TMAO (trimethylamine N-oxide) is produced by gut bacteria from choline, lecithin, and L-carnitine-rich foods (mainly fish, meat, egg, and dairy). High levels are associated with heart disease, hardening of the arteries, diabetes, and colon cancer. However, the role of TMAO in these diseases is still controversial. Read more to find out how TMAO levels may affect your health and what you can do to reduce them.
What Is TMAO?
Potential foods that increase TMAO are those rich in choline, lecithin, and L-carnitine, like red meat, eggs, dairy, and saltwater fish [R].
TMAO Blood Test
You can check your TMAO levels with a blood test. However, the test is relatively new and the referent values are still being established.
In a study with 349 healthy subjects, the median value was 3.45 μM. Many had levels close to this value (2.25-5.79 μM). However, values as low as 0.73 μM and as high as 126 μM were also recorded [R].
TMAO levels tend to increase with age [R].
Why Is High TMAO Bad?
1) High TMAO Increases Heart Disease Risk
In a meta-analysis of 19 studies with 19,256 subjects, high TMAO levels were associated with an increased risk of heart diseases, such as heart failure and stroke. Furthermore, people with high levels of TMAO sources, like L-carnitine and choline, were 1.4 times more likely to suffer from heart failure, stroke, or other heart diseases [R].
In another meta-analysis of 11 studies with 7716 subjects, those with elevated levels of this compound had a 23% higher risk of heart diseases and a 55% higher risk of dying (from all causes) [R].
High TMAO levels increased the risk of blood clots, heart attack, and stroke in over 4,000 subjects [R].
Similarly, high levels of this compound were associated with increased mortality in 720 patients with heart failure [R].
In rats, TMAO increases with age and causes oxidative stress and inflammation in blood vessels, leading to endothelial (blood vessel lining) dysfunction, which increases the risk of heart disease [R].
2) High TMAO May Cause Hardening of the Arteries
High levels of TMAO were associated with increased cIMT (carotid intima-media thickness), an early marker for hardening of the arteries (atherosclerosis), in 220 patients irrespective of other factors, such as insulin resistance, obesity, and fatty liver [R].
Elevated levels of this compound were also associated with higher risk of hardening of the arteries in 220 subjects with chronic kidney disease [R].
Dietary TMAO, L-carnitine, and choline increased the hardening of the arteries in atherosclerosis-prone mice. The effect was blocked by antibiotics, which decreased the activity of gut bacteria [R, R].
3) High TMAO Is Associated with Diabetes
Of 191 heart disease patients, those with high TMAO were more likely to have diabetes [R].
All of these increase the risk of developing diabetes.
4) High TMAO Impairs Kidney Function
Chronic kidney disease patients had higher TMAO levels compared to controls (521 patients and 3,166 controls). Furthermore, higher TMAO in chronic kidney disease patients was associated with a 2.8-fold increase in mortality risk [R].
In 179 chronic kidney disease patients, high TMAO was associated with faulty kidney function, chronic inflammation (high IL-6 and CRP), and increased mortality. After kidney transplantation, TMAO levels decreased back to normal [R].
High levels of this compound were also associated with worse kidney function and advanced chronic kidney disease in 227 patients with heart disease [R].
In animals, high dietary TMAO or choline levels caused kidney damage and dysfunction [R].
In another study, high TMAO levels, caused by a high-fat diet, increased oxidative stress and inflammation in the kidneys and lead to kidney damage and dysfunction in mice [R].
5) High TMAO Increases Inflammation
It also increased inflammation and oxidative stress in human blood vessel cells [R].
6) High TMAO Increases the Risk of Cancer
In 1,670 women, there was a link between higher TMAO and colon cancer. Women with the highest levels of choline, the source of TMAO, were at a 2.4-times greater risk of developing the disease [R].
In 138 subjects, those who had colon cancer had higher TMAO levels. Elevated TMAO levels also predicted lower disease-free survival among colon cancer patients [R].
However, in another study, only elevated choline but not TMAO was associated with increased risk of colon cancer in 1,288 men [R].
7) High TMAO Causes Liver Dysfunction
In addition, high levels were associated with worse outcomes in patients with primary sclerosing cholangitis, an immune-related disease of the liver [R].
A high conversion rate of choline into methylamines, such as TMAO, decreases choline levels and causes fatty liver disease in mice [R].
