Choline  is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). To maintain health, it must be obtained from the diet as choline or as choline phospholipids, like phosphatidylcholine. Humans, as well as most other animal species, do make choline de novo; however, production is generally insufficient. Choline is often not classified as a vitamin, but as a nutrient with an amino acid–like metabolism. In most animals, choline phospholipids are necessary components in cell membranes, in the membranes of cell organelles, and in very low-density lipoproteins. Choline is required to produce acetylcholine – a neurotransmitter – and S-adenosylmethionine (SAM), a universal methyl donor. Upon methylation SAM is transformed into homocysteine. Symptomatic choline deficiency – rare in humans – causes nonalcoholic fatty liver disease and muscle damage. Excessive consumption of choline (greater than 7.5 g/day) can cause low blood pressure, sweating, diarrhea and fish-like body odor due to trimethylamine, which forms in its metabolism. Rich dietary sources of choline and choline phospholipids include organ meats and egg yolks, dairy products, peanuts, certain beans, nuts, seeds and vegetables with pasta and rice also contributing to choline intake in the American diet. Chemistry
The cholines are a family of water-soluble quaternary ammonium compounds. Choline is the parent compound of the cholines class, consisting of ethanolamine having three methyl substituents attached to the amino function. Choline hydroxide is known as choline base.
Daily 8–20 g doses of choline, for example, have been found to cause low blood pressure, nausea, diarrhea and fish-like body odor. The odor is due to trimethylamine (TMA) formed by the gut microbes from the unabsorbed choline (see trimethylaminuria).The liver oxidizes TMA to trimethylamine N-oxide (TMAO). Elevated levels of TMA and TMAO in the body have been linked to increased risk of atherosclerosis and mortality. 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. However, choline intake has not been shown to increase the risk of dying from cardiovascular diseases. 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. Such factors may have not been properly accounted for in certain studies observing TMA and TMAO level related mortality. Causality may be reverse or confounding and large choline intake might not increase mortality in humans. For example, kidney dysfunction predisposes for cardiovascular diseases, but can also decrease TMA and TMAO excretion. Health effects
Neural tube closure
Some human studies showed low maternal intake of choline to significantly increase the risk of neural tube defects (NTDs) in newborns. Folate deficiency also causes NTDs. Choline and folate, interacting with vitamin B12, act as methyl donors to homocysteine to form methionine, which can then go on to form SAM (S-adenosylmethionine). SAM is the substrate for almost all methylation reactions in mammals.