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TMAO

Trimethylamine N-oxide (TMAO) is a compound generated by gut microbial metabolism which is associated increased disease risk. However, it's questionable whether this association reflects causality.

Our evidence-based analysis on tmao features 11 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
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Summary of TMAO

Trimethylamine N-oxide (TMAO) is a compound generated by gut microbial metabolism that has been implicated in increased disease risk. Systematic reviews and meta-analyses[1][2] (whose results are shown in Figure 1) determined that TMAO is associated with a significantly higher risk of both all-cause mortality and cardiovascular events. One possible mechanism for TMAO's effects may be disruption of cholesterol transport by increasing forward transport and decreasing reverse cholesterol transport[3]. However, whether these associations are actually causal is open to question.[4][5]

TMAO has been shown to be generated from substrates with a trimethylamine (TMA) moiety such as L-carnitine and choline[3]. L-carnitine is found in a variety of both plant and animal sources. However, levels of free L-carnitine are highest in meat products[6] and very low in fruits, vegetables, nuts, and grains. L-carnitine is also added into some popular energy drinks[7] with the expectation that it increases performance and helps to burn fat, although the evidence for those expectations is not clear. While vegetarians and vegans have considerably lower dietary intake of carnitine, studies show that their circulating levels in the blood are not drastically lower than people who consume meat and remain generally within the normal range[8]. This is because carnitine can be synthesized in the liver, kidney, and brain[9] if not enough is consumed in the diet.

Several studies[10] have now demonstrated that dietary L-carnitine can be converted in the gut to TMA, at which point TMA can then be converted to TMAO in the liver by the enzyme flavin monooxygenase. However, researchers in 2013 discovered that a compound called γ-butyrobetaine (γ-BB) was formed[11] as an intermediate between L-carnitine and TMA formation in mice.

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Human Effect Matrix

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The Human Effect Matrix looks at human studies to tell you what supplements affect TMAO.

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Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Supplement Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-d Strong - See study
One study found an increase.
grade-d Minor - See study
A decrease in urinary TMAO has been noted with supplementation of PQQ, which is thought to be due to increased activity of the FMO3 enzyme.

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Click here to see all 11 references.