The DOI matches its Crossref record; 133 of the 133 references it cites were found in a registry or an index; 1 of the 214 sources its claims cite were checked for support.
Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease
Open accessAbstract
Trimethylamine N-oxide (TMAO) is a biologically active molecule and is a putative promoter of chronic diseases including atherosclerosis in humans. Host intestinal bacteria produce its precursor trimethylamine (TMA) from carnitine, choline, or choline-containing compounds. Most of the TMA produced is passively absorbed into portal circulation, and hepatic flavin-dependent monooxygenases (FMOs) efficiently oxidize TMA to TMAO. Both observational and experimental studies suggest a strong positive correlation between increased plasma TMAO concentrations and adverse cardiovascular events, such as myocardial infarction, stroke, and death. However, a clear mechanistic link between TMAO and such diseases is not yet validated. Therefore, it is debated whether increased TMAO concentrations are the cause or result of these diseases. Here, we have tried to review the current understanding of the properties and physiological functions of TMAO, its dietary sources, and its effects on human metabolism. Studies that describe the potential role of TMAO in the etiology of cardiovascular and other diseases are also discussed.
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186 Not checked yet · 23 No basis given · 22 Own interpretation · 1 Supported · 1 Own method · 1 Own result
Every source the paper cites for this claim was checked and supports it.
In the paper
“A second pathway converting carnitine to TMA involves production of the intermediate γ-butyrobetaine in the ileum, with subsequent conversion of γ-butyrobetaine to TMA in the cecum and colon (62).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.1. Trimethylamine Formation by Bacteria
What the sources say
- Supportedcites [62] source
The Discussion (page not provided) describes a second pathway from L-carnitine through γ-butyrobetaine to TMA. It places γ-butyrobetaine formation in the latter jejunum and ileum, and TMA production from γ-butyrobetaine in the cecum and proximal large bowel, matching the cited sentence. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Both observational and experimental studies suggest a strong positive correlation between increased plasma TMAO concentrations and adverse cardiovascular events, such as myocardial infarction, stroke, and death.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Host intestinal bacteria produce its precursor trimethylamine (TMA) from carnitine, choline, or choline-containing compounds.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, a clear mechanistic link between TMAO and such diseases is not yet validated.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“A recent study in men observed that people with higher Firmicutes to Bacteroidetes enrichment generated more TMA after a challenge meal (28).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.1. Trimethylamine Formation by Bacteria
What the sources say
- Not checked yetcites [28] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“We know that gut microbiota are required for these nutrients to be converted to TMA because gnotobiotic mice do not produce such TMA (1,96), and antibiotic treatment of standard mice decreases TMA formation (1).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.1. Trimethylamine Formation by Bacteria
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
In the paper
“oral flora (Streptococcus sanguis, a facultative anaerobe) also can form TMA from choline (25).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.1. Trimethylamine Formation by Bacteria
What the sources say
- Not checked yetcites [25] source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A YeaW/YeaX gene pair encodes for oxygenase and oxidoreductase activities that have substrate promiscuity for γ-butyrobetaine, L-carnitine, choline, and betaine.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.1. Trimethylamine Formation by Bacteria
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“FMO3 has tenfold higher specific activity in the liver than does FMO1 (13).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [13] source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“The bile salt, cholic acid, induces FMO3 via the bile acid-activated nuclear receptor FXR (13).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 78
- Probably not a substantial claim. 31
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Most of the TMA produced is passively absorbed into portal circulation, and hepatic flavindependent monooxygenases (FMOs) efficiently oxidize TMA to TMAO.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Trimethylamine N-oxide (TMAO) is a biologically active molecule and is a putative promoter of chronic diseases including atherosclerosis in humans.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > Abstract
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In some normal healthy women, modest trimethylaminuria occurs just at the onset of and during menstruation and then disappears (82).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [82] Mitchell SC, 2001, Drug Metab. Dispos.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“After 300 g/day of cooked brussels sprouts for three weeks, people eating brussels sprouts showed significant increases in their urinary TMA/TMAO ratio, suggesting a decrease in TMA N oxidation (24).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [24] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“TMA can be used for methanogenesis in the gastrointestinal tract; in human intestine, this pathway is active in bacteria belonging to the genera Methanomassiliicoccus and Methanomethylophilus (18,21,38) as well as in Methanobrevibacter smithii and Methanosphaera stadtmanae (41).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Thus, mutations in FMO3 in humans that result in excretion of TMA in sweat and breath present as fish-odor syndrome (trimethylaminuria).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Although FMO3 and FMO1 genes are important in the formation of TMAO, a genomewide association study failed to find any significant host genetic influences on circulating TMAO concentrations and proposed that dietary factors and gut microbes may be the major determinants of circulating TMAO concentrations (49).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [49] source
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The circulating TMAO concentrations of patients with renal dysfunction increased as kidney function decreased, and abnormally high TMAO concentrations resolved after kidney transplantation (106)”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.3. Excretion of Trimethylamine N-Oxide
What the sources say
- Not checked yetcites [106] source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both mRNA and protein were found in 30% of fetal livers in the first trimester of pregnancy but not in the second and third trimesters; however, they could be detected again by 21 postnatal days.Expression of FMO3 then gradually increased to 8% of adult levels at about age nine months, 20% by 11 years, and did not reach adult levels until after 18 years (64, 133).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The elucidation of microbial TMA-generating pathways is ongoing, and it is likely that part of TMAproducing microbial metabolism remains undiscovered (41).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.1. Trimethylamine Formation by Bacteria
What the sources say
- Not checked yetcites [41] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Most TMA is absorbed into the hepatic portal circulation by passive diffusion across the enterocyte membranes and then is efficiently converted to TMAO by hepatic FMO1 and FMO3 (13); about 95% of TMA is oxidized as it is subsequently excreted in urine in a 3:95 TMA:TMAO ratio (132).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [13] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“most cases of trimethylaminuria are inherited in an autosomal recessive pattern.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, it is debated whether increased TMAO concentrations are the cause or result of these diseases.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“In addition to TMA, other substrates for FMO3 include the pharmaceutical drugs cimetidine, chlorpromazine, ketoconazole, morphine, propranolol, ranitidine, sulindac, tamoxifen and tyramine (71).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [71] Mackay RJ, 2011, Clin. Biochem. Rev.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Orthologs and homologs of the CntA/CntB and YeaW/YeaX gene pairs are found in a variety of gut microbiota: Gammaproteobacteria (Klebsiella pneumoniae, E. coli, Citrobacter, Providencia, and Shigella), Betaproteobacteria (Achromobacter), Firmicutes (Sporosarcina), and Actinobacteria; they appear to be absent in Bacteroidetes (41).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.1. Trimethylamine Formation by Bacteria
What the sources say
- Not checked yetcites [41] source
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Carriers of an FMO3 mutation may have mild symptoms of trimethylaminuria or experience temporary episodes of fish-like body odor (71).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [71] Mackay RJ, 2011, Clin. Biochem. Rev.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Small amounts of FMO1 mRNA are also found in the adult small intestine (71).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [71] Mackay RJ, 2011, Clin. Biochem. Rev.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“TMAO is a small molecule (75.1 Da) and is readily filtered by the kidneys.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.3. Excretion of Trimethylamine N-Oxide
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Testosterone suppresses and estrogen induces FMO3 expression.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Thus, FMO3 activity is 100 times higher in female than in male mice; more modest gender-related differences are observed in humans (13).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [13] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“After administration of radiolabeled TMA or TMAO to people, 94.5% of the dose label was excreted in the urine within 24 h; only 4% of the dose was excreted in the feces and <1% in the breath (2).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.3. Excretion of Trimethylamine N-Oxide
What the sources say
- Not checked yetcites [2] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“It is passively excreted in the proximal tubules of the chicken nephron via a probenecid-sensitive transporter at the luminal side, whereas N-oxidation of TMA occurs via a quinidine-sensitive transporter at the basal side.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.3. Excretion of Trimethylamine N-Oxide
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“it may exacerbate several chronic diseases including atherosclerosis, diabetes, and chronic kidney diseases (20).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 1. INTRODUCTION
