Replacing red meat with non-soy legumes alters choline metabolites but not systemic inflammation or proxies of gut barrier function in healthy males in a 6-week RCT

While the health burden of high red and processed meat intake has been acknowledged in observational studies, studying the effects and mechanisms in controlled settings with healthy participants have generated mixed findings. We aimed to investigate whether a partial replacement of unprocessed and processed red meat (from 760 g/week to 200 g/week) with non-soy legume foods in apparently healthy men (age 37.9 y, BMI 25.5 ± 3.3 kg/m², mean±SD) yields beneficial effects on low-grade inflammation through changes in proxies of gut barrier function and choline metabolites. This study was a randomised, 6-week parallel trial with groups (allocation ratio 1:1) following their habitual diet with a reference red meat intake (Meat, n = 51) or with partial substitution with legumes (Bean, n = 51). We report no major differences in high-sensitivity-CRP or glycoprotein acetyls, Olink cytokines and immune modulators between the groups at 6-wk using one-way baseline-adjusted analysis of covariance. Lower concentration of plasma cholines, and higher urine dimethylamine excretion were observed in the Bean group (all P < 0.05), while no differences in urine trimethylamine-N-Oxide (TMAO) or gut barrier function occurred. We found BMI, TMAO, and gut barrier function explaining the variance within the Olink biomarkers, and linked some to diet, TMAO and/or gut barrier function. Partial replacement of red meat with non-soy legumes for 6-weeks altered choline metabolites but did not lead to significant changes in low-grade inflammation. Our results highlight the robustness of the inflammatory markers to changes in healthy individuals with an intact gut barrier.