0 to 8.0). 

Results Related to Change in Fasting Insulin

Significant difference between diet groups (both Mediterranean diets vs. low-fat diet, P≤0.001). Mean pmol per L change (95% CI):

  • Mediterranean diet and olive oil: –9.7 (–15.3 to –3.8)
  • Mediterranean diet and nuts: –9.7 (–15.9 to –3.5)
  • Low-fat diet: 6.5 (–3.8 to 16.7).

Results Related to Change in Total Cholesterol

Significant difference in one comparison (Mediterranean diet and nuts vs. low-fat diet, P≤0.05). Mean mg per dL change (95% CI):

  • Mediterranean diet and olive oil: –3.90 (–8.10 to 0.35)
  • Mediterranean diet and nuts: –5.0 (–8.6 to –1.4)
  • Low-fat diet: 0.74 (–3.80 to 5.30).

Results Related to Change in LDL-Cholesterol

No significant difference across groups. Mean mg per dL change (95% CI):

  • Mediterranean diet and olive oil: –5.8 (–9.8 to –1.8)
  • Mediterranean diet and nuts: –3.80 (–7.30 to –0.39)
  • Low-fat diet: –0.56 (–4.60 to 3.50).

Results Related to Change in HDL-Cholesterol

Significant difference between diet groups (both Mediterranean diets vs. low-fat diet, P≤0.01). Mean mg per dL change (95% CI):

  • Mediterranean diet and olive oil: 2.4 (3.1 to 1.6) 0.94 (0.10 to 1.80)
  • Mediterranean diet and nuts:0.94 (0.10 to 1.80)
  • Low-fat diet: –0.37 (–1.20 to 0.40).

Results Related to Change in Serum Triglyerides

Significant difference in one comparison (Mediterranean diet-nut vs. low-fat diet, P≤0.05). Mean mg per dL change (95% CI):

  • Mediterranean diet and olive oil: –3.0 (–11.8 to 5.9)
  • Mediterranean diet and nuts: –7.6 (–14.0 to –1.1)
  • Low-fat diet: 2.4 (–4.4 to 9.2).

Results Related to Change in Body Weight

No difference across diet groups. Mean (95% CI):

  • Mediterranean diet and olive oil: –0.19 (–0.46 to 0.07)
  • Mediterranean diet and nuts: –0.26 (–0.59 to 0.08)
  • Low-fat diet: –0.24 (–0.48 to 0.01).

Results Related to BMI.

No difference across diet groups. Mean (95% CI):

  • Mediterranean diet and olive oil: –0.12 (–0.24 to 0.06)
  • Mediterranean diet and nuts: –0.09 (–0.24 to 0.05)
  • Low-fat diet: –0.37 (–1.20 to 0.44).

Results Related to Prevalence/Incidence of Overweight/Obesity

None.

Results Related to Waist Circumference

No difference across diet groups. Mean in cm (95% CI):

  • Mediterranean diet and olive oil:–0.82 (–1.80 to 0.14)
  • Mediterranean diet and nuts: –0.29 (–0.95 to 0.37)
  • Low-fat diet: –0.37 (–1.20 to 0.44).

Results Related to Percent Body Fat

None.

Confounders
Total Energy Intake Physical Activity Baseline BMI Sex Age Alcohol Intake Others
    x (body weight) x x    

 

 

 

Author Conclusion:

Conclusion

Compared with a low-fat diet, Mediterranean diets supplemented with olive oil or nuts have beneficial effects on cardiovascular risk factors.

Strengths and limitations

  • Ensuring adherence to dietary instructions is difficult in a feeding trial
  • Nutritional education about low-fat diet was less intense than education about Mediterranean diets.

 

Reviewer Comments:

Results support the conclusions that both Mediterranean diets improve CVD risk factors. However, the free Mediterranean diet components (olive oil, nuts) provided to participants and the dietitian support and biochemical tests for dietary compliance likely raised participant compliance to a level not typical of people receiving general dietary advice who attempt to follow the Mediterranean diet on their own. 

 


Research Design and Implementation 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 nutrition or dietetics practice?
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 used? (Concurrent preferred over historical controls.)
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?
Yes
  3.5. If case control or cross-sectional 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. Criterion may not be applicable in some cross-sectional studies.)
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?
N/A
  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.)
No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?
No
  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?
No
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?
No
  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?
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?
No
  10.1. Were sources of funding and investigators’ affiliations described?
Yes
  10.2. Was the study free from apparent conflict of interest?
No