Effect of Egg Consumption on Circulating Choline, Betaine, and Trimethylamine N-Oxide in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Publisher Pubmed



Aryaeian N ; Heydarian A ; Tahvilian N ; Hosseini H ; Ahmadi AR ; Davarpanah SH
Source: Nutrition Journal Published:2025

Abstract

Background and objective: Eggs are rich in choline and other methyl donors that may influence metabolic health, yet their effects on circulating metabolites such as choline, betaine, and trimethylamine N-oxide (TMAO) remain unclear. Understanding these effects is critical due to potential links with cardiometabolic risk. This study aimed to systematically evaluate and quantitatively synthesize the effects of egg consumption on plasma levels of choline, betaine, and TMAO in randomized controlled trials (RCTs), and to explore potential effect modifiers. Methods: A systematic search of electronic databases was conducted to identify RCTs examining the effects of egg consumption on circulating choline, betaine, and TMAO. Data were pooled using random-effects meta-analyses. Subgroup analyses were performed based on age, body mass index, health status, study design, duration, and egg dosage. Meta-regression was conducted to assess the influence of age, dose, and duration. Publication bias was evaluated using Egger’s and Begg’s tests, funnel plots, and trim-and-fill analysis. The certainty of evidence was assessed using the NutriGRADE tool, which is specifically recommended for nutrition meta-analyses. Results: Six RCTs (n = 5 for betaine and TMAO; n = 6 for choline) were included. Multi-arm trials were combined into single pairwise comparisons per outcome, as per Cochrane Handbook Sect. 23.3.4, to avoid unit-of-analysis errors. No significant overall effects were observed for choline (WMD = 0.10; 95% CI: − 0.92 to 1.12; p = 0.847), betaine (WMD = 0.21; 95% CI: − 8.50 to 8.92; p = 0.962), or TMAO (WMD = − 0.08; 95% CI: − 0.47 to 0.32; p = 0.692). High heterogeneity was noted for choline and betaine (I² > 85%), but low for TMAO (I² = 23%). Subgroup analyses showed significant choline increases among older adults (> 45 years) and individuals with metabolic syndrome or obesity. Meta-regression revealed a negative association between egg dose and both choline and betaine levels (p < 0.001). Publication bias was suggested for betaine but not for choline or TMAO. The NutriGRADE assessment indicated moderate certainty of evidence for choline (score 7.75), betaine (7.05), and TMAO (7.25), with downgrades mainly due to imprecision and heterogeneity. Conclusions: No clear effect of egg consumption on circulating choline, betaine, or TMAO levels could be demonstrated. Age and metabolic status may influence choline responses, and higher egg doses may attenuate choline and betaine levels. Based on NutriGRADE, the overall certainty of evidence was rated as moderate for all three outcomes. Further long-term, high-quality RCTs are needed to clarify these associations. © 2025 Elsevier B.V., All rights reserved.