Diet, Trimethylamine Metabolism, and Mitochondrial DNA: An Observational Study

Scope Mitochondrial DNA copy number (mtDNAcn) and its methylation level in the D‐loop area have been correlated with metabolic health and are suggested to vary in response to environmental stimuli, including diet. Circulating levels of trimethylamine‐n‐oxide (TMAO), which is an oxidative derivative of the trimethylamine (TMA) produced by the gut microbiome from dietary precursors, have been associated with chronic diseases and are suggested to have an impact on mitochondrial dynamics. This study is aimed to investigate the relationship between diet, TMA, TMAO, and mtDNAcn, as well as DNA methylation. Methods and results Two hundred subjects with extreme (healthy and unhealthy) dietary patterns are recruited. Dietary records are collected to assess their nutrient intake and diets’ quality (Healthy Eating Index). Blood levels of TMA and TMAO, circulating levels of TMA precursors and their dietary intakes are measured. MtDNAcn, nuclear DNA methylation long interspersed nuclear element 1 (LINE‐1), and strand‐specific D‐loop methylation levels are assessed. There is no association between dietary patterns and mtDNAcn. The TMAO/TMA ratio is negatively correlated with d ‐loop methylation levels but positively with mtDNAcn. Conclusions These findings suggest a potential association between TMA metabolism and mitochondrial dynamics (and mtDNA), indicating a new avenue for further research.