Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts
Ramon Estruch, Emilio Ros, Jordi Salas-Salvado, Maria-Isabel Covas, Dolores Corella, Fernando Aros, Enrique Gomez-Gracia, Valentina Ruiz-Gutierrez, Miquel Fiol, Jose Lapetra, Rosa M Lamuela-Raventos, Lluis Serra-Majem, Xavier Pinto, Josep Basora, Miguel A Munoz, Jose V Sorli, J Alfredo Martinez, Montserrat Fito, Alfredo Gea, Miguel A Hernan, Miguel A Martinez-Gonzalez, PREDIMED Study Investigators - New England Journal of Medicine, 2018
In high-risk Spanish adults without cardiovascular disease, a Mediterranean diet supplemented with extra-virgin olive oil or mixed nuts reduced major cardiovascular events versus a reduced-fat control diet (hazard ratios 0.69 and 0.72). Absolute event rates were low, so the absolute reduction was modest, and the composite benefit was driven largely by stroke. This is the 2018 corrected-and-republished version: the original 2013 report was withdrawn after randomization protocol deviations were identified, though the revised hazard ratios were essentially unchanged.
Key findings
- Mediterranean diet with extra-virgin olive oil reduced major cardiovascular events versus control: HR 0.69 (95% CI 0.53-0.91).
- Mediterranean diet with mixed nuts reduced major cardiovascular events versus control: HR 0.72 (95% CI 0.54-0.95).
- Absolute event rates were low (control about 4.4% vs roughly 3.4-3.8% in the diet groups), so the absolute risk reduction was modest (about 0.6-1.0 percentage points over about 4.8 years).
- This is the 2018 corrected-and-republished version after the 2013 report was withdrawn for randomization protocol deviations; revised hazard ratios were essentially unchanged.
Effect measures
- Hazard Ratio: 0.6995% CI 0.53-0.91
- Hazard Ratio: 0.7295% CI 0.54-0.95
Why this evidence tier (Moderate)
- Risk of bias:
- A randomized trial, but the integrity of randomization is the central concern: the original 2013 report was withdrawn after protocol deviations (enrollment of household members without randomization, non-randomized assignment at one site, inconsistent randomization tables at another). The 2018 re-analysis no longer relies solely on the assumption that all participants were randomly assigned.
- Precision:
- Adequately sized (7,447 participants); both hazard-ratio intervals exclude 1.0, though they sit close to it.
- Directness:
- Directly tests a dietary pattern against hard cardiovascular events in a primary-prevention population, exactly the question of interest.
- Consistency:
- Revised estimates were essentially unchanged from the 2013 figures and align with broader evidence favouring Mediterranean dietary patterns.
- Funding / COI:
- Funded by the Spanish government agency Instituto de Salud Carlos III, but supplemental foods were donated by industry: extra-virgin olive oil by Hojiblanca and Patrimonio Comunal Olivarero, walnuts by the California Walnut Commission, almonds by Borges, and hazelnuts by Morella Nuts. Co-authors E. Ros and J. Salas-Salvado report nut-industry grants and advisory roles. Food-industry donations supporting a trial that found benefit from those very foods is a relevant conflict; sponsors are stated to have had no role in design or analysis.
Moderate certainty. A positive primary-prevention diet trial, downgraded by the randomization protocol deviations behind its withdrawal and republication and by food-industry donations, and tempered by a modest absolute benefit.
- Population:
- Spanish adults aged 55-80 years (57% women) at high cardiovascular risk but without cardiovascular disease at enrollment; primary prevention; multicenter trial in Spain; median follow-up 4.8 years.
- Conflicts of interest:
- Government-funded, but extra-virgin olive oil and nuts were donated by the food industry - a relevant conflict for a trial reporting benefit from those foods. Co-authors E. Ros and J. Salas-Salvado disclose nut-industry research grants and unpaid advisory roles. Sponsors and donors are stated to have had no role in design, analysis, or reporting.
- Funding:
- Instituto de Salud Carlos III (Spanish government; CIBEROBN / RTIC networks). Supplemental foods donated by industry: olive oil (Hojiblanca, Patrimonio Comunal Olivarero), walnuts (California Walnut Commission), almonds (Borges), hazelnuts (Morella Nuts).
Limitations
- The original 2013 report (PMID 23432189) was withdrawn after randomization protocol deviations were identified; this is the 2018 corrected-and-republished version (erratum PMID 29897867).
- Absolute event rates were low and the absolute risk reduction was modest (about 0.6-1.0 percentage points over about 4.8 years).
- Supplemental olive oil and nuts were donated by food companies whose products the trial found beneficial.
- Conducted in high-cardiovascular-risk Spanish adults, which limits generalizability to lower-risk or non-Mediterranean populations.