Abstract 13412: 24-Hour Water-Only Fasting Acutely Reduces Trimethylamine N-Oxide: the FEELGOOD Trial
Background: Routine, periodic fasting is associated with lower risk of diabetes and coronary artery disease (CAD), and may reduce weight and improve metabolic parameters. Multiple related biological pathways are acutely affected by water-only fasting, potentially leading to long-term health improvements including lower CAD. Trimethylamine N-oxide (TMAO) is produced by intestinal bacteria and may increase CAD risk. This study evaluated the change in TMAO due to fasting in apparently healthy people.
Methods: The FEELGOOD Trial (clinicaltrials.gov NCT01059760) included subjects free of cardiovascular disease who had never fasted for more than 12 hours (N=24). All individuals participated in a randomized cross-over trial of 24-hour water-only fasting and 24 hours of ad libitum eating. In this secondary analysis of stored samples, TMAO was measured by liquid chromatography-mass spectrometry.
Results: Age averaged 43.6±13.5 years, 66.7% were female, and baseline TMAO averaged 27.1 ng. TMAO was reduced at the end of the 24-hour fasting intervention compared to the eating day (14.3 ng vs. 28.2 ng, p=0.034). The change in TMAO during the fasting day averaged -10.8 ng compared to an average increase of +2.6 ng during the eating day (p=0.23). For those randomized to fast the first day, the difference in TMAO change on the fast day vs. eating day (-12.1 ng, n=12) was similar to the TMAO change of those randomized to eat on the first day (-14.6 ng, n=12). For those who fasted the first day, TMAO levels were found to have returned to baseline after the full 48 hours of the study (baseline: 22.5 ng, 48 hours: 28.8 ng, p=0.55).
Conclusion: Water-only 24-hour fasting reduced plasma levels of TMAO, a potential risk factor for CAD. The rapid resumption of TMAO production after renewed caloric intake suggests that fasting-reduced TMAO likely resulted from elimination of the substrate for TMAO production. Elimination of TMAO-producing bacteria may also account for this, but recolonization likely would take more time than it was observed to take for resumption of TMAO production. These findings suggest that routine, periodic fasting (multiple episodes over time on a regular basis) may have long-term impact on TMAO levels and related CAD risk, but this requires further investigation.
Author Disclosures: B.D. Horne: None. J.E. Cox: None. J.B. Muhlestein: None. V.T. Le: None. A.R. Butler: None. H.T. May: None. J.F. Carlquist: None. J.L. Anderson: None.
- © 2014 by American Heart Association, Inc.