Plasma Trimethylamine N-Oxide and Its Precursors: Population Epidemiology, Parent–Child Concordance, and Associations with Reported Dietary Intake in 11- to 12-Year-Old Children and Their Parents

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Trimethylamine N-oxide (TMAO) is a microbiome- and diet-derived metabolite implicated in adverse cardiovascular outcomes. To date, studies of plasma TMAO concentrations have largely focused on individuals with metabolic disease. As such, data on TMAO concentrations in population settings and parent–child dyads are lacking.</jats:p> </jats:sec> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>This study aimed to investigate parent–child concordance, age, and sex effects on plasma concentrations of TMAO and its precursors [l-carnitine, choline, betaine, and dimethylglycine (DMG)]. Associations between concentrations of TMAO and its precursors and self-reported dietary intakes of animal protein (i.e., red meat, meat products, chicken, fish, milk products, and cheese) and fast-food meals were also investigated.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A total of 1166 children (mean ± SD age: 11 ± 0.5 y, 51% female) and 1324 parents (mean ± SD age: 44 ± 5.1 y, 87% female) had a biomedical assessment as part of Growing Up in Australia's Child Health Checkpoint. Plasma TMAO and precursor concentrations were quantified using ultra-high-pressure LC coupled with tandem MS.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Familial dyads significantly contributed to plasma TMAO and precursor concentrations (P &amp;lt; 0.0001), explaining 37% of variance for TMAO concentrations. Least-square mean ± SE plasma TMAO was lower in children (0.79 ± 0.02 µM on the log-scale) than in adults (1.22 ± 0.02 µM). By contrast, children's betaine (40.30 ± 0.34 µM) and DMG concentrations (1.02 ± 0.01 µM on the log-scale) were higher than adults’ betaine (37.50 ± 0.32 µM) and DMG concentrations (0.80 ± 0.01 µM) (P &amp;lt; 0.0001). Mean values of all metabolites, except adult TMAO, were higher in males than in females (P &amp;lt; 0.001). Greater reported intake of red meat and fish was associated with higher TMAO concentrations in both children [estimates (95% CIs) for red meat: 0.06 (0.01, 0.10); fish: 0.11 (0.06, 0.17)] and adults [red meat: 0.13 (0.08, 0.17); meat products: 0.07 (0.03, 0.12); and fish: 0.09 (0.04, 0.14)].</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Age, sex, and shared family factors, including diet, contribute to variation in plasma concentrations of TMAO and its precursors.</jats:p> </jats:sec>

Plasma B Vitamers: Population Epidemiology and Parent-Child Concordance in Children and Adults

“…Given the ubiquitous availability of these vitamers in foods [3], different B vitamer concentrations by sex and age may solely represent differences in the amounts of foods consumed [47,48], and/or an upregulation by feedback response of the enzymatic machinery involved in metabolic reactions associated with increased energy intake and production (e.g., the Krebs cycle, amino and fatty acid metabolism). Sexual dimorphism has been observed in several groups of nutritional metabolites (e.g., vitamin B12, vitamin C, vitamin D, vitamin B6, folates, lipids, amino acids, trimethylamine N-oxide (TMAO), betaine, choline, carnitine, dimethylglycine), and genetic variants have been associated with the status of some of these metabolites [46,[49][50][51][52][53][54][55]. Differences in hormonal fluctuations, body composition, food intake, and growth rates may all explain sex-specific differences in circulating nutritional metabolites (e.g., B vitamers) [10,11,20,28,48,56].…”

Trimethylamine N-oxide (TMAO) Is not Associated with Cardiometabolic Phenotypes and Inflammatory Markers in Children and Adults

“…We reported strong family effects (i.e. 13–37% of variability explained), a positive association with age, higher concentrations in males, and positive associations with reported fish and red meat intakes ( 25 ). Building on these findings, in this population-derived cohort of parents and children (aged 11–12 y), we aimed to investigate how concentrations of TMAO and its precursors are associated with: 1 ) MetS scores; 2 ) cardiovascular preclinical phenotypes; and 3 ) circulating inflammatory biomarkers.…”

“…For the current study, a total of 2490 plasma samples (1166 children and 1324 adults) were shipped, on dry ice in thermally monitored boxes, to the Liggins Institute. Sample tubes were randomized onto 96-well FluidX plates, keeping parent-child pairs (1123 pairs) on the same plate, then stored at −80°C prior to each assay, as previously described ( 25 ).…”

“…We previously characterized parent-child concordance ( N = 1324 parents and N = 1166 children), age, and sex-effects on plasma concentrations of TMAO and its precursors (i.e. carnitine, choline, betaine, and DMG) ( 25 ). We also evaluated associations between concentrations of TMAO and precursors and self-reported dietary intakes of animal protein (i.e.…”

“…We also evaluated associations between concentrations of TMAO and precursors and self-reported dietary intakes of animal protein (i.e. red meat, meat products, chicken, fish, milk products, and cheese) and fast-food meals ( 25 ). We reported strong family effects (i.e.…”