What the sources say
- Not checked yetcites [20] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In Britain, it is estimated that the incidence of carrier status for trimethylaminuria is 1% (82)”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [82] Mitchell SC, 2001, Drug Metab. Dispos.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“More than 300 variants or single-nucleotide polymorphisms have been reported in FMO3.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“FMO1 mRNA and protein are expressed in the human liver during the first trimester, declining gradually in the second and third trimesters, and disappearing completely by about the third postnatal day in the liver and kidney (71).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.2. Trimethylamine N-Oxide Formation from Trimethylamine in Humans
What the sources say
- Not checked yetcites [71] Mackay RJ, 2011, Clin. Biochem. Rev.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Colonization of gnotobiotic mice with choline-converting bacteria not only increases cecal TMA production but also lowers serum choline concentration (96).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2.1. Trimethylamine Formation by Bacteria
What the sources say
- Not checked yetcites [96] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The adequate intake is 550 mg/day for men and 425 mg/day for women, with upward adjustment in pregnant and lactating women; the upper intake limit ranges from 1,000 mg/day in children to 3,500 mg/day in adults (56).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.3. L-Choline and Choline-Containing Compounds
What the sources say
- Not checked yetcites [56] Inst. Med., Natl. Acad., 1998
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Choline is present as free choline and choline esters (such as PtdCho) in foods (130), and these forms of choline are absorbed differently in the intestines.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.3. L-Choline and Choline-Containing Compounds
What the sources say
- Not checked yetcites [130] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a small study in healthy Bavarian subjects, dietary intake of fish, meat, or eggs was not associated with plasma TMAO concentrations, but dairy intake was positively associated with plasma TMAO concentrations (94).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.5. Diet Patterns and Trimethylamine N-Oxide
What the sources say
- Not checked yetcites [94] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, 100 g of spinach contains 577 mg betaine, 100 g of cod or beef contain 7 mg betaine, and 100 g of eggs contain <1 mg betaine.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.4. Betaine
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“In 1998, the US Institute of Medicine (Food and Nutrition Board) established adequate intake and tolerable upper intake limit values for choline, based on limited human studies (56).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.3. L-Choline and Choline-Containing Compounds
What the sources say
- Not checked yetcites [56] Inst. Med., Natl. Acad., 1998
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“TMA is formed in male ejaculate and vaginal secretions, and as noted in Section 2.2, TMA formation may be regulated by sex hormones (13), and cycle-dependent variations in TMA occur in women (82).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.2. Trimethylamine Is a Ligand for Trace Amine-Associated Receptor 5
What the sources say
- Not checked yetcites [13] source
- Not checked yetcites [82] Mitchell SC, 2001, Drug Metab. Dispos.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The foods that contain the most betaine are of plant origin, especially spinach, beets and grains grown in high osmotic environments (129, 130).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.4. Betaine
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The bioavailability of L-carnitine in vegetarians (who are adapted to low-carnitine diets) was higher than in carnivores (42); therefore, less carnitine reaches the bacteria of the lower intestine in vegetarians.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.2. L-Carnitine
What the sources say
- Not checked yetcites [42] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For example, 100 g of cod contains 89 mg total choline (choline + PtdCho + phosphocholine + sphingomyelin + glycerophosphocholine) compared to 100 g of beef, which contains 73 mg total choline, or 100 g of eggs, which contain 266 mg total choline (28).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.3. L-Choline and Choline-Containing Compounds
What the sources say
- Not checked yetcites [28] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“For example, 100 g of cod contains 300 mg TMAO compared to 100 g of beef or of egg, which contain <1 mg TMAO (28).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.1. Fish
What the sources say
- Not checked yetcites [28] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“TAAR5 is the most highly expressed TAAR gene in humans and may constitute an olfactory detector of TMA that elicits innate behaviors (117).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.2. Trimethylamine Is a Ligand for Trace Amine-Associated Receptor 5
What the sources say
- Not checked yetcites [117] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“TMAO production, following a challenge with L-carnitine, was significantly greater in omnivores versus vegans, and there were specific bacterial taxa associated with both dietary status and plasma TMAO concentration (63).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.2. L-Carnitine
What the sources say
- Not checked yetcites [63] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Plants use betaine in their roots as an osmolyte to help them retain intracellular water (33).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.4. Betaine
What the sources say
- Not checked yetcites [33] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“TMAO and TMA are present in high concentrations in fish and other seafood.Marine fish (e.g., cod, haddock, halibut, herring, skate) have higher concentrations than do freshwater fish (e.g., trout) (9).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.1. Fish
What the sources say
- Not checked yetcites [9] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Animal products like meat, fish, poultry, and milk (whey fraction) are highest in carnitine, whereas plants contain little carnitine (42).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.2. L-Carnitine
What the sources say
- Not checked yetcites [42] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“About 15% of the PtdCho in eggs was converted to TMA, and peak plasma TMA concentrations were achieved between 6 and 8 h after ingestion of the eggs (79).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.3. L-Choline and Choline-Containing Compounds
What the sources say
- Not checked yetcites [79] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The foods that contain the most choline are of animal origin, especially eggs and liver; however, most of the foods we eat contain some amounts of choline or choline compounds (129, 130).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.3. L-Choline and Choline-Containing Compounds
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“For example, 100 g of asparagus contains 0.2 mg carnitine, 100 g of egg contains <1 mg carnitine, 100 g of cod contains 4 mg carnitine while 100 g of beef contains 39 mg carnitine, (28).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.2. L-Carnitine
What the sources say
- Not checked yetcites [28] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“TMAO is an osmolyte in tissues and acts as a molecular chaperone that stabilizes proteins.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.1. Trimethylamine N-Oxide Is an Osmolyte and Protein Stabilizer
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Choline is absorbed in the small intestine via mediated transport, whereas PtdCho is absorbed intact via the lymphatic system or is hydrolyzed by pancreatic lipases and absorbed as glycerophosphocholine (125).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.3. L-Choline and Choline-Containing Compounds
What the sources say
- Not checked yetcites [125] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It retains the folded state of proteins and counteracts the effect of denaturants, such as pH, urea, and high pressure (6,13,29).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.1. Trimethylamine N-Oxide Is an Osmolyte and Protein Stabilizer
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Human TAAR5 can be selectively activated in a concentrationdependent manner by TMA but not by TMAO (117).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.2. Trimethylamine Is a Ligand for Trace Amine-Associated Receptor 5
What the sources say
- Not checked yetcites [117] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Even though high concentrations of circulating plasma TMAO increase cholesterol influx to peritoneal macrophages (118), cholesterol efflux or cholesterol biosynthesis appears to be unchanged.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.3. Trimethylamine N-Oxide and Sterol Metabolism
What the sources say
- Not checked yetcites [118] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Trace amine-associated receptors (TAARs) belong to the family of G protein-coupled receptors and are olfactory receptors (117).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.2. Trimethylamine Is a Ligand for Trace Amine-Associated Receptor 5
What the sources say
- Not checked yetcites [117] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Carnitine also can be synthesized endogenously from two essential amino acids, lysine and methionine (63).This occurs in kidney, liver, and brain (42).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 3.2. L-Carnitine
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Rather, these processes appear to be regulated by either TMA or other unidentified enzymatic substrates or products of FMO3.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.3. Trimethylamine N-Oxide and Sterol Metabolism
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The administration of antibiotics eliminated the FMO3 substrate TMA and normalized intestinal cholesterol absorption and fecal neutral sterol loss seen in FMO3 antisense oligonucleotide-treated mice (121).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.3. Trimethylamine N-Oxide and Sterol Metabolism
What the sources say
- Not checked yetcites [121] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In both the clinical cohorts, kidney function was not normal [normal glomerular filtration rate (GFR) is ∼100 mL/min]; the mean GFRs in both groups were 73 and 74 mL/min, respectively (range 60-87), values compatible with some loss of kidney function.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.1. High trimethylamine N-oxide correlates with cardiovascular disease.
