Choline
Overview
Choline is a water-soluble essential nutrient
Essential nutrient
An essential nutrient is a nutrient required for normal body functioning that either cannot be synthesized by the body at all, or cannot be synthesized in amounts adequate for good health , and thus must be obtained from a dietary source...

. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation.

The cation appears in the head groups of phosphatidylcholine
Phosphatidylcholine
Phosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup.They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically...

 and sphingomyelin
Sphingomyelin
Sphingomyelin is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphorylcholine and ceramide...

, two classes of phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

 that are abundant in cell membranes. Choline is the precursor molecule for the neurotransmitter acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 which is involved in many functions including memory and muscle control.

Choline must be consumed through the diet in order for the body to remain healthy.
Discussions
Encyclopedia
Choline is a water-soluble essential nutrient
Essential nutrient
An essential nutrient is a nutrient required for normal body functioning that either cannot be synthesized by the body at all, or cannot be synthesized in amounts adequate for good health , and thus must be obtained from a dietary source...

. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation.

The cation appears in the head groups of phosphatidylcholine
Phosphatidylcholine
Phosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup.They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically...

 and sphingomyelin
Sphingomyelin
Sphingomyelin is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphorylcholine and ceramide...

, two classes of phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

 that are abundant in cell membranes. Choline is the precursor molecule for the neurotransmitter acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 which is involved in many functions including memory and muscle control.

Choline must be consumed through the diet in order for the body to remain healthy. It is used in the synthesis of the constructional components in the body's cell membranes. Unfortunately, dietary recommendations have discouraged people from eating high choline foods, such as egg and fatty meats. The 2005 National Health and Nutrition Examination Survey stated that only 2% of postmenopausal women consume the recommended intake for choline.

History

Choline was discovered by Adolph Strecker
Adolph Strecker
Adolph Strecker was a German chemist who is remembered primarily for his work with amino acids.- Life and work :...

 in 1864 and chemically synthesized
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...

 in 1866. In 1998 choline was classified as an essential nutrient
Essential nutrient
An essential nutrient is a nutrient required for normal body functioning that either cannot be synthesized by the body at all, or cannot be synthesized in amounts adequate for good health , and thus must be obtained from a dietary source...

 by the Food and Nutrition Board of the Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...

 (U.S.A.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

).

Choline's importance as a nutrient was first appreciated in the early research on insulin functions when choline was found to be the necessary nutrient in preventing fatty liver.
In 1975 scientists discovered that the administration of choline increased the synthesis and release of acetylcholine by neurons. These discoveries lead to the increased interest in dietary choline and brain function.
Today, we know Choline to be a dietary nutrient important for all cells to function normally. We have come to learn that humans require choline in their diet in order to sustain normal life. Choline is required for synthesis of essential components of membranes and is an important source of labile methyl groups.

Recent Research

A recent study in Nov 2010 by Leslie M. Fischer, Kerry Ann da Costa, Lester Kwock, Joseph Galanko, and Steven Zeisel was to test postmenopausal women with low estrogen levels and see if they were more susceptible to the risk of organ dysfunction if not given a sufficient choline filled diet. When deprived of choline in their diet almost 80% of the men and postmenopausal women developed liver or muscle damage. The study also found that young women can supply more choline because pregnancy is a time when the body's demand for choline are highest. Choline is particularly used to support the fetus's developing nervous system.

Chemistry

Choline is a quaternary
Quaternary ammonium cation
Quaternary ammonium cations, also known as quats, are positively charged polyatomic ions of the structure NR4+, R being an alkyl group or an aryl group. Unlike the ammonium ion and the primary, secondary, or tertiary ammonium cations, the quaternary ammonium cations are permanently charged,...

 saturated
Saturation (chemistry)
In chemistry, saturation has six different meanings, all based on reaching a maximum capacity...

 amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...

 with the chemical formula
Chemical formula
A chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....

 (CH3)3N
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...

+CH2CH2OH
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...

X,
where X is a counterion
Counterion
A counterion is the ion that accompanies an ionic species in order to maintain electric neutrality. In table salt the sodium cation is the counterion for the chlorine anion and vice versa.In a charged transition metal complex, a simple A counterion is the ion that accompanies an ionic species in...

 such as chloride
Chloride
The chloride ion is formed when the element chlorine, a halogen, picks up one electron to form an anion Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. The chloride ion, and its salts such as sodium chloride, are very soluble in water...

 (see choline chloride
Choline chloride
Choline chloride is an organic compound and a quaternary ammonium salt. It has a choline cation with chloride anion. Alternative names are hepacholine, biocolina and lipotril.-Synthesis:...

), hydroxide
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...

 or tartrate
Tartaric acid
Tartaric acid is a white crystalline diprotic organic acid. It occurs naturally in many plants, particularly grapes, bananas, and tamarinds; is commonly combined with baking soda to function as a leavening agent in recipes, and is one of the main acids found in wine. It is added to other foods to...

