Quick Navigation


Choline is a molecule mostly used for either its cognitive boosting properties (turning into acetylcholine, the learning neurotransmitter) or as a liver health agent, able to reduce liver fat. It's found in high amounts in eggs; the yolks in particular.

Our evidence-based analysis on choline features 38 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
Last Updated:

Easily stay on top of the latest nutrition research

Become an Examine Member to get access to all of the latest nutrition research:

  • Unlock information on 400+ supplements and 600+ health topics.
  • Get a monthly report summarizing studies in the health categories that matter specifically to you.
  • Access detailed breakdowns of the most important scientific studies.

Try FREE for 14 days

Research Breakdown on Choline

1Sources and Structure

1.1Biological Significance

Choline is metabolized within a cells mitochondria (via mitochondrial choline oxidase) and then again in the mitochondria by betaine aldehyde dehydrogenase, with this irreversible two-stage process resulting in production of trimethylglycine.[1][2]

2Molecular Targets

2.1Methyl Donation

Choline is known to be oxidized into the metabolite trimethylglycine (TMG) within a cells mitochondria,[1][2] and TMG plays a role in supporting methyl donation processes either directly (methylating homocysteine) or indirectly through supporting bodily production of S-adenosyl methionine (SAMe). Supplemental choline can, vicariously through these two metabolites, confer beneficial properties to whole body methylation.

It has been noted that in subjects with a mutation in the 5-methyltetrahydrofolate reductase (MTHFR) enzyme, the enzyme responsible for producing SAMe from folic acid, that the body seems to place more burden on choline and the betaine homocysteine methyltransferase enzyme. This has been demonstrated in men with the MTHFR C677T genotype (reduced activity) where 300mg, 500mg, or 1,100mg choline was given fro 12 weeks and appeared to improve methylation to a relatively larger degree in those with impaired MTHFR function.[3]



Supplementation of 1,000mg choline (via 2,400mg choline bitartrate) appears to increase steady state plasma choline from 7.33µM to 11.1-11.7µM (51-60%) in otherwise healthy postmenopausal women.[4]



Although there appear to be no differences between youth and elderly in fasting choline concentrations in serum or the response of serum choline to supplementation (50mg/kg choline in the form of choline bitartrate), it appears that the increase in choline containing compounds in the brain in the elderly (19% higher than baseline) was significantly less than that seen in youth (60%).[5]

4.2Cholinergic Neurotransmission

Choline is converted into acetylcholine (ACh) via the enzyme choline acetyltransferase (ChAT).

5Cardiovascular Health


It is known that trimethylamine compounds (choline and trimethylglycine) can be metabolized by intestinal bacteria to form the gas trimethylamine (TMA) which is reminiscient of rotting fish[6] but is absorbed through the colon wall and is metabolized by flavin monooxygenase (FMO3 in particular) to form odourless trimethylamine N-oxide (TMAO).[7][8] When fed to mice when their normal chow diet (0.08-0.09% choline) was enhanced to either 0.5% or 1% choline by weight the higher doses were able to accelerate formation of atherosclerotic lesions; these lesions were highly correlated with serum TMAO and with hepatic FMO3 expression which was higher in female rats (1,000-fold).[9] This study also confirmed that suppression of gastrointestinal flora (with antibiotics) reduced serum TMAO increases from dietary choline and prevented the increase in atherogenesis from choline (which appears to be mediated via TMAO) and that isotopically labelled oral choline products were found to be labelled TMAO; strongly suggesting a direct metabolic conversion.[9] This paper has a few responses which are catered to prescribing possible solutions to the 'problematic' metabolism,[10] commenting on intestinal metabolism,[11] or commenting on the metabolonomic approach.[12]

Preliminary (fairly convincing) that the metabolite of choline known as TMAO can be pro-atherogenic while choline itself does not appear to be pro-atherogenic, although ingestion of choline begets metabolism into TMAO

Production of trimethylamine from supplemental choline (27mM) has been noted in humans up to 18mM with Choline Chloride and 10mM with Choline stearate, but none with Lecithin.[13] Similar lack of effects have been noted with lecithin and betaine elsewhere.[8] A later study, however, did see an increase in TMAO upon phosphatidylcholine challenge conisting of eating two hardboiled eggs along with deuterium-labelled phosphatidylcholine; this increase was ablated when broad-spectrum antibiotics were administered to reduce intestinal microflora, suggesting that TMAO can be produced by intestinal microflora from choline sources.[14] A prospective observational study also linked TMAO blood levels to adverse cardiovascular events, with those in the highest quartile of TMAO levels having a hazard ratio of 2.54 (95% CI 1.96 to 3.28) compared to the highest quartile.[14] 

Dietary choline sources, including lecithin (phosphatidylcholine), may increase serum TMAO in humans, although the evidence is mixed. Higher TMAO levels may lead to increased risk of cardiovascular disease.

