Difference between revisions of "Choline" - New World Encyclopedia

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'''Choline''' is a water-soluble [[organic compound]] that is classified as an [[essential nutrient]] for humans (Higdon and Drake 2008; PDR 2008; Swan and Zeisel 2000). This natural [[amine]] is involved in a number of important functions, including used in the synthesis of phospholipids and other structural components of [[cell membrane]]s, is a precursor for the important [[neurotransmitter]] [[acetylcholine]], and serves as a major source of methyl groups (Higdon and Drake 2008).
+
'''Choline''' is a water-soluble [[organic compound]] that is classified as an [[essential nutrient]] for humans (Higdon and Drake 2008; PDR 2008; Swan and Zeisel 2000). This natural [[amine]] is involved in a number of important functions, including its use in the synthesis of phospholipids and other structural components of [[cell membrane]]s, as a precursor for the important [[neurotransmitter]] [[acetylcholine]], and as a major source of methyl groups (Higdon and Drake 2008).
  
While historically choline had been grouped within the [[Vitamin B]] complex ''(vitamin B<sub>p</sub>)'', it is not technically a [[vitamin]] (Higdon and Drake 2008). Vitamins are organic (carbon-containing) nutrients obtained through the diet and essential in small amounts for normal metabolic reactions. While choline is essential in small amounts for humans, it can be synthesized in the human body from other starting materials, rather than obtained through the diet. However, choline cannot be manufactured at sufficient rates by the body, and thus must be consumed in the diet for optimal health. The Food and Nutrition Board of the Institute of Medicine of the National Academy of Sciences established an Adequate Intake level (AI) of 550 milligrams per day for adult males and 425 milligrams per day for adult females (450 mg/day for pregnant females and 550 mg/day for those breast-feeding) (Higdon and Drake 2008).  
+
While historically choline had been grouped within the [[Vitamin B]] complex ''(vitamin B<sub>p</sub>)'', it is not technically a [[vitamin]] (Higdon and Drake 2008). Vitamins are organic (carbon-containing) nutrients obtained through the diet and essential in small amounts for normal [[metabolism|metabolic]] reactions. While choline is essential in small amounts for humans, it can be synthesized in the [[human body]] from other starting materials, rather than being obtained through the diet. However, choline often cannot be manufactured at sufficient rates to meet the demands of the body, and thus must be consumed in the diet for optimal health. The Food and Nutrition Board of the Institute of Medicine of the National Academy of Sciences established an Adequate Intake level (AI) of 550 milligrams per day for adult males and 425 milligrams per day for adult females (450 mg/day for pregnant females and 550 mg/day for those breast-feeding) (Higdon and Drake 2008).  
  
Although dietary intake is necessary for humans, as an ubiquitous component of cell membranes, choline occurs in all foods, and thus dietary deficiency is rare (Bender and Bender 2005).
+
Although dietary intake often is necessary for humans, choline is a ubiquitous component of cell membranes and common in foods, and thus dietary deficiency is rare (Bender and Bender 2005). Nonetheless, the recognition, through scientific inquiry, of the role of choline has had important implications, from making it an additive in those infant formulas not made with cow's milk to supplementing the mixtures provided intravenously to hospital patients, who otherwise might develop fat accumulation in their livers and death of liver cells (Swan and Zeisel 2004). Too much choline also can have deleterious effects, whether resulting from overuse of supplements or from contributing to a genetic condition that does not allow the choline metabolic product [[trimethylamine]] to be properly broken down (Hidgon and Drake 2008; Swan and Zeisel 2000).
 
   
 
   
 
==Chemistry==
 
==Chemistry==
 
[[Image:Choline_Molecule.png|thumb|right|240px|Choline (C<sub>5</sub>H<sub>14</sub>NO<sup>+</sup>)]]
 