plainn = 75- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Dietary supplementation of TMAO also decreased intestinal cholesterol absorption.The effect is consistent with reduced expression of the cholesterol transporter Niemann-Pick C1-like 1 but again does not explain reductions in RCT (118).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.3. Trimethylamine N-Oxide and Sterol Metabolism
What the sources say
- Not checked yetcites [118] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“People at risk for CVD and stroke have high plasma TMAO concentrations; they also have higher concentrations of the TMAO precursors, i.e., choline, betaine, and carnitine in plasma.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1. Trimethylamine N-Oxide and Cardiovascular Disease
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“When C57Bl/6 female mice were fed either a low-or high-cholesterol diet, FMO3 knockdown greatly reduced hepatic FMO3 expression with corresponding increases in plasma TMA concentrations and reductions in TMAO concentrations (121).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.3. Trimethylamine N-Oxide and Sterol Metabolism
What the sources say
- Not checked yetcites [121] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“FMO3 inhibition stimulated fecal neutral sterol loss and basal and liver X receptor-dependent macrophage RCT (121).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.3. Trimethylamine N-Oxide and Sterol Metabolism
What the sources say
- Not checked yetcites [121] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, both studies conclude that FMO3 inhibition has definite positive effects on cholesterol and glucose homeostasis and that TMAO does not seem to be a critical player.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.3. Trimethylamine N-Oxide and Sterol Metabolism
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The study concluded that plasma concentrations of TMAO were confounded by impaired kidney function because it was increased with declining GFR (85).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.1. High trimethylamine N-oxide correlates with cardiovascular disease.
What the sources say
- Not checked yetcites [85] source
plaindirectn = 339- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“FMO3 knockdown altered several steps of cholesterol balance, including intestinal cholesterol absorption, hepatic cholesterol ester storage, and macrophage RCT in a dietary cholesterol-dependent manner (121).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.3. Trimethylamine N-Oxide and Sterol Metabolism
What the sources say
- Not checked yetcites [121] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Mouse peritoneal macrophages incubated with TMA express scavenger receptors, accumulate cholesterol, and form foam cells.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2. Apolipoprotein E (Apo E
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interpretation of such results is difficult, as normal mouse diets contain 0.1% choline, and the authors treated mice with amounts of choline twelve times higher; these levels are not physiologic.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.2. Mice treated with trimethylamine N-oxide develop cardiovascular disease.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Normal mouse diets contain 0.1% choline.
In the paper
“This cohort had a mean eGFR of 83 mL/min (63).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.1. High trimethylamine N-oxide correlates with cardiovascular disease.
What the sources say
- Not checked yetcites [63] source
plainn = 2,595- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“TMAO feeding did not change the expression of hepatic cholesterol exporters, but striking reductions in bile acid pool size and species, along with reduced expression of the cytochrome P450 family of enzymes, Cyp7a1 and Cyp27a1, were noted (118).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.3. Trimethylamine N-Oxide and Sterol Metabolism
What the sources say
- Not checked yetcites [118] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that, although chronic elevation of TMAO can be detrimental in mice, the ability of FMO3 to reorganize cholesterol balance is most likely not mediated through TMAO.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.3. Trimethylamine N-Oxide and Sterol Metabolism
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together these results provide evidence that TMAO alters pathways for cholesterol elimination from the body and causes reductions in RCT.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 4.3. Trimethylamine N-Oxide and Sterol Metabolism
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Humans carry about 75% of their plasma cholesterol in low-density lipoprotein (LDL) particles, whereas mice carry most of their cholesterol in high-density lipoprotein (HDL) particles (57).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.4. Trimethylamine N-oxide-cause or result of atherosclerosis.
What the sources say
- Not checked yetcites [57] Jawien J, 2004, J. Physiol. Pharmacol.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, there are strong data that suggest an association between TMAO and CVD risk, but there are equally strong inconsistencies.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.4. Trimethylamine N-oxide-cause or result of atherosclerosis.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A meta-analysis of 11 eligible studies and 13 cohorts (n = 222,364) found that fish consumption was inversely associated with CVD and may even reduce mortality due to CVD (50,51).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.4. Trimethylamine N-oxide-cause or result of atherosclerosis.
hedgedconditionaln = 222,364- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the existing mouse data may support the hypothesis that TMAO causes atherosclerosis, but given the concerns discussed above, we should be cautious about extrapolating data from a particular mouse model to humans.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.4. Trimethylamine N-oxide-cause or result of atherosclerosis.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Chronic choline supplementation of atherosclerosis-prone low-density lipoprotein receptor (LDLR -/-) mice increased plasma TMAO concentrations and increased expression of inflammatory genes in vascular cells (52).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.2. Mice treated with trimethylamine N-oxide develop cardiovascular disease.
What the sources say
- Not checked yetcites [52] Herlaar E, 1999, Trends Mol. Med.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Uremia accelerates atherosclerosis and arterial calcification in patients with chronic renal failure (22,74).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.4. Trimethylamine N-oxide-cause or result of atherosclerosis.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Apo E-knockout mice have a shift in plasma lipoproteins from HDL, the major lipoprotein in wild-type mice, to cholesterolenriched remnants of chylomicrons and VLDLs, and these mice have phenotypes similar to those of Apo E-deficient humans (57).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.4. Trimethylamine N-oxide-cause or result of atherosclerosis.
What the sources say
- Not checked yetcites [57] Jawien J, 2004, J. Physiol. Pharmacol.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Serum concentration of TMAO was inversely associated with eGFR and was markedly higher in patients receiving dialysis (59,81); hemodialysis efficiently removed TMAO from blood (8).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.2.1. Trimethylamine N-oxide correlates with renal disease.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“TMAO is cleared from plasma by the kidney.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.2. Trimethylamine N-Oxide and Kidney Disease
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If TMAO causes CVD, then eating more fish should be associated with increased risk for heart disease; it is not.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.4. Trimethylamine N-oxide-cause or result of atherosclerosis.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Fish contain high concentrations of TMA, and gut bacteria convert this TMA to TMAO in people who eat fish.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As noted above in Section 2.3, TMAO is excreted by the kidneys, and this metabolite is elevated in patients with kidney disease.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.4. Trimethylamine N-oxide-cause or result of atherosclerosis.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These macrophages had excess cholesterol accumulation and foam cell formation (118).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.3. Macrophages treated with trimethylamine N-oxide develop the atherosclerotic phenotype.
What the sources say
- Not checked yetcites [118] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Increased TMAO concentrations were associated with systemic inflammatory markers and predicted a reduced fiveyear survival (81).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.2.1. Trimethylamine N-oxide correlates with renal disease.
What the sources say
- Not checked yetcites [81] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Apo E knockout mice are considered to be one of the most relevant models for atherosclerosis because they are hypercholesterolemic and develop spontaneous arterial lesions (87).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.4. Trimethylamine N-oxide-cause or result of atherosclerosis.
What the sources say
- Not checked yetcites [87] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“TMA can be used for methanogenesis in the gastrointestinal tract, and bacteria belonging to the genera Methanomassiliicoccus and Methanomethylophilus have this pathway (18,21,38,41).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 6. TARGETING TRIMETHYLAMINE, HEPATIC FLAVIN MONOOXYGENASE, AND TRIMETHYLAMINE N-OXIDE PATHWAYS IN DISEASE THERAPY
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Knockdown of FMO3 in LIRKO mice suppressed FoxO1 expression (and improved glucose tolerance) by upregulating sterol regulatory element binding protein 2 (SREBP2) (77).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.3.2. Animals with altered trimethylamine N-oxide metabolism, or treated with trimethylamine N-oxide, develop diabetes.
What the sources say
- Not checked yetcites [77] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“TMAO was used also as a urinary marker in a mouse model of gastric tumorigenesis (60).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.4. Trimethylamine N-Oxide and Cancer
What the sources say
- Not checked yetcites [60] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“To this end, oral charcoal adsorbent (AST-120) has been clinically used to remove uremic toxins, such as indoxyl sulfate, in patients with advanced renal failure (86).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 6. TARGETING TRIMETHYLAMINE, HEPATIC FLAVIN MONOOXYGENASE, AND TRIMETHYLAMINE N-OXIDE PATHWAYS IN DISEASE THERAPY
What the sources say
- Not checked yetcites [86] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“When C57BL/6J mice were fed either a high-choline diet or a diet supplemented with TMAO for six weeks, plasma concentrations of TMAO increased and were associated with corresponding increases in tubulointerstitial fibrosis and collagen deposition, as well as increases in kidney injury marker-1.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.2.2. Mice treated with trimethylamine N-oxide develop renal damage.
