Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra‐Virgin Olive Oil or Nuts

Multicenter randomized trial in Spain among adults without established cardiovascular disease but at high cardiovascular risk. Participants were assigned 1:1:1 to Mediterranean diet with extra-virgin olive oil, Mediterranean diet with nuts, or reduced-fat control; the active intervention arms included 2543 participants in the EVOO group and 2454 in the nuts group.

The active intervention was a Mediterranean diet supplemented with either extra-virgin olive oil or mixed nuts, compared with a reduced-fat control diet. The EVOO group received 1 liter of extra-virgin olive oil per household per week, with advice to consume at least 4 tablespoons per person per day and a free supply of 15 liters every 3 months; the nuts group received 30 g/day per person of mixed nuts (15 g walnuts, 7.5 g hazelnuts, 7.5 g almonds) with free 3-month allotments. No total calorie restriction was advised.

Both Mediterranean diet supplementation strategies reduced major cardiovascular events compared with the reduced-fat control diet in this high-risk primary-prevention population. Primary end-point events were 96 (3.8%) with EVOO, 83 (3.4%) with nuts, and 109 (4.4%) with control; adjusted hazard ratios versus control were 0.69 (0.53-0.91) for EVOO and 0.72 (0.54-0.95) for nuts. Incidence rates per 1000 person-yr were 8.1, 8.0, and 11.2, respectively. No relevant diet-related adverse effects were reported.

The intervention was dietary and could not be fully blinded, and adherence relied on questionnaires plus biomarker assessment in subsamples rather than full-arm biochemical verification. The trial was conducted in a specific high-risk Spanish population, which may limit generalizability to other settings. Some site-level randomization deviations were noted in the source packet.