The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index; 8 of the 53 sources its claims cite were checked for support.
Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women
Open accessAbstract
AIMS: Carnitine and choline are major nutrient precursors for gut microbiota-dependent generation of the atherogenic metabolite, trimethylamine N-oxide (TMAO). We performed randomized-controlled dietary intervention studies to explore the impact of chronic dietary patterns on TMAO levels, metabolism and renal excretion. METHODS AND RESULTS: Volunteers (N = 113) were enrolled in a randomized 2-arm (high- or low-saturated fat) crossover design study. Within each arm, three 4-week isocaloric diets (with washout period between each) were evaluated (all meals prepared in metabolic kitchen with 25% calories from protein) to examine the effects of red meat, white meat, or non-meat protein on TMAO metabolism. Trimethylamine N-oxide and other trimethylamine (TMA) related metabolites were quantified at the end of each diet period. A random subset (N = 13) of subjects also participated in heavy isotope tracer studies. Chronic red meat, but not white meat or non-meat ingestion, increased plasma and urine TMAO (each >two-fold; P < 0.0001). Red meat ingestion also significantly reduced fractional renal excretion of TMAO (P < 0.05), but conversely, increased fractional renal excretion of carnitine, and two alternative gut microbiota-generated metabolites of carnitine, γ-butyrobetaine, and crotonobetaine (P < 0.05). Oral isotope challenge revealed red meat or white meat (vs. non-meat) increased TMA and TMAO production from carnitine (P < 0.05 each) but not choline. Dietary-saturated fat failed to impact TMAO or its metabolites. CONCLUSION: Chronic dietary red meat increases systemic TMAO levels through: (i) enhanced dietary precursors; (ii) increased microbial TMA/TMAO production from carnitine, but not choline; and (iii) reduced renal TMAO excretion. Discontinuation of dietary red meat reduces plasma TMAO within 4 weeks.
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32 Own result · 21 Not checked yet · 8 Own interpretation · 6 Own method · 2 Partly supported · 1 Supported so far · accuracy not yet measured
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In the paper
“Interestingly, in small cross-sectional observational studies, plasma levels of TMAO were modestly increased in omnivores relative to vegans/vegetarians, and in recent clinical challenge studies, TMA and TMAO generation from oral carnitine was observed to be substantially reduced in vegans/vegetarians.3,19”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Introduction
What the sources say
- Partly supportedcites [3] Koeth, 2013, Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis, Nat Med sourceExperimental — accuracy not yet measured
The Results section, “Vegans and vegetarians produce less TMAO from L-carnitine” (page unavailable), reports markedly reduced TMAO production after an oral carnitine challenge in long-term vegans/vegetarians. It does not report a corresponding reduction in TMA generation in those human participants; the passages reporting TMA measurements concern mice. (LLM, conf=0.85)
- Supportedcites [19] Koeth, 2018, L-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans, J Clin Invest source
The clinical challenge results report minimal TMAO production from oral carnitine in vegans/vegetarians at baseline, while omnivores readily produced it. The paper also reports greater microbial conversion to TMA in omnivores. Supplementation increased TMAO production in some vegans/vegetarians, but the Discussion says their production capacity remained lower overall. Page numbers were not supplied in the passages. (LLM, conf=0.93)
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- Partly supported
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In the paper
“In contrast, the fractional renal excretion of carnitine, c-butyrobetaine, and crotonobetaine increased significantly (P < 0.0001, P < 0.0001, and P = 0.0007, respectively) on the red meat diet in comparison to the non-meat diet (Figure 5D-F).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Chronic dietary exposure to red meat diet differentially impacts fractional renal excretion of trimethylamine N-oxide vs. carnitine and its metabolites
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, very modest but statistically significant reductions were noted in plasma betaine and urine choline concentrations following chronic consumption of the red meat diet compared with the non-meat or white meat diets (Figures 2A and 3).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Results
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In the paper
“Two additional carnitine related metabolites generated by gut microbiota, c-butyrobetaine, and crotonobetaine, 16,19 both showed significant increases in both plasma (P < 0.0001 and P = 0.004, respectively) and urine (P < 0.0001 each) concentrations following 4 weeks of the red meat diet, though the relative magnitude of the increase was smaller than that for TMAO (Figures 2A and 3).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“Two additional carnitine related metabolites generated by gut microbiota, c-butyrobetaine, and crotonobetaine, 16,19 both showed significant increases in both plasma (P < 0.0001 and P = 0.004, respectively) and urine (P < 0.0001 each) concentrations following 4 weeks of the red meat diet, though the relative magnitude of the increase was smaller than that for TMAO (Figures 2A and 3).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Notably, plasma levels of TMAO were most strongly correlated to choline and carnitine (and choline and carnitine with one another), particularly following 4 weeks of the red meat and white meat diets.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Results
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, increased level of dietary-saturated fat had no effect on plasma concentrations of TMAO.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Results
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Further, we too had performed unpublished untargeted metabolomics analyses and identified symmetric dimethylarginine (SDMA) as being highly correlated with renal function (r > 0.80; P < 0.0001) in both men and women alike (data not shown), and alternative published studies have similarly suggested SDMA serves as an excellent endogenous marker of renal function. 25”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Chronic dietary exposure to red meat diet differentially impacts fractional renal excretion of trimethylamine N-oxide vs. carnitine and its metabolites
What the sources say
- Not checked yetcites [25] Kielstein, 2006, Symmetric dimethylarginine (SDMA) as endogenous marker of renal function–a meta-analysis, Nephrol Dial Transplant source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, the 24 h urine d3-TMA and d3-TMAO recovered following ingestion of d3-carnitine was significantly (several-fold) higher in subjects following either the red meat or white meat diets compared to the non-meat diet (Figure 7A and B).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Chronic dietary exposure to red meat diet differentially impacts fractional renal excretion of trimethylamine N-oxide vs. carnitine and its metabolites
plaindirectn = 13- Asserted: passes — The authors put it forward as true.