What the sources say
- Not checked yetcites [109] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The study concluded that this increased excretion of TMAO could be due to tubulointerstitial distortions (4).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.2.1. Trimethylamine N-oxide correlates with renal disease.
What the sources say
- Not checked yetcites [4] source
hedgedconditionaln = 77- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“SREBP2 directly activates microRNA 182, which in turn regulates FoxO1 expression (77).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.3.2. Animals with altered trimethylamine N-oxide metabolism, or treated with trimethylamine N-oxide, develop diabetes.
What the sources say
- Not checked yetcites [77] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Liver insulin receptor knockout (LIRKO) mice are unable to respond to insulin in the liver and display several features of diabetes, such as hyperglycemia, hyperinsulinemia, and dyslipidemia.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.3.2. Animals with altered trimethylamine N-oxide metabolism, or treated with trimethylamine N-oxide, develop diabetes.
What the sources say
- Not checked yetcites [15] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the existing mouse data may support the hypothesis that TMAO causes renal disease, but given the concerns discussed in Section 5.1.4,scientists and clinicians should be cautious about extrapolating data from a particular mouse model to humans.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.2.3. Trimethylamine N-oxide-cause or result of renal dysfunction.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Even though it needs to be demonstrated in humans, introducing Lactobacillus paracasei in mice expressing human baby flora decreased fecal choline and was associated with reduced concentrations of TMA and dimethylamine in the liver and plasma lipoproteins (73).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 6. TARGETING TRIMETHYLAMINE, HEPATIC FLAVIN MONOOXYGENASE, AND TRIMETHYLAMINE N-OXIDE PATHWAYS IN DISEASE THERAPY
What the sources say
- Not checked yetcites [73] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It was suggested that the accumulation of TMAO in end-stage renal disease patients who receive chronic hemodialysis is mainly due to the previously unrecognized limitation of chronic dialysis (45).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.2.3. Trimethylamine N-oxide-cause or result of renal dysfunction.
What the sources say
- Not checked yetcites [45] source
hedgeddirect- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it.
In the paper
“In high-fat-fed C57Bl/6 mice, TMAO feeding increases the glucose intolerance induced by the diet as measured by higher fasting insulin levels and the homeostasis model assessment (HOMA) for insulin resistance scores along with altered insulin signaling and increased inflammatory markers (44).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.3.2. Animals with altered trimethylamine N-oxide metabolism, or treated with trimethylamine N-oxide, develop diabetes.
What the sources say
- Not checked yetcites [44] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“And the investigators did not determine, using antibiotics, whether conversion of choline to TMAO was required for the choline effects.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.2.3. Trimethylamine N-oxide-cause or result of renal dysfunction.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“However, long-term usage of antibiotics can promote the emergence of antibiotic-resistant bacterial strains and repopulation of microbes after its withdrawal.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 6. TARGETING TRIMETHYLAMINE, HEPATIC FLAVIN MONOOXYGENASE, AND TRIMETHYLAMINE N-OXIDE PATHWAYS IN DISEASE THERAPY
What the sources say
- Not checked yetcites [20] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“TMAO is cleared more efficiently than urea by the normal kidney function but not by dialysis (45).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.2.3. Trimethylamine N-oxide-cause or result of renal dysfunction.
What the sources say
- Not checked yetcites [45] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It also significantly lowered plasma TMAO concentrations and mitigated choline-enhanced macrophage foam cell formation and atherosclerosis in Apo e -/-mice (119).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 6. TARGETING TRIMETHYLAMINE, HEPATIC FLAVIN MONOOXYGENASE, AND TRIMETHYLAMINE N-OXIDE PATHWAYS IN DISEASE THERAPY
What the sources say
- Not checked yetcites [119] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“One should also consider the side effects associated with inhibiting FMOs as they are major xenobiotic metabolizing enzymes (23).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 6. TARGETING TRIMETHYLAMINE, HEPATIC FLAVIN MONOOXYGENASE, AND TRIMETHYLAMINE N-OXIDE PATHWAYS IN DISEASE THERAPY
What the sources say
- Not checked yetcites [23] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Inhibiting FMO enzymes, however, may not be ideal as it causes accumulation of TMA, leading to a fishy odor and inflammation as observed in antisense oligonucleotide-treated mice (102, 121).”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 6. TARGETING TRIMETHYLAMINE, HEPATIC FLAVIN MONOOXYGENASE, AND TRIMETHYLAMINE N-OXIDE PATHWAYS IN DISEASE THERAPY
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Plasma TMAO concentration is a valid proxy for the biologically relevant TMAO exposure at target tissues.
“Both observational and experimental studies suggest a strong positive correlation between increased plasma TMAO concentrations and adverse cardiovascular events, such as myocardial infarction, stroke, and death.”
“TMAO-mediated atherosclerosis could potentially be a significant cause of heart and kidney disease, but the underlying mechanisms whereby TMAO is related to heart and kidney disease need to be fully elucidated and validated.”
The paper relies on this without support.
Fish contain high concentrations of TMA, and gut bacteria convert this TMA to TMAO in people who eat fish.
“Fish contain high concentrations of TMA, which are converted to TMAO by bacteria in the gut of people who eat fish.”
The paper relies on this without support.
Renal clearance determines plasma TMAO concentrations.
“Because renal clearance is a determinant of plasma TMAO concentrations, kidney function and TMAO must be correlated even if TMAO does not cause kidney damage.”
The paper relies on this without support.
Normal mouse diets contain 0.1% choline.
“Interpretation of such results is difficult, as normal mouse diets contain 0.1% choline, and the authors treated mice with amounts of choline twelve times higher; these levels are not physiologic.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“TMA is generated in the gut from betaine, L-carnitine and its metabolite γ-butyrobetaine (GBB), choline and other choline-containing compounds, which are present in the diet.”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [18]
In the citing paper
“Nearly 95% of TMA is oxidized and it is afterwards excreted in urine in a 3:95 TMA: TMAO ratio within 24 h, only 4% is excreted in feces and less than 1% is eliminated in the breath [18].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [18]
In the citing paper
“It has been demonstrated in gnotobiotic mice that gut bacteria are essential to transform the dietary compounds into TMA [18].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [18]
In the citing paper
“FMO1 has tenfold lower specific activity in the liver than does FMO3, so FMO3 is the main enzyme responsible for the conversion of TMA into TMAO [18].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [18]
In the citing paper
“For example, oral charcoal adsorbent (AST-120) has been clinically used to remove uremic toxins such as indoxyl sulfate from patients with advanced renal failure.”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [18]
In the citing paper
“The gene cluster responsible for the conversion of choline into TMA has been identified.”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [18]
In the citing paper
“However, a compound that removes specifically TMAO has not yet been discovered [18,95].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [18]
In the citing paper
“CutC and CutD are necessary for that transformation; so they could be used like targets as their inhibition eradicates the production of TMA [18].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [18]
In the citing paper
“Nevertheless, there could be several problems with this approach as an accumulation of TMA leads to trimethylaminuria, which is characterized by fishy odor (similar to rotten fish) and induce inflammation [18,75,99].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [18]
In the citing paper
“Another problem would be that TMAO is not the only substrate for FMO3; morphine, propranolol and tyramine are also metabolized by FMO3 [18].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [18]
In the citing paper
“CutC and CutD are necessary for that transformation; so they could be used like targets as their inhibition eradicates the production of TMA [18].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [18]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.4. Trimethylamine N-oxide-cause or result of atherosclerosis.
“Fish contain high concentrations of TMA, which are converted to TMAO by bacteria in the gut of people who eat fish.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 1. INTRODUCTION
“This absorbed TMA is delivered to the liver where flavin-dependent monooxygenase (FMO) isoforms 1 and 3 convert it to TMAO.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 2. Apolipoprotein E (Apo E
“Mouse peritoneal macrophages incubated with TMA express scavenger receptors, accumulate cholesterol, and form foam cells.”
§ Annual Review of Nutrition Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease > 5.1.3. Macrophages treated with trimethylamine N-oxide develop the atherosclerotic phenotype.
