A common dietary nutrient feeds a gut pathway linked to atrial fibrillation

Have your competent? doctor decipher this since choline is helpful in brain health and reducing your dementia risk. Your doctor better know of all these 17 research articles! OR COMPLETE FUCKING INCOMPETENCE!

• choline (17 posts to October 2011)

 A common dietary nutrient feeds a gut pathway linked to atrial fibrillation

A 5,090-person cohort and complementary mouse experiments trace how a diet-linked microbial pathway could reshape atrial structure, electrical activity, and autonomic control.

Study: Gut microbial trimethylamine N-oxide generation promotes risk of atrial fibrillation via muscarinic receptor-mediated autonomic dysfunction. Image Credit: Lightspring / Shutterstock

Want to read later? Download your PDF copy by clicking here.

A recent study published in The Journal of Clinical Investigation suggests that trimethylamine N-oxide (TMAO), produced when gut microbes convert nutrients such as choline into trimethylamine (TMA), which is then oxidized in the liver, is independently associated with prevalent atrial fibrillation (AF) in humans and may promote AF susceptibility, onset, and progression in mice. By inhibiting muscarinic receptor 2 signaling, TMAO may disrupt autonomic regulation, with increased sympathetic tone proposed as one mechanism contributing to AF. These findings suggest that diet, through its effects on the gut microbiome and TMAO production, may influence AF susceptibility, although dietary effects were tested only in mice, and the human findings came from a cardiovascular referral cohort.

AF remains a major contributor to cardiovascular disease (CVD)-related illness and death worldwide. Elevated TMAO levels have been associated with CVD-related changes, including cardiac fibrosis and inflammation. However, the biological mechanisms through which TMAO may promote AF remain unclear. An improved understanding of the gut microbiome-related changes that influence AF development could help researchers develop more targeted treatments to reduce the global burden of AF and CVD. Future studies will need to determine whether therapeutic strategies targeting TMAO can safely reduce AF and how differences in gut microbiome composition, liver metabolism, and kidney filtration affect circulating TMAO levels.

About the study

In the present study, researchers investigated whether TMAO generated through the gut microbiome could promote AF development. To do so, they quantified TMAO, choline, and betaine levels in plasma samples obtained from 5,090 individuals from the Cleveland Clinic GeneBank who were undergoing elective cardiac catheterization, using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Individuals with a myocardial infarction during the preceding four weeks or elevated troponin I at enrollment were excluded.

The team also used genetically engineered mice expressing the CREM-IbΔC-X variant of the human cyclic adenosine monophosphate (cAMP) response element modulator gene to investigate AF development. These animals received TMAO- or choline-supplemented diets in separate experiments. The researchers conducted transesophageal electrical pacing studies to determine AF inducibility among wild-type C57BL/6J mice fed TMAO-supplemented or standard diets. They placed electrodes in the esophagus of the animals to deliver electrical impulses and promote arrhythmias in the heart. They separately used serial needle-electrode electrocardiograms (ECGs) to monitor the first onset of paroxysmal AF and progression to persistent AF, defined as AF detected across 10 consecutive ECG recordings, in CREM-IbΔC-X mice receiving different diets, with wild-type mice included in separate control experiments.

The team also explored the effects of iodomethylcholine (IMC), a selective inhibitor of choline trimethylamine-lyase (CutC/D), on TMAO levels. They analyzed microbial DNA from cecal samples, used echocardiography to assess the effects of choline and IMC on cardiac structure, and performed cardiac electrical mapping to examine the electrophysiological effects of choline supplementation. They exposed human and murine cardiac cells, including fibroblasts and cardiomyocytes, to physiologically relevant TMAO levels and examined interleukin-1β (IL-1β) and NLRP3 expression. They also performed murine ECG experiments using MCC950, a chemical compound that inhibits the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome.

The researchers used logistic regression to estimate odds ratios (ORs) for prevalent AF. The models accounted for variables such as age, sex, smoking habits, comorbidities, and laboratory findings, including high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR).

Results

The team found that plasma TMAO, betaine, and choline levels were independently and significantly associated with AF prevalence. For TMAO, the adjusted odds ratio comparing the highest with the lowest concentration tertile was 1.7 (95% confidence interval, 1.3-2.1). The TMAO- or choline-supplemented CREM-IbΔC-X mice developed AF earlier than chow-fed controls, without significant differences in body mass or appreciable liver-related pathologies.

Viva Saliva Book: The ultimate guide to saliva Book preview Download eBook Compilation of the top interviews, articles, and news in the last year.Download the latest edition

The genetically modified animals also showed higher plasma TMAO levels after choline supplementation. These findings suggest that TMAO may contribute to AF onset and progression in mice, and that reducing gut microbial production of TMAO may help lower AF susceptibility in this model. Mice fed TMAO diets showed an increased likelihood of developing AF in the transesophageal pacing study. In fact, mice receiving TMAO supplementation showed an 11-fold increase in AF inducibility in both sexes compared with controls.