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In the paper
“Plasma levels of each of the monitored metabolites following 4 weeks of low-vs.high-saturated fat diets failed to show any significant differences (Figure 4A).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Results
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 27
- Probably not a substantial claim. 10
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Notably, a clinical prognostic value of TMAO has been supported by multiple meta-analyses reaffirming that elevated circulating TMAO levels are associated with both CVD and mortality risks across multiple cohorts and continents.[10][11][12]”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Introduction
What the sources say
- Not checked yetcites [10] Schiattarella, 2017, Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysis, Eur Heart J source
- Supportedcites [11] Qi, 2018, Circulating trimethylamine N-oxide and the risk of cardiovascular diseases: a systematic review and meta-analysis of 11 prospective cohort studies, J Cell Mol Med source
The Discussion reports that a meta-analysis of 11 prospective cohorts found higher baseline TMAO associated with increased cardiovascular-event and all-cause mortality risks. The Results (Study characteristics) place those cohorts in North America, Europe and New Zealand. The paper describes this as potential prognostic power, while cautioning that further studies are needed to establish prognostic efficacy. (LLM, conf=0.88)
- Supportedcites [12] Heianza, 2017, Gut microbiota metabolites and risk of major adverse cardiovascular disease events and death: a systematic review and meta-analysis of prospective studies, J Am Heart Assoc source
The Discussion reports that high circulating TMAO was associated with increased risks of major adverse cardiovascular events and all-cause death in a meta-analysis of prospective studies. The Strengths and Limitations section says participants came mainly from Europe and the United States, supporting the claim’s cross-continent scope. The paper cautions that its results may not apply to other racial or ethnic groups. (LLM, conf=0.92)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Some of these TMA containing compounds can participate in TMA/TMAO formation in a gut microbiota-dependent manner, and also be generated by gut microbiota metabolism of L-carnitine.1,3,16,19”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Introduction
What the sources say
- Partly supportedcites [1] Wang, 2011, Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease, Nature sourceExperimental — accuracy not yet measured
The Results section on TMAO formation from dietary phosphatidylcholine reports an obligate role for gut microbiota and the pathway PC → choline → TMA → TMAO. The Discussion also describes gut-flora-dependent TMA formation from trimethylamine-containing species. Our copy does not support the additional claim that these compounds are generated by gut microbiota metabolism of L-carnitine (searched: L-carnitine, carnitine). No page numbers are provided in the indexed passages. (LLM, conf=0.88)
- Partly supportedcites [3] Koeth, 2013, Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis, Nat Med sourceExperimental — accuracy not yet measured
The Results section, “TMAO production from dietary L-carnitine is inducible” (page unavailable), shows that gut microbiota are required to produce TMA and TMAO from L-carnitine in mice. The cited passages do not establish that other TMA-containing compounds are both generated from L-carnitine and subsequently participate in TMA/TMAO formation. (LLM, conf=0.82)
- Supportedcites [16] Koeth, 2014, γ-butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO, Cell Metab source
The Results section identifies γ-butyrobetaine (γBB) as a gut-microbial product of L-carnitine and an intermediate subsequently converted to TMA and TMAO. The Discussion likewise describes the L-carnitine → γBB → TMA pathway, followed by host conversion of TMA to TMAO. (LLM, conf=0.92)
- Supportedcites [19] Koeth, 2018, L-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans, J Clin Invest source
The Discussion states that γ-butyrobetaine (γBB) is produced by gut microbiota-dependent metabolism of ingested l-carnitine in humans and is an intermediate in TMAO formation. It also describes the microbial conversion of γBB to TMA, supporting both parts of the attributed claim. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
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
“First, compared to the other metabolites, the fractional excretion of TMAO was found to be both higher, and to demonstrate a remarkably broader range of values extending from nearly zero to over 700%, with a sizable proportion of subjects (almost half) showing >100%, particularly following the white meat and non-meat diet interventions.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Chronic dietary exposure to red meat diet differentially impacts fractional renal excretion of trimethylamine N-oxide vs. carnitine and its metabolites
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, examination of the carnitine content of the diets (Supplementary ma- terial online, Table S1) reveals the baseline diet had 2 Â the carnitine level (56 mg) of the non-meat (high-saturated fat) diet (22 mg).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Results
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Similarly, no changes in plasma concentrations of other TMA containing compounds (choline, carnitine, cbutyrobetaine, and crotonobetaine; all P > 0.05, Figure 4B and D-F) were noted with high-vs.low-saturated fat except for a modest reduction in betaine levels with increased saturated fat (P < 0.05; Figure 4C).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Results
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“We also noted that following the red meat diet, subjects showed a modest but significant (P = 0.006; Supplementary material online, Table S3) increase in serum creatinine (still within the normal range), while urine creatinine concentrations were increased (within normal range).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Chronic dietary exposure to red meat diet differentially impacts fractional renal excretion of trimethylamine N-oxide vs. carnitine and its metabolites
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Notably, in contrast to creatinine, none of the surrogate indicators of renal function showed significant changes in plasma or urine levels based on diet, and all were highly correlated with creatinine (Supplementary material online, Tables S3 and S4).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Chronic dietary exposure to red meat diet differentially impacts fractional renal excretion of trimethylamine N-oxide vs. carnitine and its metabolites
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In analyses examining the relationship between plasma and urine levels of TMAO, plasma TMAO levels were highly correlated with concurrently collected spot urine TMAO concentration (r = 0.41, P < 0.0001; N = 113) or urine TMAO/creatinine (r = 0.55, P < 0.0001; N = 113), and 24 h urine TMAO collections (r = 0.74, P < 0.001; N = 13).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Results
plaincorrelationaln = 113 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, no significant change in renal clearance of choline and only modest changes with betaine were observed among the three diets (Figure 5C).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Chronic dietary exposure to red meat diet differentially impacts fractional renal excretion of trimethylamine N-oxide vs. carnitine and its metabolites
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“On average, plasma TMAO levels increased approximately three-fold (P < 0.0001) during the red meat diet, compared with the white meat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .or non-meat diets, with some subjects showing over a 10-fold increase (Figure 2A).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“this in- crease was substantially less than the 3.8-fold and 7.9-fold higher car- nitine content present in the red meat diet compared with the white meat and non-meat diets, respectively (Supplementary material on- line, Table S1).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“While the total choline content of the red meat diet provided approximately 15% and 28% more compared with the average daily total choline content of the white meat and non-meat diets, respectively (Supplementary material online, Table S1)”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“subjects experienced on average an absolute change in median TMAO level of 5.9 lM and 5.7 lM during the red meat diet arm (compared with non-meat and white meat diets, respectively)”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Trimethylamine N-oxide (TMAO) is a gut microbiota-generated metabolite with mechanistic links to the pathogenesis of atherosclerotic heart disease.[1][2][3][4][5]”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Introduction
What the sources say
- Not checked yetcites [1] Wang, 2011, Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease, Nature source
- Not checked yetcites [2] Tang, 2013, Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk, N Engl J Med source
- Not checked yetcites [3] Koeth, 2013, Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis, Nat Med source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Carnitine is enriched in red meat, 3 and higher total choline content is found in beef and other meats, liver, and egg yolks.17”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Introduction
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Beyond choline and carnitine, potential nutrient precursors for TMA production have been reported, including the carnitine related metabolites c-butyrobetaine and crotonobetaine, and the choline oxidation product betaine.1,16,19”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Introduction
What the sources say
- Not checked yetcites [1] Wang, 2011, Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease, Nature source
- Not checked yetcites [16] Koeth, 2014, γ-butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO, Cell Metab source
- Not checked yetcites [19] Koeth, 2018, L-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans, J Clin Invest source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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
“Based upon the many epidemiological and nutrition studies suggesting a positive association between red meat ingestion and CVD risks, [27][28][29][30][31][32][33] most dietary recommendations advise limiting red meat ingestion.26”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
What the sources say
- Not checked yetcites [26] Piepoli, 2016, 2016 European guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR), Eur Heart J source
- Not checked yetcites [27] Abete, 2014, Association between total, processed, red and white meat consumption and all-cause, CVD and IHD mortality: a meta-analysis of cohort studies, Br J Nutr source
- Not checked yetcites [28] O'Connor, 2017, Total red meat intake of >/=0.5 servings/d does not negatively influence cardiovascular disease risk factors: a systemically searched meta-analysis of randomized controlled trials, Am J Clin Nutr source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- 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
“Moreover, adherence to a red meat diet raises systemic TMAO levels by three different mechanisms: (i) enhanced nutrient density of dietary TMA precursors; (ii) increased microbial TMA/TMAO production from carnitine, but not choline; and (iii) reduced renal TMAO excretion.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
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
“This dietary intervention study had a randomized three-period crossover design.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Trial participants and study designs
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.