. Choline chloride
Choline chloride
Choline chloride is an organic compound and a quaternary ammonium salt. It has a choline cation with chloride anion. Alternative names are hepacholine, biocolina and lipotril.-Synthesis:...

 can form a low-melting deep eutectic solvent
Deep eutectic solvent
A deep eutectic solvent or DES is a type of ionic solvent with special properties composed of a mixture which forms a eutectic with a melting point much lower than either of the individual components. The first generation eutectic solvents were based on mixtures of quaternary ammonium salts with...

 mixture with urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....

 with unusual properties. The salicylate salt is used topically for pain relief of aphthous ulcer
Aphthous ulcer
An aphthous ulcer , also known as a canker sore, is a type of mouth ulcer which presents as a painful open sore inside the mouth or upper throat characterized by a break in the mucous membrane. Its cause is unknown, but they are not contagious...

s.

Choline hydroxide

Choline hydroxide is one of the class of phase transfer catalyst
Phase transfer catalyst
In chemistry, a phase transfer catalyst or PTC is a catalyst that facilitates the migration of a reactant from one phase into another phase where reaction occurs. Phase transfer catalysis is a special form of heterogeneous catalysis. Ionic reactants are often soluble in an aqueous phase but...

s that are used to carry the hydroxide
Hydroxide
Hydroxide is a diatomic anion with chemical formula OH−. It consists of an oxygen and a hydrogen atom held together by a covalent bond, and carrying a negative electric charge. It is an important but usually minor constituent of water. It functions as a base, as a ligand, a nucleophile, and a...

 ion into organic systems, and, therefore, is considered a strong base
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...

. It is the least costly phase transfer catalyst, and is used as a cheap method of stripping photoresist
Photoresist
A photoresist is a light-sensitive material used in several industrial processes, such as photolithography and photoengraving to form a patterned coating on a surface.-Tone:Photoresists are classified into two groups: positive resists and negative resists....

s in circuit boards. Choline hydroxide is not completely stable, and it slowly breaks down into trimethylamine
Trimethylamine
Trimethylamine is an organic compound with the formula N3. This colorless, hygroscopic, and flammable tertiary amine has a strong "fishy" odor in low concentrations and an ammonia-like odor at higher concentrations...

.

Physiology

Choline and its metabolites are needed for three main physiological
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...

 purposes: structural integrity and signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...

 roles for cell membranes, cholinergic neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...

 (acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 synthesis
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...

), and a major source for methyl group
Methyl group
Methyl group is a functional group derived from methane, containing one carbon atom bonded to three hydrogen atoms —CH3. The group is often abbreviated Me. Such hydrocarbon groups occur in many organic compounds. The methyl group can be found in three forms: anion, cation and radical. The anion...

s via its metabolite, trimethylglycine
Trimethylglycine
Trimethylglycine is an organic compound that occurs in plants as either glycine betaine or a choline-containing glycine betaine compound. Trimethylglycine was the first betaine discovered by science; originally it was simply called betaine because, in the 19th century, it was discovered in sugar...

 (betaine) which participates in the S-adenosylmethionine (SAMe) synthesis pathways
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...

.

Choline Deficiency signs

Most common signs of choline deficiencies are fatty liver and hemorrhagic kidney necrosis. Dietary intake of a choline full diet can reduce the severity of the deficiency. A study of this on animals has created some controversy due to the inconsistency in dietary modifying factors.
Choline deficiency in animals compromises renal function. Choline low diets can also cause infertility, growth impairment, bone abnormalities, and hypertension. Choline deficiency is considered to both initiate and promote cancer activities.

Required choline levels in diet were determined by feeding healthy humans a choline-deficient diet until they developed biochemical changes consistent with choline deficiency.

Fish odor syndrome

Choline is a precursor
Precursor (chemistry)
In chemistry, a precursor is a compound that participates in the chemical reaction that produces another compound. In biochemistry, the term "precursor" is used more specifically to refer to a chemical compound preceding another in a metabolic pathway....

 to trimethylamine
Trimethylamine
Trimethylamine is an organic compound with the formula N3. This colorless, hygroscopic, and flammable tertiary amine has a strong "fishy" odor in low concentrations and an ammonia-like odor at higher concentrations...

, which some persons are not able to break down due to a genetic disorder called trimethylaminuria
Trimethylaminuria
Trimethylaminuria , also known as fish odor syndrome or fish malodor syndrome, is a rare metabolic disorder that causes a defect in the normal production of the enzyme Flavin containing monooxygenase 3...

. Persons suffering from this disorder may suffer from a strong fishy or otherwise unpleasant body odor
Body odor
Body odor or body odour, sometimes colloquially abbreviated as B.O., is the smell of bacteria growing on the body. The bacteria multiply rapidly in the presence of sweat, but sweat itself is almost completely odorless to humans....

, 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.

Groups at risk for choline deficiency

Vegetarians, vegans, endurance athletes, and people who drink a lot of alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

 may be at risk for choline deficiency
Deficiency
A deficiency is generally a lack of something. It may also refer to:*A deficient number, in mathematics, a number n for which σ A deficiency is generally a lack of something. It may also refer to:...

 and may benefit from choline supplements.

In general, people who do not eat many whole eggs may have to pay close attention to get enough choline in their diets. Studies on a number of different populations have found that the average intake of choline was below the Adequate Intake (AI).