Choline supplementation altered the structure and function of the heart. Left atrial size was significantly increased at five and eight weeks, while IMC treatment attenuated the enlargement at eight weeks. In choline-supplemented mice, optical mapping revealed a nonsignificant reduction in conduction velocity but significantly shortened action-potential duration at 80% repolarization and reduced cardiac wavelength. In HEK293 cells engineered to express muscarinic receptor 2 (M2R), TMAO inhibited receptor signaling in the presence of the M2R agonist carbachol. Together with higher heart rates in choline-fed mice, this finding supported a possible role for autonomic dysfunction in promoting AF, although sympathetic activity was not directly measured.

While choline accelerated AF onset, IMC treatment delayed the onset of paroxysmal and persistent AF and reduced TMAO levels by suppressing the microbial conversion of choline to TMA under both aerobic and anaerobic conditions, thereby reducing subsequent TMAO formation in the liver. Choline altered gut microbial communities in association with AF. IMC, on the other hand, attenuated these changes by reversing the loss of gut microbiome diversity and reducing the choline-associated increase in overall Firmicutes abundance, although individual species showed differing patterns. An exploratory analysis also linked Parvibacter caecicola to the timing of paroxysmal AF onset in mice, although the authors noted that this association requires further investigation. TMAO also did not increase NLRP3 or IL-1β expression at physiologically relevant concentrations, and MCC950 did not delay AF development, suggesting that NLRP3 inflammasome activation was not a major mechanism in this mouse model.

Conclusions

The findings demonstrate that higher plasma TMAO levels were independently associated with prevalent AF in humans, whereas direct TMAO exposure or gut microbial production of TMA from dietary choline promoted AF onset and progression in mouse models. However, the human analysis was observational and assessed existing rather than incident AF, while the mechanistic and therapeutic findings came from mice and cell experiments. No human dietary or IMC intervention was tested, and AF recurrence following IMC withdrawal was not examined.

Together, the preclinical findings support clinical investigation of TMAO-lowering approaches as potential strategies for AF prevention. In future studies, researchers should explore different molecules that can reduce TMAO levels and determine how gut microbiome composition, hepatic FMO3 activity, and renal clearance influence circulating TMAO levels and treatment responses in humans.

Journal reference:

• Arjunan, S. et al. (2026). Gut microbial trimethylamine N-oxide generation promotes risk of atrial fibrillation via muscarinic receptor-mediated autonomic dysfunction. The Journal of Clinical Investigation. DOI: 10.1172/JCI201684, https://www.jci.org/articles/view/201684

This molecule links your diet to stroke and Alzheimer’s—here’s how to stop it

 Here's more information on this, not quite as alarming. Ask your doctor for clarification. This is not going to change my habits on eggs, red meat and dairy.

Trimethylamine N-oxide (TMAO) in human health

This choline research sounds positive.

Association of dietary choline intake with incidence of dementia, Alzheimer's disease and mild cognitive impairment: a large population-based prospective cohort study

In conclusion, our findings suggest that moderate dietary choline intake, ranging from 332.89 mg/d to 353.93 mg/d, is associated with lower odds of dementia and better cognitive performance.

Source: The American journal of clinical nutrition.

Carnitine is more nuanced, ask your competent? doctor for clarification.

Heart Failure Among Meat-Eaters A Byproduct Of How Gut Bacteria Digests Food

The latest here:

This molecule links your diet to stroke and Alzheimer’s—here’s how to stop it

Red meat and eggs feed gut bacteria that make TMAO—a molecule now tied to stroke, Alzheimer’s, and heart failure. This new review reveals how diet, probiotics, and even statins could help stop it in its tracks.

Review: Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health. Image Credit: zizou7 / Shutterstock

What you feed your gut microbiota can influence your risk of heart disease and neurodegeneration. Recent research has highlighted the role of trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, as a key biomarker in health, metabolism, and disease.

In a recent review published in the journal Metabolites, a team of scientists in Italy investigated the role of diet and gut bacteria in the biosynthesis of TMAO, as well as the impact of this metabolite on the risk of neurodegenerative and cardiovascular diseases.

Gut-microbiome metabolites

The human gut microbiota plays a crucial role in processing dietary components, especially by producing metabolites that influence health. One such compound, TMAO, forms when gut bacteria break down choline and carnitine, which are found in red meat, eggs, and dairy. These are converted to trimethylamine (TMA), which is then oxidized by the liver enzyme flavin-containing monooxygenase 3 (FMO3) to produce TMAO.

Genetic variation in FMO3, as well as differences in sex hormones and liver function, can influence how efficiently TMA is converted to TMAO, thereby affecting individual susceptibility to disease.

Initially recognized for its osmoprotective role in marine organisms, TMAO has gained attention in human health due to its strong correlation with cardiovascular diseases, atherosclerosis, peripheral artery disease, hypertension, and neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases.