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
“Lastly, in contrast to TMAO, the fractional renal excretion of choline, betaine, carnitine, and c-butyrobetaine were significantly less than 100%, indicating that after filtering through the kidneys, most of these metabolites are reabsorbed, but less so following chronic dietary red meat exposure (Figure 5B-E).”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Chronic dietary exposure to red meat diet differentially impacts fractional renal excretion of trimethylamine N-oxide vs. carnitine and its metabolites
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies have also shown dose-dependent TMA/TMAO formation with egg ingestion.2,18”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Introduction
What the sources say
- Not checked yetcites [2] Tang, 2013, Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk, N Engl J Med source
- Not checked yetcites [18] Miller, 2014, Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study, Am J Clin Nutr 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.
None of the sources cited for this claim have been checked yet.
In the paper
“However, some recent meta-analyses suggest the association between red meat ingestion and adverse changes to traditional CVD risk factors is not as strong, 28 despite the relatively consistent association with hard endpoints like heart attack, stroke, mortality, and CVD development.[29][30][31][32][33]”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
What the sources say
- Not checked yetcites [28] O'Connor, 2017, Total red meat intake of >/=0.5 servings/d does not negatively influence cardiovascular disease risk factors: a systemically searched meta-analysis of randomized controlled trials, Am J Clin Nutr source
- Not checked yetcites [29] Schwingshackl, 2017, Food groups and risk of all-cause mortality: a systematic review and meta-analysis of prospective studies, Am J Clin Nutr source
- Not checked yetcites [30] Haring, 2017, Red meat consumption and cardiovascular target organ damage (from the Strong Heart Study), J Hypertens source
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.
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
“beyond quantity, the quality of diet composition (with respect to protein source, but not saturated fat content) impacts overall TMAO metabolism and excretion.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
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
“Reduced urine TMAO levels were recently reported in an observational study among subjects following a Mediterranean diet in a post hoc cross-sectional analysis comparing omnivores vs. vegetarians or vegans 35 ; moreover, a trend towards reduced urinary TMAO levels was observed among subjects with increased reported compliance with the Mediterranean diet (based on the PREDIMED trial compliance tool”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
What the sources say
- Not checked yetcites [35] De Filippis, 2016, High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome, Gut 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.
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
“Fractional excretion calculations utilized creatinine plasma and urine concentrations, which varied based on diet, though we also quantified three separate alternative metabolites identified to serve as surrogate markers of renal function, and observed qualitatively comparable results.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Limitations
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.
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
“the increases in plasma TMAO observed with the red meat diet would correspond to an approximate 4.5% increase in relative risk of mortality compared with the non-meat diet, and a 4.3% difference in mortality compared with white meat diet.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
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.
It may state two separate claims as one.
- The authors state this as an assumption: The changes in TMAO observed after one month of diet can be extrapolated to the mean follow-up of 4.3 years used in the meta-analysis.
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
“the present studies are the first to directly explore the relationship of dietary protein source to plasma TMAO levels with defined isocaloric randomized diets, and the time needed to reduce TMAO levels with dietary changes.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
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
“The present studies thus suggest that a diet rich in red meat would be associated with heightened TMAO levels, and potential heightened thrombotic event risk.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
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.
It may state two separate claims as one.
In the paper
“numerous epidemiological studies show a dose-dependent heightened risk of thrombotic events, CVD, and mortality risks with red meat consumption.[29][30][31][32][33]”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
What the sources say
- Not checked yetcites [29][30][31][32][33]
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
“The kidney is an important organ to maintain homoeostasis of plasma metabolites, 23 yet little is known about factors impacting renal excretion of TMAO or its related metabolites.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Chronic dietary exposure to red meat diet differentially impacts fractional renal excretion of trimethylamine N-oxide vs. carnitine and its metabolites
What the sources say
- Not checked yetcites [23] Thurau, 1964, Autoregulation of renal blood flow and glomerular filtration rate, including data on tubular and peritubular capillary pressures and vessel wall tension, Circ Res
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.
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
“Only two visits of blood and urine for each diet arm were collected, which may not reflect the total intra-individual variability in subjects.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Limitations
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The Mediterranean diet in the PREDIMED trial, which showed a 30% reduction in CVD risk, was characterized by avoidance of red meat as a protein source.36,37”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
What the sources say
- Not checked yetcites [36] Estruch, 2013, Primary prevention of cardiovascular disease with a Mediterranean diet, N Engl J Med source
- Not checked yetcites [37] Estruch, 2018, Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts, N Engl J Med 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
“TMAO has been shown to directly interact with platelets (human and murine), increasing their responsiveness, and promoting a prothrombotic phenotype.4,5”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Discussion
What the sources say
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
“Blood collection time after meal was not controlled, which may lead to fluctuation of plasma metabolite levels.”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Limitations
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.
The paper relies on this without support.
Few studies have systematically explored the influence of chronic dietary patterns on TMA and TMAO production, metabolism, and renal excretion.
“Few studies have systematically explored the influence of chronic dietary patterns on TMA and TMAO production, metabolism, and renal excretion.”
The paper relies on this without support.
The direct contribution of TMAO to CVD pathogenesis in humans is unclear.
“the direct contribution of TMAO to CVD pathogenesis in humans is unclear, and the impact of dietary interventions on TMAO have not been extensively investigated.”
The paper relies on this without support.
The impact of dietary interventions on TMAO has not been extensively investigated.
“the direct contribution of TMAO to CVD pathogenesis in humans is unclear, and the impact of dietary interventions on TMAO have not been extensively investigated.”
The paper relies on this without support.
Little is known about factors impacting renal excretion of TMAO or its related metabolites.
“yet little is known about factors impacting renal excretion of TMAO or its related metabolites.”
The authors state this as an assumption.
The changes in TMAO observed after one month of diet can be extrapolated to the mean follow-up of 4.3 years used in the meta-analysis.
“assuming changes observed following 1 month of diet can be extended to the mean length of follow-up (4.3 year) in the meta-analysis”
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
“There are, however, safety concerns about augmenting dietary protein above the 0.8 g·kg−1·d−1 range, especially from animal sources, because of concerns of accelerating coronary artery disease and HF incidence, as well as the potential for accelerating CKD progression.123–125”
From Malnutrition and Cachexia in Inpatients With Acute Cardiac Conditions: A Scientific Statement From the American Heart Association (2026) · cites this paper as [124]
Experimental — accuracy not yet measuredIn the citing paper
“A randomized controlled trial found that chronic ingestion of red meat, but not white meat or non-meat, increased plasma and urine levels of TMAO.142”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [142]
In the citing paper
“In a recent human dietary intervention study examining protein source (red meat vs white meat vs non-meat), substantially higher levels of circulating TMAO were observed when subjects consumed a red meat diet (equivalent to 8oz of steak daily for 1 month)111.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [111]
In the citing paper
“In addition to having enhanced nutrient density of TMA(O) precursors (including carnitine), isotope tracer studies showed the red meat rich diet induced functional remodeling of the gut microbial community to enhance carnitine→→TMA transformation, but not choline→TMA generation111.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [111]
In the citing paper
“The TMAO pathway is an excellent example of this, given the nutrient precursors are more abundant in a Western diet, and diets rich in phosphatidylcholine and carnitine are associated with heightened levels of TMAO, whereas vegetarian or vegan diets have reduced nutrient precursors111, 118.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [111]
In the citing paper
“Notably, however, TMAO levels appear to be driven more so by the gut microbial community composition than by the dietary intervention, and significant variation in TMAO production among individuals on a given diet is observed14, 111.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [111]
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
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Trial participants and study designs
“each separated by a 2-7 weeks washout period”
§ Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women > Limitations
“with 2-week wash-out diets between each intervention dietary period”
Citations
Cites
2 retracted
RETRACTED: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet
Estruch, R., Ros, E., Salas-Salvadó, J., Covas, M.-I., Corella, D., Arós, F., Gómez-Gracia, E., Ruiz-Gutiérrez, V., Fiol, M., Lapetra, J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1200303 · Cited by 4,257
RetractedEstruch, R., Ros, E., Salas-Salvadó, J., Covas, M.-I., Corella, D., Arós, F., Gómez-Gracia, E., Ruiz-Gutiérrez, V., Fiol, M., Lapetra, J., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmc1806491 · Cited by 1,008
RetractedEuropean Guidelines on cardiovascular disease prevention in clinical practice (version 2012)
Authors/Task Force Members:, Perk, J., De Backer, G., Gohlke, H., Graham, I., Reiner, Ž., Verschuren, M., Albus, C., Benlian, P., Boysen, G., et al. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs092 · Cited by 8,490
2016 European Guidelines on cardiovascular disease prevention in clinical practice
Piepoli, M. F., Hoes, A. W., Agewall, S., Albus, C., Brotons, C., Catapano, A. L., Cooney, M.-T., Corrà, U., Cosyns, B., Deaton, C., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw106 · Cited by 6,457
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y.-M., et al. (2011) · Nature · doi:10.1038/nature09922 · Cited by 5,597
Self-citationIntestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3145 · Cited by 4,386
Self-citationEstruch, R., Ros, E., Salas-Salvadó, J., Covas, M.-I., Corella, D., Arós, F., Gómez-Gracia, E., Ruiz-Gutiérrez, V., Fiol, M., Lapetra, J., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1800389 · Cited by 3,616
Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1109400 · Cited by 3,400 · cited 1×
“Studies have also shown dose-dependent TMA/TMAO formation with egg ingestion.(2,18) Beyond choline and carnitine, potential nutrient precursors for TMA production have been reported, including the carnitine related metabolites c-butyrobetaine and crotonobetaine, and the choline oxidation product betaine.”
