Abstract

ObjectivesTrimethylamine n-oxide (TMAO) is linked to the gut microbiome's metabolism of choline, carnitine, and betaine and is associated with adverse cardiovascular health. In a secondary analysis, we assessed the plasma TMAO response to a high-fat high-sugar meal challenge devoid of choline, carnitine, or betaine in metabolically healthy male (n = 48) and female (n = 49) participants residing near Davis, California, USA.MethodsThe standardized meal challenge was a 3000-gram shake containing 60% kilocalories from fat (shortening and palm oil), 25% kilocalories from carbohydrate (granulated white sugar), and 15% kilocalories from protein (pasteurized egg white). The shake contained limited amounts of direct TMAO-precursors including 2.9 mg of choline and 0.76 mg of betaine. Blood samples were collected at fasting and 0.5, 3, and 6 hours after consuming the meal challenge. TMAO was measured by liquid chromatography-high resolution mass spectrometry using the MxP Quant 500 kit (Biocrates, Innsbruck, Austria). Differences in TMAO concentration by time were assessed by ANOVA and values are means ± standard deviation.ResultsTMAO response demonstrated a post-prandial rise in concentration that peaked at 3 hours and returned to fasting levels by 6 hours. Mean TMAO levels at fasting, 0.5, 3, and 6 hours were 5.27 ± 3.43 μM, 6.09 ± 6.01 μM, 6.87 ± 8.11 μM, 4.76 ± 4.00 μM, respectively. Significant differences were observed between fasting and 3 hours (P = 0.039), and 3 and 6 hours (P = 0.011).ConclusionsPlasma TMAO concentration was affected by a high-fat high-sugar meal challenge despite providing limited amounts of direct TMAO-precursors. The circadian rhythm of the gut microbiome or the host, or the gut microbiome's utilization of phosphatidylcholine from biological sources may contribute to these results. Understanding the regulation of TMAO and its relationship to meals is critical to identifying its role in the etiology of diabetes and cardiovascular disease.Funding SourcesThis work was funded in part by the USDA-Agricultural Research Service (2032–51,530-025–00D) and the National Institute of Health (RO1HL148110).

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