Estruch · Annals of internal medicine 2006 · Multicenter randomized controlled trial · n=772

Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial.

Cited 1685 times in the scientific literature.

Level 2 - randomized trial

Multicenter randomized controlled trial

PubMed 16818923 · doi:10.7326/0003-4819-145-1-200607040-00004 · record verified 2026-08-28

What was done

This was a 3-month substudy of the PREDIMED multicenter randomized primary prevention trial across primary care centers affiliated with 10 teaching hospitals. 772 asymptomatic participants aged 55 to 80 years at high cardiovascular risk were randomized to one of three groups: a low-fat diet (n = 257), a Mediterranean diet supplemented with free virgin olive oil (1 L/week, n = 257), or a Mediterranean diet supplemented with free nuts (30 g/day, n = 258). Participants in the Mediterranean diet groups received nutritional education. Measured outcomes at 3 months were body weight, blood pressure, lipid profile, plasma glucose levels, and inflammatory molecules.

What was found

The completion rate was 99.6%. Compared with the low-fat diet, the 2 Mediterranean diets produced beneficial changes in most outcomes. Compared with the low-fat diet, mean changes in the Mediterranean diet with olive oil and nuts groups were: plasma glucose -0.39 mmol/L (95% CI, -0.70 to -0.07 mmol/L) and -0.30 mmol/L (CI, -0.58 to -0.01 mmol/L); systolic blood pressure -5.9 mm Hg (CI, -8.7 to -3.1 mm Hg) and -7.1 mm Hg (CI, -10.0 to -4.1 mm Hg); and cholesterol-to-HDL cholesterol ratio -0.38 (CI, -0.55 to -0.22) and -0.26 (CI, -0.42 to -0.10), respectively. The olive oil Mediterranean diet reduced C-reactive protein levels by 0.54 mg/L (CI, 1.04 to 0.03 mg/L) versus low-fat.

Why it matters

This trial provides clear short-term experimental evidence that Mediterranean diets enriched with virgin olive oil or nuts improve multiple intermediate markers of cardiovascular risk more effectively than a standard low-fat diet.

Limits

The intervention lasted only 3 months and measured intermediate biomarkers rather than clinical cardiovascular endpoints. Nutritional education was less intense for the low-fat control group than for the Mediterranean diet groups. The study population was limited to older individuals at high cardiovascular risk.

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