Does Choline Cause Inflammation? A Look at the Nuanced Evidence

November 1, 2025 •

4 min read

Research indicates that adequate dietary intake of choline is associated with lower levels of inflammatory markers in healthy adults. However, a complex picture emerges when considering how choline metabolism by gut bacteria can influence inflammatory pathways, raising the question: does choline cause inflammation?

Quick Summary

Choline's effect on inflammation is complex and context-dependent. While adequate intake is linked to reduced inflammation, excess consumption can lead to the production of TMAO by gut microbes, a metabolite associated with inflammatory processes.

Key Points

Normal Choline Intake is Anti-Inflammatory: For healthy adults, consuming adequate amounts of choline has been linked to lower levels of inflammatory markers like C-reactive protein.
TMAO is the Pro-Inflammatory Metabolite: Inflammation associated with high choline intake is primarily due to its gut microbial metabolite, trimethylamine N-oxide (TMAO), not choline itself.
Choline Activation of the Cholinergic Pathway: Choline is a precursor to acetylcholine, which helps regulate and suppress inflammatory responses via the body's nervous system.
Choline Deficiency is Also Inflammatory: In animal studies, a lack of choline has been shown to induce inflammation and weaken the immune system, particularly in the gut.
Context and Microbiome are Key: The impact of choline on inflammation is highly dependent on the individual's gut microbiome and overall dietary habits, emphasizing the need for balanced nutrition.

Choline is an essential nutrient vital for several critical bodily functions, including cell membrane structure, nervous system signaling, and liver function. While the body can produce some choline, it relies heavily on dietary sources such as eggs, meat, and vegetables. The relationship between this vital nutrient and inflammation, however, is not straightforward. The answer to whether choline causes inflammation depends on factors like dosage, overall diet, and individual gut microbiome composition.

The Anti-Inflammatory Role of Adequate Choline

For most people consuming adequate amounts of choline, the nutrient is associated with anti-inflammatory benefits. This is supported by several lines of research:

Lower Inflammatory Markers: The ATTICA study, a cross-sectional survey of healthy adults, found that participants with higher dietary choline and betaine intake had significantly lower concentrations of C-reactive protein, interleukin-6, and tumor necrosis factor-α—all markers of systemic inflammation.
Cholinergic Anti-Inflammatory Pathway: Choline is a precursor for the neurotransmitter acetylcholine (ACh). This pathway, known as the cholinergic anti-inflammatory pathway, involves the vagus nerve and can help regulate and temper the immune system's inflammatory responses. Systemic administration of choline has been shown to reduce TNF-α release from stimulated macrophages.
Modulation of Cytokines: In animal models, choline treatment has been shown to attenuate the increase in pro-inflammatory cytokines like TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10.
Phosphatidylcholine Benefits: Phosphatidylcholine (PC), a key form of choline found in foods, also possesses anti-inflammatory properties. In studies, PC has been shown to suppress inflammatory responses by regulating pathways like NF-κB, which is heavily involved in triggering inflammation. PC supplementation has also been found to ameliorate systemic inflammation and improve gut barrier damage in mice.

The Pro-Inflammatory Link: The TMAO Connection

Some of the confusion surrounding choline and inflammation stems from its metabolism by gut bacteria into the compound trimethylamine N-oxide (TMAO), which is associated with increased inflammation and cardiovascular risk.

The TMAO pathway works as follows:

Dietary Intake: Individuals consume foods rich in choline and other precursors like carnitine.
Microbial Conversion: Certain bacteria in the gut metabolize the choline into trimethylamine (TMA).
Liver Oxidation: TMA is absorbed into the bloodstream and sent to the liver, where it is oxidized into TMAO by enzymes like flavin-containing monooxygenases (FMOs).
Inflammatory Activation: Elevated levels of TMAO are linked to inflammatory pathways in a number of studies, contributing to conditions such as atherosclerosis and other cardiovascular diseases.

It is crucial to emphasize that this pathway is driven by the interaction between the diet and the gut microbiome, not choline alone. Some studies specifically note that TMAO, not choline or TMA, significantly correlated with markers of disease activity in patients.