6Sexuality and Pregnancy


One study measuring choline intake in mothers and the effects on the offspring noted that consumption of 930mg choline per day (during the 12 weeks of the third trimester) was able to reduce genetic expression of cortisol production in their offspring.[15]

7Peripheral Organ Systems


A deficiency in dietary choline is known to increase hepatic fatty acid (triglyceride) accumulation[16] and impair triglyceride release from the liver into plasma[17] due to reduced phosphatidylcholine (PC) synthesis; PC synthesis promotes vLDL (a lipoprotein) synthesis which effluxes triglycerides from the liver into plasma[18][19] since PC itself is a necessary component of vLDL. This reduced production of PC is mostly due to reduced levels of the choline metabolite Trimethylglycine (TMG), since TMG directly initiates the first state of PC production (methylation via the BHMT enzyme[20]) and by supporting S-adenosyl methionine (SAMe) production it also supports the final synthetic stage (phosphatidylethanolamine N-methyltransferase, which requires SAMe to creatine PC[21]).

A choline deficiency, secondary to creating a deficiency of TMG, is able to reduce or prevent the transport of triglycerides into the blood and to peripheral tissues from the liver (such as adipose or skeletal muscle) resulting in both a state of low blood triglyceride and fatty liver

8Nutrient-Nutrient Interactions

8.1Trimethylglycine (TMG or Betaine)

Trimethylglycine (TMG for short, and also known to incorrectly be referred to as betaine) is a metabolite of choline that occurs in the diet and mediates the methylation properties of choline supplementation.

It appears that supplementation of TMG at the dose of 1,000mg daily has been able to increase steady state concentrations of TMG from 31.4+/-13.6µM to 52.5+/-26.5µM (a 67% increase from baseline levels)[22] whereas supplementation of the same dose of choline (1,000mg of choline via 2,400mg choline bitartrate) was able to increase steady state TMG from a median value of 30.7µM to 54.6-65µM (a 77-111% increase) alongside serum increases in choline itself (from 7.33µM to 11.1-11.7µM).[4] This suggests that, at least at supplemental doses up to 1,000mg, that choline and trimethylglycine are equipotent at increasing serum TMG and methylation.

At least up to the dose of 1,000mg, it seems that TMG and choline are of the same potency in increasing bodily levels of TMG and overall methylation


Trimethylamine (TMA) is a metabolite of many small weight amino acid molecules (such as choline) that is known to have a fishy odour, and urinary levels are usually low enough to be without scent unless the person has abnormally high levels in their urine and body secretions (Trimethylaminuria) which is a condition known as "Fish Odour Syndrome";[23] it is caused by either a mutation in the liver enzyme flavin containing mono-oxygenase type 3 (FMO3[24]) which metabolizes TMA known as 'Primary trimethylaminuria' or from excess production of TMA in the intestinal tract from bacteria known as 'Secondary trimethylaminuria'.[25][26] It is medically benign (ie. not a medical concern), but adherence to supplementation goes down since many subjects would rather not smell like fish and its mild trimethylaminuria could affect anywhere between 1 in 20 or 1 in 100 of persons.[27]

Traditionally speaking, trimethylaminuria has been associated with dietary choline intake[25][28][29] although it may also arise from trimethylglycine supplementation in high levels;[30] in these instances, it appears that 100mg of Riboflavin (Vitamin B2) twice daily has limited evidence (case study) in reducing the scent of fish in those consuming supplementation.[30]

It is possible that riboflavin can reduce the smell of fish that arises from when somebody with a mutation in the FMO3 gene (genetic susceptability to the fishy smell from some of these dietary factors) supplements choline