“Peritoneal macrophages obtained from C57BL/6J mice, fed a TMAO-supplemented diet for more than three weeks, showed increased mRNA levels of two macrophage scavenger receptors (CD36 and SR-A1), which are implicated in atherosclerosis (118).”
Citations
Cites
Heart Disease and Stroke Statistics—2016 Update: A Report From the American Heart Association
Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., Das, S. R., de Ferranti, S., Després, J.-P., Fullerton, H. J., et al. (2016) · Circulation · doi:10.1161/cir.0000000000000350 · Cited by 6,596
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y.-M., et al. (2011) · Nature · doi:10.1038/nature09922 · Cited by 5,597
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3145 · Cited by 4,386
Self-citationIntestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1109400 · Cited by 3,400 · cited 4×
“However, consumption of ≥2 eggs, which contain mostly PtdCho, results in increased formation of TMAO (79, 110).”
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The Inverse Relation between Fish Consumption and 20-Year Mortality from Coronary Heart Disease
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Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk
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Microbiota in health and diseases
Hou, K., Wu, Z.-X., Chen, X.-Y., Wang, J.-Q., Zhang, D., Xiao, C., Zhu, D., Koya, J. B., Wei, L., Li, J., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00974-4 · Cited by 3,171
“Mechanistically, TMAO can activate the mitogenactivated protein kinase (MAPK) and NF-κB signaling pathways in endothelial cells and smooth muscle cells.(132) The MAPK signaling pathway can be stimulated by growth factors, pathogen-associated molecules, and inflammatory cytokines, which follows by a MAPKKK-MAPKK-MAPK-T…”
BackgroundYang, W., & Cong, Y. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00661-4 · Cited by 715
Janeiro, M., Ramírez, M., Milagro, F., Martínez, J., & Solas, M. (2018) · Nutrients · doi:10.3390/nu10101398 · Cited by 631
“Some studies revealed that the genes CutC and CutD, which are present in the cluster Cut, are indispensable for Desulfovibrio alaskensis and Desulfovibrio desulfuricans to transform choline into TMA [18].”
BackgroundInfluentialHow the immune system shapes atherosclerosis: roles of innate and adaptive immunity
Roy, P., Orecchioni, M., & Ley, K. F. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00584-1 · Cited by 610
Microbiome–metabolome reveals the contribution of gut–kidney axis on kidney disease
Chen, Y., Chen, D., Chen, L., Liu, J., Vaziri, N. D., Guo, Y. P., & Zhao, Y. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-018-1756-4 · Cited by 430
Gut microbiota and cardiovascular disease: opportunities and challenges
Kazemian, N., Mahmoudi, M., Halperin, F. A., Wu, J. C., & Pakpour, S. (2020) · Microbiome · doi:10.1186/s40168-020-00821-0 · Cited by 404
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“, 2013; Ma and Li, 2018), as it has been shown to be essential for converting dietary compounds into TMA in gnotobiotic mice and human studies (Wang et al., 2011; Tang and Hazen, 2014; Zeisel and Warrier, 2017), and changes in the gut microbiota have marked effects on TMAO levels.”
BackgroundThe Impact of CKD on Uremic Toxins and Gut Microbiota
Rysz, J., Franczyk, B., Ławiński, J., Olszewski, R., Ciałkowska-Rysz, A. D., & Gluba-Brzózka, A. (2021) · Toxins · doi:10.3390/toxins13040252 · Cited by 324
“Trimethylamine formed in the first step is later absorbed and converted to TMAO by flavin monooxygenase enzymes in the liver [134].”
BackgroundGut Microbiota Dysbiosis: Pathogenesis, Diseases, Prevention, and Therapy
Shen, Y., Fan, N., Ma, S., Cheng, X., Yang, X., & Wang, G. (2025) · MedComm · doi:10.1002/mco2.70168 · Cited by 404
Handelsman, Y., Jellinger, P. S., Guerin, C. K., Bloomgarden, Z. T., Brinton, E. A., Budoff, M. J., Davidson, M. H., Einhorn, D., Fazio, S., Fonseca, V. A., et al. (2020) · Endocrine Practice · doi:10.4158/cs-2020-0490 · Cited by 248
“One mechanism might be that meat and dairy cause higher levels of trimethylamine N-oxide, which has been associated with development and progression of atherosclerosis, primarily by altering the gut microbiome (47).”
Rethinking healthy eating in light of the gut microbiome
Armet, A. M., Deehan, E. C., O’Sullivan, A. F., Mota, J. F., Field, C. J., Prado, C. M., Lucey, A. J., & Walter, J. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.04.016 · Cited by 252
Gut microbiota dependent trimethylamine N-oxide aggravates angiotensin II–induced hypertension
Jiang, S., Shui, Y., Cui, Y., Tang, C., Wang, X., Qiu, X., Hu, W., Fei, L., Li, Y., Zhang, S., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102115 · Cited by 237
Liu, Y., & Dai, M. (2020) · Mediators of Inflammation · doi:10.1155/2020/4634172 · Cited by 235
“For humans, most of the plasma cholesterol is contained in low-density lipoprotein (LDL) particles, whereas most of their cholesterol is in high-density lipoprotein (HDL) particles for mice.”
BackgroundInfluentialThe gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases
Zhen, J., Zhou, Z., He, M., Han, H.-X., Lv, E., Wen, P., Liu, X., Wang, Y., Cai, X., Tian, J., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1085041 · Cited by 248
“L-carnitine is predominantly contained in red meat (35), while most betaine is found in fish, beetroot, and grains grown in high osmotic environments, such as beans (36).”
BackgroundTrimethylamine N-oxide (TMAO) in human health
Gątarek, P., & Kałużna‐Czaplińska, J. (2020) · EXCLI journal · doi:10.17179/excli2020-3239 · Cited by 235
“TMA is formed from the dietary compounds present in the diet, which is then immediately absorbed and converted into TMA by various enzymes (Wang et al., 2019; Zeisel and Warrier, 2017).”
BackgroundKonopelski, P., & Mogilnicka, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031222 · Cited by 220
“TMAO synthesis increases after phosphatidylcholine- and L-carnitine-rich meals [53], and depends on the metabolism by gut microbiota, which was demonstrated in humans [54].”
BackgroundInfluentialFeng, Y., Cao, G., Chen, D., Vaziri, N. D., Chen, L., Zhang, J., Wang, M., Guo, Y. P., & Zhao, Y. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03155-9 · Cited by 201
Wu, M., Yang, S., Wang, S., Cao, Y., Zhao, R., Li, X., Xing, Y., & Liu, L. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00223 · Cited by 202
Gut microbiota in atherosclerosis: focus on trimethylamine N‐oxide
Zhu, Y., Li, Q., & Jiang, H. (2020) · Apmis · doi:10.1111/apm.13038 · Cited by 210
Arias, N., Arboleya, S., Allison, J., Kaliszewska, A., Higarza, S. G., Gueimonde, M., & Arias, J. L. (2020) · Nutrients · doi:10.3390/nu12082340 · Cited by 210
Ge, X., Zheng, L., Zhuang, R., Yu, P., Xu, Z., Liu, G., Xi, X., Zhou, X., & Fan, H. (2019) · Advances in Nutrition · doi:10.1093/advances/nmz064 · Cited by 204
“trimethylamine (TMA) by hepatic flavin-dependent monooxygenases (14, 15).”
BackgroundCanyelles, M., Tondo, M., Cedó, L., Farràs, M., Escolá‐Gil, J. C., & Blanco‐Vaca, F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103228 · Cited by 197
Microbial Contribution to the Human Metabolome: Implications for Health and Disease
Treuren, W. V., & Dodd, D. (2019) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-043559 · Cited by 180
“Given how the story of TMAO and CVD has captivated physicians, nutritionists, and microbiologists alike, there is no doubt that future studies will seek to address these questions.”