[[Image:Choline_Molecule.png|thumb|right|240px|Choline (C<sub>5</sub>H<sub>14</sub>NO<sup>+</sup>)]]
Choline is a [[quaternary ammonium cation|quaternary]] [[saturation (chemistry)|saturated]] [[amine]] with the [[chemical formula]] ([[methyl|CH<sub>3</sub>]])<sub>3</sub>[[Nitrogen|N]]<sup>+</sup>[[methylene|CH<sub>2</sub>]]CH<sub>2</sub>[[hydroxyl|OH]]X<sup>−</sup>.
+
[[Image:Choline chloride.png|thumb|right|240px|Choline chloride]]
where X<sup>−</sup> is a [[counterion]] such as [[chloride]] (see [[choline chloride]]), [[hydroxyl|hydroxide]] or [[Tartaric acid|tartrate]].
+
[[Image:Cholina.png|thumb|right|240px|Synthesis]]
 +
Choline is a [[quaternary ammonium cation|quaternary]] [[saturation (chemistry)|saturated]] [[amine]] with the [[chemical formula]] C<sub>5</sub>H<sub>14</sub>NO<sup>+</sup>, or
 +
([[methyl|CH<sub>3</sub>]])<sub>3</sub>[[Nitrogen|N]]<sup>+</sup>[[methylene|CH<sub>2</sub>]]CH<sub>2</sub>[[hydroxyl|OH]]X<sup>−</sup>,
 +
where X<sup>−</sup> is a [[counterion]] such as [[chloride]], [[hydroxyl|hydroxide]], or [[Tartaric acid|tartrate]]. (Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair.) Choline is a derivative of the amino acid [[serine]] (Bender and Bender 2005), but is not a protein or amino acid (Swan and Zeisel 2000).  
  
C<sub>5</sub>H<sub>14</sub>NO<sup>+</sup>
+
Choline was discovered by [[Andreas Strecker]] in 1864, and [[chemical synthesis|chemically synthesized]] in 1866. In the human body, it can be manufactured in the [[liver]]. Humans synthesize choline in small amounts by conversion of phosphatidylethanolamine (a phospholipid) to phosphatidylcholine, involving three methylation reactions, each using the compound S-adenosyl methionine (SAM) as a methyl group donor (Higdon and Drake 2008). Phosphatidylcholine can then be metabolized to provide choline.
  
Choline was discovered by Andreas Strecker in 1864 and [[chemical synthesis|chemically synthesized]] in 1866.  
+
Choline is used in the synthesis of phosphatidylcholine, which is also known popularly as [[lecithin]] (although lecithin technically refers to a broader group of substances, one of which is phosphatidylcholine). Lecithin is common in health food stores and the lecithin from peanuts and soya beans is used as an emulsifying agent (Bender and Bender 2005; Swan and Zeisel 2000). [[Choline chloride]], in mixture with [[urea]], is used as a solvent ([[deep eutectic solvent|DES]]) and the [[salicylate]] salt is used topically for pain relief of [[aphthous ulcer]]s.
  
 +
[[Choline hydroxide]] is one of the class of [[phase transfer catalyst]]s, which are used to carry the [[hydroxide]] ion into organic systems. It is far and away the least costly phase transfer catalyst, and gets a lot of use in stripping photoresists in printed circuit board production. Choline hydroxide is not completely stable and it spontaneously, slowly breaks down to release [[trimethylamine]]. It is a strong base.
  
 +
==Dietary requirements and sources==
 +
In 1998, choline was classified as an [[essential nutrient]] by the [[Food and Nutrition Board]] (FNB) of the [[Institute of Medicine]] ([[United States|U.S.]]) (Higdon and Drake 2008). While this board found insufficient scientific evidence to calculate a RDA (Recommended Daily Allowance, now Reference Daily Intake), they did set an Adequate Intake level (AI) (Higdon and Drake 2008). This ranged from 125 milligrams per day for infants 0 to 6 months of age, to 550 milligrams per day for adolescent (14 to 18 years old) and adult males (19 and above) and breastfeeding females (Higdon and Drake 2008). The level for adult females was set at 425 milligrams per day. The FNB also established the tolerable upper intake level (UL) for choline at 3.5 grams per day for adults, based primarily on preventing [[hypotension]] (low blood pressure), as well as the fishy body order when it is broken down by [[bacteria]] in the [[large intestine]], resulting in increased excretion of trimethylamine (Hidgon and Drake 2008; Swan and Zeisel 2000).
  
 +
The foods richest in [[phosphatidylcholine]]&mdash;the major delivery form of choline&mdash;are [[egg yolks]], [[soybean|soy]], and cooked [[beef]], [[chicken]], [[veal]], and [[turkey]] [[liver]]s. Many foods contain trace amounts of free choline, even iceberg [[lettuce]]. To what extent these trace forms are usable by [[absorption (digestive)|human digestion]] is still debated. In 2004, the [[United States Department of Agriculture|USDA]] released its first database of the choline content in common foods (Howe et al. 2004).
  
