Abstract

Studies implicate choline and betaine metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD). We conducted a systematic review and random-effects meta-analysis to quantify a summary estimated effect of dietary choline and betaine on hard CVD outcomes (incidence and mortality). Eligible studies were prospective studies in adults with comprehensive diet assessment and follow-up for hard CVD endpoints. We identified six studies that met our criteria, comprising 18,076 incident CVD events, 5343 CVD deaths, and 184,010 total participants. In random effects meta-analysis, incident CVD was not associated with choline (relative risk (RR): 1.00; 95% CI: 0.98, 1.02) or betaine (RR: 0.99; 95% CI: 0.98, 1.01) intake. Results did not vary by study outcome (incident coronary heart disease, stroke, total CVD) and there was no evidence for heterogeneity among studies. Only two studies provided data on phosphatidylcholine and CVD mortality. Random effects meta-analysis did not support an association between choline and CVD mortality (RR: 1.09, 95% CI: 0.89, 1.35), but one study supported a positive association and there was significant heterogeneity (I2 = 84%, p-value < 0.001). Our findings do not support an association between dietary choline/betaine with incident CVD, but call for further research into choline and CVD mortality.

Highlights

  • A recent body of literature implicates dietary choline and betaine metabolite trimethylamineN-oxide (TMAO) in cardiovascular disease (CVD) risk [1,2,3,4,5,6,7,8]

  • To better understand the role of dietary choline and betaine in CVD risk, we systematically reviewed the literature for studies of dietary choline or betaine with respect to CVD incidence or mortality, and used random-effects meta-analysis to generate summary relative risks

  • From 5398 unique abstracts, we identified 31 publications for full text review, and six eligible manuscripts reporting estimated effects of dietary choline or betaine on cardiovascular disease outcomes (Table 1)

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Summary

Introduction

A recent body of literature implicates dietary choline and betaine metabolite trimethylamine. N-oxide (TMAO) in cardiovascular disease (CVD) risk [1,2,3,4,5,6,7,8] These findings raise questions about the role of choline and betaine consumption in CVD risk. To better understand the role of dietary choline and betaine in CVD risk, we systematically reviewed the literature for studies of dietary choline or betaine with respect to CVD incidence or mortality, and used random-effects meta-analysis to generate summary relative risks. Our investigation has public health implications and addresses the extent to which associations between TMAO and CVD impact dietary advice related to consumption of TMAO precursors choline and betaine

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