Background: Evidence from individual trials comparing Mediterranean to low-fat diets to modify cardiovascular risk factors remains preliminary.

Methods: We systematically searched MEDLINE, EMBASE, Biosis, Web of Science, and the Cochrane Central Register of Controlled Trials from their inception until January 2011, as well as contacted experts in the field, to identify randomized controlled trials comparing Mediterranean to low-fat diets in overweight/obese individuals, with a minimum follow-up of 6 months, reporting intention-to-treat data on cardiovascular risk factors. Two authors independently assessed trial eligibility and quality.

Results: We identified 6 trials, including 2650 individuals (50% women) fulfilling our inclusion criteria. Mean age of enrolled patients ranged from 35 to 68 years, mean body mass index from 29 to 35 kg/m(2). After 2 years of follow-up, individuals assigned to a Mediterranean diet had more favorable changes in weighted mean differences of body weight (-2.2 kg; 95% confidence interval [CI], -3.9 to -0.6), body mass index (-0.6 kg/m(2); 95% CI, -1 to -0.1), systolic blood pressure (-1.7 mm Hg; 95% CI, -3.3 to -0.05), diastolic blood pressure (-1.5 mm Hg; 95% CI, -2.1 to -0.8), fasting plasma glucose (-3.8 mg/dL, 95% CI, -7 to -0.6), total cholesterol (-7.4 mg/dL; 95% CI, -10.3 to -4.4), and high-sensitivity C-reactive protein (-1.0 mg/L; 95% CI, -1.5 to -0.5). The observed heterogeneity across individual trials could, by and large, be eliminated by restricting analyses to trials with balanced co-interventions or trials with restriction of daily calorie intake in both diet groups.

Conclusion: Mediterranean diets appear to be more effective than low-fat diets in inducing clinically relevant long-term changes in cardiovascular risk factors and inflammatory markers.