In 1998 choline was classified as an [[essential nutrient]] by the [[Food and Nutrition Board]] of the [[Institute of Medicine]] ([[United States|U.S.A.]]).
+
The most often available choline [[dietary supplement]] is [[lecithin]], derived from soy or egg yolks, often used as a [[food additive]]. [[Phosphatidylcholine]] (often used synonymously with lecithin, although it is just one of the compounds classified as lecithin) is also available as a supplement, in pill or powder form. Supplementary choline is also available as choline chloride, which comes as a liquid due to its hydrophilic properties. Choline chloride is sometimes preferred as a supplement because phosphatidylcholine can have gastrointestinal side effects.
  
 +
==Function==
 +
[[Image:Choline_metabolism.png|thumb|300px|right|Choline metabolism. (Choline is green box at left, second from the bottom.)]]
 +
Choline and its [[metabolites]] are needed for three main [[physiology|physiological]] purposes: Structural integrity and [[cell signaling|signaling]] roles for cell membranes, cholinergic [[neurotransmission]] ([[acetylcholine]] [[protein biosynthesis|synthesis]]), and as a major source for [[methyl group]]s via its metabolite. Choline also is used for lipid transport and metabolism.
  
[[Choline chloride]], in mixture with [[urea]] is used as a solvent ( [[deep eutectic solvent|DES]] ) and the [[salicylate]] salt is used topically for pain relief of [[aphthous ulcer]]s.
+
Choline is involved in the synthesis of phospholipids ''phosphatidylcholine'' and ''sphingomyelin,'' which are structural components of cell membranes (Higdon and Drake 2008). These two choline-containing phospholipids also are precursors for intracellular messenger molecules (diacyglycerol and ceramide); two other choline metabolites, sphingophosphorylcholine and platelet activating factor (PAF), also are known as cell-signaling molecules (Higdon and Drake 2008).
 
 
C<sub>5</sub>H<sub>14</sub>NO<sup>+</sup>
 
  
==Physiology==
+
Choline is a precursor for synthesis of acetylcholine, which is a key [[neurotransmitter]]. A derivative of both choline and [[acetic acid]], acetylcholine is active both at the synapses between neurons and in the stimulation of muscle cells at the neuromuscular junction, and also stimulates secretion of glands.
[[Image:Choline_metabolism.png|thumb|300px|right|Choline metabolism. (Choline is green box at left, second from the bottom.)]]
 
Choline and its [[metabolites]] are needed for three main [[physiology|physiological]] purposes: structural integrity and [[cell signaling|signaling]] roles for cell membranes, cholinergic [[neurotransmission]] ([[acetylcholine]] [[protein biosynthesis|synthesis]]), and as a major source for [[methyl group]]s via its metabolite, [[trimethylglycine]] (betaine) that participates in the [[S-adenosylmethionine]] synthesis [[metabolic pathway|pathways]].  
 
  
When choline is [[metabolism|metabolized]] by the [[body]], it may form [[trimethylamine]], a compound with a fishy odor. Hence, when large amounts of choline are taken the person may suffer from a fishy [[body odor]].
+
Choline may be oxidized to form [[betaine]], which is a source of methyl groups (a carbon attached to three hydrogen atoms) for [[methylation]] reactions (Higdon and Drake 2008). Betaine ([[trimethylglycine]]) participates in the [[S-adenosylmethionine]] synthesis [[metabolic pathway|pathways]]. The conversion of homocysteine to methionine may utilize methyl groups from betaine, which is important health-wise since elevated levels of homocysteine in the blood is associated with increased risk of [[cardiovascular disease]] (Higdon and Drake 2008).  
  
==Choline as a supplement==
+
Choline also is important for lipid transport and metabolism, with phosphatidylcholine a required component of very low density lipoproteins (VLDL), used for transport of fat and cholesterol through the blood to tissues requiring them (Higdon and Drake 2008). Without sufficient phosphatidylcholine, [[cholesterol]] and [[fat]] accumulate within the liver (Higdon and Drake 2008).
It is well established that supplements of methyl group transfer vitamins [[vitamin B6|B6]], [[vitamin B12|B12]], [[folic acid]] reduce the [[blood]] [[titer]] of [[homocysteine]] and prevent [[cardiovascular disease|heart disease]]. Choline is a necessary source of methyl groups for methyl group transfer. Supplements of [[lecithin]]/choline by Central Soya scientists reduced heart disease in [[clinical trial|laboratory studies]]. The reduction in heart disease with lecithin supplements may however relate more to the [[cholesterol]] carrying capacity of lecithin than to the methyl group transfer role of choline.{{Specify|date=December 2006}}
 