BackgroundSelf-citationGut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk
Zhu, W., Gregory, J. C., Org, E., Buffa, J. A., Gupta, N., Wang, Z., Li, L., Fu, X., Wu, Y., Mehrabian, M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.011 · Cited by 1,968
Self-citationDe Filippis, F., Pellegrini, N., Vannini, L., Jeffery, I. B., La Storia, A., Laghi, L., Serrazanetti, D. I., Di Cagno, R., Ferrocino, I., Lazzi, C., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-309957 · Cited by 1,638
Cited by
Sorted by citations
Gut microbiota and cardiovascular disease.
Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051
Self-citationTargeting inflammation in atherosclerosis — from experimental insights to the clinic
Soehnlein, O., & Libby, P. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00198-1 · Cited by 1,085
Targher, G., Byrne, C. D., & Tilg, H. (2020) · Gut · doi:10.1136/gutjnl-2020-320622 · Cited by 879
“89”
Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer
Song, M., Chan, A. T., & Sun, J. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.06.048 · Cited by 752
Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives
Liu, J., Tan, Y., Cheng, H., Zhang, D., Feng, W., & Peng, C. (2022) · Aging and disease · doi:10.14336/ad.2022.0104 · Cited by 529
“disease, obesity, atherosclerosis, diabetes, heart failure, hypertension [37-39]”
BackgroundIntestinal Microbiota in Cardiovascular Health and Disease
Tang, W. H. W., Bäckhed, F., Landmesser, U., & Hazen, S. L. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.03.024 · Cited by 524
Self-citationMultiple Parallel Hits Hypothesis in Nonalcoholic Fatty Liver Disease: Revisited After a Decade
Tilg, H., Adolph, T. E., & Moschen, A. R. (2020) · Hepatology · doi:10.1002/hep.31518 · Cited by 455
“(82) The gut microbiota converts nutrients such as choline or carnitine into trimethylamine, which is metabolized by liver flavin monooxygenases to trimethylamine N-oxide (TMAO),(83) while discontinuation of red meat consumption reduced TMAO levels within 4 weeks.(84) Numerous studies have demonstrated an association…”
BackgroundTrøseid, M., Andersen, G. Ø., Broch, K., & Hov, J. R. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102649 · Cited by 416
“For now, dietary interventions, including adherence to a Mediterranean diet [104] or discontinuation of dietary red meat [33], are more accessible ways of reducing TMAO levels and possibly, cardiovascular risk.”
BackgroundYang, S., Li, X., Yang, F., Zhao, R., Pan, X., Liang, J., Tian, L., Li, X., Liu, L., Xing, Y., et al. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01360 · Cited by 360
Self-citationTMAO: how gut microbiota contributes to heart failure
Zhang, Y., Wang, Y., Ke, B., & Du, J. (2020) · Translational research · doi:10.1016/j.trsl.2020.08.007 · Cited by 311
Crimarco, A., Springfield, S., Petlura, C., Streaty, T., Cunanan, K., Lee, J., Fielding-Singh, P., Carter, M. M., Topf, M. A., Wastyk, H. C., et al. (2020) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa203 · Cited by 286
“, beef and pork), have a relatively high content of carnitine and choline, which are precursors to TMAO (15).”
BackgroundMethodMicrobiota Metabolites in Health and Disease
McCarville, J. L., Chen, G. Y., Cuevas, V. D., Troha, K., & Ayres, J. S. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-071219-125715 · Cited by 255
Food as medicine: targeting the uraemic phenotype in chronic kidney disease
Mafra, D., Borges, N. A., Lindholm, B., Shiels, P. G., Evenepoel, P., & Stenvinkel, P. (2021) · Nature Reviews Nephrology · doi:10.1038/s41581-020-00345-8 · Cited by 238
Trimethylamine N-oxide (TMAO) in human health
Gątarek, P., & Kałużna‐Czaplińska, J. (2020) · EXCLI journal · doi:10.17179/excli2020-3239 · Cited by 235
“…diabetes (Tai et al., 2015), kidney failure (Bain et al., 2006; Tang et al., 2015; Missailidis et al., 2016; Stubbs et al., 2016; Mafune et al., 2016), neurological disorders (Cryan and Dinan, 2012), and cancer (stomach, colon) (Erdman and Poutahidis, 2015; Dey and Ciorba, 2016; Wang et al., 2019).”
BackgroundKonopelski, P., & Mogilnicka, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031222 · Cited by 220
Sasso, J. M., Ammar, R. M., Tenchov, R., Lemmel, S. A., Kelber, O., Grieswelle, M., & Zhou, Q. A. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00127 · Cited by 229
Vegetarian and vegan diets: benefits and drawbacks
Wang, T., Masedunskas, A., Willett, W. C., & Fontana, L. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad436 · Cited by 222
“62,63 Animal and human studies have shown that higher levels of circulating TMAO increase the risk of developing CVD, independent of traditional cardiometabolic risk factors, by inducing vascular inflammation and platelet activation.”
BackgroundWestern diets and chronic diseases
Adolph, T. E., & Tilg, H. (2024) · Nature Medicine · doi:10.1038/s41591-024-03165-6 · Cited by 224
Gupta, N., Buffa, J. A., Roberts, A. B., Sangwan, N., Skye, S. M., Li, L., Ho, K. J., Varga, J., DiDonato, J. A., Tang, W. H. W., et al. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314139 · Cited by 187
Self-citationNonalcoholic Fatty Liver Disease Pandemic Fuels the Upsurge in Cardiovascular Diseases
Cai, J., Zhang, X., Ji, Y., Zhāng, P., She, Z., & Li, H. (2020) · Circulation Research · doi:10.1161/circresaha.119.316337 · Cited by 182
Bekhit, A. E. A., Giteru, S. G., Holman, B. W. B., & Hopkins, D. L. (2021) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12764 · Cited by 170
“Dietary fat was reported not to have an association with plasma TMA-N-O or its metabolites (Boutagy et al., 2015; Wang et al., 2019).”
