[2][3] Choline is used to synthesize acetylcholine, a neurotransmitter involved in muscle control and numerous functions of the nervous system.
[3] Foods rich in choline include meats, poultry, eggs, and other animal-based products, cruciferous vegetables, beans, nuts, and whole grains.
[2] Choline is not formally classified as a vitamin despite being an essential nutrient with an amino acid–like structure and metabolism.
[4] Choline is required to produce acetylcholine – a neurotransmitter – and S-adenosylmethionine (SAM), a universal methyl donor.
[2] Symptomatic choline deficiency causes non-alcoholic fatty liver disease and muscle damage.
[7] The synthesis of choline from ethanolamine may take place in three parallel pathways, where three consecutive N-methylation steps catalyzed by a methyl transferase are carried out on either the free-base,[8] phospho-bases,[9] or phosphatidyl-bases.
[12] In the hepatic PEMT route, 3-phosphoglycerate (3PG) receives 2 acyl groups from acyl-CoA forming a phosphatidic acid.
[6] In humans, certain PEMT-enzyme mutations and estrogen deficiency (often due to menopause) increase the dietary need for choline.
Absorbed choline leaves the enterocytes via the portal vein, passes the liver and enters systemic circulation.
Fat-soluble choline-containing compounds (phosphatidylcholines and sphingomyelins) are either hydrolyzed by phospholipases or enter the lymph incorporated into chylomicrons.
Blood plasma choline levels in healthy fasting adults is 7–20 micromoles per liter (μmol/L) and 10 μmol/L on average.
[13][6] They have high binding affinity for choline, transport it primarily to neurons and are indirectly associated with the acetylcholine production.
[14] CTL1s have moderate affinity for choline and transport it in almost all tissues, including the intestines, liver, kidneys, placenta, and mitochondria.
[4] Choline is a precursor to acetylcholine, a neurotransmitter that plays a necessary role in muscle contraction, memory and neural development.
[6] In the United States, food labels express the amount of choline in a serving as a percentage of Daily Value (%DV) based on the Adequate Intake of 550 mg/day.
Severe deficiency causes muscle damage and non-alcoholic fatty liver disease,[5] which may develop into cirrhosis.
[4] Estrogen production is a relevant factor which predisposes individuals to deficiency along with low dietary choline intake.
Their unavailability leads to the inability of mitochondrial membranes to maintain proper electrochemical gradient, which, among other things, is needed for degrading fatty acids via β-oxidation.
Daily 8–20 g doses of choline, for example, have been found to cause low blood pressure, nausea, diarrhea and fish-like body odor.
Thus, excessive choline intake has been hypothetized to increase these risks in addition to carnitine, which also is formed into TMA and TMAO by gut bacteria.
[28] It is plausible that elevated TMA and TMAO levels are just a symptom of other underlying illnesses or genetic factors that predispose individuals for increased mortality.
[29] Low maternal intake of choline is associated with an increased risk of neural tube defects (NTDs).
[update][2] Choline deficiency can cause fatty liver, which increases cancer and cardiovascular disease risk.
[6] However, observational studies of free populations have not convincingly shown an association between low choline intake and cardiovascular diseases or most cancers.
[32][33] Studies observing the effect between higher choline intake and cognition have been conducted in human adults, with contradictory results.
Choline concentrations in amniotic fluid can be ten times higher than in maternal blood.
[35] Choline is in high demand during pregnancy as a substrate for building cellular membranes (rapid fetal and mother tissue expansion), increased need for one-carbon moieties (a substrate for methylation of DNA and other functions), raising choline stores in fetal and placental tissues, and for increased production of lipoproteins (proteins containing "fat" portions).
[39] During this time, the demand is high for sphingomyelin, which is made from phosphatidylcholine (and thus from choline), because this material is used to myelinate (insulate) nerve fibers.
[40] Choline is also in demand for the production of the neurotransmitter acetylcholine, which can influence the structure and organization of brain regions, neurogenesis, myelination, and synapse formation.
[52][12] In 1850, Theodore Nicolas Gobley extracted from the brains and roe of carps a substance he named lecithin after the Greek word for egg yolk, lekithos, showing in 1874 that it was a mixture of phosphatidylcholines.