TMAO Cancer Research Results

TMAO, Trimethylamine-N-oxide: Click to Expand ⟱
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Trimethylamine-N-oxide (TMAO) is a gut microbiota–derived metabolite produced from dietary precursors such as choline, phosphatidylcholine, and carnitine. In cancer, the current literature points to TMAO as generally pro-tumorigenic in several solid-tumor settings, especially colorectal cancer, hepatocellular carcinoma, and possibly prostate cancer, where it has been linked to higher proliferation, migration, angiogenesis, EMT, and inflammatory signaling. Mechanistically, reported pathways include VEGFA-driven angiogenesis, PI3K/AKT, MAPK, oxidative/inflammatory stress, and metabolic reprogramming. However, the picture is not uniformly one-directional: in some immune-competent models, particularly triple-negative breast cancer and pancreatic cancer, TMAO has been reported to enhance antitumor immunity and improve response to checkpoint blockade. So the fairest summary is that TMAO is usually associated with cancer-promoting biology in tumor-cell–centric studies, but can be context-dependent when the immune microenvironment is considered

higher TMAO has been linked to several AD-relevant axes: neuroinflammation, vascular dysfunction, BBB/glymphatic impairment, oxidative stress, and amyloid/tau-associated pathology.


-high concentrations of polyphenols (e.g., resveratrol, catechins, quercetin, and quercetin-3-O-glucoside), which act synergistically to protect various target organs from elevated TMAO levels
-clinical studies demonstrated that high-dose atorvastatin (80 mg) or the combination of atorvastatin/ezetimibe or rosuvastatin can significantly reduce TMAO levels, likely due to their direct action on the TMAO-producing gut flora
-Gut dysbiosis → TMA/TMAO production

-Increase plant-forward foods and fiber to shift gut microbiota away from high TMA production.
-TMAO is cleared renally and rises with kidney impairment.
-Sunflower lecithin ≈ 3–5% choline by weight

Dietary choline intake ∼ 350 mg/d was associated with the lowest risk of clinical diagnosis of AD in older adults.
Health Canada Adequate level is 550mg/day for men and 425mg/day for females.

| Source                 | Typical serving | Choline/serving | Main choline form   | TMAO relevance                            |
| ---------------------- | --------------: | --------------: | ------------------- | ------------------------------------------ |
| Egg yolk               |    1 large yolk |     ~125–150 mg | Phosphatidylcholine | High                                       |
| Whole egg              |         1 large |     ~145–150 mg | Phosphatidylcholine | High                                       |
| Beef liver             |            3 oz |        ~350+ mg | Mixed choline forms | High                                       |
| Chicken liver          |            3 oz |     ~240–290 mg | Mixed               | High                                       |
| Salmon                 |            3 oz |       ~70–90 mg | Mixed               | Moderate; fish also contains TMAO directly |
| Beef                   |            3 oz |      ~70–110 mg | Choline + carnitine | High TMAO relevance                        |
| Chicken breast         |            3 oz |       ~60–75 mg | Mixed               | Moderate                                   |
| Soy lecithin           | 1 tbsp, ~7–10 g |     ~200–500 mg | Phosphatidylcholine | Moderate–high, depends on dose             |
| Sunflower lecithin     | 1 tbsp, ~7–10 g |     ~200–500 mg | Phosphatidylcholine | Moderate–high, depends on dose             |
| Egg lecithin           | 1 tbsp, ~7–10 g |     ~400–900 mg | Phosphatidylcholine | High                                       |
| High-PC lecithin       |          1 g PC | ~130 mg choline | Phosphatidylcholine | High if taken daily                        |
| Soybeans, cooked       |           ½ cup |         ~100 mg | Mixed               | Moderate                                   |
| Wheat germ             |           ¼ cup |          ~50 mg | Mixed               | Low–moderate                               |
| Milk                   |           1 cup |       ~35–45 mg | Mixed               | Low–moderate                               |
| Broccoli / cauliflower |    1 cup cooked |       ~30–60 mg | Mixed               | Low                                        |
| Potato                 |        1 medium |       ~25–45 mg | Mixed               | Low                                        |


Scientific Papers found: Click to Expand⟱
6107- Chol,    Choline supplements: An update
- Review, AD, NA
*memory↑, Extensively used as food supplements, they have been shown to represent an effective strategy for boosting memory and enhancing cognitive function. Numerous clinical reports suggest that GPC can improve memory and attention in patients with Alzheimer
*cognitive↑,
*Dose↝, GPC is considered one of the most used sources of choline due to its high choline content (41% of choline by weight) and its ability to cross the blood-brain barrier.
*BBB↑,
*cardioP↑, Choline plays a protective role in the heart and may be a promising candidate to improve doxorubicin-induced cardiotoxicity via vagal activity and Nrf2/HO-1 pathway
*ROS↓, by inhibiting the ROS-mediated Ca2+/calmodulin-dependent protein kinase II pathway
*TMAO↑, In contrast, a choline‐ or carnitine‐rich diet was reported to promote atherosclerosis in mice as it increased the formation of TMAO produced by gut microbiota-related metabolite of choline
*memory∅, Choline supplements in the form of lecithin and choline chloride did not significantly improve memory performance in humans although some papers have reported positive outcomes in cognitive function of animal models
*eff↑, However, other choline supplements such as citicoline, choline bitartrate, and GPC appear to be very promising in the treatment of elderly patients suffering from dementia (49, 52, 54, 157, 158).