Elevated TMAO levels have been associated with increased platelet aggregation, endothelial dysfunction, and systemic inflammation—mechanisms that contribute to heart disease and stroke. TMAO also increases intracellular calcium release in platelets, enhancing their reactivity and promoting thrombus formation.

Furthermore, TMAO promotes oxidative stress and inflammation by activating the NLRP3 inflammasome and impairing the SIRT3–SOD2 mitochondrial defense pathway, contributing to both vascular damage and neuroinflammation.

Schematic representation of TMAO biosynthesis and metabolism.

The current study

The review aimed to bridge knowledge gaps by assessing how dietary components, microbiota composition, and potential therapies influence TMAO levels and disease risk.

Researchers analyzed how specific gut bacteria metabolize dietary choline, carnitine, betaine, and other precursors into TMA, which is then transformed into TMAO in the liver. They also evaluated findings from experimental models, clinical trials, and epidemiological studies to clarify TMAO’s involvement in disease.

Dietary patterns were examined by comparing TMAO levels in individuals consuming red meat-heavy diets versus those following plant-based or Mediterranean diets. The team also explored probiotic interventions, nutraceutical compounds, and even pharmaceutical agents that may modulate TMAO synthesis or metabolism.

Major findings

TMAO levels are strongly shaped by both diet and gut microbiota composition. Red meat, eggs, and dairy intake elevate TMAO levels, while plant-based or Mediterranean diets—rich in fiber and polyphenols—are associated with lower levels.

TMAO contributes to cardiovascular disease by impairing nitric oxide production, disrupting lipid and cholesterol metabolism, promoting foam cell formation, and increasing platelet hyperreactivity. It also impairs endothelial progenitor cell function and alters pathways crucial for neovascularization and vascular repair.

Beyond heart disease, the review connects TMAO to cognitive decline, blood–brain barrier dysfunction, and beta-amyloid and tau aggregation—hallmarks of Alzheimer’s. It is also implicated in Parkinson’s disease through mitochondrial dysfunction and chronic inflammation.

Elevated TMAO was associated with poor outcomes in heart failure, increased mortality in peripheral artery disease, and heightened risk of stroke and hypertension.

Schematic representation of TMAO transport into endothelial cells via the endothelial TMAO transporter (ETT) and its clinical implications.

Therapeutic and lifestyle interventions

Interventions that reduce TMAO include:

• Dietary changes, such as reducing red meat and increasing fiber/polyphenols.
• Probiotics, particularly certain strains of Lactobacillus and Bifidobacterium, which modulate the microbiota to reduce TMA production. However, not all probiotics are effective—formulations like VSL#3 have shown no impact on TMAO levels in trials.
• Nutraceuticals, including resveratrol, quercetin, and the polyphenol-rich supplement Taurisolo®, have shown promising results in reducing TMAO and protecting vascular health.

The review also highlighted the potential role of pharmaceuticals:

• Statins may lower TMAO by modulating gut microbiota and bile acid metabolism.
• ACE inhibitors and loop diuretics indirectly influence TMAO clearance or synthesis via effects on renal excretion and gut flora.
• Monitoring TMAO may enhance cardiovascular risk stratification, particularly in patients with comorbidities.

Despite these advances, the review acknowledged several limitations, including inconsistent probiotic outcomes, variation in individual microbiomes, and a lack of long-term human trials.

Conclusions

TMAO has emerged as a central metabolite linking diet, gut microbiota, host genetics, and disease. The review emphasized that dietary and probiotic strategies, along with personalized approaches based on microbiome and genetic profiling, could offer powerful tools for mitigating TMAO-associated health risks.

Monitoring TMAO levels may also improve the early detection of cardiovascular and neurodegenerative diseases. While research is ongoing, simple changes—such as shifting to a plant-rich diet, using targeted probiotics, or considering nutraceuticals like Taurisolo®—could offer a preventive edge in long-term health.

Journal reference:

• Caradonna, E., Abate, F., Schiano, E., Paparella, F., Ferrara, F., Vanoli, E., Difruscolo, R., Goffredo, V. M., Amato, B., Setacci, C., Setacci, F., & Novellino, E. (2025). Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health. Metabolites, 15(4), 220. DOI: 10.3390/metabo15040220, https://www.mdpi.com/2218-1989/15/4/220

Gut microbes impact stroke severity via the trimethylamine N-oxide pathway

What we really need to know is if this TMAO is normal after stroke we get better recovery.  WHOM do we ask that question AND get an answer? Then how do we make TMAO normal?

