title: Intervention Trials with the Mediterranean Diet in Cardiovascular Prevention: Understanding Potential Mechanisms through Metabolomic Profiling.
abstract: Large observational epidemiologic studies and randomized trials support the benefits of a Mediterranean dietary pattern on cardiovascular disease (CVD). Mechanisms postulated to mediate these benefits include the reduction of low-grade inflammation, increased adiponectin concentrations, decreased blood coagulation, enhanced endothelial function, lower oxidative stress, lower concentrations of oxidized LDL, and improved apolipoprotein profiles. However, the metabolic pathways through which the Mediterranean diet influences CVD risk remain largely unknown. Investigating specific mechanisms in the context of a large intervention trial with the use of high-throughput metabolomic profiling will provide more solid public health messages and may help to identify key molecular targets for more effective prevention and management of CVD. Although metabolomics is not without its limitations, the techniques allow for an assessment of thousands of metabolites, providing wide-ranging profiling of small molecules related to biological status. Specific candidate plasma metabolites that may be associated with CVD include branched-chain and aromatic amino acids; the glutamine-to-glutamate ratio; some short- to medium-chain acylcarnitines; gut flora metabolites (choline, betaine, and trimethylamine N-oxide); urea cycle metabolites (citrulline and ornithine); and specific lipid subclasses. In addition to targeted metabolites, the role of a large number of untargeted metabolites should also be assessed. Large intervention trials with the use of food patterns for the prevention of CVD provide an unparalleled opportunity to examine the effects of these interventions on plasma concentrations of specific metabolites and determine whether such changes mediate the benefits of the dietary interventions on CVD risk.
authors.affiliation: Department of Preventive Medicine and Public Health, University of Navarra-Navarra Institute for Health Research, Pamplona, Spain.|Biomedical Research Networking Center Consortium-Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.
authors.forename: Miguel Á
authors.initials: MÁ
authors.lastname: Martínez-González
authors.affiliation: Department of Preventive Medicine and Public Health, University of Navarra-Navarra Institute for Health Research, Pamplona, Spain.|Biomedical Research Networking Center Consortium-Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Ruiz-Canela
authors.affiliation: Departments of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Adela
authors.initials: A
authors.lastname: Hruby
authors.affiliation: Departments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.affiliation: Hellenic Health Foundation, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Departments of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Departments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
keywords: cardiovascular disease; coronary heart disease; feeding trials; nuts; olive oil