April 25th, 2013
Another Cleveland Clinic Study Links TMAO to Atherosclerosis
Larry Husten, PHD
A new study from the Cleveland Clinic research group headed by Stanley Hazen offers more evidence in support of the hypothesis that TMAO (trimethylamine-N-oxide) may play a role in the development of heart disease. The new research, published in the New England Journal of Medicine, follows closely on a related study published recently in Nature Medicine that received broad public attention.
The Nature Medicine paper demonstrated that digestive tract bacteria metabolize carnitine into TMAO, which had previously been linked to atherosclerosis in animals. The new research in NEJM focuses on another pathway that leads to TMAO production and provides for the first time a credible association between TMAO and cardiovascular disease in humans.
In the first phase of the new study, the researchers gave a precursor of TMAO, lecithin, to a group of healthy volunteers both before and after receiving antibiotics. Without antibiotics, the lecithin was metabolized to TMAO. But when the intestinal bacteria were suppressed by the antibiotics, TMAO production was significantly reduced.
In the second phase, the researchers measured fasting plasma TMAO levels in 4007 patients undergoing coronary angiography. After 3 years of follow-up, people in the highest quartile of TMAO had more than twice the risk for having a major adverse cardiovascular event than people in the lowest quartile (HR 2.54, CI 1.96-3.28, p<0.001). This association was independent of traditional risk factors.
In an accompanying editorial, Joseph Loscalzo praises the research but notes that “much remains to be done to determine the precise role of TMAO in atherothrombogenesis — whether it has a direct effect on pathogenesis, is an epiphenomenal biomarker, or is a precursor to a more direct effector.” In any case, Loscalzo is supportive of a significant role for gut bacteria: “Atherosclerosis,” he writes, “has long been recognized to be partially driven by inflammation, and the gut metagenome appears to contribute to this inflammatory milieu.”
One Response to “Another Cleveland Clinic Study Links TMAO to Atherosclerosis”
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Association does not mean causality:
The last paragraph of Larry Husten‘s post is notable because it is an excellent example of scientific attitude we like to see more often in the conclusions of the studies.
Actually TMAO might be a biomarker that results from some internal inflammatory (oxidative) process, and not a CAUSE of atherosclerosis. On the other hand,“Phosphatidylcholine is a vital substance found in every cell of the human body. Thus, some researchers have used mutant mouse models with severe oxidative damage as a model of “accelerated aging” to investigate the possible role of phosphatidylcholine supplementation as a way of slowing down aging-related processes and improving brain functioning and memory capacity in dementia. However, a systematic review of clinical trials in humans found that lecithin or phosphatidylcholine supplementation does not benefit patients with dementia (http://en.wikipedia.org/wiki/Phosphatidylcholine#cite_note-westonapricecholineheart-17)”