RELATIONSHIP OF CHOLINE AND TRIMETHYLAMINE-N-OXIDE INTAKE WITH METABOLIC AND HEALTH OUTCOMES IN HUMANS
This dissertation is focused on dietary choline and its derivative trimethylamine-N-oxide (TMAO). Recent discoveries have implicated circulating TMAO as a candidate risk factor for cardiovascular disease (CVD) among patients, but whether TMAO and dietary choline play a causative role in the disease process remains controversial. This dissertation describes 1) the production of TMAO from its dietary precursors (TMAO, choline and L-carnitine) in healthy individuals, 2) its metabolic fate within the body, and 3) the relationship between dietary choline and high blood pressure, a major risk factor for CVD. In Chapter 1, a randomized crossover feeding study was conducted where 40 healthy men consumed a test meal consisting of either fish (TMAO), eggs (choline), beef (choline and L-carnitine) or a fruit control. Postprandial blood collected for 6 hours after consumption of the test meal revealed that fish consumption yielded the highest increase in plasma TMAO metabolites among the test meals. Furthermore, production of TMAO following consumption of eggs or beef varied among individuals and correlated with the gut microbiome. The overall findings show that TMAO can be temporarily elevated in healthy individuals following consumption of various foods, especially heart-healthy fish. High variation in plasma TMAO in response to the same meals indicates metabolic differences among individuals that may be due to other factors such as composition of the gut microbiome. In Chapter 2, the metabolic fate of dietary TMAO was investigated. Participants enrolled in the feeding study consumed 50 mg deuterium-labeled methyl d9-TMAO (d9-TMAO) in the fruit control arm. We found that d9-TMAO entered circulation within 15 min and that 96% of the tracer was excreted in urine within 24 hours. These results demonstrate rapid absorption of intact TMAO along with its efficient elimination from the human body. In Chapter 3 the hypothesis that increased choline intake may increase CVD risk through elevated blood pressure was investigated. Using cross-sectional 2007-10 National Health and Nutrition Examination Survey, we examined the relationship of choline intake with blood pressure and prevalence odds of hypertension in a general U.S. population. We found a borderline inverse association between choline intake and odds of hypertension in women but not in men. Furthermore, supplemental choline use by both sexes showed a significant inverse association with hypertension. We concluded that choline intake is not associated with blood pressure, a risk factor of CVD, in this population. Taken together, evidence in this dissertation does not support the hypothesis that dietary choline increases disease risks by elevating baseline circulating TMAO in healthy adults. More epidemiologic and experimental evidence are still needed to further confirm or dispute this hypothesis.
Choline; Nutrition; Gut microbiota; Hypertension; NHANES; Randomized controlled trial; Trimethylamine-N-oxide
Caudill, Marie A.
Cassano, Patricia Ann; Parker, Robert Stanley; Soloway, Paul
Ph. D., Nutrition
Doctor of Philosophy
dissertation or thesis