BackgroundMethodInfluentialGut microbes impact stroke severity via the trimethylamine N-oxide pathway
Zhu, W., Romano, K. A., Li, L., Buffa, J. A., Sangwan, N., Prakash, P., Tittle, A. N., Li, X. S., Fu, X., Androjna, C., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2021.05.002 · Cited by 167
Self-citationLong-Term Changes in Gut Microbial Metabolite Trimethylamine N-Oxide and Coronary Heart Disease Risk
Heianza, Y., Ma, W., DiDonato, J. A., Sun, Q., Rimm, E. B., Hu, F. B., Rexrode, K. M., Manson, J. E., & Qi, L. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.060 · Cited by 161
“A more recent study reported similar associations that intake of red meat increased TMAO levels, and discontinuation of red meat intake reduced plasma TMAO levels within 4 weeks (29).”
BackgroundBergeron, N., Chiu, S., Williams, P. T., M King, S., & Krauss, R. M. (2019) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz035 · Cited by 160
Self-citationZhu, C., Sawrey-Kubicek, L., Beals, E., Rhodes, C. H., Houts, H. E., Sacchi, R., & Zivkovic, A. M. (2020) · Nutrition Research · doi:10.1016/j.nutres.2020.03.005 · Cited by 153
Trimethylamine N-Oxide in Relation to Cardiometabolic Health—Cause or Effect?
Papandreou, C., Moré, M. I., & Bellamine, A. (2020) · Nutrients · doi:10.3390/nu12051330 · Cited by 157
“Isotope tracing experiments revealed that TMAO was primarily generated from the L-carnitine; in addition, meat consumption led to a slight decrease in fractional renal TMAO excretion, possibly explaining in part the TMAO increase [95].”
BackgroundInfluentialWang, Q., Shen, Y., Wang, X., Fu, S., Zhang, X., Zhang, Y., & Wang, R. (2020) · Aging · doi:10.18632/aging.102645 · Cited by 135
“Yet, TMAO levels might be affected by modifications in gut microbiota composition, which possibly modulate TMA production [41].”
BackgroundLi, J., Li, Y., Ivey, K. L., Wang, D. D., Wilkinson, J. E., Franke, A., Lee, K. H., Chan, A., Huttenhower, C., Hu, F. B., et al. (2022) · Gut · doi:10.1136/gutjnl-2020-322473 · Cited by 137
Potential TMA-Producing Bacteria Are Ubiquitously Found in Mammalia
Rath, S., Rud, T., Pieper, D. H., & Vital, M. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02966 · Cited by 134
Colon Carcinogenesis: The Interplay Between Diet and Gut Microbiota
Loke, Y. L., Chew, M. T., Ngeow, Y. F., Lim, W. W.-D., & Peh, S. C. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.603086 · Cited by 138
“Trimethylamine-N-Oxide Trimethylamine-N-oxide (TMAO) is a gut microbiotadependent metabolite of saltwater fish, eggs, dairy products, and especially, red meat (Velasquez et al., 2016; Chan et al., 2019; Wang et al., 2019).”
BackgroundOrgan, C. L., Li, Z., Sharp, T. E., Polhemus, D. J., Gupta, N., Goodchild, T. T., Tang, W. H. W., Hazen, S. L., & Lefer, D. J. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.016223 · Cited by 128
Self-citationBiomarkers of meat and seafood intake: an extensive literature review
Cuparencu, C., Praticò, G., Hemeryck, L., Harsha, P. S. C. S., Noerman, S., Rombouts, C., Xi, M., Vanhaecke, L., Hanhineva, K., Brennan, L., et al. (2019) · Genes & Nutrition · doi:10.1186/s12263-019-0656-4 · Cited by 125
Rudzki, L., Stone, T. W., Maes, M. H. J., Misiak, B., Samochowiec, J., & Szulc, A. (2021) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110240 · Cited by 125
Vegetable-Based Diets for Chronic Kidney Disease? It Is Time to Reconsider
Cases, A., Cigarrán, S., Mas, S., & González‐Parra, E. (2019) · Nutrients · doi:10.3390/nu11061263 · Cited by 130
“A recent study of non-CKD populations revealed that TMAO production was mainly associated with the ingestion of red meat (rich in L-carnitine), while L-carnitine enhanced TMAO production in omnivores but not in vegetarians [67,68].”
BackgroundBuffa, J. A., Romano, K. A., Copeland, M. F., Cody, D. B., Zhu, W., Galvez, R., Fu, X., Ward, K., Ferrell, M., Dai, H. J., et al. (2021) · Nature Microbiology · doi:10.1038/s41564-021-01010-x · Cited by 115
Self-citationGao, Q., Wang, Y., Wang, X., Fu, S., Zhang, X., Wang, R., & Zhang, X. (2019) · Aging · doi:10.18632/aging.102352 · Cited by 119
“Whereas TMAO accumulation could be influenced by modifications in intestinal microbiota composition, which potentially modulates TMA generation [24].”
BackgroundRecent advances in modulation of cardiovascular diseases by the gut microbiota
Masenga, S. K., Hamooya, B., Hangoma, J., Hayumbu, V., Ertuglu, L. A., Ishimwe, J., Rahman, S., Saleem, M., Laffer, C. L., Elijovich, F., et al. (2022) · Journal of Human Hypertension · doi:10.1038/s41371-022-00698-6 · Cited by 121
“Since TMAO and p-cresylsulfate are eliminated through the kidney [71], the age-related decline in kidney function, which is seen in both men and women, may exacerbate the systemic accumulation of these metabolites further enhancing pathways that lead to cardiovascular disease [72].”
BackgroundSimó, C., & García‐Cañas, V. (2020) · Food & Function · doi:10.1039/d0fo01237h · Cited by 112
Winther, S. A., Oellgaard, J., Tofte, N., Tarnow, L., Wang, Z., Ahluwalia, T. S., Jorsal, A., Theilade, S., Parving, H., Hansen, T. W., et al. (2019) · Diabetes Care · doi:10.2337/dc19-0048 · Cited by 111
“, increased variation is observed where TMAO levels are low) (44).”
BackgroundSelf-citationThe complexities of the diet-microbiome relationship: advances and perspectives
Leeming, E. R., Louca, P., Gibson, R., Menni, C., Spector, T. D., & Roy, C. I. L. (2021) · Genome Medicine · doi:10.1186/s13073-020-00813-7 · Cited by 116
“For instance, trimethylamine N-oxide (TMAO), a product of trimethylamine (TMA) transformation by the liver, has been extensively associated with the negative health effects linked to red meat consumption [99].”
