Differential effect of short-term popular diets on TMAO and other cardio-metabolic risk markers

Dietary nutrient intake and its metabolism by the gut microbiome have recently been implicated in cardiovascular disease (CVD) risk. In particular, trimethylamine N-oxide (TMAO), a metabolite of the gut microbiota, has been shown to be a predictor of incident CVD events. Elevated levels of branched-chain amino acids (BCAA) have also been associated with an increased propensity for insulin resistance. To study the association of dietary intake with systemic TMAO, its nutrient precursors, and BCAA levels on fasting plasma levels of TMAO and its nutrient precursors and BCAA, we conducted an exploratory post-hoc analysis of 3 popular diets – high fat (Atkins), Mediterranean (South Beach), and very low fat (Ornish) – using plasma samples from a prior randomized, crossover study, with each isocaloric dietary phase lasting 4 weeks. Metabolites were quantified using stable isotope dilution HPLC with on-line tandem mass spectrometry. Compared to the low fat Ornish phase, the high fat Atkins dietary phase was characterized by increased levels of TMAO (3.3 vs. 1.8 μM, p = 0.01), and the BCAA valine (272.8 vs. 235.8 μM, p = 0.005) and leucine (105.9 vs. 96.4 μM, p = 0.01). The high fat Atkins dietary phase was also associated with higher levels of TMAO (3.3 vs 1.6 μM, p = 0.04), valine (272.8 vs. 240.7 μM, p = 0.004), and leucine (105.9 vs. 96.4 μM, p = 0.01) compared to baseline. These data suggest that over a 4-week interval, a saturated fat diet that is predominantly animal-based, compared to an isocaloric, low fat, predominantly plant-based diet, is associated with heightened risk for cardiometabolic derangements, as monitored by a higher plasma levels of both TMAO and BCAA. •This is the first study to assess effects of popular diets on gut metabolites.•A high fat (Atkins) diet was associated with high levels of atherogenic metabolites.•A low fat (Ornish) diet was associated with low levels of atherogenic metabolites.