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

Andraos, Stephanie; Jones, Bronwyn; Lange, Katherine; Clifford, Susan A; Thorstensen, Eric B.; Kerr, Jessica A; Wake, Melissa; Saffery, Richard; Burgner, David; O’Sullivan, Justin M.

doi:10.1093/cdn/nzaa179

Cited by 20 publications

(19 citation statements)

References 66 publications

(61 reference statements)

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“…The key finding that plasma TMAO did not change after dietary choline intake is at odds with some former studies indicating positive associations with TMAO concentrations and adverse cardiovascular outcomes [ 11 , 35 , 38 , 39 , 40 , 41 , 42 ], although past findings are inconsistent [ 43 , 44 , 45 ]. However, this result is consistent with the previously recognized mechanistic role of TMAO in accelerated atherosclerosis [ 46 ] and hints that increased production of the gut microbiota-dependent PC metabolite, TMAO, rather than the presence of or exposure to its substrates (e.g., choline, carnitine, betaine, etc. ), is probably the overriding factor for the development of future cardiovascular events in humans.…”

Section: Discussionsupporting

confidence: 90%

Comparison between Egg Intake versus Choline Supplementation on Gut Microbiota and Plasma Carotenoids in Subjects with Metabolic Syndrome

et al. 2022

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We previously demonstrated that intake of three eggs/d for 4 weeks increased plasma choline and decreased inflammation in subjects with metabolic syndrome (MetS). The purpose of the current study was to further explore the effects of phosphatidylcholine (PC) provided by eggs versus a choline bitartrate (CB) supplement on the gut microbiota, trimethylamine N-oxide (TMAO) formation, and plasma carotenoids lutein and zeaxanthin in MetS. This randomized, controlled crossover clinical trial included 23 subjects with MetS. Following a washout period of 2 weeks without consuming any choline-containing foods, subjects were randomly allocated to consume either three eggs/d or a CB supplement for 4 weeks (both diets had a choline equivalent of 400 mg/day). DNA was extracted from stool samples to sequence the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and the α-diversity of the community were determined using QIIME software. Plasma TMAO, methionine, betaine, and dimethylglycine (DMG) were quantified by stable isotope dilution liquid chromatography with tandem mass spectrometry. Plasma carotenoids, lutein, and zeaxanthin were measured using reversed-phase high-performance liquid chromatography. There were significant increases in plasma lutein and zeaxanthin after egg intake compared to the baseline or intake of CB supplement (p < 0.01). In contrast, TMAO was not different between treatments compared to the baseline (p > 0.05). Additionally, while diet intervention had no effects on microbiota diversity measures or relative taxa abundances, a correlation between bacterial biodiversity and HDL was observed. Following egg intake, the observed increases in plasma lutein and zeaxanthin may suggest additional protection against oxidative stress, a common condition in MetS.

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Section: Discussionsupporting

confidence: 90%

Comparison between Egg Intake versus Choline Supplementation on Gut Microbiota and Plasma Carotenoids in Subjects with Metabolic Syndrome

et al. 2022

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“…For example, TMAO was not associated with atherosclerosis measures in healthy early-middle-aged adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study [ 34 ]. Furthermore, in a cohort of parents and children, TMAO was not related to metabolic syndrome nor markers of cardiovascular risk in either generation [ 35 ]. Thus, determining the relationships between TMAO and risk factors of CVD remain an important area of research prior to adopting dietary modifications to reduce TMAO concentrations.…”