BackgroundThe bright and the dark sides of L-carnitine supplementation: a systematic review
Sawicka, A. K., Renzi, G., & Olek, R. A. (2020) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-020-00377-2 · Cited by 113
Meat consumption and risk of ischemic heart disease: A systematic review and meta-analysis
Papier, K., Knüppel, A., Syam, N. R., Jebb, S. A., & Key, T. J. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1949575 · Cited by 119
“Another mechanism that might be specific to red meat intake is trimethylamine-N-oxide (TMAO), which might contribute to an increased risk of IHD by promoting atherosclerosis (Wang et al. 2019; Heianza et al. 2020; Tang et al. 2013); red meat intake can lead increased circulating TMAO derived from intestinal microbiota…”
BackgroundModifiable Cardiovascular Risk, Hematopoiesis, and Innate Immunity
Schloss, M. J., Świrski, F. K., & Nahrendorf, M. (2020) · Circulation Research · doi:10.1161/circresaha.120.315936 · Cited by 114
Nutritional Metabolomics and the Classification of Dietary Biomarker Candidates: A Critical Review
Rafiq, T., Azab, S. M., Teo, K. K., Thabane, L., Anand, S. S., Morrison, K. M., de Souza, R. J., & Britz‐McKibbin, P. (2021) · Advances in Nutrition · doi:10.1093/advances/nmab054 · Cited by 110
Brunt, V. E., Casso, A. G., Gioscia‐Ryan, R. A., Sapinsley, Z. J., Ziemba, B. P., Clayton, Z. S., Bazzoni, A. E., VanDongen, N. S., Richey, J. J., Hutton, D. A., et al. (2021) · Hypertension · doi:10.1161/hypertensionaha.120.16895 · Cited by 111
Sankowski, B., Księżarczyk, K., Raćkowska, E., Szlufik, S., Koziorowski, D., & Giebułtowicz, J. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.10.038 · Cited by 105
Xu, J., Moore, B. N., & Pluznick, J. L. (2022) · Hypertension · doi:10.1161/hypertensionaha.122.18558 · Cited by 119
Peña-Jorquera, H., Cid-Jofré, V., Landaeta-Díaz, L., Petermann-Rocha, F., Martorell, M., Zbinden-Foncea, H., Ferrari, G., Jorquera-Aguilera, C., & Cristi-Montero, C. (2023) · Nutrients · doi:10.3390/nu15143244 · Cited by 103
“Trimethylamine N-oxide (TMAO) is a compound that has gained interest due to its potential mechanistic links to atherosclerosis heart disease [81].”
BackgroundMamic, P., Chaikijurajai, T., & Tang, W. H. W. (2020) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2020.12.001 · Cited by 100
“Red meat is particularly high in TMAO precursors, but, reassuringly, dramatic reduction in circulating TMAO levels can be achieved after only few weeks of cessation of red meat intake [41].”
BackgroundSelf-citationLow Fibre Intake is Associated with Gut Microbiota Alterations in Chronic Heart Failure
Mayerhofer, C. C. K., Kummen, M., Holm, K., Broch, K., Awoyemi, A., Vestad, B., Storm-Larsen, C., Seljeflot, I., Ueland, T., Bohov, P., et al. (2020) · ESC Heart Failure · doi:10.1002/ehf2.12596 · Cited by 97
“These results confirm the findings of a recent crossover study, which demonstrated an association between red meat and raised TMAO levels.(27) Our data suggest that TMAO is more related to dietary patterns than to microbiota alterations in HF, again emphasizing the importance of including dietary data in microbiota-re…”
ResultMetabolites Linking the Gut Microbiome with Risk for Type 2 Diabetes
Zhu, T., & Goodarzi, M. O. (2020) · Current Nutrition Reports · doi:10.1007/s13668-020-00307-3 · Cited by 100
Can Meat and Meat-Products Induce Oxidative Stress?
Macho‐González, A., Garcimartín, A., López‐Oliva, M. E., Bastida, S., Benedı́, J., Ros, G., Nieto, G., & Sánchez-Muniz, F. J. (2020) · Antioxidants · doi:10.3390/antiox9070638 · Cited by 106
Xiang, F., Zhang, Z., Xie, J., Xiong, S., Chen, Y., Liao, D., Xia, B., & Lin, L. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06341-5 · Cited by 100
“The long-term intake of red meat significantly increases the levels of the carnitine metabolites trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), leading to endothelial dysfunction and adverse cardiovascular events [241].”
Gut-Heart Axis: The Role of Gut Microbiota and Metabolites in Heart Failure
Snelson, M., Muralitharan, R. R., Liu, C., Markó, L., Forslund, S. K., Marques, F. Z., & Tang, W. H. W. (2025) · Circulation Research · doi:10.1161/circresaha.125.325516 · Cited by 118
“146,147 These included (1) reduction in nutrient precursor density in the diet (choline and carnitine); (2) increased microbial trimethylamine/TMAO production from carnitine (but interestingly, not choline, presumably via bloom of the low abundance microbes capable of completing the multistep…”
Self-citationLee, Y., Nemet, I., Wang, Z., Lai, H. T. M., Otto, M. C. D. O., Lemaître, R. N., Fretts, A. M., Sotoodehnia, N., Budoff, M. J., DiDonato, J. A., et al. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.020646 · Cited by 95
Self-citationDiet-gut microbiota interactions on cardiovascular disease
Zhang, X., & Gérard, P. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.03.028 · Cited by 98
“The dietary precursors phosphatidylcholine [86], choline [87], and L-carnitine [33], which are commonly present in cheese, red meat, seafood, egg yolks and other western style nutrients [88], are primarily metabolized by specific gut microbial enzymes to produce high levels of trimethylamine (TMA) [63,89–91].”
BackgroundBusnelli, M., Manzini, S., & Chiesa, G. (2019) · Nutrients · doi:10.3390/nu12010079 · Cited by 92
TMAO as a potential biomarker and therapeutic target for chronic kidney disease: A review
Ye, Z., Lulu, C., Xiangchang, Z., Fang, Q., Binjie, Z., Chunyang, L., Rao, T., & Dongsheng, O. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.929262 · Cited by 91
“In addition, long-term and excessive consumption of red meat (rich in carnitine and choline) can increase TMAO production and reduce renal excretion (Wang et al., 2019).”
BackgroundTang, W. H. W., Li, X. S., Wu, Y., Wang, Z., Khaw, K., Wareham, N. J., Nieuwdorp, M., Boekholdt, S. M., & Hazen, S. L. (2021) · American Heart Journal · doi:10.1016/j.ahj.2021.01.020 · Cited by 92
Self-citationZeng, Y., Guo, M., Xia, F., Teng, F., Tan, X., Li, X., Wang, M., Long, Y., & Xu, Y. (2021) · Advances in Nutrition · doi:10.1093/advances/nmab010 · Cited by 94
“Notably, the increase in plasma TMAO concentrations was, on average, 3-fold higher compared with either white meat or nonmeat sources (75).”
BackgroundSelf-citationGut Microbial Metabolites and Blood Pressure Regulation: Focus on SCFAs and TMAO
Poll, B. G., Cheema, M. U., & Pluznick, J. L. (2020) · Physiology · doi:10.1152/physiol.00004.2020 · Cited by 85
Dietary compounds in modulation of gut microbiota-derived metabolites
Feng, W., Liu, J., Cheng, H., Zhang, D., Tan, Y., & Peng, C. Y. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.939571 · Cited by 92
Wang, M., Wang, Z., Lee, Y., Lai, H. T. M., Otto, M. C. D. O., Lemaître, R. N., Fretts, A. M., Sotoodehnia, N., Budoff, M. J., DiDonato, J. A., et al. (2022) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.316533 · Cited by 85
Self-citationWang, M., Li, X. S., Wang, Z., Otto, M. C. D. O., Lemaître, R. N., Fretts, A. M., Sotoodehnia, N., Budoff, M. J., Nemet, I., DiDonato, J. A., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad089 · Cited by 84
Self-citationAndrikopoulos, P., Aron‐Wisnewsky, J., Chakaroun, R., Myridakis, A., Forslund, S. K., Nielsen, T., Adriouch, S., Holmes, B., Chilloux, J., Vieira‐Silva, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39824-4 · Cited by 88
“Within each western blot, the same amount of protein was loaded between samples and normalised accordingly.”