The choline researcher Dr. Steven Zeisel
Steven Zeisel
Steven H. Zeisel, M.D., PhD is a Kenan Distinguished University Professor in Nutrition and Pediatrics; former Chairman, Department of Nutrition; Director Nutrition Research Institute, Director UNC Human Clinical Nutrition Research Center, Director UNC Center for Excellence in Children’s Nutrition,...

 wrote: "A recent analysis of data from NHANES
National Health and Nutrition Examination Survey
The National Health and Nutrition Examination Survey is a survey research program conducted by the National Center for Health Statistics to asses the health and nutritional status of adults and children in the United States, and to track changes over time. The survey combines interviews and...

 2003–2004 revealed that for [American] older children, men, women and pregnant women, mean
Mean
In statistics, mean has two related meanings:* the arithmetic mean .* the expected value of a random variable, which is also called the population mean....

 choline intakes are far below the AI. Ten percent or fewer had usual choline intakes at or above the AI."

Food sources of choline

The Adequate Intake
Dietary Reference Intake
The Dietary Reference Intake is a system of nutrition recommendations from the Institute of Medicine of the U.S. National Academy of Sciences. The DRI system is used by both the United States and Canada and is intended for the general public and health professionals...

 (AI) of choline is 425 mg (milligrams) per day for adult women; higher for pregnant and breastfeeding
Breastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...

 women. The AI for adult men is 550 mg/day. There are also AIs for children and teens.

Animal and plant foods Choline (mg) Calories
5 ounces (142 g) raw beef liver
Liver (food)
The liver of mammals, fowl, and fish are commonly eaten as food by humans. Domestic pig, ox, lamb, calf, chicken, and goose livers are widely available from butchers and supermarkets....

 
473  192 Entry for "Beef, variety meats and by-products, liver, raw"
in the USDA Nutrients database

Large hardboiled egg
Egg (food)
Eggs are laid by females of many different species, including birds, reptiles, amphibians, and fish, and have probably been eaten by mankind for millennia. Bird and reptile eggs consist of a protective eggshell, albumen , and vitellus , contained within various thin membranes...

 
113  78 Entry for one large "Egg, whole, cooked, hard-boiled"
in the USDA Nutrients database

Half a pound (227 g) cod
Cod
Cod is the common name for genus Gadus, belonging to the family Gadidae, and is also used in the common name for various other fishes. Cod is a popular food with a mild flavor, low fat content and a dense, flaky white flesh. Cod livers are processed to make cod liver oil, an important source of...

 fish
190  238 Entry for "Fish, cod, Atlantic, cooked, dry heat" in the USDA Nutrients database
Half a pound of chicken
Chicken
The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...

 
149  270 Entry for "Milk, lowfat, fluid, 1% milkfat, with added vitamin A and vitamin D" in the USDA Nutrients database
Quart of milk
Milk
Milk is a white liquid produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals before they are able to digest other types of food. Early-lactation milk contains colostrum, which carries the mother's antibodies to the baby and can reduce the risk of many...

, 1% fat
173  410 Entry for "Milk, lowfat, fluid, 1% milkfat, with added vitamin A and vitamin D" in the USDA Nutrients database
A tablespoon (8 g) soy lecithin
Lecithin
Lecithin is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues, and in egg yolk, composed of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides, and phospholipids .The word lecithin was originally coined in 1847 by...

 
250  approx. 60
A pound (454 grams) of cauliflower
Cauliflower
Cauliflower is one of several vegetables in the species Brassica oleracea, in the family Brassicaceae. It is an annual plant that reproduces by seed...

 
177  104 Entry for "Cauliflower, cooked, boiled, drained, with salt" in the USDA Nutrients database
A pound of spinach
Spinach
Spinach is an edible flowering plant in the family of Amaranthaceae. It is native to central and southwestern Asia. It is an annual plant , which grows to a height of up to 30 cm. Spinach may survive over winter in temperate regions...

 
113  154 Entry for "Spinach, frozen, chopped or leaf, cooked, boiled, drained, without salt"
in the USDA Nutrients database

A cup of wheat germ  202  432 Entry for "Cereals ready-to-eat, wheat germ, toasted, plain"
in the USDA Nutrients database

Two cups (0.47 liters) firm tofu
Tofu
is a food made by coagulating soy milk and then pressing the resulting curds into soft white blocks. It is part of East Asian and Southeast Asian cuisine such as Chinese, Japanese, Korean, Indonesian, Vietnamese, and others. There are many different varieties of tofu, including fresh tofu and tofu...

 
142  353 Entry for "Tofu, firm, prepared with calcium sulfate and magnesium chloride (nigari) (1)"
in the USDA Nutrients database

Two cups of cooked kidney beans  108  450 . Entry for "Beans, kidney, all types, mature seeds, cooked, boiled, without salt" in the USDA Nutrients database
A cup of uncooked quinoa
Quinoa
Quinoa , a species of goosefoot , is a grain-like crop grown primarily for its edible seeds. It is a pseudocereal rather than a true cereal, or grain, as it is not a member of the grass family...

 
119  626 . Entry for "Quinoa, uncooked"
in the USDA Nutrients database

A cup of uncooked amaranth
Amaranth
Amaranthus, collectively known as amaranth, is a cosmopolitan genus of herbs. Approximately 60 species are recognized, with inflorescences and foliage ranging from purple and red to gold...