  
Choline supplements are often taken as a form of 'smart drug' or [[nootropic]], due to the role that the neurotransmitter [[acetylcholine]] plays in various [[cognition]] systems within the brain. Choline is a chemical precursor or "building block" needed to produce the neurotransmitter acetylcholine, and research suggests that memory, intelligence and mood are mediated at least in part by acetylcholine metabolism in the brain. The compound's [[quaternary amine]] renders it lipid insoluble which might suggest it would be unable to cross the [[blood-brain barrier]]. However, despite choline's lipid insolubility, a choline transporter exists that allows transport across the blood-brain barrier. The efficacy of these supplements in enhancing cognitive abilities is a topic of continuing debate.
+
==Medical issues==
 +
Choline is a precursor to [[trimethylamine]], a compound with a fishy odor. When choline is [[metabolism|metabolized]] by the [[body]], it may form trimethylamine. Hence, when large amounts of choline are taken, the person may suffer from a fishy [[body odor]]. Furthermore, some persons are not able to break down trimethylamine due to a genetic disorder. Persons suffering from this disorder, called [[trimethylaminuria]], may suffer from a strong fishy or otherwise unpleasant body odor due to the body's release of odorous trimethylamine. A body odor will occur even on a normal diet, in other words, one that is not particularly high in choline. Persons with trimethylaminuria are advised to restrict the intake of foods high in choline; this may help to reduce the sufferer's body odor.
  
Lakhan & Vieira (2008)<ref>Lakhan SE; Vieira KF. [http://www.nutritionj.com/content/7/1/2 Nutritional therapies for mental disorders]. ''Nutrition Journal'' 2008;7(2).</ref> link choline deficiency to bipolar disorder and report efficacy in lecithin supplementation based on a double-blind, placebo controlled trial.
+
Choline, when oxidized to form betaine, is involved in the providing a methyl group for conversion of homocysteine to methionine by the enzyme betaine-homocysteine methyltransferase. Since research evidence indicates that even moderately elevated homosysteine levels in the blood increase the risk of cardiovascular disease, it would seem that dietary choline may be important for decreasing the risk of cardiovascular disease; however, research evidence of such a link is lacking (Higdon and Drake 2008).
  
Some people who practice [[lucid dreaming]] use [[Galantamine]] with choline bitartrate or Alpha GPC to increase their odds of having a lucid dream. Acetylcholine precursors such as choline work synergistically with Galantamine to help improve memory and the symptoms of Alzheimer's Disease (AD).  
+
Lakhan and Vieira (2008) link choline deficiency to [[bipolar disorder]] and report efficacy in lecithin supplementation based on a double-blind, placebo controlled trial.
  
The [[Food and Drug Administration]] (FDA) requires that [[infant formula]] be made from cow's [[milk]] containing choline.<ref>Isadora B. Stehlin, "[http://www.fda.gov/fdac/features/596_baby.html Infant Formula: Second Best but Good Enough]," ''U.S. Food and Drug Administration''.</ref>
+
Choline deficiency in [[rat]]s is correlated with increased incidence of [[liver cancer]] and increased sensitivity to [[carcinogen|carcinogenic]] chemicals (Higdon and Drake 2008). Increased choline dietary intake in rats has been shown to diminish the severity of memory deficits in aged rats (Higdon and Drake 2008).  
  
Due to its role in [[lipid metabolism]], choline has also found its way into nutritional supplements which claim to reduce [[adipose tissue|body fat]]; but there is little or no [[scientific evidence|evidence]] to prove that it has any effect on reducing excess body fat or that taking high amounts of choline will increase the rate at which fat is metabolised.
+
Experiments removing choline from the diet of normal men resulted in [[liver]]s that did not work properly and leaked critical components of the liver into the blood, indicating that liver cells were dying when deprived of choline (Swan and Zeisel 2000).  
  
