Processed plant-based meat-supplemented diet versus red meat-based supplemented diet randomized cross-over trial Finding Optimal Oral Diet-1 (FOOD-1) trial

Serum Trimethylamine N-oxide (TMAO) is heightened by red-meat rich diets and associated with increased cardiovascular risk. Replacing red-meat with plant-based sources may reduce TMAO levels. FOOD-1 is a randomized, single-centre, open-label, cross-over trial. Participants were randomly assigned to a plant-based meat-supplemented diet or red-meat supplemented diet for 6 days and subsequently underwent cross-over. A 7-day washout period was required before randomization and cross-over. The primary endpoint was the between diets difference in TMAO levels. Secondary endpoints included differences in blood pressure, weight, lipid profile and N-terminal pro B-type natriuretic peptide (NTproBNP). A total of 41 participants were included, 20 assigned firstly to the plant supplemented and 21 to the red meat supplemented diet. The median age was 51(37–59) years, 46% were women and 32% had atherosclerotic cardiovascular disease. Compared with the red-meat supplemented diet, the plant-based meat supplemented diet resulted in lower TMAO levels: -0.61 log units (95% CI -0.90 to -0.33, P < 0.001). The plant-based diet was also associated with lower LDL cholesterol: -6.0 mg/dL (95%CI -10.0 to -1.9), higher body weight: + 0.6 kg (95%CI + 0.1 to + 1.0), and NTproBNP: + 0.19 log units (95%CI + 0.04 to + 0.35). No significant sequence effects were observed. In the metabolomics analysis, 11 metabolites were differently expressed by the two tested diets, related to male steroid hormone synthesis in cardiomyocyte energy and fatty acid biosynthesis. Compared to a red meat-based supplemented diet, a plant-based meat supplemented diet led to significantly lower TMAO levels, suggesting that replacing red-meat with a plant-based diet may lead to a more favourable metabolic risk profile. Trial registration: ClinicalTrials.gov Identifier: NCT04510324.