Which Supplements Raise TMAO? An In-Depth Look at Precursors

November 20, 2025 •

4 min read

According to randomized clinical trial findings, free choline supplements, specifically choline bitartrate, have been shown to significantly raise fasting TMAO levels in healthy adults. This information highlights the differential impact various nutrient sources can have on metabolism, prompting a deeper exploration into the question: what supplements raise TMAO?

Quick Summary

This guide details the specific supplements that increase TMAO, primarily focusing on how certain forms of choline and L-carnitine are metabolized by gut bacteria into the associated compound.

Key Points

Choline Bitartrate: This specific form of choline supplement is proven to raise TMAO levels in the blood and can increase platelet aggregation.
L-Carnitine: Supplementation with L-carnitine, particularly in meat-eaters, leads to elevated TMAO levels via gut microbial metabolism.
Phosphatidylcholine (Lecithin): This form of choline, commonly found in eggs and supplements, does not appear to significantly raise TMAO levels in healthy individuals.
Gut Microbiome is Key: The conversion of precursors like choline and carnitine to TMA, and subsequently TMAO, depends on the presence of specific bacteria in an individual's gut.
Pre-formed TMAO: Certain supplements, like fish or krill oil, may contain pre-formed TMAO that is absorbed directly, bypassing the gut metabolism step.
Potential Cardiovascular Risk: Elevated TMAO levels are associated with increased cardiovascular disease risk, making it important to consider supplement choices carefully.

The Gut Microbiome and TMAO Production

TMAO (trimethylamine N-oxide) is a small molecule produced in a two-step process involving the body's gut bacteria and liver. First, certain gut microbes metabolize dietary nutrients rich in trimethylamine-containing compounds, like choline and L-carnitine, into an intermediate substance called trimethylamine (TMA). This TMA is then absorbed into the bloodstream and sent to the liver, where host enzymes, primarily FMO3, oxidize it into TMAO.

Elevated levels of circulating TMAO have been correlated with an increased risk of cardiovascular issues, including atherosclerosis, heart attacks, and strokes. However, it is crucial to note that TMAO production is not a foregone conclusion simply from consuming precursor nutrients. It depends heavily on an individual's specific gut microbiome composition, as some people have the necessary bacteria for this conversion while others do not.

Choline Supplements: Form Matters

Choline is an essential nutrient for many bodily functions, including cell structure and neurotransmitter synthesis. It is available in various forms in supplements, but research indicates that not all choline supplements impact TMAO levels equally.

Choline Bitartrate: Multiple studies have shown that supplementation with choline bitartrate significantly raises plasma TMAO concentrations. In one randomized clinical trial, participants who took choline bitartrate supplements experienced a marked increase in TMAO levels and associated platelet reactivity.
Phosphatidylcholine (Lecithin): This is a common form of choline found in foods like egg yolks and also available as a supplement. Interestingly, the same study that found elevated TMAO from choline bitartrate showed no significant increase in TMAO levels from phosphatidylcholine capsules. This suggests that the chemical form of choline dictates its susceptibility to microbial conversion. Lecithin supplements have also been cited as having potential links to TMAO production through the gut microbiota.

L-Carnitine and TMAO

L-Carnitine is an amino acid derivative involved in fatty acid metabolism and is often promoted for energy and weight management. Like choline, it is also a substrate for TMA-producing gut bacteria.

L-Carnitine Supplements: Research has consistently demonstrated that L-carnitine supplementation leads to elevated TMAO levels in human subjects. This effect was observed particularly in omnivores, who possess the gut bacteria required for this conversion, whereas vegans and vegetarians tend to produce less TMAO from carnitine. The degree of increase can be substantial, with one study noting a significant TMAO rise after six months of supplementation.
High-Dose Usage: Individuals with metabolic disorders who require high-dose, chronic L-carnitine supplementation have been shown to have extremely high TMAO levels, highlighting a significant concern for long-term use in certain populations.

Betaine: The Methyl Donor

Betaine, also known as trimethylglycine, is another nutrient that contains a trimethylamine moiety and can serve as a precursor for TMAO. It is found naturally in foods like beets, spinach, and whole grains. Betaine functions as an osmolyte and methyl donor in the body.

Betaine and TMAO Link: While not as potent a TMAO-raiser as choline bitartrate or carnitine for most people, betaine can be converted to TMA by gut bacteria. The significance of this conversion in humans is debated, but some studies have found correlations between betaine levels and TMAO, particularly in diabetic populations.