 
135  716 Entry for "Amaranth, uncooked"
in the USDA Nutrients database
A grapefruit
Grapefruit
The grapefruit , is a subtropical citrus tree known for its sour fruit, an 18th-century hybrid first bred in Barbados. When found, it was named the "forbidden fruit"; it has also been misidentified with the pomelo or shaddock , one of the parents of this hybrid, the other being sweet orange The...

 
19  103 Entry for
"Grapefruit, raw, pink and red, all areas"
in the USDA Nutrients database

3 cups (710 cc) cooked brown rice
Brown rice
Brown rice is unmilled or partly milled rice, a kind of whole, natural grain. It has a mild nutty flavor, is chewier and more nutritious than white rice, but goes rancid more quickly because the germ—which is removed to make white rice—contains fats that can spoil...

 
54  649 Entry for "Rice, brown, long-grain, cooked"
in the USDA Nutrients database

A cup (146 g) of peanut
Peanut
The peanut, or groundnut , is a species in the legume or "bean" family , so it is not a nut. The peanut was probably first cultivated in the valleys of Peru. It is an annual herbaceous plant growing tall...

s
77  828 Entry for "Peanuts, all types, raw"
in the USDA Nutrients database

A cup (143 g) of almonds  74  822 Entry for 1 cup whole "Nuts, almonds"
in the USDA Nutrients database


Besides cauliflower, other cruciferous vegetables
Cruciferous vegetables
Vegetables of the family Brassicaceae are called cruciferous vegetables. The vegetables are widely cultivated, with many genera, species, and cultivars being raised for food production such as cauliflower, cabbage, cress, bok choy, broccoli and similar green leaf vegetables...

 may also be good sources of choline.

Sinapine
Sinapine
Sinapine is an alkaloidal amine found in black mustard seeds. It is considered a choline ester of sinapic acid.Sinapine was discovered by Etienne Ossian Henry in 1825.-Metabolism:...

 is an alkaloidal amine found in black mustard seeds. It is considered a choline ester of sinapic acid.

Choline and other nutrient values for many foods can be obtained online.
The USDA Nutrients Database has choline content for many foods. If the USDA Nutrients Database does not list choline content for a food, try looking for a similar food in the database Choline Content of Common Foods. Then, look up that food in the USDA Nutrients Database.

Necessary Choline for Humans

The average choline dietary in an adult human is about 7-10 mmol/day. A human infant consumes a great amount of choline from breast milk, which contains 1.5 mmol/L choline. An infant can ingest about 750μmol choline. It is for this reason choline has routinely been added to baby formula. The choline demand in a normal adult is likely to be smaller than for an infant as most of the infants choline needs to be used to develop organs in its growing body, especially the brain.

Health effects of dietary choline

Choline deficiency
Deficiency
A deficiency is generally a lack of something. It may also refer to:*A deficient number, in mathematics, a number n for which σ A deficiency is generally a lack of something. It may also refer to:...

 may play a role in liver disease
Liver disease
Liver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...

, atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

, and possibly neurological disorder
Neurological disorder
A neurological disorder is a disorder of the body's nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord, or in the nerves leading to or from them, can result in symptoms such as paralysis, muscle weakness, poor coordination, loss of sensation, seizures,...

s, One symptom of choline deficiency is an elevated level of the liver enzyme
Liver function tests
Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...

 ALT
Alanine transaminase
Alanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....

.

It is particularly important for pregnant women to get enough choline, since low choline intake may raise the rate of neural tube defects in infant
Infant
A newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth...

s, and may affect their child's memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....

. One study found that higher dietary intake of choline shortly before and after conception
Conception
Conception, or a concept, is an abstract idea or a mental symbol.Conception may also refer to:* Conception, or fertilisation, the fusion of gametes to produce a new organism.* Conception , an album by Miles Davis...

 was associated with a lower risk of neural tube defects. If low choline intake causes an elevated homocysteine
Homocysteine
Homocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...

 level, it raises the risk for preeclampsia, premature birth, and very low birth weight.

Women with diets richer in choline may have a lower risk for breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

, but other studies found no association
Association (statistics)
In statistics, an association is any relationship between two measured quantities that renders them statistically dependent. The term "association" refers broadly to any such relationship, whereas the narrower term "correlation" refers to a linear relationship between two quantities.There are many...

.

There is some evidence to suggest that choline is anti-inflammatory
Anti-inflammatory
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....

. In the ATTICA
Attica
Attica is a historical region of Greece, containing Athens, the current capital of Greece. The historical region is centered on the Attic peninsula, which projects into the Aegean Sea...

 study, higher dietary intake of choline was associated with lower levels of inflammatory markers
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

. A small study found that choline supplements reduced symptoms of allergic rhinitis
Rhinitis
Rhinitis , commonly known as a stuffy nose, is the medical term describing irritation and inflammation of some internal areas of the nose. The primary symptom of rhinitis is nasal dripping. It is caused by chronic or acute inflammation of the mucous membrane of the nose due to viruses, bacteria or...

.

