Plasma and Urine TMAO Formation and Changes to Oxidized LDL After Ingestion of Different Amounts of Egg

Determining Whether or Not Egg Ingestion Increases Concentrations of Trimethylamine N-oxide (TMAO) in Plasma and Urine and Activates LDL Oxidation in Humans

Eggs contain an essential nutrient called choline and adequate levels of choline are required for good health. Studies in mice have demonstrated that high levels of choline may increase risk of heart disease through a process that involves the breakdown of choline by gut bacteria. Previous research did not show that human consumption of eggs increases risk of heart disease. This study is designed to investigate whether the number of eggs in the diet affects blood and urine markers for heart disease.

Diets low in choline have adverse health consequences, while observations in humans and experiments in mouse models suggest that a diet containing too much choline or phosphatidylcholine may activate inflammatory pathways and increase cardiovascular disease risk through bacterial conversion of choline to trimethylamine (TMA) and its subsequent oxidation to trimethylamine N-oxide (TMAO) in the liver. What is unclear is whether choline and phosphatidylcholine in eggs is a source of TMAO formation, and if so how many eggs must be eaten before enough TMAO is generated to cause increased oxidized LDL (a biomarker for atherosclerosis mechanisms). We hypothesize that TMAO will only be formed from eggs when very large quantities are ingested and that TMAO formation will vary greatly between individuals for any given dietary exposure. This variability will be determined by 1) the dose at which dietary choline or phosphatidylcholine exceeds the absorptive capacity of the volunteer's small intestine and therefore spills into large intestine where gut bacteria have access to it and 2) the bacterial populations that constitute the volunteer's microbiome.

Inclusion Criteria:

• Healthy
• non-smoker
• Body mass index between 20 to 39 kg/m²

Exclusion Criteria:

• History of chronic system disease/s (e.g., hepatic, renal, cardiovascular, intestinal)
• Diabetes controlled by insulin
• Alcohol or illegal drug misuse/abuse
• Use of antibiotics or choline-containing supplements within three months of study
• Allergies to soy, eggs, wheat or other food
• Use of drugs or medications known to alter liver metabolism, cardiovascular and/or kidney function
• Abnormal physical examination or abnormal clinical laboratory values
• Pregnancy
• Unusual dietary habits