Context Matters: When High Choline Might Be Problematic

The effect of choline on inflammation is not always consistent and can depend on the presence of specific conditions or pathogens. For instance, an animal study demonstrated that choline supplementation aggravated the inflammatory response to H. pylori infection, likely by altering the composition of the gut microbiota. This shows that in certain pathological states, high levels of choline might have a negative effect. Furthermore, consuming excessive amounts of choline, above the tolerable upper intake level of 3.5 grams per day for adults, can also lead to side effects such as a fishy body odor and diarrhea.

The Impact of Choline Deficiency on Inflammation

On the other end of the spectrum, insufficient choline intake can also induce inflammation. Choline is critical for maintaining cellular integrity and normal function. Animal studies have shown that a choline-deficient diet can depress immunity, induce intestinal inflammation, and impair the gut's physical barrier. This highlights that a balanced, adequate intake is essential for preventing inflammatory responses caused by nutritional imbalances.

Choline vs. TMAO and Inflammation


Aspect	Adequate Dietary Choline	Elevated TMAO from Excess Choline	Choline Deficiency
Effect on Inflammation	Primarily anti-inflammatory.	Pro-inflammatory effect mediated by gut microbes.	Pro-inflammatory, leads to suppressed immunity.
Mechanism	Serves as precursor for acetylcholine, which activates the cholinergic anti-inflammatory pathway.	Gut microbiota convert excess choline to TMA, which is oxidized in the liver to TMAO.	Impairs cell function and disrupts the integrity of mucosal barriers.
Associated Conditions	Associated with lower levels of inflammatory markers like C-reactive protein.	Associated with increased risk of cardiovascular disease and certain inflammatory conditions.	Associated with liver dysfunction, neurodegeneration, and muscle damage.
Context	Standard, balanced dietary intake.	High intake of choline precursors, interacting with specific gut microbiota.	Inadequate nutritional intake, affecting critical metabolic pathways.

Conclusion

Ultimately, does choline cause inflammation? The answer is that it is far more complex than a simple yes or no. For individuals maintaining a healthy, balanced diet, choline and its primary form, phosphatidylcholine, are most often anti-inflammatory and beneficial for overall health. The pro-inflammatory concerns linked to choline are predominantly tied to the gut microbiota's metabolism of excess dietary intake into TMAO, a metabolite that has been associated with heightened inflammation. Maintaining a balanced diet rich in diverse nutrients and fiber can support a healthy gut microbiome, which in turn influences this metabolic pathway positively. Both excessive and deficient choline intake can lead to inflammatory issues, reinforcing the importance of moderation and balance in nutritional strategy.

For more in-depth information, the National Institutes of Health (NIH) provides comprehensive resources on choline and its health effects.

Frequently Asked Questions

Yes, adequate dietary choline is associated with anti-inflammatory effects. It serves as a precursor to acetylcholine, which helps regulate inflammatory responses through the nervous system.

TMAO, or trimethylamine N-oxide, is a metabolite produced when gut bacteria metabolize choline and other compounds. While TMAO has been associated with inflammatory conditions, particularly cardiovascular disease, the link is indirect and depends on a person's gut microbiome.

Yes, reducing TMAO levels can involve dietary changes, such as limiting excessive consumption of choline-rich foods, especially meat. Supporting a healthy and diverse gut microbiome is also important. In some cases, medication or inhibitors of microbial enzymes may also be used to target TMA production.

Choline is found in a wide variety of foods. Excellent sources include liver, eggs, meat, fish, and wheat germ. Other sources are vegetables, nuts, and beans.

The Adequate Intake (AI) for adult males is 550 mg per day, and for adult females, it is 425 mg per day. The AI increases to 450 mg for pregnant women and 550 mg for lactating women.

Choline supplementation in adequate, non-excessive amounts typically does not cause inflammation. However, taking high doses over 3.5 grams daily is not considered safe and may lead to negative side effects. The inflammatory risk is more tied to TMAO production from excessive intake rather than normal supplementation.

A choline deficiency can impair cell function and has been linked to inflammatory responses, particularly in the intestine, and liver dysfunction in both human and animal studies. Adequate intake is necessary to prevent these issues.