Despite its importance in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 as a precursor for acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 and membrane phosphatidylcholine
Phosphatidylcholine
Phosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup.They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically...

, the role of choline in mental illness
Mental illness
A mental disorder or mental illness is a psychological or behavioral pattern generally associated with subjective distress or disability that occurs in an individual, and which is not a part of normal development or culture. Such a disorder may consist of a combination of affective, behavioural,...

 has been little studied. In a large population-based study, blood levels of choline were inversely correlated with anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

 symptoms in subjects aged 46–49 and 70–74 years. However, there was no correlation
Correlation
In statistics, dependence refers to any statistical relationship between two random variables or two sets of data. Correlation refers to any of a broad class of statistical relationships involving dependence....

 between depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

 and choline level in this study.

The Adequate Intake
Dietary Reference Intake
The Dietary Reference Intake is a system of nutrition recommendations from the Institute of Medicine of the U.S. National Academy of Sciences. The DRI system is used by both the United States and Canada and is intended for the general public and health professionals...

 is intended to be high enough to be adequate for almost all healthy people. Many people do not develop deficiency
Deficiency
A deficiency is generally a lack of something. It may also refer to:*A deficient number, in mathematics, a number n for which σ A deficiency is generally a lack of something. It may also refer to:...

 symptoms when consuming less than the Adequate Intake of choline. The human body synthesizes some of the choline it needs, and people vary in their need for dietary choline. In one study, premenopausal women were less sensitive to a low-choline diet than men or postmenopausal women.

However, the Adequate Intake may not be enough for some people. In the same study, 6 out of 26 men developed choline deficiency symptoms while consuming the Adequate Intake (and no more) of choline. The Adequate Intake was less than the optimal intake for the male subjects in another study.

High dietary intake of choline was associated with an increased risk of colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...

 adenomas (polyps), for women in the Nurses' Health Study
Nurses' Health Study
The Nurses Health Study, established in 1976 by Dr. Frank Speizer, and the Nurses' Health Study II, established in 1989 by Dr. Walter Willett, are the most definitive long-term epidemiological studies conducted to date on older women's health. The study has followed 121,700 female registered...

. However, this could represent effects of other components in the foods from which choline was obtained. Dietary choline intake was not associated with increased risk of colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....

, for men in the Health Professionals Follow-up Study.

Similar to the effect on memory of choline consumption in utero or as a neonate discussed below, adult rodent dietary choline deficiency has been demonstrated to exacerbate memory loss and diets high in choline appear to diminish memory loss. Further, choline supplemented older mice performed as well as young three-month-old mice and it was noted that supplemented mice had more dendritic spines per neuron within the hippocampus. However, no similar work has been done in humans.

Choline as a dietary supplement

The most often available choline supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...

 is lecithin
Lecithin
Lecithin is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues, and in egg yolk, composed of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides, and phospholipids .The word lecithin was originally coined in 1847 by...

, derived from soy or egg yolks, often used as a food additive
Food additive
Food additives are substances added to food to preserve flavor or enhance its taste and appearance.Some additives have been used for centuries; for example, preserving food by pickling , salting, as with bacon, preserving sweets or using sulfur dioxide as in some wines...

. Phosphatidylcholine
Phosphatidylcholine
Phosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup.They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically...

 is also available as a supplement, in pill or powder form. Supplementary choline is also available as choline chloride, which comes as a liquid
Liquid
Liquid is one of the three classical states of matter . Like a gas, a liquid is able to flow and take the shape of a container. Some liquids resist compression, while others can be compressed. Unlike a gas, a liquid does not disperse to fill every space of a container, and maintains a fairly...

 due to its hydrophilic properties. Choline chloride is sometimes preferred as a supplement because phosphatidylcholine can have gastrointestinal side effect
Side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequences of the use of a drug.Occasionally, drugs are...

s.

It is well established that supplements of methyl group transfer vitamins B6
Vitamin B6
Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...

, B12
Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...

, folic acid
Folic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...

 reduce the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

 titer
Titer
A titer is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positive or negative. The titer corresponds to the highest dilution factor that still yields a positive...

 of homocysteine
Homocysteine
Homocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...

 and so may prevent heart disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...

. Choline or betaine supplements also may reduce homocysteine
Homocysteine
Homocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...

. Choline is a necessary source of methyl groups for methyl group transfer. Supplements of lecithin
Lecithin
Lecithin is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues, and in egg yolk, composed of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides, and phospholipids .The word lecithin was originally coined in 1847 by...

/choline were found to reduce heart disease
Heart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...

 in laboratory studies. The reduction in heart disease with lecithin supplements may however relate more to the cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

-carrying capacity of lecithin than to the methyl group transfer role of choline.

Choline supplements are often taken as a form of 'smart drug' or nootropic
Nootropic
Nootropics , also referred to as smart drugs, brain steroids, memory enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration...

, due to the role that the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 plays in various cognition
Cognition
In science, cognition refers to mental processes. These processes include attention, remembering, producing and understanding language, solving problems, and making decisions. Cognition is studied in various disciplines such as psychology, philosophy, linguistics, and computer science...