Relationship between elevated plasma trimethylamine N-oxide levels and increased stroke injury
Wu, C., Xue, F., Lian, Y., Zhang, J., Wu, D., Xie, N., Chang, W., Chen, F., Wang, L., Wei, W., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000008862 · Cited by 71
“First, previous studies have shown that changes in dietary pattern can affect TMAO levels.(1,16) To avoid the impact of dietary management after admission on baseline TMAO levels, only patients who presented within 12 hours were included in the present study.”
ResultReichard, C. A., Naelitz, B. D., Wang, Z., Jia, X., Li, J., Stampfer, M. J., Klein, E. A., Hazen, S. L., & Sharifi, N. (2021) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-21-0766 · Cited by 64
“Targeted metabolites and isotope-labeled internal standards were monitored using electrospray ionization in positive-ion mode (except for p-cresol sulfate, which was monitored using negative-ion mode) withmultiple reactionmonitoring (MRM) as previously reported (27).”
MethodSelf-citationMicrobial Tryptophan Metabolism Tunes Host Immunity, Metabolism, and Extraintestinal Disorders
Liu, M., Nieuwdorp, M., de Vos, W. M., & Rampanelli, E. (2022) · Metabolites · doi:10.3390/metabo12090834 · Cited by 86
Trimethylamine N -oxide: heart of the microbiota–CVD nexus?
Naghipour, S., Cox, A. J., Peart, J. N., Toit, E. F. D., & Headrick, J. P. (2020) · Nutrition Research Reviews · doi:10.1017/s0954422420000177 · Cited by 77
“Recent findings suggest that chronic ingestion of red meat may reduce excretion of TMAO(79).”
BackgroundInfluentialGriffin, L. E., Djurić, Z., Angiletta, C. J., Mitchell, C. M., Baugh, M. E., Davy, K. P., & Neilson, A. P. (2019) · Food & Function · doi:10.1039/c9fo00333a · Cited by 78
A Review of the Relationship between Gut Microbiome and Obesity
Zsálig, D., Berta, A., Tóth, V., Szabó, Z., Klara, S. M., Figler, M., Pusztafalvi, H., & Polyák, É. (2023) · Applied Sciences · doi:10.3390/app13010610 · Cited by 79
Microbiota in Gut‐Heart Axis: Metabolites and Mechanisms in Cardiovascular Disease
Kondapalli, N. B., Katari, V., Dalal, K. K., Paruchuri, S. M., & Thodeti, C. K. (2025) · Comprehensive physiology · doi:10.1002/cph4.70024 · Cited by 98
Association of TrimethylamineN-Oxide and Related Metabolites in Plasma and Incident Type 2 Diabetes
Lemaître, R. N., Jensen, P. N., Wang, Z., Fretts, A. M., McKnight, B., Nemet, I., Biggs, M. L., Sotoodehnia, N., Otto, M. C. D. O., Psaty, B. M., et al. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.22844 · Cited by 71
Self-citationUnraveling the Role of the Human Gut Microbiome in Health and Diseases
Khalil, M., Ciaula, A. D., Mahdi, L., Jaber, N., Palo, D. M. D., Graziani, A., Baffy, G., & Portincasa, P. (2024) · Microorganisms · doi:10.3390/microorganisms12112333 · Cited by 100
“Unabsorbed tryptophan can become the substrate for the microbiome to tryptamine, skatole, indole, and indole derivatives such as in-doxyl sulfate, indole-3-propionic acid, 3-methyl-indole, and [96].”
From taxonomy to metabolic output: what factors define gut microbiome health?
Wilmanski, T., Rappaport, N., Diener, C., Gibbons, S. M., & Price, N. D. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1907270 · Cited by 73
“Microbial breakdown products of phosphatidylcholine and carnitine, particularly trimethylamine converted in the liver to TMAO, are commonly elevated in individuals on diets high in red meat.(121) TMAO has been shown to promote cardiovascular disease in animal models,(122) and is associated with increased risk of cardi…”
BackgroundGut microbiome and cardiovascular disease
Zhao, Y., & Wang, Z. (2020) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000720 · Cited by 70
Self-citationNeural Mechanisms in Cardiovascular Health and Disease
Ziegler, K. A., Engelhardt, S. H., Carnevale, D., McAlpine, C. S., Guzik, T. J., Dimmeler, S., & Świrski, F. K. (2025) · Circulation Research · doi:10.1161/circresaha.125.325580 · Cited by 89
“241,242 Finally, the aging process significantly alters the function and regulation of the ANS.”
Assessment of peripheral endothelial function predicts future risk of solid-tumor cancer
Toya, T., Sara, J. D. S., Corban, M., Taher, R., Godo, S., Herrmann, J., Lerman, L. O., & Lerman, A. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487319884246 · Cited by 71
“For example, red meat raises the risk of CVD by increasing the plasma level of trimethylamine-N-oxide, as well as the risk of colorectal cancer.(33,34) Nevertheless, we could not adjust for the influence of diet and nutrition due to lack of data.”
BackgroundSoldán, M., Argalášová, Ľ., Hadvinová, L., Galileo, B., & Babjaková, J. (2024) · Nutrients · doi:10.3390/nu16183134 · Cited by 89
“However, Vanegas et al. found that the consumption of whole grains instead of refined grains leads to reduced numbers of pro-inflammatory Enterobacteriaceae [88,100,109,120].”
BackgroundDietary metabolic signatures and cardiometabolic risk
Shah, R. V., Steffen, L. M., Nayor, M. G., Reis, J. P., Jacobs, D. R., Allen, N. B., Lloyd‐Jones, D. M., Meyer, K. A., Cole, J. B., Piaggi, P., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac446 · Cited by 70
Li, Z. H. (2024) · Gut · doi:10.1136/gutjnl-2024-331880 · Cited by 79
“13 14 17 This compound has been identified as an independent predictor and promoter of AS. 18 19 Studies have demonstrated that reducing TMAO production through interventions leads to a decrease in AS symptoms in both animals and humans.”
BackgroundCostabile, G., Vetrani, C., Bozzetto, L., Giacco, R., Bresciani, L., Rio, D. D., Vitale, M., Pepa, G. D., Brighenti, F., Riccardi, G., et al. (2021) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqab188 · Cited by 68
Delgado, J., Ansorena, D., HECKE, T. V., Astiasarán, I., SMET, S. D., & Estévez, M. (2020) · Meat Science · doi:10.1016/j.meatsci.2020.108278 · Cited by 67
Modulation of Endothelial Function by TMAO, a Gut Microbiota-Derived Metabolite
Querio, G., Antoniotti, S., Geddo, F., Levi, R. C., & Gallo, M. P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065806 · Cited by 70
“Indeed, it is now widely accepted that the microbial diversity of the gut is strictly influenced by the diet and vice versa, as the gut microbiota’s metabolism of different dietderived compounds can influence the host’s health [45].”
BackgroundXylitol is prothrombotic and associated with cardiovascular risk
Witkowski, M., Nemet, I., Li, X. S., Wilcox, J. D., Ferrell, M., Alamri, H. S., Gupta, N., Wang, Z., Tang, W. H. W., & Hazen, S. L. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae244 · Cited by 69
“42 Erythritol was quantified by stable isotope dilution LC-MS/MS as previously described.”