Gut microbes impact stroke severity via the trimethylamine N-oxide pathway

• Weifei Zhu ⁸
• Kymberleigh A. Romano
• Lin Li
• 
  
• Adeline M. Hajjar
• Joseph A. DiDonato
• Stanley L. Hazen
• Show all authors
• Show footnotes

Published:June 16, 2021DOI:https://doi.org/10.1016/j.chom.2021.05.002

Highlights

• •
  Gut microbial transplantation studies show stroke severity is a transmissible trait
• •
  The metaorganismal TMAO pathway impacts infarct size and functional impairment
• •
  Gut microbial CutC increases host TMAO levels, cerebral infarct size, and functional deficits

Summary

Clinical studies have demonstrated associations between circulating levels of the gut-microbiota-derived metabolite trimethylamine-N-oxide (TMAO) and stroke incident risk. However, a causal role of gut microbes in stroke has not yet been demonstrated. Herein we show that gut microbes, through dietary choline and TMAO generation, directly impact cerebral infarct size and adverse outcomes following stroke. Fecal microbial transplantation from low- versus high-TMAO-producing human subjects into germ-free mice shows that both TMAO generation and stroke severity are transmissible traits. Furthermore, employing multiple murine stroke models and transplantation of defined microbial communities with genetically engineered human commensals into germ-free mice, we demonstrate that the microbial cutC gene (an enzymatic source of choline-to-TMA transformation) is sufficient to transmit TMA/TMAO production, heighten cerebral infarct size, and lead to functional impairment. We thus reveal that gut microbiota in general, specifically the metaorganismal TMAO pathway, directly contributes to stroke severity.

Graphical abstract

• View Large Image
• Figure Viewer
• Download Hi-res image

 

Cleveland Clinic Finds Link Between Gut Microbes and Stroke

 Well shit Cleveland Clinic already researched and reported on this in November 2014.

Cleveland Clinic Research Shows Gut Bacteria Byproduct Impacts Heart Failure

The latest here:

Cleveland Clinic Finds Link Between Gut Microbes and Stroke

According to the World Stroke Organization, globally, 1 in 4 adults over the age of 25 will have a stroke in their lifetime. So, how exactly can we reduce our risk? Well, according to a recent study from Cleveland Clinic, focusing on our gut health can help to protect us from severe strokes.

Gut health and stroke risk

The state of our gut can influence our health in a number of ways, from our immune system to our mental health. That said, a recent study suggests that certain gut microbes can cause a profound change in stroke severity. 

The study

The study, published in Cell Host & Microbe, Recently, was done by a group of researchers from the Cleveland Clinic. For the purpose of the study, the researchers transplanted various microbial communities into multiple murine stroke models in an effort to better understand the causal role of gut microorganisms in stroke.

SizeSquares/Shutterstock

The theme of the study isn’t a new one for study author Dr. Hazen, who also happens to be chair of the Department of Cardiovascular & Metabolic Sciences and director of Cleveland Clinic’s Center for Microbiome & Human Health.

For him and his team, the study builds on more than a decade of research related to the gut microbiome’s role in cardiovascular health and disease, including the adverse effects of TMAO (trimethylamine N-oxide) – a byproduct produced when gut bacteria digest certain nutrients abundant in red meat and other animal products.

How was the study done? 

For the study, Dr. Hazen and his team compared brain damage in preclinical stroke models between those with elevated or reduced TMAO levels.

“Functionality after a stroke – which occurs when blood flow to the brain is blocked – is a major concern for patients,” said Dr. Hazen, who is also co-section head of Preventive Cardiology & Cardiac Rehabilitation in Cleveland Clinic’s Miller Heart, Vascular & Thoracic Institute. “To understand if choline and TMAO affect post-stroke functionality, in addition to stroke severity, we compared performance on various tasks pre-stroke, and then both in the short- and long-term following stroke.”

What did the study find?

It appears that those with higher levels of TMAO not only had more extensive brain damage but also faced a greater degree of motor and cognitive functional deficits following stroke. 

“In this study, we found that dietary choline and TMAO produced greater stroke size and severity, and poorer outcomes in animal models,” said Dr. Hazen, “Remarkably, simply transplanting gut microbes capable of making TMAO was enough to cause a profound change in stroke severity…This new study…for the first time provides proof that gut microbes in general – and through TMAO specifically – can directly impact stroke severity or post-stroke functional impairment,”

The study also revealed that CutC, a gut microbe enzyme critical to TMAO production, drove heightened stroke severity and worsened outcomes.

 So what now?

Simple: focus on your gut.

Dr. Weifei Zhu, Ph.D. has also led the study. She believes that targeting the CutC gut microbe enzyme may help prevent stroke. 

“When we genetically silenced the gut microbe gene that encodes CutC, stroke severity significantly diminished,” she said. 

 

“Ongoing research is exploring this treatment approach, as well as the potential for dietary interventions to help reduce TMAO levels and stroke risk, since both a Western diet and a diet rich in red meat are known to elevate TMAO levels. Switching to plant-based protein sources helps to lower TMAO.”

Switching to plant-based protein sources won’t only help to lower TMAO levels, but it could also have amazing benefits for your health.