BackgroundInfluentialThe Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases
Fogelson, K. A., Dorrestein, P. C., Zarrinpar, A., & Knight, R. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.02.022 · Cited by 177
NAFLD, and cardiovascular and cardiac diseases: Factors influencing risk, prediction and treatment
Targher, G., Corey, K. E., & Byrne, C. D. (2020) · Diabetes & Metabolism · doi:10.1016/j.diabet.2020.101215 · Cited by 174
Wallace, T. C., Blusztajn, J. K., Caudill, M. A., Klatt, K. C., Natker, E., Zeisel, S. H., & Zelman, K. M. (2018) · Nutrition Today · doi:10.1097/nt.0000000000000302 · Cited by 169
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Clinical epidemiology of infectious disease among patients with chronic kidney disease
Ishigami, J., & Matsushita, K. (2018) · Clinical and Experimental Nephrology · doi:10.1007/s10157-018-1641-8 · Cited by 167
Trimethylamine-N-Oxide (TMAO) Predicts Cardiovascular Mortality in Peripheral Artery Disease
Roncal, C., Martínez-Aguilar, E., Orbe, J., Ravassa, S., Fernández‐Montero, A., Saenz‐Pipaon, G., Ugarte, A., de Mendoza, A. E., Rodríguez, J. A., Fernandez-Alonso, S., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-52082-z · Cited by 165
Bioactivity and health effects of ruminant meat lipids. Invited Review
Vahmani, P., Ponnampalam, E. N., Kraft, J., Mapiye, C., Bermingham, E. N., Watkins, P. J., Proctor, S. D., & Dugan, M. E. R. (2020) · Meat Science · doi:10.1016/j.meatsci.2020.108114 · Cited by 178
McClements, D. J. (2020) · Food Hydrocolloids · doi:10.1016/j.foodhyd.2020.106404 · Cited by 168
The gut microbiome and cardiovascular disease: current knowledge and clinical potential
Ahmad, A. F., Dwivedi, G., O’Gara, F., Caparros-Martin, J. A., & Ward, N. C. (2019) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00376.2019 · Cited by 165
Trimethylamine N-Oxide in Relation to Cardiometabolic Health—Cause or Effect?
Papandreou, C., Moré, M. I., & Bellamine, A. (2020) · Nutrients · doi:10.3390/nu12051330 · Cited by 157
“However, current reviews critically evaluating the cause to effect relationship and the nature of TMAO’s association to cardiometabolic diseases are missing [8].”
BackgroundInfluentialBenítez‐Páez, A., Kjølbæk, L., del Pulgar, E. M. G., Brahe, L. K., Astrup, A. V., Matysik, S., Schött, H.-F., Krautbauer, S., Liebisch, G., Boberska, J., et al. (2019) · mSystems · doi:10.1128/msystems.00209-19 · Cited by 141
Role of the intestinal microbiome and its therapeutic intervention in cardiovascular disorder
Luqman, A., Hassan, A., Ullah, M., Naseem, S., Ullah, M., Zhang, L., Din, A. U., Ullah, K., Ahmad, W., & Wang, G. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1321395 · Cited by 145
Yang, W., Zhang, S., Zhu, J., Jiang, H., Jia, D., Ou, T., Qi, Z., Zou, Y., Qian, J., Sun, A., et al. (2019) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2019.07.004 · Cited by 118
Precision (Personalized) Nutrition: Understanding Metabolic Heterogeneity
Zeisel, S. H. (2020) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-032519-051736 · Cited by 135
Self-citationRisk of Heart Failure in Patients With Nonalcoholic Fatty Liver Disease
Mantovani, A., Byrne, C. D., Benfari, G., Bonapace, S., Simon, T. G., & Targher, G. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.11.007 · Cited by 115
Can diet modulate trimethylamine N-oxide (TMAO) production? What do we know so far?
Coutinho‐Wolino, K. S., Cardozo, L., Leal, V. D. O., Mafra, D., & Stockler‐Pinto, M. B. (2021) · European Journal of Nutrition · doi:10.1007/s00394-021-02491-6 · Cited by 116
“Nowadays, it is common knowledge that TMAO can act as an active chemical molecule, which is capable of interfering in the homeostasis of several metabolic pathways in humans, thereby contributing to the development of chronic diseases such as atherosclerosis, diabetes, and kidney diseases [32] (Fig.”
BackgroundWinther, S. A., Oellgaard, J., Tofte, N., Tarnow, L., Wang, Z., Ahluwalia, T. S., Jorsal, A., Theilade, S., Parving, H., Hansen, T. W., et al. (2019) · Diabetes Care · doi:10.2337/dc19-0048 · Cited by 111
“Thus, it has been speculated that TMAO is a biomarker associated with CVD but not the cause of CVD (35), even though it has been the”
BackgroundDiet, Gut Microbiota and Non-Alcoholic Fatty Liver Disease: Three Parts of the Same Axis
Quesada‐Vázquez, S., Aragonès, G., Bas-Prior, J. M. D., & Escoté, X. (2020) · Cells · doi:10.3390/cells9010176 · Cited by 111
“VLDL production and the hepatic lipid transfer are modulated by dietary choline, and the choline metabolism is affected by the gut microbiota dysbiosis [33].”
BackgroundDietary Strategies for Management of Metabolic Syndrome: Role of Gut Microbiota Metabolites
Croci, S., D'Apolito, L. I., Gasperi, V., Catani, M. V., & Savini, I. (2021) · Nutrients · doi:10.3390/nu13051389 · Cited by 111
“activity; it is noteworthy that TMA-producing bacterial strains (such as Escherichia fergusonii, Clostridium sporogenes, and Proteus penneri) have been detected in the human gut [31,85].”
BackgroundPraveenraj, S. S., Sonali, S., Anand, N., Hediyal, T. A., Vichitra, C., Kalyan, M., Kanna, P. V., Chandana, K. A., Paneyala, S., Mahalakshmi, A. M., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02990-5 · Cited by 116
“These two steps are called microbiotadependent pathways and human endogenous pathways, respectively [6, 40, 41].”
BackgroundNutritional Influences on One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity
Bozack, A. K., Saxena, R., & Gamble, M. V. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082117-051757 · Cited by 105
“While TMAO has been linked to risk for cardiovascular disease (150), it is unclear whether or not this relationship is causal (174).”
The Intestinal Microbiota and Metabolites in the Gut-Kidney-Heart Axis of Chronic Kidney Disease
Huang, Y., Xin, W., Xiong, J., Yao, M., Zhang, B., & Zhao, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.837500 · Cited by 93
“, 2017), and studies have demonstrated a positive correlation between the level of Enterococcus and the concentration of Trimethylamine N-Oxide (TMAO), which can serve as a potential biomarker of renal or cardiac dysfunction (Tang et al., 2015; Xu et al., 2017; Zeisel and Warrier, 2017; Liu et al., 2019).”
BackgroundInfluentialZeisel, S. H., Klatt, K. C., & Caudill, M. A. (2018) · Advances in Nutrition · doi:10.1093/advances/nmx004 · Cited by 98
Self-citationPharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline
Nguyen, V., Taine, E. G., Meng, D., Cui, T., & Tan, W. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063385 · Cited by 105
“In adult rats with isoproterenol (ISO)-induced myocardial dysfunctions, TRG prevented ISO-induced myocardial injury by downregulating the expression of the proteins Hsp27 and α B-crystallin [34].”
BackgroundGut Microbial Metabolite Trimethylamine N -Oxide Aggravates Pulmonary Hypertension
Huang, Y., Lin, F., Tang, R., Bao, C., Zhou, Q., Ye, K., Shen, Y., Liu, C., Hong, C., Yang, K., et al. (2022) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2021-0414oc · Cited by 82
Gut bacterial phospholipase Ds support disease-associated metabolism by generating choline
Chittim, C. L., Campo, A. M.-D., & Balskus, E. P. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0294-4 · Cited by 94
Contribution of Trimethylamine N-Oxide (TMAO) to Chronic Inflammatory and Degenerative Diseases
Constantino-Jonapa, L. A., Espinoza-Palacios, Y., Escalona‐Montaño, A. R., Hernández-Ruiz, P., Amezcua-Guerra, L. M., Amedei, A., & Aguirre‐García, M. M. (2023) · Biomedicines · doi:10.3390/biomedicines11020431 · Cited by 99
“For example, it acts as a protein stabilizer, preserving its structure and enzymatic activity as well as counteracting the effects of pH, urea, and increased pressure [6].”