 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
Mood
Mood may refer to:*Mood , a relatively long lasting emotional state*Grammatical mood, one of a set of morphologically distinctive forms that are used to signal modality*Mood , a city in Iran*Mood District, a district in Iran...

 are mediated at least in part by acetylcholine metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 in the brain. In a study on rats, a correlation
Correlation
In statistics, dependence refers to any statistical relationship between two random variables or two sets of data. Correlation refers to any of a broad class of statistical relationships involving dependence....

 was shown between choline intake during pregnancy and mental task performance of the offspring
Offspring
In biology, offspring is the product of reproduction, of a new organism produced by one or more parents.Collective offspring may be known as a brood or progeny in a more general way...

; but the same correlation has not been shown in humans. However, this human study admits that "[w]omen in the current study consumed their usual diets. They were not eating choline-enriched diets and were not receiving choline supplementation. Therefore, our results indicate that choline concentrations in a physiologic range observed among women consuming a regular diet during pregnancy are not related to IQ in their offspring. We cannot rule out the possibility that choline supplementation could have an IQ effect."

The compound's quaternary amine renders it lipid-insoluble, which might suggest it would be unable to cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

. However, despite choline's lipid insolubility, a choline transporter that allows transport across the blood-brain barrier exists. The efficacy of these supplements in enhancing cognitive abilities is a topic of continuing debate.

The Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 (FDA) requires that infant formula
Infant formula
Infant formula is a manufactured food designed and marketed for feeding to babies and infants under 12 months of age, usually prepared for bottle-feeding or cup-feeding from powder or liquid . The U.S...

 not made from cow's milk
Milk
Milk is a white liquid produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals before they are able to digest other types of food. Early-lactation milk contains colostrum, which carries the mother's antibodies to the baby and can reduce the risk of many...

 be supplemented with choline.

Due to its role in lipid metabolism
Lipid metabolism
Lipid metabolism refers to the processes that involve the intercourse and degradation of lipids.The types of lipids involved include:* Bile salts* Cholesterols* Eicosanoids* Glycolipids* Ketone bodies* Fatty acids - see also fatty acid metabolism...

, choline has also found its way into nutritional supplements that claim to reduce body fat
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...

; but there is little or no evidence
Scientific evidence
Scientific evidence has no universally accepted definition but generally refers to evidence which serves to either support or counter a scientific theory or hypothesis. Such evidence is generally expected to be empirical and properly documented in accordance with scientific method such as is...

 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.

Pharmaceutical uses

Choline is used in the treatment of liver disorders, Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

, and bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

.

Some studies show that as a supplement, choline is also used in treating hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...

, glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

, atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

, and, possibly, neurological disorders.

Choline has also been proven to have a positive effect on those suffering from alcoholism
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...

.

The current NIH funded research study COBRIT is gathering data regarding potential benefit of longterm citicoline
Citicoline
Citicoline , also known as cytidine diphosphate-choline & cytidine 5'-diphosphocholine is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline...

 treatment for recovery after traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...

.

Medical imaging

Choline can be labelled with carbon-11 or fluorine-18 which are radioactive positron emittor
Positron emission
Positron emission or beta plus decay is a type of beta decay in which a proton is converted, via the weak force, to a neutron, releasing a positron and a neutrino....

s enabling medical imaging on a positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...

(PET) scanner. This is usually performed by a nuclear medicine physician. Uses include imaging prostate and breast cancer.

Pregnancy and brain development

Introduction

Choline may be produced both de novo (from scratch) by methylation of phosphatidylethanolamine by N-methyltranferase (PEMT) to form phosphatidylcholine in the liver or it may be consumed from the diet. It has been demonstrated that both de novo production and dietary consumption are necessary as humans eating diets that lack choline develop fatty liver, liver damage, and muscle damage. However, because of the close interplay between choline, folate, methionine, and vitamin B12, (whose pathways overlap)the function of choline can be complex.

To begin with, methionine can be formed two ways, either from methyl groups derived from folate, or from methyl groups derived from betaine (which gets its methyl groups from choline). Changes in one of these pathways is compensated for by the other,and if these pathways do not adequately supply methyl groups to produce methionine, the precursor to methionine, homocysteine, rises.

Choline in food exists as either a free or esterified form (choline bound to another compound, such as phosphytidylcholine). Although all forms are most likely usable, there is some evidence that they are differentially bioavaliable (able to be used by the body). Lipid soluble forms (like phosphytidylcholine) bypass the liver once absorbed, while water soluble forms (such as free choline) enter the liver portal circulation and are generally absorbed by the liver. Both pregnancy and lactation increase demand for choline dramatically. This demand may be met by upregulation of PEMT via increasing estrogen levels to produce more choline de novo, but even with increased PEMT activity the demand for choline is still so high that bodily stores are generally depleted. This is exemplified by the observation that Pemt -/- mice (mice lacking functional PEMT) will abort at 9–10 days unless fed supplemental choline.

While maternal stores of choline are depleted during pregnancy and lactation, the placenta accumulates choline by pumping choline against the concentration gradient in to the tissue, where it is then stored in various forms, most interestingly as acetylcholine, (an uncommon occurrence outside of neural tissue). The fetus itself is exposed to a very high choline environment as a result, and choline concentrations in amniotic fluid can be ten times higher than in maternal blood. It is assumed that this high concentration allows choline to be abundantly available to tissues and cross the blood brain barrier effectively.