References

Zhu, W., Romano, K. A., Li, L., Buffa, J. A.,et al. (2021). Gut microbes impact stroke severity via the trimethylamine N-oxide pathway. Cell host & microbe, S1931-3128(21)00230-4. Advance online publication. ttps://doi.org/10.1016/j.chom.2021.05.002

 

Red meat raises heart disease risk through gut bacteria

Be careful out there. Maybe 50 years from now your doctor will have copied someone else's diet protocol.  Paleo diet not ok?

Red meat raises heart disease risk through gut bacteria

Healthline/Medical News Today | December 13, 2018

Scientists have uncovered further evidence of how a diet rich in red meat interacts with gut bacteria to raise the risk of heart disease.

Advertisement

They found that people who ate red meat as their main source of protein for 1 month had levels of trimethylamine N-oxide (TMAO) that were two to three times higher than those in people who got their protein primarily from white meat or non-meat sources.
Gut bacteria produce TMAO as a byproduct when they feed on certain nutrients during digestion.
Previous studies have implicated high circulating levels of TMAO in the development of artery-blocking plaques and raised risk of heart-related conditions.
In the recent research, scientists at the Cleveland Clinic in Ohio uncovered two mechanisms through which a diet rich in red meat raises TMAO levels.

It appears that not only does frequent consumption of red meat enhance gut bacteria production of TMAO, but it also reduces elimination of the compound through the kidneys.

The European Heart Journal has published a report on the study and its findings.
"This is the first study of our knowledge," says senior study author Dr. Stanley L. Hazen, who chairs the Department of Cellular and Molecular Medicine in the Cleveland Clinic's Lerner Research Institute, "to show that the kidneys can change how effectively they expel different compounds depending on the diet that one eats—other than salts and water."

• See Also: Iron-rich foods for vegetarians and vegans

TMAO as a predictor of heart disease risk

In previous work, Dr. Hazen and his team had found that TMAO alters blood platelets to raise the risk of thrombosis, or blood clots.
Their work revealed that TMAO modifies calcium signaling in blood platelets. In addition, it showed that platelets respond differently to blood-clotting triggers when blood levels of TMAO are high.

The team proposed that the compound could be a powerful predictor of the risk of heart attack, stroke, and death—even when cholesterol and blood pressure levels are healthy.

Others have since replicated the findings and, like Dr. Hazen and his team, have continued to investigate TMAO and its impact on health.
Research from the University of Leicester in the UK, for example, demonstrated that people with acute heart failure fared worse if they had higher circulating levels of TMAO.
Clinical trials are also underway to test TMAO as a predictive marker of heart disease risk.

Red meat diet compared with other diets

The recent study assigned 113 individuals to follow three tightly controlled diets in a random order for 4 weeks each with a "washout diet" preceding the changeover.
The diets differed according to their main source of protein. In the red meat diet, 12% of the daily calories came from lean red meat in the form of pork or beef, while in the white meat diet, these calories came from lean white poultry meat.
In the non-meat diet, 12% of the daily calorie intake came from "legumes, nuts, grains, [and] isoflavone-free soy products."
In all three diets, protein accounted for 25% of the daily calories, and the remaining 13% of this protein came from "eggs, dairy, and vegetable sources."

After 4 weeks on the red meat diet, "the majority of" the individuals had raised levels of TMAO in their blood and urine.

On average, compared with levels during the white meat and non-meat diets, blood levels of TMAO during the red meat diet were up to three times higher. For some individuals, the levels were 10 times higher. Urine samples revealed a similar pattern.

Reduced kidney efficiency

The study also yielded an unexpected result. While on the red meat diet, the study participants' kidneys were less efficient at expelling TMAO.
However, in the 4 weeks after ceasing the red meat diet, their blood and urine levels of TMAO fell.
Dr. Hazen says that the findings show that people can reduce their risk of heart-related problems by changing what they eat.
Gut production of TMAO was lower and kidney elimination was higher when the individuals followed the white meat or non-meat protein diet.
This suggests, says Dr. Hazen, that these types of diet are more healthful for the heart and body.

"We know lifestyle factors are critical for cardiovascular health, and these findings build upon our previous research on TMAO's link with heart disease."
—Dr. Stanley L. Hazen

• See Also: Osteoporosis: Could probiotics protect bone health?

To read more, click here.

Paleo diet linked to heart disease biomarker

So ask your doctor to translate this into diet protocols for all your needs. 

But I bet your stroke hospital is so fucking incompetent it doesn't even have ANY DIET PROTOCOL.
For stroke prevention; for dementia prevention; for cognitive improvement; for cholesterol reduction; for plaque removal; for Parkinsons prevention; for inflammation reduction; for blood pressure reduction. You can't be expected to figure this out on your own, your doctor is being paid for medical expertise. Demand that some expertise be delivered.   

 

Paleo diet linked to heart disease biomarker

• Download PDF Copy

Nov 29 2018Reviewed by Kate Anderton, B.Sc.