Shanmugham, M., Bellanger, S., & Leo, C. H. (2023) · Pharmaceuticals · doi:10.3390/ph16040504 · Cited by 103
“In most individuals, about half of the TMAO generated is excreted without any modifications within 24 h, through urine (95%), feces (4%), as well as by sweat and breath (less than 1%) [23].”
BackgroundMetabolic functions of the human gut microbiota: the role of metalloenzymes
Rajakovich, L. J., & Balskus, E. P. (2018) · Natural Product Reports · doi:10.1039/c8np00074c · Cited by 91
A Clinician’s Guide for Trending Cardiovascular Nutrition Controversies
Freeman, A. M., Morris, P. B., Aspry, K. E., Gordon, N. F., Barnard, N. D., Esselstyn, C. B., Ros, E., Devries, S. R., O’Keefe, J. H., Miller, M. J., et al. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.05.030 · Cited by 93
“Another concern has been the relatively high content of trimethylamine N-oxide in fish (129), a molecule that may be detrimental for CV and general health (130).”
BackgroundYang, P., Li, X., Song, B., He, M. R., Wu, C., & Leng, X. (2021) · Aquaculture and Fisheries · doi:10.1016/j.aaf.2021.03.003 · Cited by 83
Li, T., Gua, C., Wu, B., & Chen, Y. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.12.069 · Cited by 89
Álvarez‐Mercado, A. I., & Plaza‐Díaz, J. (2022) · Nutrients · doi:10.3390/nu14194116 · Cited by 92
“Smooth muscle cells and endothelial cells can respond to TMAO by triggering the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways [48].”
BackgroundServillo, L., D’Onofrio, N., Giovane, A., Casale, R., Cautela, D., Castaldo, D., Iannaccone, F., Neglia, G., Campanile, G., & Balestrieri, M. L. (2018) · Food Chemistry · doi:10.1016/j.foodchem.2018.03.114 · Cited by 76
Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases
Stec, A., Sikora, M., Maciejewska, M., Paralusz-Stec, K., Michalska, M. N., Sikorska, E., & Rudnicka, L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043494 · Cited by 89
Holmes, A., Finger, C. E., Morales‐Scheihing, D., Lee, J., & McCullough, L. D. (2020) · Translational research · doi:10.1016/j.trsl.2020.07.012 · Cited by 88
“Elevated TMAO levels are associated with an increased risk of atherosclerosis and other chronic vascular diseases (93, 94).”
BackgroundNguyen, T. T., Kościółek, T., Daly, R. E., Vázquez‐Baeza, Y., Swafford, A. D.-E., Knight, R. D., & Jeste, D. V. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.10.003 · Cited by 89
Yu, D., Shu, X., Rivera, E. S., Zhang, X., Cai, Q., Calcutt, M. W., Xiang, Y., Li, H., Gao, Y., Wang, T. J., et al. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.118.010606 · Cited by 81
“T rimethylamine-N-oxide (TMAO) has gained much attention recently because of its potential adverse effects on atherosclerosis and cardiovascular disease (CVD).(1,2) TMAO is a gut microbial–host cometabolite of dietary trimethylamines (mainly choline and carnitine).”
BackgroundGood or bad: gut bacteria in human health and diseases
Wang, H., Wei, C.-X., Lu, M., & Zhu, L. (2018) · Biotechnology & Biotechnological Equipment · doi:10.1080/13102818.2018.1481350 · Cited by 90
Liang, Y., Dai, X., Cao, Y. L., Wang, X., Lu, J., Xie, L., Liu, K., & Li, X. (2022) · Biochimie · doi:10.1016/j.biochi.2022.10.009 · Cited by 79
Role of the Gut Microbiome in the Development of Atherosclerotic Cardiovascular Disease
Samarraie, A. A., Pichette, M., & Rousseau, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065420 · Cited by 78
Rajakovich, L. J., Fu, B., Bollenbach, M., & Balskus, E. P. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2101498118 · Cited by 79
Cardiorenal syndrome: clinical diagnosis, molecular mechanisms and therapeutic strategies
Zhao, B., Hu, X., Wang, W., & Zhou, Y. (2025) · Acta Pharmacologica Sinica · doi:10.1038/s41401-025-01476-z · Cited by 91
“In addition, elevated serum TMAO levels are an independent risk factor for hospitalisation events in patients on haemodialysis [25, 26].”
Plasma Trimethylamine N-Oxide and Risk of Cardiovascular Events in Patients With Type 2 Diabetes
Croyal, M., Saulnier, P., Aguesse, A., Gand, E., Ragot, S., Roussel, R., Halimi, J., Ducrocq, G., Cariou, B., Montaigne, D., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa188 · Cited by 73
Gut Microbiota in Liver Disease: What Do We Know and What Do We Not Know?
Jiang, L., & Schnabl, B. (2020) · Physiology · doi:10.1152/physiol.00005.2020 · Cited by 64
Breast Cancer: Lifestyle, the Human Gut Microbiota/Microbiome, and Survivorship
Bodai, B. I., & Nakata, T. E. (2020) · The Permanente Journal · doi:10.7812/tpp/19.129 · Cited by 73
Roles of Gut Microbial Metabolites in Diabetic Kidney Disease
Fang, Q., Liu, N., Zheng, B., Guo, F., Zeng, X., Huang, X., & Ouyang, D. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.636175 · Cited by 71
“Moreover, in some bacteria of the gender Acinetobacter and Serratia, CntA and CntB gens encode the two subunits of the oxidoreductase enzyme necessary to convert L-carnitine into TMA (35).”
BackgroundSchneider, C., Okun, J. G., Schwarz, K. V., Hauke, J., Zorn, M., Nürnberg, C., Ungerer, M. N., Ringleb, P. A., & Mundiyanapurath, S. (2020) · European Journal of Neurology · doi:10.1111/ene.14253 · Cited by 64
“TMA is rapidly absorbed in the bloodstream and oxidized to TMAO by flavin-containing monooxygenase-3 and is subsequently secreted in urine [4].”
BackgroundYu, H., Geng, W., Zheng, Z., Gao, J., Guo, D., & Wang, Y. (2019) · Theranostics · doi:10.7150/thno.33459 · Cited by 68
“In people, TMAO is mostly eliminated from body though urine, and is also excreted though breathe and sweat [8].”
BackgroundMethodHuo, X., Li, J., Cao, Y., Li, S., Shao, P., Leng, J., Li, W., Liu, J., Yang, K., Ronald, C. W., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00710 · Cited by 65
TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats
Gawryś-Kopczyńska, M., Konop, M., Maksymiuk, K. M., Kraszewska, K., Derzsi, L., Sozański, K., Hołyst, R., Pilz, M., Samborowska, E., Dobrowolski, L., et al. (2020) · eLife · doi:10.7554/elife.57028 · Cited by 67
Meng, F., Li, N., Li, D., Song, B., & Li, L. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.111902 · Cited by 68
Orman, M., Bodea, S., Funk, M. A., Campo, A. M.-D., Bollenbach, M., Drennan, C. L., & Balskus, E. P. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b04883 · Cited by 64
Costabile, G., Vetrani, C., Bozzetto, L., Giacco, R., Bresciani, L., Rio, D. D., Vitale, M., Pepa, G. D., Brighenti, F., Riccardi, G., et al. (2021) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqab188 · Cited by 68
Myocardial infarction and gut microbiota: An incidental connection
Vahed, S. Z., Barzegari, A., Tamayo, M. Z., Letourneur, D., & Pavon‐Djavid, G. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.11.008 · Cited by 65
Targeting Trimethylamine N-Oxide: A New Therapeutic Strategy for Alleviating Atherosclerosis
Jing, L., Zhang, H., Xiang, Q., Shen, L., Guo, X., Zhai, C., & Hu, H. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.864600 · Cited by 69
“In addition to being excreted in the urine, TMAO can be eliminated through sweat, feces, and the respiratory tract (33).”