Functions in the fetus

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 addition of methylation to DNA and other functions), raising choline stores in fetal and placental tissues, and for increased production of lipoproteins (proteins containing "fat" portions). In particular, there is interest in the impact of choline consumption on the brain. This stems from choline's use as a material for making cellular membranes, (particularly in making phosphotidylcholine). Human brain growth is most rapid during the third trimester of pregnancy and continues to be rapid to approximately five years of age. During this time there is high demand for shiphingomyelin, which is made from phosphytidyl choline, (and thus from choline), because this material is used to myelinate (insulate) nerve fibers. 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. Acetylcholine is even present in the placenta and may help control cell proliferation/differentiation (increases in cell number and changes of multi use cells in to dedicated cellular functions) and parturition. Choline may also impact methylation of CpG dinucleotides in DNA in the brain - this methylation can change genome expression (which genes are turned on and which are turned off) and thus fetal programming (the act of arranging so that certain genes are by default turned off or turned on in the absence of external forces).

What choline does within the fetus is determined by choline's concentration. At low choline concentrations it is preferentially shunted towards making phospholids. As concentrations rise, free choline is converted to betain in liver mitochondria, and betaine is used as a source of methyl groups for DNA methylation, etc. However, should concentrations of choline decrease enough, the PEMT pathway is up regulated, (activated). The PEMT pathway allows for creation of new choline without consuming choline from the diet. This pathway has been shown to produce up to 30% of needed phosphotidylcholine. Interestingly, PEMT produced phosphytidyl choline tends to have longer less saturated fatty acids than that produced directly from choline via the CDP-choline pathway.

Concentration is also important in getting choline in to the brain for use to prevent neural nonclosure and poor brain development. Choline uptake in to the brain is controlled by a low-affinity (not particularly efficient) transporter located at the blood brain barrier. Transport occurs when arterial plasma choline concentrations increase above 14 umol/L, which can occur during a spike in choline concentration after consuming choline rich foods. Neurons, conversely, acquire choline by both high and low affinity transporters. Choline is stored as membrane bound phosphytidyl choline which can then be used for acetylcholine neurotransmitter synthesis later. Acetylcholine is formed as needed, travels across the synapse, and transmits the signal to the following neuron. Afterwards acetycholinesterase degrades it, and the free choline is taken up by a high affinity transporter in to the neuron again.

Neural tube closure

While folate is most well known for preventing neural tube nonclosure, (and this is the basis for its addition to prenatal vitamins), folate and choline metabolism are interrelated. Both choline and folate (with the help of vitamin B12) can act as methyl donors to homocysteine to form methionine, which can then go on to form SAM and act as a methyl donor for methylation of DNA. It has been demonstrated that dietary choline deficiency alone without concurrent folate deficiency can decrease SAM concentration, suggesting that both folate and choline important sources of methyl groups for SAM production. Inhibition of choline absorption and use is associated with neural tube defects in mice and it has been suggested this may also occur in humans. A retrospective case control study (a study collects data after the fact from cases that occur without the investigator causing them to occur) of 400 cases and 400 controls indicated that women with the lowest daily choline intake had a 4 fold greater risk of having a child with a neural tube defect than women in the highest quartile of intake.

Choline in utero and long-term memory

Maternal dietary consumption or lack of consumption of choline during late pregnancy in rodents was related to irreversible changes in hippocampal function in adult rodents, including changes in long term memory capacity. Increased consumption of choline in rodent dams by about four time dietary recommendations during days 11-17 of pregnancy increased hippocampal cell proliferation and decreased apoptosis (programmed cell death) of these cells in their fetuses. This may occur because in choline deficient cells in culture, and in fetal rodent brains from choline deficient dams, the promoter of CDKN3, a gene which inhibits cell proliferation in the brain, is not properly methylated. This leaves CDKN3 active, decreasing cell proliferation in the brain. Increased choline consumption by rodent dams has shown improved auditory and visuaspatial memory in offspring as well as preventing age-related memory decline as their offspring grew old. The capacity of choline consumption by dams to improve the memory of their offspring has been shown in a variety of memory tests, including: the radial-arm maze, Morris water maze, passive avoidance paradigms, and measures of attention. It has also been demonstrated in a variety of rat strains - including Sprague-Dawley and Long-Evans and in mice.This suggests that the effect of choline consumption on the fetus in utero is universal among rodents. However, the mechanism behind this response is not fully understood. It has been suggested that the effect of neonatal choline on memory comes from increasing the amount of choline in the brain and subsequently, the amount of acetylcholine that can be produced and released. However, the amount of choline that accumulates in the brain after consumption of choline by pregnant dams does not seem to be sufficient to change the acetylcholine release. Instead, it has been noted that choline consumption by dams increases phosphocholine and betaine in the fetal brain.

These findings are in rodents, a species with faster brain maturation and a more mature brain at birth than is typical for humans. In humans the brain continues to develop after birth, and does not become similar to its adult structure until around 4 years of age. It has been suggested that by feeding infants formula instead of milk, and presumably through differences in choline amount in the breast milk of mothers consuming different choline levels, the still developing brain of an infant may be impacted. This may, in part, contribute to the differences seen between individual adult humans in memory and recall.