MethodSelf-citationMei, Z., Chen, G., Wang, Z., Usyk, M., Yu, B., Baeza, Y. V., Humphrey, G. C., Benítez, R. A. S., Li, J., Williams-Nguyen, J. S., et al. (2021) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqab001 · Cited by 62
“Consistently, a recent dietary intervention study also suggested that higher intake of dietary red meat could increase systemic TMAO concentrations through microbial TMA production from dietary carnitine, but not choline (45).”
BackgroundSelf-citationBalancing the Equation: A Natural History of Trimethylamine and Trimethylamine-N-oxide
Loo, R. L., Chan, Q. M., Nicholson, J. K., & Holmes, E. C. (2022) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00851 · Cited by 63
The Nutritional Supplement L-Alpha Glycerylphosphorylcholine Promotes Atherosclerosis
Wang, Z., Hazen, J. E., Jia, X., Org, E., Zhao, Y., Osborn, L. J., Nimer, N. A., Buffa, J. A., Culley, M. K., Krajcik, D., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413477 · Cited by 52
“d6-choline [(N,N-dimethyl-d6)-choline, iodide salt] and [N,N,N-trimethyld9] glycerylphosphorylcholine (d9-GPC) were chemically synthesized and purified in our lab, as previously reported [21,71].”
MethodSelf-citationLi, S., Chen, S. X., Lu, X., Fang, A., Chen, Y., Huang, R.-Z., Lin, X., Huang, Z.-H., Ma, J.-F., Huang, B., et al. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03581-7 · Cited by 63
Circulating trimethylamine N-oxide levels following fish or seafood consumption
Wang, Z., Tang, W. H. W., O’Connell, T. F., Garcia, E., Jeyarajah, E. J., Li, X. S., Jia, X., Weeks, T. L., & Hazen, S. L. (2022) · European Journal of Nutrition · doi:10.1007/s00394-022-02803-4 · Cited by 63
“In recent dietary intervention studies, we observed that differences in chronic dietary protein source differentially impacted a subject’s fractional renal excretion of TMAO [14].”
BackgroundSelf-citationThe dietary source of trimethylamine N-oxide and clinical outcomes: an unexpected liaison
Evans, M., Dai, L., Avesani, C. M., Kublickiene, K. R., & Stenvinkel, P. (2023) · Clinical Kidney Journal · doi:10.1093/ckj/sfad095 · Cited by 68
“A study on protein source (red meat versus white meat versus non-meat) found that subjects consuming approximately 220 g of steak/day for 1 month had higher TMAO levels accompanied by a reduced fractional renal excretion rate of TMAO [33].”
BackgroundTacconi, E., Palma, G., Biase, D. D., Luciano, A., Barbieri, M., de Nigris, F., & Bruzzese, F. (2023) · Nutrients · doi:10.3390/nu15030563 · Cited by 62
Wu, W., Panyod, S., Liu, P., Chen, C., Kao, H., Chuang, H.-L., Chen, Y., Zou, H.-B., Kuo, H., Kuo, C.-H., et al. (2020) · Microbiome · doi:10.1186/s40168-020-00912-y · Cited by 58
Self-citationPosicionamento sobre o Consumo de Gorduras e Saúde Cardiovascular – 2021
Izar, M. C. D. O., Lottenberg, A. M., Giraldez, V. Z. R., Santos, R. D., Machado, R. M., Bertolami, A., Assad, M. H. V., Saraiva, J. F. K., Faludi, A. Á., Moreira, A. S. B., et al. (2021) · Arquivos Brasileiros de Cardiologia · doi:10.36660/abc.20201340 · Cited by 78
Trimethylamine-N-Oxide Pathway: A Potential Target for the Treatment of MAFLD
Li, X., Hong, J. W., Wang, Y., Pei, M., Wang, L., & Gong, Z. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.733507 · Cited by 59
Self-citationNutrition, gut microbiota, and alzheimer’s disease
Romanenko, M., Kholin, V., Koliada, A., & Vaiserman, A. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.712673 · Cited by 56
“Moreover, red meat intake decreased TMAO renal excretion (115).”
BackgroundGut Microbiota Modulation as a Novel Therapeutic Strategy in Cardiometabolic Diseases
Mutalub, Y. B., Abdulwahab, M., Mohammed, A., Yahkub, A. M., Al-Mhanna, S. B., Yusof, W., Tang, S. P., Rasool, A. H. G., & Mokhtar, S. S. (2022) · Foods · doi:10.3390/foods11172575 · Cited by 64
Nutrition and Rheumatoid Arthritis in the ‘Omics’ Era
Cassotta, M., Forbes-Hernández, T. Y., Cianciosi, D., Elexpuru-Zabaleta, M., Cano, S. S., Azpíroz, I. D., Bullón, B., Regolo, L., Álvarez-Suárez, J. M., Giampieri, F., et al. (2021) · Nutrients · doi:10.3390/nu13030763 · Cited by 60
Milani, C., Alessandri, G., Mancabelli, L., Mangifesta, M., Lugli, G. A., Viappiani, A., Longhi, G., Anzalone, R., Duranti, S., Turroni, F., et al. (2020) · Applied and Environmental Microbiology · doi:10.1128/aem.01864-20 · Cited by 54
“Notably, choline, a quaternary amine principally found in meats, is known as a precursor of trimethylamine (35, 36).”
BackgroundGut microbiome and its meta-omics perspectives: profound implications for cardiovascular diseases
Xu, J., & Yang, Y. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1936379 · Cited by 61
“The conversion of TMAO in humans has been shown to arise via a multistep, metaorganismal, and microbe-dependent pathway commencing with the dietary precursors including choline,(94) phosphatidylcholine,(94,95) carnitine,(18) betaine,(94) γ-butyrobetaine (γ-BB),(96) and trimethyllysine (TML),(97) which are most abundan…”
Background
Metadata
- Authors
- Wang, Z., Bergeron, N., Levison, B. S., Li, X. S., Chiu, S., Jia, X., Koeth, R. A., Li, L., Wu, Y., Tang, W. H. W., Krauss, R. M., & Hazen, S. L.
- Affiliations
- Cleveland Clinic (US)
- Touro University California (US)
- Department of Atherosclerosis Research, Children’s Hospital Oakland Research Institute, Martin Luther King Jr Way, Oakland, CA, USA
- Cleveland State University (US)
- Corresponding author
- Hazen, Stanley L
- ORCID
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-12-10
- Volume
- 40
- Issue
- 7
- Pages
- 583-594
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- PMC
- PMC6374688
- OpenAlex
- W2904124435
- Semantic Scholar
- e6c31002dc7272f769757169c410825c0b0308a3
- Cited by
- 496
- References
- 40
- Citations by year
- 2026: 62 · 2025: 70 · 2024: 62 · 2023: 59 · 2022: 72 · 2021: 73 · 2020: 68 · 2019: 28 · 2018: 1
- FWCI
- 15.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Heart Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Touro Scholar (Touro College) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (HL103866, R01 HL126827, R01 DK106000, RO1 HL106003, R01 HL130819)
- Leducq Foundation
- Clinical and Translational Science Unit
- 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 › Agricultural and Biological Sciences › Animal Science and Zoology › Meat and Animal Product Quality
- Keywords
- trimethylamine N-oxide, red meat, white meat, L-carnitine, choline, gut microbiota, renal excretion, saturated fat, dietary protein, isotope tracers
- MeSH terms
- Red Meat, Adult, Aged, Animals, Diet, Dietary Proteins, Feeding Behavior, Female, Humans, Male, Methylamines, Middle Aged, Poultry, Reference Values, Cross-Over Studies, Young Adult, Renal Elimination
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.
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