==Fish odor syndrome==
+
===Choline as a supplement===
{{main|trimethylaminuria}}
+
Choline supplements may be taken for possible prevention of [[cardiovascular disease|heart disease]]. Choline supplements also are taken often as a form of "smart drug" or [[nootropic]], due to the role that the neurotransmitter [[acetylcholine]] plays in various [[cognition]] systems within the brain. Research suggests that memory, intelligence, and mood are mediated at least in part by acetylcholine metabolism in the brain. The choline compound's [[quaternary amine]] renders it lipid insoluble, which might suggest it would be unable to cross the [[blood-brain barrier]]. However, despite choline's lipid insolubility, a choline transporter exists that allows transport across the blood-brain barrier. The efficacy of these supplements in enhancing cognitive abilities is a topic of continuing debate.
Choline is a precursor to [[trimethylamine]], which some persons are not able to break down due to a genetic disorder. Persons suffering from this disorder, called [[trimethylaminuria]], may suffer from a strong fishy or otherwise unpleasant body odor due to the body's release of odorous trimethylamine. A body odor will occur even on a normal diet - ''i.e.'', one that is not particularly high in choline. Persons with trimethylaminuria are advised to restrict the intake of foods high in choline; this may help to reduce the sufferer's body odor.
 
  
==Choline hydroxide ==
+
Some people who practice [[lucid dreaming]] use [[Galantamine]] with choline bitartrate or Alpha GPC to increase their odds of having a lucid dream. Acetylcholine precursors such as choline are believed to work synergistically with Galantamine to help improve memory and the symptoms of [[Alzheimer's Disease]] (AD).  
[[Choline hydroxide]] is one of the class of [[phase transfer catalyst]]s which are used to carry the [[hydroxide]] ion into organic systems. It is far and away the least costly phase transfer catalyst, and gets a lot of use in stripping photoresists in printed circuit board production. Choline hydroxide is not completely stable and it spontaneously, slowly breaks down to release [[trimethylamine]]. It is a strong base.
 
  
==Sources==
+
The [[Food and Drug Administration]] (FDA) requires that [[infant formula]] that is not made with cow's [[milk]] must contain choline (Stehlin 1996).
The foods richest in [[phosphatidylcholine]]—the major delivery form of choline—are [[egg yolks]], [[soybean|soy]] and cooked [[beef]], [[chicken]], [[veal]] and [[turkey]] livers. Many foods contain trace amounts of free choline, even iceberg [[lettuce]]. To what extent these trace forms are usable by [[absorption (digestive)|human digestion]] is still debated. In 2004, the [[United States Department of Agriculture|USDA]] released its first database of the choline content in common foods.<ref>"[http://www.nal.usda.gov/fnic/foodcomp/Data/Choline/Choline.html USDA Database for the Choline Content of Common Foods -  2004]," ''USDA Nutrient Data Laboratory''</ref>
 
  
The most often available choline [[dietary supplement]] is [[lecithin]], derived from soy or egg yolks, often used as a [[food additive]]. [[Phosphatidylcholine]] is also available as a supplement, in pill or powder form. Supplementary choline is also available as choline chloride, which comes as a liquid due to its hydrophilic properties. Choline chloride is sometimes preferred as a supplement because phosphatidylcholine can have gastrointestinal side effects.
+
Due to its role in [[lipid metabolism]], choline has also found its way into nutritional supplements that claim to reduce [[adipose tissue|body fat]]; but there is little or no [[scientific evidence|evidence]] to prove that it has any effect on reducing excess body fat or that taking high amounts of choline will increase the rate at which fat is metabolized.
  
 
==Additional images==
 
==Additional images==
 
<gallery>
 
<gallery>
Image:Choline chloride.png|[[Choline chloride]]
 
 
  Image:Choline hydroxide.png|Choline hydroxide
 
  Image:Choline hydroxide.png|Choline hydroxide
  Image:Cholina.png|Synthesis
+
  </gallery>
</gallery>
 
  
 
==References==
 
==References==
<references/>
+
* Bender, D.A., and A.E. Bender. 2005. ''A Dictionary of Food and Nutrition''. New York: Oxford University Press. ISBN 0198609612.
* Bender, D. A., and A. E. Bender. 2005. ''A Dictionary of Food and Nutrition''. New York: Oxford University Press. ISBN 0198609612.
+
* Higdon, J., and V. J. Drake. 2008. [http://lpi.oregonstate.edu/infocenter/othernuts/choline Micronutrient Research for Optimum Health: Choline.] ''Linus Pauling Institute'' (Oregon State University). Retrieved July 17, 2008.
 