BackgroundBalancing the Equation: A Natural History of Trimethylamine and Trimethylamine-N-oxide
Loo, R. L., Chan, Q. M., Nicholson, J. K., & Holmes, E. C. (2022) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00851 · Cited by 63
Yang, J. J., Lipworth, L. P., Shu, X., Blot, W. J., Xiang, Y., Steinwandel, M. D., Li, H., Gao, Y., Zheng, W., & Yu, D. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz318 · Cited by 53
“Despite its vital role in the human body, choline can also serve as a dietary precursor of TMAO via the gut microbial metabolism (2), a potential risk factor for CVD and related deaths.”
BackgroundYuan, J., Liu, X., Liu, C., Ang, A. F., Massaro, J., Devine, S. A., Auerbach, S. H., Blusztajn, J. K., Au, R., & Jacques, P. F. (2022) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqac193 · Cited by 61
“However, the role of choline-derived TMAO remains uncertain given that TMAO production could also be affected by the gut microbe and liver function.”
BackgroundInfluentialThe Liver as a Hub in Thermogenesis
Abumrad, N. A. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.018 · Cited by 63
“…L-carnitine is converted by gut microbiota to trimethylamine N-oxide (TMAO), which is associated with adverse cardiovascular outcomes, but a mechanistic understanding of this association and its relevance at L-carnitine levels used in health supplements is lacking (Zeisel and Warrier, 2017).”
BackgroundCholine Pathway Nutrients and Metabolites and Cognitive Impairment After Acute Ischemic Stroke
Zhong, C., Lu, Z., Che, B., Qian, S., Zheng, X., Wang, A., Bu, X., Zhang, J., Ju, Z., Xu, T., et al. (2021) · Stroke · doi:10.1161/strokeaha.120.031903 · Cited by 59
Heumel, S., Rodovalho, V. D. R., Urien, C., Specque, F., Rodrigues, P. B., Robil, C., Delval, L., Sencio, V., Descat, A., Deruyter, L., et al. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2325067 · Cited by 70
“28 Relative to D0, the concentration of TMAO decreased significantly on D7 but recovered on D14 (Figure 4(b)).”
BackgroundVia, A. D., Gargari, G., Taverniti, V., Rondini, G., Velardi, I., Gambaro, V., Visconti, G. L., Vitis, V. D., Gardana, C., Ragg, E. M., et al. (2019) · Nutrients · doi:10.3390/nu12010062 · Cited by 64
“Then, approximately 95% of the absorbed TMA is oxidized in the liver by flavin monooxygenases and excreted in the urine within 24 h [31,39].”
BackgroundLiang, X., Zhang, Z., Lv, Y., Tong, L., Liu, T., Yi, H., Zhou, X., Yu, Z., Tian, X., Cui, Q., et al. (2020) · Nutrition · doi:10.1016/j.nut.2020.110941 · Cited by 62
Tacconi, E., Palma, G., Biase, D. D., Luciano, A., Barbieri, M., de Nigris, F., & Bruzzese, F. (2023) · Nutrients · doi:10.3390/nu15030563 · Cited by 62
“These bacteria produce toxic metabolites, such as secondary bile salt from primary bile salt, hydrogen sulfide, trimethylamine-Noxide (TMAO) from choline, indoxyl sulfate from amino acid tryptophan, and many more which are likely to promote inflammation, and prolonged inflammation can develop into cancer [5,7,31,32].”
BackgroundInfluentialTMA/TMAO in Hypertension: Novel Horizons and Potential Therapies
Zhang, W., Wang, Y., Zhang, A., Ding, Y., Zhang, X., Jia, Q.-J., Zhu, Y., Li, Y., Lv, S., & Zhang, J. (2021) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-021-10115-x · Cited by 59
Trimethylamine-N-Oxide Pathway: A Potential Target for the Treatment of MAFLD
Li, X., Hong, J. W., Wang, Y., Pei, M., Wang, L., & Gong, Z. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.733507 · Cited by 59
Luo, T., Guo, Z., Liu, D., Guo, Z., Wu, Q., Li, Q., Lin, R., Chen, P., Ou, C., & Chen, M. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2077602 · Cited by 56
“We observed that three kinds of TMA-producing strains, Clostridium-asparagiforme, Desulfovibriodesulfuricans and Desulfovibrio-alaskensi, were enriched in DKO mice, and these species have been reported to be classical bacteria governing choline-to-TMA transformation.(27,28) To achieve detailed mechanistic insight into…”
BackgroundNutrition, one-carbon metabolism and arsenic methylation
Abuawad, A. K., Bozack, A. K., Saxena, R., & Gamble, M. V. (2021) · Toxicology · doi:10.1016/j.tox.2021.152803 · Cited by 55
Gut Microbial-Derived Metabolites as Immune Modulators of T Helper 17 and Regulatory T Cells
Calvo‐Barreiro, L., Zhang, L., Abdel‐Rahman, S. A., Naik, S. P., & Gabr, M. T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021806 · Cited by 62
Gut Microbiotic Features Aiding the Diagnosis of Acute Ischemic Stroke
Xiang, L., Lou, Y., Liu, L., Liu, Y., Zhang, W., Deng, J., Guan, Y., She, M., You, X., Liu, M., et al. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.587284 · Cited by 55
“TMAO is produced when hepatic flavin mono-oxygenases act on trimethylamine, a waste product of gut microbes (Zeisel and Warrier, 2017).”
BackgroundAlzheimer’s disease and gut microbiota: does trimethylamine N-oxide (TMAO) play a role?
Arrona Cardoza, P., Spillane, M. B., & Morales Marroquin, E. (2022) · Nutrition Reviews · doi:10.1093/nutrit/nuab022 · Cited by 53
The Gut Microbial Metabolite Trimethylamine N-oxide, Incident CKD, and Kidney Function Decline
Wang, M., Tang, W. H. W., Li, X. S., Otto, M. C. D. O., Lee, Y., Lemaître, R. N., Fretts, A. M., Nemet, I., Sotoodehnia, N., Sitlani, C. M., et al. (2024) · Journal of the American Society of Nephrology · doi:10.1681/asn.0000000000000344 · Cited by 60
Gut microbiota dependant trimethylamine N-oxide and hypertension
Mutengo, K. H., Masenga, S. K., Mweemba, A., Mutale, W., & Kirabo, A. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1075641 · Cited by 53
“Trimethylamine from the gut reaches the liver by portal circulation, where host hepatic FMO3 incorporates oxygen atoms into trimethylamine to form TMAO (Gątarek and Kałużna-Czaplińska, 2021).”
BackgroundInfluentialChen, Y., Yang, C. H., Dai, Q., Tan, J., Dou, C., & Luo, F. (2023) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-01872-9 · Cited by 53
“Trimethylamine-N-oxide (TMAO), a gut microbial-dependent metabolite of dietary choline, has been demonstrated to have a close correlation with multiple diseases such as cardiovascular disease, cancer, and kidney disease [12, 13].”
BackgroundMechanisms of hepatic and renal injury in lipid metabolism disorders in metabolic syndrome
Rong, J., Zhang, Z., Peng, X., Li, P., Zhao, T., & Zhong, Y. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.100394 · Cited by 56
“TMAO is excreted from the body through the kidneys [130].”
Background
Metadata
- Authors
- Zeisel, S. H., & Warrier, M.
- Affiliations
- University of North Carolina System (US)
- Corresponding author
- Zeisel, Steven H.
- ORCID
- Zeisel, Steven H.
- Venue
- Annual Review of Nutrition
- Publisher
- Annual Reviews
- Published
- 2017-08-21
- Volume
- 37
- Issue
- 1
- Pages
- 157-181
- ISSN
- 0199-9885 (ISSN-L)
- 1545-4312
- OpenAlex
- W2566137938
- Cited by
- 475
- References
- 133
- Citations by year
- 2026: 25 · 2025: 60 · 2024: 57 · 2023: 75 · 2022: 64 · 2021: 70 · 2020: 51 · 2019: 42 · 2018: 26 · 2017: 4
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Keywords
- trimethylamine N-oxide, trimethylamine, gut microbiota, cardiovascular disease, heart disease, kidney disease, atherosclerosis, flavin-dependent monooxygenase, L-carnitine, choline, food sources, myocardial infarction, stroke
- MeSH terms
- Animals, Bacteria, Diet, Female, Heart Diseases, Humans, Kidney Diseases, Liver, Male, Methylamines, Microbiota
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