Trimethylamine N-oxide (TMAO) is a gut metabolite created during the digestion process of egg, red meat or dairy-derived nutrients choline and carnitine, A study published by the Miller Family Heart and Vascular Institute at Cleveland Clinic has for the first time linked TMAO to chronic kidney disease and illustrates the crucial relevance of nutrition. Approximately 20 million Americans are estimated to have kidney disease. It causes a progressive loss of kidney function over time, with waste product accumulating in the blood.
Previous studies have linked the metabolite to heart disease and blood tests are a tool to predict the risk of future heart attack, stroke and death. TMAO forms in the gut during digestion of choline and carnitine, nutrients that are prevalent in animal products such as red meat and liver. Choline is also abundant in egg yolk and high-fat dairy products. The new study offers further insight into the relationship between cardiovascular disease and chronic kidney disease.
The research participants consisted of 521 patients with chronic kidney disease and 3,166 subjects without chronic kidney disease. The TMAO fasting levels were measured and the subjects were followed for five years. It was determined that TMAO levels were higher in patients with chronic kidney disease, and elevated TMAO levels were associated with greater mortality risk in both subject groups. The researchers used animal models to determine that chronic dietary exposures to choline and TMAO were associated with development and progression of chronic kidney disease.
“It’s a triple whammy” said Dr Hazen. “Elevated plasma TMAO levels in subjects are linked to future cardiac risks, and in subjects with normal renal function, elevated levels predict long-term future risk for development of chronic kidney disease; animal model studies show that long-term exposure to higher levels of TMAO promotes renal functional impairment and atherosclerosis; and as the kidneys lose function, TMAO isn’t eliminated as easily, and levels further rise, increasing cardiovascular and kidney disease risks further.”
“Our studies raise the exciting prospects of nutritional interventions to help retard development and progression of chronic kidney disease. Regrettably, very little is known about diet and renal disease progression,” said Dr. Tang, the second study author.
W. H. W. Tang, Z. Wang, D. J. Kennedy, Y. Wu, J. A. Buffa, B. Agatisa-Boyle, X. S. Li, B. S. Levison, S. L. Hazen. Gut Microbiota-Dependent Trimethylamine N-Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease. Circulation Research, 2014; 116 (3): 448 DOI: 10.1161/CIRCRESAHA.116.305360