+
* Howe, J.C., J.R. Williams, J. Holden, S.H. Zeisel, and M.-H. Mar. 2005. [http://www.nal.usda.gov/fnic/foodcomp/Data/Choline/Choline.pdf USDA Database for the Choline Content of Common Foods: 2004.] ''U.S. Department of Agriculture, Agricultural Research Service''. Retrieved July 17, 2008.
 
+
* Lakhan, S.E., and K.F. Vieira. 2008. [http://www.nutritionj.com/content/7/1/2 Nutritional therapies for mental disorders.] ''Nutrition Journal'' 7(2). Retrieved July 17, 2008.
* Higdon, J., and V. J. Drake. 2008. [http://lpi.oregonstate.edu/infocenter/othernuts/choline Micronutrient Research for Optimum Health: Choline]. ''Linus Pauling Institute'' (Oregon State University). Retrieved July 17, 2008.
+
* Physicians Desk Reference (PDR). 2008. [http://www.pdrhealth.com/drugs/altmed/altmed-mono.aspx?contentFileName=ame0336.xml&contentName=Choline&contentId=492 Choline.] ''PDRHealth''. Retrieved July 17, 2008.
 
+
* Stehlin, I.B. [http://www.fda.gov/fdac/features/596_baby.html Infant formula: Second best but good enough.] ''U.S. Food and Drug Administration''. Retrieved July 17, 2008.
* Physicians Desk Reference (PDR). 2008. [http://www.pdrhealth.com/drugs/altmed/altmed-mono.aspx?contentFileName=ame0336.xml&contentName=Choline&contentId=492 Choline]. ''PDRHealth''. Retrieved July 17, 2008.
+
* Swan, N., and S. Zeisel. 2000. An Interview with Professor Steven Zeisel, Department of Nutrition, University of North Carolina, School of Public Health. ''Radio National: The Health Report'' April 17, 2000.
 
 
* Swan, N., and S. Zeisel. 2000. [http://www.abc.net.au/rn/talks/8.30/helthrpt/stories/s119524.htm An Interview with Professor Steven Zeisel, Department of Nutrition, University of North Carolina, School of Public Health]. ''Radio National: The Health Report'' April 17, 2000. Retrieved July 17, 2008.
 
  
  

Latest revision as of 23:57, 13 January 2023


Choline
Choline-skeletal.png
IUPAC name (2-Hydroxyethyl)trimethylammonium
Identifiers
CAS number [62-49-7]
PubChem 305
MeSH Choline
SMILES C[N+](C)(C)CCO
Properties
Molecular formula C5H14NO+
Molar mass 104.17 g/mol
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)

Choline is a water-soluble organic compound that is classified as an essential nutrient for humans (Higdon and Drake 2008; PDR 2008; Swan and Zeisel 2000). This natural amine is involved in a number of important functions, including its use in the synthesis of phospholipids and other structural components of cell membranes, as a precursor for the important neurotransmitter acetylcholine, and as a major source of methyl groups (Higdon and Drake 2008).

While historically choline had been grouped within the Vitamin B complex (vitamin Bp), it is not technically a vitamin (Higdon and Drake 2008). Vitamins are organic (carbon-containing) nutrients obtained through the diet and essential in small amounts for normal metabolic reactions. While choline is essential in small amounts for humans, it can be synthesized in the human body from other starting materials, rather than being obtained through the diet. However, choline often cannot be manufactured at sufficient rates to meet the demands of the body, and thus must be consumed in the diet for optimal health. The Food and Nutrition Board of the Institute of Medicine of the National Academy of Sciences established an Adequate Intake level (AI) of 550 milligrams per day for adult males and 425 milligrams per day for adult females (450 mg/day for pregnant females and 550 mg/day for those breast-feeding) (Higdon and Drake 2008).

Although dietary intake often is necessary for humans, choline is a ubiquitous component of cell membranes and common in foods, and thus dietary deficiency is rare (Bender and Bender 2005). Nonetheless, the recognition, through scientific inquiry, of the role of choline has had important implications, from making it an additive in those infant formulas not made with cow's milk to supplementing the mixtures provided intravenously to hospital patients, who otherwise might develop fat accumulation in their livers and death of liver cells (Swan and Zeisel 2004). Too much choline also can have deleterious effects, whether resulting from overuse of supplements or from contributing to a genetic condition that does not allow the choline metabolic product trimethylamine to be properly broken down (Hidgon and Drake 2008; Swan and Zeisel 2000).

