Trimethylamine-N-oxide (TMAO) is a microbiota-dependent and primarily animal-protein-derived proatherogenic metabolite. The ecological impact of pork—the most popular animal protein worldwide—on the human microbiome, and in the physiological context of TMAO and other biogenic amines, remains unknown. Poultry being the recommended heart-healthier animal protein, we investigated—if pork intake results in inferior-to-chicken TMAO-response while consuming a diet based on the Dietary Guidelines for Americans (DGA).

Methods and Results

In a randomized, controlled, all-food-provided, crossover, feeding trial, healthy adults consumed 156 g day−1 of lean-pork or chicken (active-control) as primary proteins. Mixed-effect modeling shows pork as noninferior to chicken for circulating TMAO response and microbiota-generated essential TMAO-precursor—trimethylamine (97.5% CI, n = 36/protein). Markers of lipid metabolism, inflammation and oxidative stress, serum levels of betaine, choline, L-carnitine, composition and functional-capability of the microbiota, and association of baseline TMAO-levels with TMAO-response (both, r > 0.6, p = 0.0001) are nondistinguishable between the protein groups. TMAO reduction and similar shifts in microbiota and biogenic-amine signatures postdiet in both groups indicate a background DGA-effect.


Unlike extrapolating negative results, this study presents noninferiority-testing based evidence. Consuming pork as a predominant protein within an omnivorous DGA-diet does not exacerbate TMAO-response. Results highlight the importance of understanding protein-TMAO interactions within dietary patterns.