Fish

15 studies evaluated the possible relationship between fish and TMAO. 13 studies demonstrated that levels of urinary or plasma TMAO and/or TMA are significantly associated with the intake of fish ^{[11][12][13][14][15][16][17][18][19][20][21][22][23]}[11,12,20,21,24,27,28,30,31,32,33,34,36]. One of the earliest studies evaluated 46 different foods and demonstrated that only fish and other sea-products significantly increase urinary TMAO [12]. Cho et al. ^[14][21] supposed that the rapid rise in circulating TMAO in response to fish consumption might demonstrate that the absorption of intact dietary TMAO is independent of the microbiota. In one paper, the association of fish and shellfish intake with TMAO plasma concentrations was limited to men only ^[19][31]. Only two papers demonstrated no association. Rohrmann et al. ^[24][17] revealed that meat, egg or fish consumption is not associated with TMAO, choline or betaine concentrations. Thus, a prospective cohort study showed that dietary intake of fish does not significantly impact the TMAO value in immunodeficient subjects ^[25][35].

Table 1Table 2 shows the four studies that specifically evaluated the influence on TMA and TMAO of eating different types of fish. TMAO was higher in subjects that eat saltwater fish and shellfish but not freshwater fish ^[16][27]. These data were confirmed in another study that evidenced higher TMAO values in the group that consumed shellfish and dark meat fish (tuna steak, mackerel, salmon, sardines, bluefish and swordfish) ^[23][36]. Another paper showed that cod intake has stronger effects on plasma and urine TMAO concentrations than salmon intake ^[21][33]. One study evaluated cooking methods and demonstrated that TMAO values are strongly associated with deep-fried fish consumption ^[16][27].

3. Eggs

17 studies that assessed the correlation between egg consumption and increased TMAO were evaluated. Robust correlations between TMAO and eggs were demonstrated in six studies ^{[26][27][28][29][18][22]}[13,14,19,25,30,34]. Pignanelli et al. ^[29][25] described that the intake of egg yolk contributes significantly to plasma levels of TMAO. The phosphatidylcholine in egg yolk, via action of the intestinal microbiome, may be the major contributor to production of TMAO. The increase in TMAO induced by egg consumption has also been related to cardiovascular risk. Tang et al. studied the effects on plasma TMAO after a test dose of two hard-boiled eggs and found that patients in the highest quartile for TMAO had a 2.5-fold increase in the three-year risk of myocardial infarction or stroke ^[26][13]. In contrast, studies mainly starting from 2014 have assessed little or no effect of egg consumption on TMAO levels ^{[12][30][24][31][14][32][33][16][19][25][34]}[12,15,17,18,21,22,23,27,31,35,37]. Some of these studies have revealed that plasma choline and betaine increase dose-dependently with egg intake. Many of these studies have been funded by the egg industry ^{[30][31][14][32][33][34]}[15,18,21,22,23,37].

4. Meat

12 studies ^{[12][24][13][14][35][16][17][18][19][22][25][23]}[12,17,20,21,26,27,28,30,31,34,35,36] evaluated the possible correlation between meat consumption and an increase of TMAO. Seven studies showed that the levels of urinary or plasma TMAO and/or TMA are significantly associated with the intake of meat. In most of these studies, the differences between white meat, red meat and preserved meat were not evaluated. Yu et al. showed that TMAO is strongly associated with deep-fried meat but not with red meat or poultry ^[16][27]. In one study, the effect on TMAO of meat and fish was compared. Fish was shown to induce a two-fold increase in urinary TMAO compared to meat ^[23][36]. Five papers ^{[27][28][21][23][34]}[14,19,33,36,37] demonstrated that ingestion of meats has no measurable effects on plasma or urinary TMAO.

5. Dairy

Eight studies that assessed the correlation between fermented and non-fermented dairy consumption and increased TMAO were evaluated. Two papers ^[24][36][17,29] showed a positive association between dairy food consumption and plasma TMAO concentrations. Lower circulating and urinary TMAO with fermented dairy consumption compared to non-fermented dairy consumption has been shown ^[36][29].

6. Plant-Based Foods

Three papers evaluated plant-based food consumption ^[27][34][14,37]. Ingestion of fruits, vegetables, cereals [12] and fibre ^[25][35] did not significantly impact TMAO concentrations. Different foods were evaluated by Yu et al. ^[16][27]; they showed that consumption of soy foods or legumes does not modify urinary or plasma TMAO values.