  1. ^ a b Choline oxidation and choline dehydrogenase.
  2. ^ a b Ueland PM. Choline and betaine in health and disease. J Inherit Metab Dis. (2011)
  3. ^ Yan J et al.. MTHFR C677T genotype influences the isotopic enrichment of one-carbon metabolites in folate-compromised men consuming d9-choline. Am J Clin Nutr. (2011)
  4. ^ a b Wallace JM, et al. Choline supplementation and measures of choline and betaine status: a randomised, controlled trial in postmenopausal women. Br J Nutr. (2012)
  5. ^ Cohen BM, et al. Decreased brain choline uptake in older adults. An in vivo proton magnetic resonance spectroscopy study. JAMA. (1995)
  6. ^ al-Waiz M, et al. The exogenous origin of trimethylamine in the mouse. Metabolism. (1992)
  7. ^ Lang DH, et al. Isoform specificity of trimethylamine N-oxygenation by human flavin-containing monooxygenase (FMO) and P450 enzymes: selective catalysis by FMO3. Biochem Pharmacol. (1998)
  8. ^ a b Zhang AQ, Mitchell SC, Smith RL. Dietary precursors of trimethylamine in man: a pilot study. Food Chem Toxicol. (1999)
  9. ^ a b Wang Z, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. (2011)
  10. ^ Rak K, Rader DJ. Cardiovascular disease: the diet-microbe morbid union. Nature. (2011)
  11. ^ Davidson S. Flagging flora: heart disease link. Nature. (2011)
  12. ^ Mayr M. Recent highlights of metabolomics in cardiovascular research. Circ Cardiovasc Genet. (2011)
  13. ^ Zeisel SH, Wishnok JS, Blusztajn JK. Formation of methylamines from ingested choline and lecithin. J Pharmacol Exp Ther. (1983)
  14. ^ a b Tang WH1, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. (2013)
  15. ^ Jiang X, et al. Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans. FASEB J. (2012)
  16. ^ Bruni C, Hegsted DM. Effects of choline-deficient diets on the rat hepatocyte. Electron microscopic observations. Am J Pathol. (1970)
  17. ^ Lombardi B, Pani P, Schlunk FF. Choline-deficiency fatty liver: impaired release of hepatic triglycerides. J Lipid Res. (1968)
  18. ^ Sowden MP, et al. Apolipoprotein B mRNA and lipoprotein secretion are increased in McArdle RH-7777 cells by expression of betaine-homocysteine S-methyltransferase. Biochem J. (1999)
  19. ^ Yao ZM, Vance DE. The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. J Biol Chem. (1988)
  20. ^ Emmert JL, et al. Hepatic and renal betaine-homocysteine methyltransferase activity in pigs as affected by dietary intakes of sulfur amino acids, choline, and betaine. J Anim Sci. (1998)
  21. ^ Ridgway ND, Vance DE. Kinetic mechanism of phosphatidylethanolamine N-methyltransferase. J Biol Chem. (1988)
  22. ^ Alfthan G, et al. The effect of low doses of betaine on plasma homocysteine in healthy volunteers. Br J Nutr. (2004)
  23. ^ Humbert JA, Hammond KB, Hathaway WE. Trimethylaminuria: the fish-odour syndrome. Lancet. (1970)
  24. ^ Treacy EP, et al. Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication. Hum Mol Genet. (1998)
  25. ^ a b Mitchell SC. The fish-odor syndrome. Perspect Biol Med. (1996)
  26. ^ Fraser-Andrews EA, et al. Fish odour syndrome with features of both primary and secondary trimethylaminuria. Clin Exp Dermatol. (2003)
  27. ^ Zschocke J, et al. Mild trimethylaminuria caused by common variants in FMO3 gene. Lancet. (1999)
  28. ^ Pardini RS, Sapien RE. Trimethylaminuria (fish odor syndrome) related to the choline concentration of infant formula. Pediatr Emerg Care. (2003)
  29. ^ Rehman HU. Fish odor syndrome. Postgrad Med J. (1999)
  30. ^ a b Riboflavin-Responsive Trimethylaminuria in a Patient with Homocystinuria on Betaine Therapy.
  31. Warber JP, et al. The effects of choline supplementation on physical performance. Int J Sport Nutr Exerc Metab. (2000)
  32. Spector SA, et al. Effect of choline supplementation on fatigue in trained cyclists. Med Sci Sports Exerc. (1995)
  33. Deuster PA, et al. Choline ingestion does not modify physical or cognitive performance. Mil Med. (2002)
  34. Harris RC, Söderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond). (1992)
  35. Diet and Refsum's disease. The determination of phytanic acid and phytol in certain foods and the application of this knowledge to the choice of suitable convenience foods for patients with Refsum's disease.
  36. Rawson ES, et al. Creatine supplementation does not improve cognitive function in young adults. Physiol Behav. (2008)
  37. Benton D, Donohoe R. The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. Br J Nutr. (2011)
  38. Phytanic acid: measurement of plasma concentrations by gas–liquid chromatography–mass spectrometry analysis and associations with diet and other plasma fatty acids.