Use of dietary phytochemicals for inhibition of trimethylamine N-oxide formation

Iglesias‐Carres, Lisard; Hughes, Michael D.; Steele, Cortney N.; Ponder, Monica A.; Davy, Kevin P.; Neilson, Andrew P.

doi:10.1016/j.jnutbio.2021.108600

Cited by 34 publications

(72 citation statements)

References 222 publications

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“…However, its reported low levels in foodstuffs (maximum levels of 25 mM in balsamic vinegars, red wine and cold-pressed extra virgin olive oils [11]) make the inhibition of TMA-lyases virtually impossible in a normal diet. Some phenolic compounds have shown their ability to reduce TMAO levels in different models [10]. Thus, we selected two phenolic compounds highly consumed by humans: gallic acid and chlorogenic acid [30].…”

Section: Discussionmentioning

confidence: 99%

“…Following absorption into circulation, the second step occurs in the liver, where TMA is further oxidized by flavin-containing monooxygenase 3 (FMO3) into TMAO [9]. Various strategies have been proposed to control TMAO formation as a means to reduced CVD risk [10]. Reducing TMAO formation through TMA-lyase inhibition has shown promising anti-atherosclerotic effects in mice [11].…”

Section: Introductionmentioning

confidence: 99%

“…It is believed that the reported cardioprotective effects of fruit and vegetal consumption are attributed, at least to some extent, to their bioactive phytochemicals [12,13]. While various mechanisms of action have been proposed, an emerging theory is that phytochemicals may also mediate their cardioprotective effect in part through the inhibition of TMAO formation [10]. Some intervention strategies based on phytochemical supplementation (i.e., allicin and 3,3-dimethyl-1butanol) have been successful to reduce TMA and/or TMAO formation in animal models [11,14,15] and humans [16,17].…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, their study showed that some phenolic compounds from orange juice were able to modulate choline and L-carnitine microbial conversion to TMA in a fecal fermentation model. Of note, in vitro studies that target the gut microbiome profile and/or function can potentially provide a reasonable estimation of the activity of tested conditions in vivo, as no absorption of tested compound is required [10]. A high-throughput in vitro screening assay could significantly advance pre-clinical data on the use of phytochemicals for reducing TMA production in a rapid, systematic, and inexpensive manner.…”

Section: Introductionmentioning

confidence: 99%

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Development of a High Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation

Iglesias‐Carres

Essenmacher

Racine

et al. 2021

Preprint

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Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). Reduction of TMA formation has been shown to provide to cardioprotective effects, and some phytochemicals may produce such reduction. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20 % fecal slurry (1:10 in PBS), 100 M choline, and 12 h fermentation. Also, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50 % reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80 -90 % in. TMA production inhibition), with IC50 around 5 mM. Nor DMB neither gallic acid and chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA lyase activity or expression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Development of a High Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation

Iglesias‐Carres

Essenmacher

Racine

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Following absorption into circulation, the second step occurs in the liver, where TMA is further oxidized by flavin-containing monooxygenase 3 (FMO3) into TMAO [ 9 ]. Various strategies have been proposed to control TMAO formation as a means to reduce CVD risk [ 10 ]. Reducing TMAO formation through TMA-lyase inhibition has shown promising anti-atherosclerotic effects in mice [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a High-Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation

et al. 2021

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Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). A reduction in TMA formation has shown cardioprotective effects, and some phytochemicals may reduce TMA formation. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study the inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20% fecal slurry (1:10 in PBS), 100 µM choline, and 12 h fermentation. Additionally, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50% reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80–90% TMA production inhibition), with IC50 around 5 mM. Neither DMB nor gallic acid or chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA-lyase activity or expression.

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Cardiovascular risk of dietary trimethylamine oxide precursors and the therapeutic potential of resveratrol and its derivatives

Hou,

Chen,

Hazeena

et al. 2024

FEBS Open Bio

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Overall diet, lifestyle choices, genetic predisposition, and other underlying health conditions may contribute to higher trimethylamine N‐oxide (TMAO) levels and increased cardiovascular risk. This review explores the potential therapeutic ability of RSV to protect against cardiovascular diseases (CVD) and affect TMAO levels. This review considers recent studies on the association of TMAO with CVD. It also examines the sources, mechanisms, and metabolism of TMAO along with TMAO‐induced cardiovascular events. Plant polyphenolic compounds, including resveratrol (RSV), and their cardioprotective mechanism of regulating TMAO levels and modifying gut microbiota are also discussed here. RSV's salient features and bioactive properties in reducing CVD have been evaluated. The close relationship between TMAO and CVD is clearly understood from currently available data, making it a potent biomarker for CVD. Precise investigation, including clinical trials, must be performed to understand RSV's mechanism, dose, effects, and derivatives as a cardioprotectant agent.

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Use of dietary phytochemicals for inhibition of trimethylamine N-oxide formation

Cited by 34 publications

References 222 publications

Development of a High Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation

Development of a High Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation

Development of a High-Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation

Cardiovascular risk of dietary trimethylamine oxide precursors and the therapeutic potential of resveratrol and its derivatives

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