Betaine and Trimethylamine-N-Oxide as Predictors of Cardiovascular Outcomes Show Different Patterns in Diabetes Mellitus: An Observational Study

Lever M, George PM, Slow S, Bellamy D, Young JM, Ho M, McEntyre CJ, Elmslie JL, Atkinson W, Molyneux SL, Troughton RW, Frampton CM, Richards AM, Chambers ST · PLoS One

The betaine paradox stated precisely: in participants without diabetes, LOW plasma betaine predicted events (secondary MI HR 2.1, unstable angina HR 2.3), while in those with diabetes HIGH plasma betaine predicted them (heart failure HR 3.1, all cardiovascular events HR 2.8). The authors attribute the reversal to loss of betaine from tissues via urinary excretion.

Population

Adults sampled four months after an acute coronary admission, median follow-up about 5 years

Intervention

Plasma betaine, dimethylglycine and trimethylamine-N-oxide measured; no supplement given

Comparator

Top versus bottom quintile of each metabolite

Limitations

Observational, in a post-acute-coronary population, with only 79 participants who had diabetes; plasma betaine is a marker of many things at once and no one was supplemented.