The DOI matches its Crossref record; 133 of the 133 references it cites were found in a registry or an index; 4 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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Claims the paper makes
184 Not checked yet · 23 No basis given · 22 Own interpretation · 2 Supported · 1 Partly supported · 1 Own method · 1 Own result · accuracy not yet measured
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.
- 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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, the degree of rise in TMAO concentrations was not completely concordant with the degree of reduction in the estimated glomerular filtration rate (eGFR) (108).”
§ 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
- Supportedcites [108] source
In the discussion of Stubbs et al. (passage 1; page not provided), the paper says the degree and pattern of rising TMAO levels were not uniformly concordant with the reduction in GFR. The same passage discusses the association between serum TMAO and eGFR, supporting the citing sentence’s paraphrase. (LLM, conf=0.93)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The Women's Health Initiative and the alpha-tocopherol, beta-carotene cancer prevention observational studies reported that alterations in choline metabolism and plasma TMAO concentrations were predicted risk factors for colorectal cancer (7,83).”
§ 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
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
The Discussion reports that alterations in choline metabolism were associated with higher colorectal cancer risk in postmenopausal women and that plasma TMAO may be a potential predictor. The claim overstates this as an established risk factor: the paper presents TMAO as a potential biomarker, with its clearest associations for rectal cancer and for women with low vitamin B12. This verdict addresses the Women's Health Initiative finding, not the separately cited ATBC study. (LLM, conf=0.84)
- Partly supportedcites [83] sourceExperimental — accuracy not yet measured
The Discussion links the choline derivative TMAO to elevated colorectal cancer risk, citing the Women’s Health Initiative study (reference 35). But this ATBC paper’s own Results concern TMAO and aggressive prostate cancer, not colorectal cancer; it does not report an ATBC finding that choline-metabolism changes or plasma TMAO predicted colorectal cancer risk. (LLM, conf=0.88)
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.
- Partly 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.
- 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.
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.
- Based: passes — The paper gives a 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
“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.
- Based: passes — The paper gives a reason why it holds.
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.
- 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.
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.
- 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.
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.
- 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.
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.
- 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.
- 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 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.
- 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
“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.
- 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
“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.
- 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
“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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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]
Experimental — accuracy not yet measuredIn 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
“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
“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
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Heart Disease and Stroke Statistics—2016 Update: A Report From the American Heart Association
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Trimethylamine N-oxide: role in cell senescence and age-related diseases
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Fecal microbiota transplantation is a promising therapy for kidney diseases
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Gut microbiota involved in myocardial dysfunction induced by sepsis
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Factors influencing breath analysis results in patients with diabetes mellitus
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Nephrolithiasis: A Red Flag for Cardiovascular Risk
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Changes in Choline Metabolites and Ceramides in Response to a DASH-Style Diet in Older Adults
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Gut–Kidney–Heart: A Novel Trilogy
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Gut microbiota: Implications in pathogenesis and therapy to cardiovascular disease (Review)
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Classification of Human Gender from Sweat Odor using Electronic Nose with Machine Learning Methods
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Direct and Indirect Methods for Studying Human Gut Microbiota
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A benzoxazole derivative as an inhibitor of anaerobic choline metabolism by human gut microbiota
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Trimethylamine N-oxide and kidney diseases: what do we know?
Güngör, Ö., Hasbal, N. B., & Alaygut, D. (2023) · Brazilian Journal of Nephrology · doi:10.1590/2175-8239-jbn-2023-0065en · Cited by 14
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Mechanistic Development of Cancers Associated with Processed Meat Products: A Review
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Bjørnestad, E. Ø., Dhar, I., Svingen, G. F. T., Pedersen, E. R., Svenningsson, M. M., Tell, G. S., Ueland, P. M., Ørn, S., Sulo, G., Laaksonen, R., et al. (2021) · European Heart Journal Open · doi:10.1093/ehjopen/oeab007 · Cited by 9
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Influence of Trimethylamine N-Oxide on Platelet Activation
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Research Progress on the Correlation Between Hypertension and Gut Microbiota
Cui, X.-M., Zhang, T., Xie, T., Guo, F.-X., Zhang, Y., Deng, Y.-J., Wang, Q., Guo, Y.-X., Dong, M.-H., & Luo, X. (2024) · Journal of Multidisciplinary Healthcare · doi:10.2147/jmdh.s463880 · Cited by 11
Immune modulation of gut microbiota and its metabolites in chronic hepatitis B
Li, S.-Q., Shen, Y., Zhang, J., Weng, C., Wu, S., & Jiang, W. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1285556 · Cited by 9
Karaağaç, Y. (2023) · Eurasian Journal of Medicine · doi:10.5152/eurasianjmed.2023.23070 · Cited by 9
TMAO and the gut microbiome: implications for the CVD-CKD-IBD axis
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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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