Chemistry

Choline (C5H14NO+)
Choline chloride
Synthesis

Choline is a quaternary saturated amine with the chemical formula C5H14NO+, or (CH3)3N+CH2CH2OHX, where X is a counterion such as chloride, hydroxide, or tartrate. (Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair.) Choline is a derivative of the amino acid serine (Bender and Bender 2005), but is not a protein or amino acid (Swan and Zeisel 2000).

Choline was discovered by Andreas Strecker in 1864, and chemically synthesized in 1866. In the human body, it can be manufactured in the liver. Humans synthesize choline in small amounts by conversion of phosphatidylethanolamine (a phospholipid) to phosphatidylcholine, involving three methylation reactions, each using the compound S-adenosyl methionine (SAM) as a methyl group donor (Higdon and Drake 2008). Phosphatidylcholine can then be metabolized to provide choline.

Choline is used in the synthesis of phosphatidylcholine, which is also known popularly as lecithin (although lecithin technically refers to a broader group of substances, one of which is phosphatidylcholine). Lecithin is common in health food stores and the lecithin from peanuts and soya beans is used as an emulsifying agent (Bender and Bender 2005; Swan and Zeisel 2000). Choline chloride, in mixture with urea, is used as a solvent (DES) and the salicylate salt is used topically for pain relief of aphthous ulcers.

Choline hydroxide is one of the class of phase transfer catalysts, which are used to carry the hydroxide ion into organic systems. It is far and away the least costly phase transfer catalyst, and gets a lot of use in stripping photoresists in printed circuit board production. Choline hydroxide is not completely stable and it spontaneously, slowly breaks down to release trimethylamine. It is a strong base.

Dietary requirements and sources

In 1998, choline was classified as an essential nutrient by the Food and Nutrition Board (FNB) of the Institute of Medicine (U.S.) (Higdon and Drake 2008). While this board found insufficient scientific evidence to calculate a RDA (Recommended Daily Allowance, now Reference Daily Intake), they did set an Adequate Intake level (AI) (Higdon and Drake 2008). This ranged from 125 milligrams per day for infants 0 to 6 months of age, to 550 milligrams per day for adolescent (14 to 18 years old) and adult males (19 and above) and breastfeeding females (Higdon and Drake 2008). The level for adult females was set at 425 milligrams per day. The FNB also established the tolerable upper intake level (UL) for choline at 3.5 grams per day for adults, based primarily on preventing hypotension (low blood pressure), as well as the fishy body order when it is broken down by bacteria in the large intestine, resulting in increased excretion of trimethylamine (Hidgon and Drake 2008; Swan and Zeisel 2000).

The foods richest in phosphatidylcholine—the major delivery form of choline—are egg yolks, soy, and cooked beef, chicken, veal, and turkey livers. Many foods contain trace amounts of free choline, even iceberg lettuce. To what extent these trace forms are usable by human digestion is still debated. In 2004, the USDA released its first database of the choline content in common foods (Howe et al. 2004).

The most often available choline dietary supplement is lecithin, derived from soy or egg yolks, often used as a food additive. Phosphatidylcholine (often used synonymously with lecithin, although it is just one of the compounds classified as lecithin) is also available as a supplement, in pill or powder form. Supplementary choline is also available as choline chloride, which comes as a liquid due to its hydrophilic properties. Choline chloride is sometimes preferred as a supplement because phosphatidylcholine can have gastrointestinal side effects.

Function

Choline metabolism. (Choline is green box at left, second from the bottom.)

Choline and its metabolites are needed for three main physiological purposes: Structural integrity and signaling roles for cell membranes, cholinergic neurotransmission (acetylcholine synthesis), and as a major source for methyl groups via its metabolite. Choline also is used for lipid transport and metabolism.

Choline is involved in the synthesis of phospholipids phosphatidylcholine and sphingomyelin, which are structural components of cell membranes (Higdon and Drake 2008). These two choline-containing phospholipids also are precursors for intracellular messenger molecules (diacyglycerol and ceramide); two other choline metabolites, sphingophosphorylcholine and platelet activating factor (PAF), also are known as cell-signaling molecules (Higdon and Drake 2008).

