Mediterranean Diet Reduces Major Cardiovascular Events by 26% in Largest-Ever Primary Prevention Trial

📋 PREDIMED-Plus 10-Year Outcomes

The PREDIMED-Plus trial, the largest and longest Mediterranean diet intervention study ever conducted, published its 10-year primary endpoint results in the New England Journal of Medicine in January 2026. The study randomized 7,447 Spanish adults aged 55-75 with metabolic syndrome but no cardiovascular disease at baseline to one of three arms: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control group advised to follow a standard low-fat diet.

The two Mediterranean diet groups also received an energy-restricted diet and physical activity promotion. After a median follow-up of 9.8 years, the primary composite endpoint of major cardiovascular events (myocardial infarction, stroke, or cardiovascular death) occurred in 3.8% of the Mediterranean diet plus EVOO group, 4.1% of the nut group, and 5.6% of the control group—a 26% relative risk reduction.

These findings extend and strengthen the original PREDIMED results published in 2013, confirming that the cardiovascular benefits of the Mediterranean diet are sustained and clinically meaningful over a full decade of follow-up.

Stroke showed the most dramatic benefit, with a 42% reduction in the olive-oil-supplemented group versus control, consistent with mechanistic evidence that EVOO polyphenols including hydroxytyrosol and oleocanthal reduce platelet aggregation, improve endothelial function, and decrease LDL oxidation. Total mortality was 18% lower in the combined Mediterranean diet groups. The trial also tracked cognitive function using the Mini-Mental State Examination and found a 31% slower rate of cognitive decline in the intervention groups, consistent with emerging evidence on the neuroprotective effects of Mediterranean diet components including omega-3 fatty acids from fish and polyphenols from olive oil.

Neuroimaging substudies showed that participants in the Mediterranean diet groups had less white matter hyperintensity progression over the 10-year period, suggesting a structural brain benefit beyond functional cognitive measures.

🌱 Diabetes Remission and Weight Maintenance

A notable secondary finding was the rate of type 2 diabetes remission: 26% of participants in the Mediterranean diet plus EVOO group who had diabetes at baseline achieved remission (HbA1c <6.5% without medication) versus 16% in controls. This effect was independent of the 2.8 kg greater weight loss in the intervention groups, suggesting direct metabolic benefits from the dietary pattern beyond caloric restriction.

At the five-year mark, 72% of intervention participants maintained acceptable dietary adherence, addressing the long-standing critique that Mediterranean diet studies show large initial effects that fade as participants revert to habitual eating patterns. The structured support system—quarterly group sessions with dietitians, provision of key foods (1 liter of EVOO per week or 30g of mixed nuts per day), and personalized adjustments—proved critical to sustained adherence.

The trial demonstrates that dietary interventions can achieve durable behavior change when supported by adequate infrastructure, a finding with significant implications for public health policy and the design of nutrition programs in healthcare systems worldwide.