More than twice the amount of a key biomarker linked closely to heart disease has been found in the blood of people on the paleo diet.
Researchers from Edith Cowan University have just completed the world’s first major study examining the impact of the paleo diet on gut bacteria.

Image Credit: MaraZe / Shutterstock

The controversial paleo (or ‘caveman’) diet advocates eating meat, vegetables, nuts and limited fruit, therefore excluding grains, legumes, dairy, salt, refined sugar and processed oils.
ECU researchers compared 44 people on the diet with 47 following a traditional Australian diet.
They measured the amount of trimethylamine-n-oxide (TMAO) in the participants’ blood. High levels of TMAO, an organic compound produced in the gut, are associated with an increased risk of cardiovascular disease.
Heart disease kills one Australian every 12 minutes.
Not good for the gut
Lead researcher Dr Angela Genoni from ECU’s School of Medical and Health Sciences said:
“Those who promote the paleo diet often cite it as beneficial for your gut health, but this research suggests there were adverse differences in those who followed the dietary pattern.”
She said the reason TMAO was so elevated in people on the paleo diet appeared to be due to the higher intake of red meats, but also because of the lack of whole grain intake.
“The paleo diet excludes all grains and we know that whole grains are a fantastic source of resistant starch, and many other fermentable fibres which are vital to the health of your gut microbiome,” Dr Genoni said.
“Because TMAO is produced in the gut, a lack of whole grains might change the populations of bacteria enough to enable higher production of this compound.
“Additionally, the paleo diet includes greater servings per day of red meat, which provides the precursor compounds to produce TMAO.”

Source:

http://www.ecu.edu.au/

Gut microbes associated with CV risk

You'll have to have your doctor explain this one to you and provide intervention protocols.

Gut microbes associated with CV risk

“Our largest environmental exposure is what we eat, and that is all perceived through the filter of our gut microbiome,” Stanley L. Hazen, MD, PhD, chair of the department of cellular and molecular medicine, section head of preventive cardiology and rehabilitation and director of the Center for Microbiome and Human Health at Cleveland Clinic, said in the presentation. “The gut microbiome is an active participant in many facets of cardiovascular disease and thrombosis.”

The initial discovery and structural identification of gut microbe-derived metabolites that are associated with CVD risk occurred nearly a decade ago with untargeted metabolomics, according to the presentation. Data from healthy patients were reviewed for the development of CVD over a period of time. Patients’ serum levels were analyzed for the chemical signatures that predicted future CVD risk, and of the metabolites that predicted risks, a third of them are linked to gut microbes, Hazen said.

A study published in Nature in 2011 found that three compounds linked to phosphatidylcholine metabolism, also termed lecithin, suggested a common pathway: choline, betaine and trimethylamine N-oxide (TMAO).

Diet and intestinal microbes are mechanically linked to atherosclerotic heart disease. A diet rich in phosphatidylcholine, a Western diet, also feeds the gut microbes. The microbes generate trimethylamine (TMA) as a waste product of dietary lecithin. After the TMA leaves the gut, it goes into the liver where it is converted to TMAO. In animal studies, TMAO accelerated heart disease development.

The clinical relevance of this was validated in a study published in Nature in 2011, which found that choline, betaine and TMAO dose-dependently track CV events. Beyond association, the study proved causation because a diet rich in choline led to TMAO generation and accelerated atherosclerosis, Hazen said.

“The relationship between plasma TMAO levels and incident CVD and mortality risks in subjects is a steeper curve than what you see with LDL cholesterol, triglycerides or C-reactive protein, for example,” Hazen said.

2 more pages at link.

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Your doctor should put this post and the previous one on DMB together to create a stroke prevention protocol. You'll have to hope your doctor is the genius one that can do this right the first time.  OR we could ask our fucking failures of stroke associations  to fail once again at translating research into protocols. But since none of them have an entry point for survivors that won't work at all.

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

• Zeneng Wang,
• Elizabeth Klipfell,
• Brian J. Bennett,
• Robert Koeth,
• Bruce S. Levison,
• Brandon DuGar,
• Ariel E. Feldstein,
• Earl B. Britt,
• Xiaoming Fu,
• Yoon-Mi Chung,
• Yuping Wu,
• Phil Schauer,
• Jonathan D. Smith,
• Hooman Allayee,
• W. H. Wilson Tang,
• Joseph A. DiDonato,
• Aldons J. Lusis
• & Stanley L. Hazen

• Affiliations
• Contributions
• Corresponding author

Nature

472,

57–63

(07 April 2011)

doi:10.1038/nature09922

Received

29 July 2009

Accepted

09 February 2011

Published online

06 April 2011

Article tools

• Full text

• PDF

• Citation
• Reprints
• Rights & permissions
• Article metrics

Abstract

• Abstract•
• References•
• Author information•
• Supplementary information

Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO) and betaine—were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.