Comparison of Key Precursor Supplements


Supplement Precursor	Primary Use	Impact on TMAO	Key Findings
Choline Bitartrate	Cognitive support, liver function	High	A clinical trial showed a significant increase in TMAO levels and platelet aggregation.
L-Carnitine	Energy, fat metabolism	High (especially in omnivores)	Multiple studies confirm elevated TMAO and potential links to cardiovascular risk.
Phosphatidylcholine	Cell membrane health, emulsifier	Minimal to None	A study comparing it to choline bitartrate found no significant TMAO increase from phosphatidylcholine capsules.
Betaine	Methyl donor, osmoprotectant	Moderate	Can be converted to TMA by gut microbes, with variable impact based on individual microbiota and health status.
Fish/Krill Oil	Omega-3 fatty acids	Direct Source	May contain pre-formed TMAO, leading to direct absorption and elevated levels.

Other Dietary Influences on TMAO

The interplay between diet, gut microbiota, and TMAO is complex. Factors beyond supplement type can influence TMAO levels:

Dietary Habits: The composition of the gut microbiota is highly influenced by diet. For example, individuals on plant-based diets often have lower baseline TMAO levels compared to those on omnivorous diets, which contain more TMAO precursors like choline and carnitine from meat and dairy.
Fish and Seafood: Many marine organisms naturally contain high levels of TMAO, which can be directly absorbed by the body upon consumption, bypassing the microbial conversion process.
Individual Variation: Gut microbiome composition and liver enzyme (FMO3) activity vary between individuals, leading to different metabolic responses to the same supplements.

Managing TMAO Levels from Supplements

For those concerned about managing TMAO levels while supplementing, several strategies may be considered:

Choose the right form: If supplementing with choline, opt for phosphatidylcholine instead of choline bitartrate, as research indicates it has a negligible impact on TMAO in healthy individuals.
Consider dietary sources: Prioritize obtaining choline from whole foods like eggs, which, in controlled studies, did not raise TMAO levels like its supplemental counterpart.
Support a healthy gut: A diverse, plant-rich diet containing fiber and polyphenols can help promote a gut microbiome that produces less TMAO. Incorporating prebiotics and some probiotics may also help modulate TMAO production.
Consult a professional: Individuals with existing cardiovascular or renal conditions should consult a healthcare provider before beginning supplementation, as TMAO levels are particularly relevant for these health concerns.

Conclusion

In summary, specific supplements containing choline bitartrate and L-carnitine are recognized for their potential to raise TMAO levels. The critical step in this process is the metabolism by gut bacteria, which converts these precursor nutrients into TMA, which is then converted to TMAO by the liver. The varying impact of different choline forms underscores the need for careful consideration of supplement choice. While the clinical significance of elevated TMAO levels remains an active area of research, particularly concerning its role as a causative agent versus a biomarker, exercising caution with certain supplements is prudent for those concerned about cardiovascular health.(https://pmc.ncbi.nlm.nih.gov/articles/PMC6627560/)

Frequently Asked Questions

TMAO, or trimethylamine N-oxide, is a metabolite produced in the body through a process involving gut bacteria and the liver. It has gained attention because high levels are correlated with an increased risk of cardiovascular disease, leading to concerns about supplements that raise its concentration.

No, the form of choline matters. Studies indicate that while choline bitartrate supplements can significantly raise TMAO, phosphatidylcholine (found in eggs and lecithin) does not cause a substantial increase in healthy individuals.

If you are concerned about elevating TMAO levels, you should consider avoiding supplements that contain choline bitartrate, as this form has been shown to produce a notable increase.

Yes, L-carnitine supplements have been consistently shown to raise plasma TMAO levels, with the conversion process dependent on the individual's gut microbiota.

Betaine can be converted to TMA by gut bacteria, but its contribution to overall TMAO levels seems less significant than that of choline bitartrate or carnitine for most people, though it may depend on individual factors.

The gut microbiome is the key factor. Certain bacteria species, present in some individuals and often linked to omnivorous diets, are responsible for converting TMAO precursor nutrients into TMA, which the liver then turns into TMAO.

Yes, TMAO is naturally present in fish and seafood and may be contained in fish oil or krill oil supplements. This pre-formed TMAO can be directly absorbed into the bloodstream.