Section: Discussionmentioning

confidence: 99%

Diet, Fecal Microbiome, and Trimethylamine N-Oxide in a Cohort of Metabolically Healthy United States Adults

et al. 2022

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TMAO is elevated in individuals with cardiometabolic diseases, but it is unknown whether the metabolite is a biomarker of concern in healthy individuals. We conducted a cross-sectional study in metabolically healthy adults aged 18–66 years with BMI 18–44 kg/m2 and assessed the relationship between TMAO and diet, the fecal microbiome, and cardiometabolic risk factors. TMAO was measured in fasted plasma samples by liquid chromatography mass spectrometry. The fecal microbiome was assessed by 16S ribosomal RNA sequencing and recent food intake was captured by multiple ASA24 dietary recalls. Endothelial function was assessed via EndoPAT. Descriptive statistics were computed by fasting plasma TMAO tertiles and evaluated by ANOVA and Tukey’s post-hoc test. Multiple linear regression was used to assess the relationship between plasma TMAO and dietary food intake and metabolic health parameters. TMAO concentrations were not associated with average intake of animal protein foods, fruits, vegetables, dairy, or grains. TMAO was related to the fecal microbiome and the genera Butyribrio, Roseburia, Coprobaciullus, and Catenibacterium were enriched in individuals in the lowest versus the highest TMAO tertile. TMAO was positively associated with α-diversity and compositional differences were identified between groups. TMAO was not associated with classic cardiovascular risk factors in the healthy cohort. Similarly, endothelial function was not related to fasting TMAO, whereas the inflammatory marker TNF-α was significantly associated. Fasting plasma TMAO may not be a metabolite of concern in generally healthy adults unmedicated for chronic disease. Prospective studies in healthy individuals are necessary.

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“…In our study sample, there was no link between plasma TMAO and markers of inflammation, and plasma TMAO concentrations were lower than those linked to poor health outcomes in adults ( 29 ). Similarly, a study of healthy 11-y-old children in Australia found no association between TMAO and inflammatory biomarkers or indicators of metabolic syndrome ( 30 ). Given the unclear biological significance of plasma TMAO in young children, this finding does not warrant restriction of egg intake during the complementary feeding period.…”

Section: Discussionmentioning

confidence: 99%

Plasma Choline Concentration Was Not Increased After a 6-Month Egg Intervention in 6–9-Month-Old Malawian Children: Results from a Randomized Controlled Trial

Bragg

Prado

Zyba

et al. 2022

Current Developments in Nutrition

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Background Eggs are a rich source of choline, an essential nutrient important for child growth and development. In a randomized trial of one egg/day among young children in Ecuador, an egg intervention led to significant improvements in growth, which was partially mediated by increased plasma choline concentration. A similar trial in Malawi (clinicaltrials.gov: NCT03385252) found little improvement in child growth or development. Objective We aimed to evaluate the effect of one egg/day for 6 months on plasma choline concentrations among Malawian children enrolled in a randomized trial. Methods Infants age 6-9 months in rural Malawi were randomized to receive one egg/day (n = 331) or serve as a nonintervention control (n = 329) for 6 months. Anthropometric, developmental, and dietary data were collected at baseline and 6 month follow up, along with a blood draw. Plasma choline, betaine, dimethylglycine, trimethylamine N-oxide (TMAO), and docosahexaenoic acid were measured at both time points using UPLC-MS/MS (n = 200 per group). Linear regression analysis was used to determine the difference in plasma choline and related metabolites between groups after 6 months of intervention. Results Plasma choline, betaine, dimethylglycine, and docosahexaenoic acid concentrations did not differ between groups at 6 month follow up. Plasma TMAO was significantly (26% [95% CI: 7%, 48%]) higher in the egg intervention group in a fully adjusted model. Conclusions Provision of one egg/day for 6 months did not result in increases in plasma choline or related metabolites, except TMAO. This may partially explain the lack of effect on growth and development. Additional interventions are needed to improve choline status, growth, and development in this population.

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

Cited by 20 publications

References 66 publications

Comparison between Egg Intake versus Choline Supplementation on Gut Microbiota and Plasma Carotenoids in Subjects with Metabolic Syndrome

Comparison between Egg Intake versus Choline Supplementation on Gut Microbiota and Plasma Carotenoids in Subjects with Metabolic Syndrome

Diet, Fecal Microbiome, and Trimethylamine N-Oxide in a Cohort of Metabolically Healthy United States Adults

Plasma Choline Concentration Was Not Increased After a 6-Month Egg Intervention in 6–9-Month-Old Malawian Children: Results from a Randomized Controlled Trial

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