Targeting Gut Microbes Could Lower Risk of Heart Disease

I hate popular press writeups of science, they never have the research they are quoting from.
If this pans out we might be able to get at the root cause of  atherosclerosis rather than attacking the quantity of circulating cholesterol. Your doctor should put this post and the previous one on TMAO together to create a stroke prevention protocol.
http://news.yahoo.com/targeting-gut-microbes-could-lower-risk-heart-disease-024208234.html
A few selected paragraphs;

For the first time, researchers find a compound in some red wines and olive oils can interfere with gut microbes in ways that could potentially help to prevent heart disease in humans.

This new study, which was done in mice, also might reveal why the Mediterranean diet, which usually includes olive oil and red wine, is healthy for the heart, the scientists said.

In the study, the researchers targeted the mice's gut microbes with a compound called DMB,— which naturally occurs in some cold-pressed extra virgin olive oils, red wines, balsamic vinegars and grape seed oils. The scientists found that the DMB treatment suppressed atherosclerosis, which is a hardening of the arteries, from developing in the mice without resulting in toxic side effects.

"This new approach shows that one can target microbes to inhibit atherosclerosis," said study senior author Dr. Stanley Hazen, section head of cardiovascular medicine at the Cleveland Clinic. [10 Amazing Facts About Your Heart]

Foods that contain DMB are often found in the so-called Mediterranean diet, which reduces the risk of heart disease. These new findings suggest that the benefits of the Mediterranean diet may stem from its effects on gut microbe activity, the researchers said.

The DMB treatment works by slowing down the microbes' production of another compound, called TMA. Normally, when gut microbes digest nutrients such as choline, lecithin and carnitine, they excrete TMA, which, in turn, gets converted by the human body into a molecule called TMAO.

Cleveland Clinic Research Shows Gut Bacteria Byproduct Impacts Heart Failure

Is your doctor monitoring these levels to assess your heart attack and stroke risk after your stroke event? What is the stroke protocol that covers such monitoring? Ask for the written explanation not a verbal one, verbal ones can't be taken to a second opinion. Remember you are not allowed to practice medicine, so even though you know about this you shouldn't presume to lord it over your doctor.

Cleveland Clinic Research Shows Gut Bacteria Byproduct Impacts Heart Failure

Clinical Study in Over 700 Subjects Finds Blood TMAO Levels Linked to Increased Risk of Heart Failure in Patients

Monday, Oct. 27, 2014
A chemical byproduct of intestinal bacteria-dependent digestion, TMAO (trimethylamine N-oxide) – already proven to contribute to heart disease and to be an accurate tool for predicting future heart attacks, stroke and death – has for the first time been linked to heart failure and worse long-term prognosis for those patients, according to Cleveland Clinic research published today in the Journal of the American College of Cardiology.
The research team was led by Stanley Hazen, M.D., Ph.D., Chair of the Department of Cellular and Molecular Medicine for the Lerner Research Institute and section head of Preventive Cardiology & Rehabilitation in the Miller Family Heart and Vascular Institute at Cleveland Clinic, and  W.H. Wilson Tang, M.D., Department of Cardiovascular Medicine in the Miller Family Heart and Vascular Institute and Lerner Research Institute.
Drs. Hazen and Tang followed 720 heart failure patients over a five-year period and found that higher TMAO levels predicted higher future risk of death from heart failure, independent of other clinically used blood tests or risk factors. Interestingly, patients who had high levels of natriuretic peptides (an indicator of advanced heart failure) but low levels of TMAO had a much lower mortality rate than individuals with elevated levels in both markers. The researchers also found that when both TMAO and BNP (a peptide typically measured in heart failure patients) levels were raised, patients had more than a 50 percent mortality rate over 5 years.
TMAO, the researchers previously found, is produced when intestinal bacteria digest certain dietary components that are found in red meat, egg yolks, liver and some energy supplements. They found in a large clinical study that high levels of TMAO can predict future adverse outcomes like heart attack, stroke, and death.
“I am excited that these studies suggest TMAO testing may not only help identify those patients at greatest risk and for whom more aggressive monitoring is needed, but also that TMAO testing may help to tailor dietary efforts to the individual in the hopes of reducing future risks among those high-risk subjects,” said Dr. Hazen.
“Our new results suggest that understanding why TMAO levels are elevated in the setting of heart failure may provide important insights into how intestinal bacteria contribute to disease progression in heart failure,” said Dr. Tang.
According to the Centers for Disease Control and Prevention, heart failure occurs when weakened heart muscles do not pump blood effectively. More than 5 million patients in the United States are affected, costing the U.S. approximately $32 billion each year.
The current study is an extension of Drs. Hazen and Tang’s previous work, in which they found TMAO is linked to increased risk of heart disease, even in the absence of known cardiovascular risks, and is produced when intestinal bacteria digest carnitine, found in red meat and some energy drinks, and the nutrient phosphatidylcholine, commonly known as lecithin. The prior research showed that higher TMAO levels in the blood were associated with poorer outcomes in heart disease. Dr. Hazen and colleagues have now confirmed that gut flora are essential in forming TMAO in humans and demonstrated a relationship between TMAO levels and future cardiac events like heart attack, stroke, and death—even in those with no prior evidence of cardiac disease risk.
The TMAO diagnostic test was selected as one of the top ten medical innovations of 2014 at the USA Medical Innovations Summit; and the biological process that makes TMAO was named one of the American Heart Association’s 2013’s Top Ten advances in heart disease science.
This research was supported by grants from the National Institutes of Health and the Office of Dietary Supplements (grants R01HL103866, 1P20HL113452).