Also, dietary TMAO causes liver damage in mice [R].
8) TMAO May Cause Obesity
Blocking FMO3 activity protects mice from becoming obese [R].
These Increase TMAO Levels
1) Animal Products
Eggs, red meat, dairy products, and fish are rich in choline, carnitine, and lecithin, which then get converted to TMAO by gut bacteria [R].
In 297 subjects, fish and meat consumption increased blood TMAO levels [R].
In 40 healthy young men, fish consumption increased TMAO levels more than beef or eggs [R].
Fish protein increased TMAO in mice more than other protein sources such as soy or casein [R].
In rats, beef diet increased TMAO levels more than chicken [R].
Dairy consumption was associated with higher TMAO levels in 271 adults [R].
On the contrary, in 38 overweight or obese women, increased consumption of dairy resulted in lower TMAO levels [R].
Should you stay away from fish and animal products because these can increase TMAO? The answer is not simple.
It seems that the benefits of other healthy ingredients found in fish outweigh the effect of higher TMAO, at least when it comes to heart disease prevention.
Therefore, you should take the studies above with a grain of salt.
2) High-Fat Diet
A short-term high-fat diet increased TMAO levels during or after meals but did not have long-term effects in 10 non-obese men [R].
3) L-Carnitine Supplements
Oral L-carnitine supplements increased TMAO levels in 31 patients on hemodialysis [R].
L-carnitine supplements can also increase TMAO levels in people with organic acidemias (these are rare inherited inborn errors of metabolism), irrespective of the meat consumption [R].
4) Gastric Bypass Surgery
However, gastric bypass surgery decreases overall heart disease risk, so the impact of high TMAO in these cases is still not understood [R].
In mice, dioxin-like pollutants, which are highly toxic environmental pollutants, increased the FMO3 enzyme production, which elevated TMAO levels [R].
6) Sleep Deprivation
Sleep deprivation increased TMAO levels in 15 healthy men [R].
Sex hormones during pregnancy increase FMO3 enzyme activity, which can increase TMAO [R].
These Decrease TMAO levels
1) Vegetarian/Vegan/Mediterranean Diet
Among 74 subjects given L-carnitine, meat eaters had greater increases in TMAO levels compared to vegans or vegetarians. This means that vegans and vegetarians have gut bacteria that produce less TMAO [R].
Among 153 people, vegetarians, vegans, and those who adhered to a Mediterranean diet (rich in fruit, legumes, and vegetables) had lower TMAO levels [R].
2) Prebiotics and Potential Probiotics
Probiotics are bacteria that, when digested, have beneficial effects. Prebiotics are plant fibers, which act as fertilizers for the growth of the good bacteria in the gut.
Soluble dietary fiber, acting as a prebiotic, reduced TMAO by over 60% in mice fed red meat [R].
In another study, a single type of prebiotics increased, whereas a prebiotic mixture decreased TMAO levels [R].
This suggests that having a high diversity of gut bacteria is important for controlling TMAO levels.
3) Vitamins D and B
In 52 adults, supplementation with vitamins B and D decreased TMAO levels [R].
Resveratrol, found in berries and grapes, decreased blood TMAO levels in atherosclerosis-prone mice [R].
A pistachio-supplemented diet decreased TMAO levels in 39 prediabetic subjects [R].
6) Brussels Sprouts
Daily consumption of Brussels sprouts decreased FMO3 enzyme activity in 10 healthy volunteers. This can result in lower TMAO levels [R].
7) DMB Can Decrease TMAO Levels
It decreases TMAO levels in mice fed high-choline or high-carnitine diets [R].
Meldonium is an anti-ischemic medication that increases blood flow and oxygen supply to the body.
This drug decreased blood TMAO levels in eight healthy adults on TMA-rich diets by increasing the elimination of TMAO through urine [R].
In rats, meldonium reduces the production of TMA from L-carnitine and, thus, decreases TMAO levels. Twenty-four hours after meldonium treatment, the TMAO levels in urine were 3.6 times lower [R].
Genes Related to TMAO Levels
FMO3 is a liver enzyme that transforms TMA into TMAO. People with mutations in FMO3 cannot convert TMA to TMAO. They accumulate TMA, which has a specific odor, and develop fish-odor syndrome (trimethylaminuria) [R].
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