Effect of Extra Virgin Olive Oil Supplementation on Gut-Derived Metabolite Trimethylamine-N-Oxide and Vascular Function in Liver Transplant Recipients

Introduction: Long term survival is compromised in liver transplant (LT) recipients by a heightened risk of atherosclerotic cardiovascular disease. Increased levels of the gut derived microbial metabolite trimethylamine N-oxide (TMAO) are positively associated with atherosclerotic vascular impairments, providing a potential therapeutic target for cardiovascular health. Cold pressed extra virgin olive oil (EVOO) has been reported to contain high concentrations of 3,3-dimethyl-1-butanol, a structural analogue of choline and an established inhibitor of TMAO generation. Therefore, the purpose of this pilot study was to test the hypothesis that dietary EVOO supplementation would reduce TMAO levels in LT recipients and improve vascular endothelial function. Methods: In this randomized controlled study, 19 LT recipients (mean±SE, age: 61±2yrs; 9 female; 5 Black) were allocated to an EVOO or a Control (CON) group. The EVOO group were provided with cold pressed EVOO and instructed to consume 60ml/day for 4 weeks, whereas CON received standard of care. Dietary intake was documented by 24-hour, 5-pass dietary recall and participants received dietary counseling on strategies to incorporate EVOO into their diet. A venous blood sample was obtained at 0 and 4 weeks. Samples were analyzed for plasma TMAO, and for plasma and red blood cell fatty acids utilizing nuclear magnetic resonance spectroscopy. Changes in vascular endothelial function were assessed in vivo by brachial artery flow mediated dilation. Results: Plasma ( week 0 vs. 4, EVOO: 24±0.5% vs. 27±0.7%, p <0.01; CON: 25±1% vs. 23±2%, p =0.08) and red blood cell (EVOO: 15±0.5% vs. 16±0.4%, p <0.01; CON: 14±0.3% vs. 14±0.3%, p =0.80) levels of oleic acid were increased following EVOO supplementation. There was no change in plasma levels of TMAO (EVOO: 6.7±2.9uM vs. 4.93±0.72%, p =0.52; CON: 8.9±3.9% vs. 8.2±2.5%, p =0.88). Endothelial function improved in EVOO ( FMD, 2.27±0.77% vs. 4.46±0.38%, p =0.01) but not in CON (4.10±1.92% vs. 3.31±0.62%, p =0.69). Conclusions: These findings demonstrate that EVOO supplementation paired with dietary counseling is a feasible intervention for LT recipients, as evidenced by high levels of objectively assessed adherence. Improvements in endothelial function in the EVOO group were observed in the absence of a reduction in TMAO, suggesting that the observed benefits of EVOO may not be mediated by a TMAO-related mechanism in LT recipients. Supported by Pauley Heart Center and Stravitz-Sanyal Institute for Liver Disease and Metabolic Health. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.