Heart Failure Among Meat-Eaters A Byproduct Of How Gut Bacteria Digests Food

But what about this?

Study: Protein from meat, fish may help men age well

Ask your doctor, s/he should know the answer as to which study has more power.

I will continue eating meat.

Heart Failure Among Meat-Eaters A Byproduct Of How Gut Bacteria Digests Food 

Our bodies are filled with bacteria, with the majority of them living in our guts, outnumbering our own cells 10 to one. For the most part, these bacteria live in harmony with our bodies, eating what we eat, and regulating our metabolism and energy. But when they’re not living in peace, they may be causing disease, as one new Cleveland Clinic study found; a byproduct of their digestion may influence a person’s heart health.
The byproduct, trimethylamine N-oxide, or TMAO, is produced when gut bacteria digest the amino acid carnitine, which is commonly found in animal food products like beef, fish, chicken, milk, and cheese. The body already produces carnitine, and stores it in almost every cell in the body, where it’s used to produce energy. Because of this, it’s not really necessary to get more. The new study found that once gut bacteria produced TMAO, it traveled to the bloodstream where it clogged arteries, leading to heart failure and overall worse outcomes.

ADVERTISEMENT

“I am excited that these studies suggest TMAO testing may not only help identify those patients at greatest risk, and for whom more aggressive monitoring is needed, but also that TMAO testing may help to tailor dietary efforts to the individual in the hopes of reducing future risks among those high-risk subjects,” said Dr. W.H. Wilson Tang, of the Department of Cardiovascular Medicine at the Miller Family Heart and Vascular Institute, in a press release.
For the study, the researchers followed 720 heart failure patients over the course of five years. They found that there were lower mortality rates when there were high levels of natriuretic peptides, a compound indicative of heart failure, and low levels of TMAO, when compared to patients who had high levels of both. The findings, that TMAO contributed to heart failure and death, were further supported when they found that high levels of TMAO and BNP — another peptide indicative of heart failure — increased risk of death by 50 percent.
Tang’s study builds on a study from 2013, in which he found that TMAO also contributed to a person’s risk of heart disease and stroke, even if a person has no history of either. Though the researchers aren’t suggesting we all stop eating meat, their findings support previous claims that red meat consumption should be limited — and they have good reason to suggest that. “A diet high in carnitine shifts our gut ‘biology’ so meat eaters actually generate more TMAO and compound their risk of cardiovascular disease,” Cleveland Clinic’s website says.

Follow Us

Heart failure is very common, affecting 5.1 million people in the U.S., according to the National Heart, Lung, and Blood Institute. It develops over time and causes the heart to weaken, making it harder for blood to flow to some parts of the body. In turn, a person’s extremities can swell, they can have trouble breathing, or feel tired.
Source: Tang WH, Hazen S, et al. Journal of the American College of Cardiology. 2014. 

 

Gut bugs are implicated in heart attacks and stroke

Written by Sharon Begley who wrote as the science editor for Newsweek and a couple of books.
Train Your Mind, Change
Your Brain: How a New Science Reveals Our Extraordinary Potential to
Transform Ourselves
The mind and the Brain : neuroplasticity and the power of mental
force 

Gut bugs are implicated in heart attacks and stroke

Thousands of heart attack victims every year have none of the notorious risk factors before their crisis - not high cholesterol, not unhealthy triglycerides. Now the search for the mystery culprits has turned up some surprising suspects: the trillions of bacteria and other microbes living in the human gut.
In a study released on Wednesday, scientists discovered that some of the bugs turn lecithin - a nutrient in egg yolks, liver, beef, pork and wheat germ - into an artery-clogging compound called TMAO(trimethylamine-N-oxide). They also found that blood levels of TMAO predict heart attack, stroke or death, and do so "independent of other risk factors," said Dr Stanley Hazen, chairman of cellular and molecular medicine at the Cleveland Clinic's Lerner Research Institute, who led the study.
That suggests a TMAO test could enter the arsenal of blood tests that signal possible cardiovascular problems ahead. "TMAO might identify people who are at risk (for heart attacks and strokes) despite having no other risk factors," Hazen said.
The discovery also suggests a new approach to preventing these cardiovascular events: altering gut bacteria so they churn out less TMAO.

Full article at the link.