Review ArticlesThe Mediterranean Diet and Cardiovascular Disease Gaps in the Evidence and Research ChallengesTemple, Norman J PhD*; Guercio, Valentina PhD†; Tavani, Alessandra SciD‡ Author Information From the *Centre for Science, Athabasca University, Alberta, Canada †Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy ‡IRCCS-Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy. Disclosure: The author declares no conflict of interest. Correspondence: Norman J. Temple, PhD, Centre for Science, Athabasca University, Athabasca, Alberta T9S 3A3, Canada. E-mail: [email protected]. Cardiology in Review 27(3):p 127-130, May/June 2019. | DOI: 10.1097/CRD.0000000000000222 Buy Metrics Abstract In this article, we critically evaluate the evidence relating to the effects of the Mediterranean diet (MD) on the risk of cardiovascular disease (CVD). Strong evidence indicating that the MD prevents CVD has come from prospective cohort studies. However, there is only weak supporting evidence from randomized controlled trials (RCTs) as none have compared subjects who follow an MD and those who do not. Instead, RCTs have tested the effect of 1 or 2 features of the MD. This was the case in the Prevenciόn con Dieta Mediterránea (PREDIMED) study: the major dietary change in the intervention groups was the addition of either extravirgin olive oil or nuts. Meta-analyses generally suggest that the MD causes small favorable changes in risk factors for CVD, including blood pressure, blood glucose, and waist circumference. However, the effect on blood lipids is generally weak. The MD may also decrease several biomarkers of inflammation, including C-reactive protein. The 7 key features of the MD can be divided into 2 groups. Some are clearly protective against CVD (olive oil as the main fat; high in legumes; high in fruits/vegetables/nuts; and low in meat/meat products and increased in fish). However, other features of the MD have a less clear relationship with CVD (low/moderate alcohol use, especially red wine; high in grains/cereals; and low/moderate in milk/dairy). In conclusion, the evidence indicates that the MD prevents CVD. There is a need for RCTs that test the effectiveness of the MD for preventing CVD. Key design features for such a study are proposed. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.