Dietary choline undergoes anaerobic metabolism by gut microbes to form trimethylamine (TMA) which is then oxidized by liver enzymes to form trimethylamine N-oxide (TMAO), a newly recognized risk marker for cardiovascular disease.[1]
However, several dietary sources of choline (e.g., eggs) actually contain phosphatidylcholine, which may not have the same TMAO-elevating effects as choline (as choline bitartrate or other forms). For example, multiple studies have shown that eating up to 3 eggs per day (about 400 mg of choline) elevates plasma choline levels but does not increase TMAO.[2][3][4][5][6][7] On the other hand, TMAO levels increase up to 3-fold following the intake of 600 mg of choline bitartrate.[8] Adding choline to the diet from beef (3–6 ounces as part of a Dietary Approaches to Stop Hypertension diet) increases plasma choline by 10% and TMAO levels by 27% in older adults with obesity.[9]
Differences in gut microbiota may explain individual differences in TMAO production following choline intake. For example, high TMAO producers had more abundant lineages of Clostridium and Ruminococcaceae and Lachnospiraceae compared to low TMAO producers.[8]
Overall, because phosphatidylcholine is the major form of choline in food and phosphatidylcholine doesn’t appear to elevate TMAO levels, there’s no reason to avoid phosphatidylcholine over fears of its TMAO-elevating effects. Furthermore, meta-analyses have found no association between dietary choline/betaine intake and the risk of cardiovascular disease outcomes (e.g., coronary artery disease or stroke).[10]
References
- ^Canyelles M, Borràs C, Rotllan N, Tondo M, Escolà-Gil JC, Blanco-Vaca FGut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease?Int J Mol Sci.(2023-Jan-18)
- ^Lemos BS, Medina-Vera I, Malysheva OV, Caudill MA, Fernandez MLEffects of Egg Consumption and Choline Supplementation on Plasma Choline and Trimethylamine-N-Oxide in a Young PopulationJ Am Coll Nutr.(2018 May 15)
- ^Wilcox J, Skye SM, Graham B, Zabell A, Li XS, Li L, Shelkay S, Fu X, Neale S, O'Laughlin C, Peterson K, Hazen SL, Tang WHWDietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial.Am J Med.(2021 Sep)
- ^Zhu C, Sawrey-Kubicek L, Bardagjy AS, Houts H, Tang X, Sacchi R, Randolph JM, Steinberg FM, Zivkovic AMWhole egg consumption increases plasma choline and betaine without affecting TMAO levels or gut microbiome in overweight postmenopausal women.Nutr Res.(2020 Jun)
- ^Missimer A, Fernandez ML, DiMarco DM, Norris GH, Blesso CN, Murillo AG, Vergara-Jimenez M, Lemos BS, Medina-Vera I, Malysheva OV, Caudill MACompared to an Oatmeal Breakfast, Two Eggs/Day Increased Plasma Carotenoids and Choline without Increasing Trimethyl Amine N-Oxide ConcentrationsJ Am Coll Nutr.(2018 Feb)
- ^DiMarco DM, Missimer A, Murillo AG, Lemos BS, Malysheva OV, Caudill MA, Blesso CN, Fernandez MLIntake of up to 3 Eggs/Day Increases HDL Cholesterol and Plasma Choline While Plasma Trimethylamine-N-oxide is Unchanged in a Healthy PopulationLipids.(2017 Mar)
- ^Thomas MS, DiBella M, Blesso CN, Malysheva O, Caudill M, Sholola M, Cooperstone JL, Fernandez MLComparison between Egg Intake versus Choline Supplementation on Gut Microbiota and Plasma Carotenoids in Subjects with Metabolic Syndrome.Nutrients.(2022 Mar 11)
- ^Clara E Cho, Niklas D J Aardema, Madison L Bunnell, Deanna P Larson, Sheryl S Aguilar, Janet R Bergeson, Olga V Malysheva, Marie A Caudill, Michael LefevreEffect of Choline Forms and Gut Microbiota Composition on Trimethylamine- N-Oxide Response in Healthy MenNutrients.(2020 Jul 25)
- ^Tate BN, Van Guilder GP, Aly M, Spence LA, Diaz-Rubio ME, Le HH, Johnson EL, McFadden JW, Perry CAChanges in Choline Metabolites and Ceramides in Response to a DASH-Style Diet in Older Adults.Nutrients.(2023 Aug 23)
- ^Katie A Meyer, Jonathan W SheaDietary Choline and Betaine and Risk of CVD: A Systematic Review and Meta-Analysis of Prospective StudiesNutrients.(2017 Jul 7)