Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial

Wilcox, Jennifer; Skye, Sarah M.; Graham, Brett H.; Zabell, Allyson; Li, Xinmin S.; Li, Lin; Shelkay, Shamanthika; Fu, Xiaoming; Neale, Sarah; O’Laughlin, Cathy; Peterson, Kimberly; Hazen, Stanley L.; Tang, W.H. Wilson

doi:10.1016/j.amjmed.2021.03.016

Cited by 18 publications

(18 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The one-carbon metabolites formed are vital to metabolic pathways involved in essential physiological functions that do not include TMAO, such as the 1-C metabolism and lipid metabolism (e.g., fatty acid β-oxidation) [36,37]. 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.…”

Section: Discussionmentioning

confidence: 93%

“…To further complicate the issue, eggs are an essential source of choline (as phosphatidylcholine), which is shown to produce TMAO (trimethylamine N-oxide) formed from the production of TMA (trimethylamine) by intestinal microbiota and followed to the conversion to TMAO by hepatic flavin-containing monooxygenases [ 8 , 9 , 10 , 11 ]. An elevated concentration of plasma TMAO is suggested to be a predictive biomarker and functional mediator in cardiovascular disease (CVD) in mice and humans [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2022

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Most of them indicated a positive association between fish and TMAO [ 58 – 60 ]. Significant associations between egg and meat consumption and TMAO levels were also reported by some studies [ 61 – 64 ] but not all [ 58 , 59 , 65 , 66 ]. In a cross-sectional study of 3973 adults, Mei et al [ 50 ] revealed that fish, red meat, and eggs were the most dietary factors that significantly increased TMAO production.…”

Section: Discussionmentioning

confidence: 52%

Association between dietary choline and betaine intake and 10.6-year cardiovascular disease in adults

Golzarand

Mirmiran

Azizi

2022

Nutr J

View full text Add to dashboard Cite

Background Several studies have assessed the association between dietary choline and betaine and cardiovascular disease (CVD), but their results are inconsistent. The present study aimed to determine the association between dietary intake of choline and betaine and the risk of CVD in the general population over a 10.6-year period of follow-up. Methods The present cohort study was conducted on participants in the third wave of the Tehran Lipid and Glucose Study (2006–2008) and was followed-up until March 2018. Dietary intake of choline and betaine was calculated using the United States Department of Agriculture (USDA) database. Patients’ medical records were used to collect data on CVD. Results In this study, 2606 subjects with no previous CVD participated and were followed-up for a median of 10.6 years. During the follow-up periods, 187 incidences of CVD were detected. Results of the Cox proportional hazards regression indicated that neither energy-adjusted total choline nor betaine was associated with the incidence of CVD. Among individual choline forms, only higher intake of free choline (FC) was associated with a lower risk of CVD (HR: 0.64, 95% CI: 0.42–0.98). There was no significant association between each 10 mg/d increase in choline and betaine content of each food category and CVD. Conclusion Our investigation indicates no association between energy-adjusted total choline and betaine and a 10.6-year risk of CVD among adults. Besides, we found no relationship between individual choline forms (except FC) and CVD. We also found energy-adjusted choline and betaine obtained from food categories were not associated with the risk of CVD.

show abstract

“…To our knowledge, no other studies besides the Lulun and Mazira Projects have evaluated change in plasma choline after an egg intervention in young children; however, several studies of egg consumption have been conducted in adults. The majority of these studies reported increases in plasma choline without changes in plasma TMAO with daily consumption of eggs ( 31–34 ). However, 1 small study noted a significant increase in plasma TMAO within hours of ingesting eggs, with large interindividual differences in change in TMAO ( 35 ).…”

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

View full text Add to dashboard Cite

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.

show abstract

Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial

Cited by 18 publications

References 37 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

Association between dietary choline and betaine intake and 10.6-year cardiovascular disease in 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

Contact Info

Product

Resources

About