6108- Chol,    Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health
- Review, Nor, NA - Review, AD, NA
*TMAO↑, The gut microbiota’s role in metabolizing phytoestrogens suggests that these compounds can modulate the microbial community structure, potentially affecting the production of TMAO from dietary choline and carnitine [5].
*ROS↑, TMAO has the ability to induce oxidative stress in cells by promoting the production of reactive oxygen species (ROS).
*NADPH↑, TMAO has been shown to increase the activity of NADPH oxidase [30], an enzyme that generates ROS as part of its normal function.
*Ca+2↑, TMAO enters platelets and facilitates the release of calcium ions (Ca2+) from intracellular stores.
*AntiAg↓, Calcium serves as a critical secondary messenger in platelet activation, and its elevated levels promote platelet aggregation and thrombus formation
*cognitive↓, TMAO has been linked to cognitive decline and neurodegenerative disorders, including Alzheimer’s disease (AD). Through an integrated analysis of genetic, epigenetic, pathological, and biochemical data, Xu et al. identified a correlation between gut m
*TJ↓, However, excessive TMAO concentrations disrupt BBB integrity by inhibiting tight junction proteins, including claudin-5 and zonula occludens-1
*CLDN1↓,
*ZO-1↓,
*Inflam↑, TMAO also triggers neuroinflammation by activating the NLRP3 inflammasome,
*NLRP3↑,
*ER Stress↑, TMAO enhances the ER stress response by activating the PERK-eIF2α pathway, which is known to impair synaptic plasticity and neuronal function, processes strongly implicated in AD progression
*cognitive↓, TMAO has been identified as the most predictive biomarker for memory impairment and cognitive decline among 56 microbiota-derived metabolic markers
*Dose↝, use of cooking methods such as boiling or stewing instead of grilling, which can produce higher amounts of TMAO
*eff↑, Studies suggest that Lactobacillus plantarum ZDY04 could help reduce TMAO concentrations and prevent TMAO-induced atherosclerosis in animal models
*other↝, Currently, no medications specifically designed to reduce blood TMAO levels exist
*other↝, a review published in 2025 has highlighted the potential role of statins in lowering TMAO levels independently of their cholesterol-lowering effects
*other↝, scientific evidence suggests that statins selectively inhibit the growth of pathogenic bacteria, such as Clostridium and Ruminococcus, while promoting beneficial species, such as Bifidobacterium and Lactobacillus

6111- Chol,    The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease
- Human, AD, NA
*Risk↑, CSF TMAO is higher in individuals with MCI and AD dementia compared to cognitively-unimpaired individuals, and elevated CSF TMAO is associated with biomarkers of AD pathology (phosphorylated tau and phosphorylated tau/Aβ42)
*TMAO↑, First, gut microbes enzymatically generate trimethylamine (TMA) from dietary constituents such as choline or l-carnitine [9]
*Dose↝, long-term dietary habits can influence TMAO accumulation via changes in gut microbiota composition, which modulates TMA production potential.
*eff↑, In this scenario, pharmacological agents designed to inhibit gut microbial TMAO production may be useful in slowing AD pathology

6112- Chol,    Trimethylamine N-oxide induced cognitive impairment through disruption of blood-brain barrier by inhibiting TGF-β pathway
- in-vivo, AD, NA
*TMAO↑, (HFD) promotes cardiovascular disease, in part because it is rich in quaternary amines such as choline, carnitine, and lecithin, which are converted to trimethylamine (TMA) by the gut microbes and increase levels of circulating TMAO
*cognitive↓, TMAO induces cognitive impairment via disrupting the BBB. TMAO treatment induced cognitive impairment and disrupted the BBB integrity in mice
*BBB↝, TMAO has been reported to regulate blood-brain barrier (BBB) integrity and suppress the expression of tight junction proteins (TJs) in the microvasculature.
*TJ↝,

6101- Chol,    Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men
- Human, Nor, NA
*TMAO↑, Choline serves as a dietary precursor for the gut microbial-generated trimethylamine (TMA) that is subsequently oxidized by the hepatic enzyme flavin-containing monooxygenase 3 (FMO3) to form (TMAO), a newly recognized risk marker for cardiovascular
*Dose↝, study meals consisted of 1 cup (237 mL) of tomato soup containing different forms of choline and provided approximately 600 mg of choline as choline bitartrate or phosphatidylcholine, compared to no choline control.
*GutMicro↝, We demonstrate for the first time that heightened TMAO response to choline bitartrate intake may largely be attributed to abundant lineages of Clostridium (in phylum Firmicutes) and may provide guidance to personalized therapeutic strategies in reduc


Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


NA, unassigned

TMAO↑, 5,  

Redox & Oxidative Stress

ROS↓, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis

NADPH↑, 1,  

Transcription & Epigenetics

other↝, 3,  

Protein Folding & ER Stress

ER Stress↑, 1,  

Migration

AntiAg↓, 1,   Ca+2↑, 1,   CLDN1↓, 1,   TJ↓, 1,   TJ↝, 1,   ZO-1↓, 1,  

Barriers & Transport

BBB↑, 1,   BBB↝, 1,  

Immune & Inflammatory Signaling

Inflam↑, 1,  

Protein Aggregation

NLRP3↑, 1,  

Drug Metabolism & Resistance

Dose↝, 4,   eff↑, 3,  

Clinical Biomarkers

GutMicro↝, 1,  

Functional Outcomes

cardioP↑, 1,   cognitive↓, 3,   cognitive↑, 1,   memory↑, 1,   memory∅, 1,   Risk↑, 1,  
Total Targets: 25

Scientific Paper Hit Count for: TMAO, Trimethylamine-N-oxide
5 Choline
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:1468  State#:%  Dir#:2
wNotes=on sortOrder:rid,rpid

 

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