mini-MED: study protocol for a randomized, multi-intervention, semi-controlled feeding trial of a Mediterranean-amplified vs. habitual Western dietary pattern for the evaluation of food-specific compounds and cardiometabolic health

BackgroundDiet is among the most influential lifestyle factors impacting chronic disease risk. Nutrimetabolomics, the application of metabolomics to nutrition research, allows for the detection of food-specific compounds (FSCs) that can be used to connect dietary patterns, such as a Mediterranean-style (MED) diet, to health. This validation study is based upon analyses from a controlled feeding MED intervention, where our team identified FSCs from eight foods that can be detected in biospecimens after consumption and may therefore serve as food intake biomarkers.MethodsIndividuals with overweight/obesity who do not habitually consume a MED dietary pattern will complete a 16-week randomized, multi-intervention, semi-controlled feeding study of isocaloric dietary interventions: (1) MED-amplified dietary pattern, containing 500 kcal/day from eight MED target foods: avocado, basil, cherry, chickpea, oat, red bell pepper, walnut, and a protein source (alternating between salmon or unprocessed, lean beef), and (2) habitual/Western dietary pattern, containing 500 kcal/day from six non-MED target foods: cheesecake, chocolate frozen yogurt, refined grain bread, sour cream, white potato, and unprocessed, lean beef. After a 2-week washout, participants complete four, 4-week intervention periods, with biospecimen sampling and outcome assessments at baseline and at intervention weeks 4, 8, 12, and 16. The primary outcome is change in the relative abundance of FSCs from the eight MED target foods in participant biospecimens from baseline to the end of each intervention period. Secondary outcomes include mean change in cardiometabolic health indicators, inflammatory markers, and adipokines. Exploratory outcomes include change in diversity and community composition of the gut microbiota.DiscussionOur stepwise strategy, beginning with identification of FSCs in whole diets and biospecimens, followed by relating these to health indicators will lead to improved methodology for assessment of dietary patterns and a better understanding of the relationship between food and health. This study will serve as a first step toward validating candidate food intake biomarkers and allow for assessment of relationships with cardiometabolic health. The identification of food intake biomarkers is critical to future research and has implications spanning health promotion and disease prevention for many chronic conditions.Trial registrationRegistered at ClinicalTrials.gov: NCT05500976; Date of registration: August 15, 2022.