Choline is a precursor for synthesis of acetylcholine, which is a key neurotransmitter. A derivative of both choline and acetic acid, acetylcholine is active both at the synapses between neurons and in the stimulation of muscle cells at the neuromuscular junction, and also stimulates secretion of glands.

Choline may be oxidized to form betaine, which is a source of methyl groups (a carbon attached to three hydrogen atoms) for methylation reactions (Higdon and Drake 2008). Betaine (trimethylglycine) participates in the S-adenosylmethionine synthesis pathways. The conversion of homocysteine to methionine may utilize methyl groups from betaine, which is important health-wise since elevated levels of homocysteine in the blood is associated with increased risk of cardiovascular disease (Higdon and Drake 2008).

Choline also is important for lipid transport and metabolism, with phosphatidylcholine a required component of very low density lipoproteins (VLDL), used for transport of fat and cholesterol through the blood to tissues requiring them (Higdon and Drake 2008). Without sufficient phosphatidylcholine, cholesterol and fat accumulate within the liver (Higdon and Drake 2008).

Medical issues

Choline is a precursor to trimethylamine, a compound with a fishy odor. When choline is metabolized by the body, it may form trimethylamine. Hence, when large amounts of choline are taken, the person may suffer from a fishy body odor. Furthermore, some persons are not able to break down trimethylamine due to a genetic disorder. Persons suffering from this disorder, called trimethylaminuria, may suffer from a strong fishy or otherwise unpleasant body odor due to the body's release of odorous trimethylamine. A body odor will occur even on a normal diet, in other words, one that is not particularly high in choline. Persons with trimethylaminuria are advised to restrict the intake of foods high in choline; this may help to reduce the sufferer's body odor.

Choline, when oxidized to form betaine, is involved in the providing a methyl group for conversion of homocysteine to methionine by the enzyme betaine-homocysteine methyltransferase. Since research evidence indicates that even moderately elevated homosysteine levels in the blood increase the risk of cardiovascular disease, it would seem that dietary choline may be important for decreasing the risk of cardiovascular disease; however, research evidence of such a link is lacking (Higdon and Drake 2008).

Lakhan and Vieira (2008) link choline deficiency to bipolar disorder and report efficacy in lecithin supplementation based on a double-blind, placebo controlled trial.

Choline deficiency in rats is correlated with increased incidence of liver cancer and increased sensitivity to carcinogenic chemicals (Higdon and Drake 2008). Increased choline dietary intake in rats has been shown to diminish the severity of memory deficits in aged rats (Higdon and Drake 2008).

Experiments removing choline from the diet of normal men resulted in livers that did not work properly and leaked critical components of the liver into the blood, indicating that liver cells were dying when deprived of choline (Swan and Zeisel 2000).

Choline as a supplement

Choline supplements may be taken for possible prevention of heart disease. Choline supplements also are taken often as a form of "smart drug" or nootropic, due to the role that the neurotransmitter acetylcholine plays in various cognition systems within the brain. Research suggests that memory, intelligence, and mood are mediated at least in part by acetylcholine metabolism in the brain. The choline compound's quaternary amine renders it lipid insoluble, which might suggest it would be unable to cross the blood-brain barrier. However, despite choline's lipid insolubility, a choline transporter exists that allows transport across the blood-brain barrier. The efficacy of these supplements in enhancing cognitive abilities is a topic of continuing debate.

Some people who practice lucid dreaming use Galantamine with choline bitartrate or Alpha GPC to increase their odds of having a lucid dream. Acetylcholine precursors such as choline are believed to work synergistically with Galantamine to help improve memory and the symptoms of Alzheimer's Disease (AD).

The Food and Drug Administration (FDA) requires that infant formula that is not made with cow's milk must contain choline (Stehlin 1996).

Due to its role in lipid metabolism, choline has also found its way into nutritional supplements that claim to reduce body fat; but there is little or no evidence to prove that it has any effect on reducing excess body fat or that taking high amounts of choline will increase the rate at which fat is metabolized.

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Vitamins
All B vitamins | All D vitamins
Retinol (A) | Thiamine (B1) | Riboflavin (B2) | Niacin (B3) | Pantothenic acid (B5) | Pyridoxine (B6) | Biotin (B7) | Folic acid (B9) | Cyanocobalamin (B12) | Ascorbic acid (C) | Ergocalciferol (D2) | Cholecalciferol (D3) | Tocopherol (E) | Naphthoquinone (K)

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