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 aimed to investigate the relationship between diet, TMA, TMAO, and mtDNAcn, as well as methylation. Methods and results 200 subjects with extreme (healthy and unhealthy) dietary patterns were recruited. Dietary records were collected to assess their diets’ quality (Healthy Eating Index). Blood levels of TMA and TMAO, circulating levels of TMA precursors and their dietary intakes were measured. MtDNAcn, nuclear DNA methylation (LINE-1) and strand-specific D-loop methylation levels were assessed. There was no association between dietary patterns and mtDNAcn. The TMAO/TMA ratio was 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.