Impact of genetic polymorphisms (genetic variation)

It has been observed that some men and women develop organ dysfunction when fed low choline diets, while others do not, and that there is a large range in choline requirements for optimal health, from 850 mg/70 kg/day to 550 mg/kg/day. This difference has been attributed to SNPs (single-nucleotide polymorphisms) in choline metabolic pathways, (SNPs change the RNA code, and can subsequently change the arrangement of the protein made from that RNA, leading to differences in protein function between the normal version and the SNP version). For example, folate pathway polymorphisms may limit the usability of folate for SAM production - thereby making a person more dependent on choline for SAM production. PEMT polymorphisms change the amount of choline that can be synthesized de novo, (increasing the amount of choline that must be supplied by the diet).

In one study, a common genetic polymorphism, MTHFDI (5,10 methylenetetrahydrofolate dehydrogenase1958A)in folate metabolsim made premenopausal women 15 times more likely to develop signs of choline deficiency on a low choline diet as non-carriers of the SNP (p < 0.0001). The impact of this SNP is quite large - 63% of the study population had at least one allele with the SNP. The MTHFD1 allele is believed to change the flux between 5,10-methylenetetrahydrofolate and 10-formyltetrahydrofolate, which influences the availability of 5-methl tetrahydrofolate for homocysteine methylation, (and subsequent methionine and then SAM production). This would mean more choline would be shunted towards methylation to make up for the lack of folate participation in the pathway. A real world application of this is that the risk of having a child with a neural tube defect is increased in mothers with the G1958A SNP in MTHFD1. Additionally, mice that are Mthfr -/- (lacking MTHFR) become choline deficient, suggesting that humans with genetic polymorphisms that alter the functionality of the enzyme may also have choline deficiency problems.

SNPs have also been found in PEMT (responsible for de novo choline production). Ziesel et al. located a SNP in the promoter region of the PEMT gene that was related to increased susceptibility to choline deficiency in women. Since sexual differences in the impact of this SNP were found, Ziesel suggests that this SNP alters the estrogen responsiveness of the promoter region of the PEMT gene. Ziesel et al. also located another SNP in exon 8 (the coding portion of a gene) of PEMT with 30% loss of function of PEMT and increased risk for nonalcoholic fatty liver disease as an end result.

It should be noted, however, that not all SNPs in choline/folate related genes have been shown to impact choline needs. C677T and A1298C polymorphisms in MTHFR and A80C polymorphism in the reduced folate carrier gene have not been found to be significant.

Choline and Lactation

Introduction to Lactation

The human mammary gland is composed of several cell types, including adipose (fat cells), muscle, ductal epithelium, and mammary epithelium (referred to sometimes as lactocytes). The mammary epithelium is the site for excretion of raw materials in to the milk supply, including choline. This occurs, for the fat portion of the milk, by apocrine secretion, where vacoules containing materials bud off of the cell in to the lumen (storage) of the alveolus, (milk secretion gland). From here the milk will be released upon stimulation with oxytocin via suckling. It has been suggested that the mammary gland may have evolved from the innate immune system, and lactation may be connected to inflammation - based on the obersvation that inflammation signaling pathways, NF-κB and Jak/Stat are found both in inflammatory responses and lactation. If this is true, it highlights the role of the mammary gland not only as a source of energy, but also as a major contributor to preparing offspring for survival in the outside world.

Choline in Milk

Choline can be found in milk as free choline, phosphocholine, glycerophosphocholine, sphingomyelin and phosphatidylcholine and choline levels within breast milk are correlated with choline levels in maternal blood. Choline consumed via breast milk has been shown to impact blood levels of choline in breast feeding infants - indicating that choline consumed in breast milk is entering the fetal system. Choline may enter the milk supply either directly from the maternal blood supply, or choline containing nutrients may be produced within the mammary epithelium. Choline reaches the milk through a transporter specific for choline from the maternal blood supply (against a concentration gradient) in to the mammary epithelial cells. At high concentrations, (concentrations greater than that typically seen in humans), choline can diffuse across the cell membrane in to the mammary epithelium cell. At more normal concentrations, it passes via what is believed to be a calcium/sodium dependent, phosphorylation related, active transporter in to the cell. It may also be produced within the mammary epithelium de novo via the PEMT pathway. Once choline containing milk has been consumed by the neonate, it is used for formation of acetylcholine, phosphatidylcholine, sphingomyelin, and choline plasmalogens for cell membrane production in mice, and the majority of the choline in milk is supplied as phosphatidylcholine (related perhaps to the release of already formed globules of cellular membrane during apocrine secretion of mammary epithelium produced nutrients). James also demonstrated that the hormone insulin may stimulate choline uptake into mouse mammary cells and prolactin encouraged choline incorporation in to lipids when cells were concurrently treated with insulin and cortisol.

Differences Between Full Term and Premature Mothers and Infants

Holmes-McNary et al. reports that choline content in mature breast milk from mothers delivering preterm was significantly lower than the choline content from mothers delivering at term. However, choline esters (choline containing compounds) did not differ in concentration between preterm and full term mothers. It has been suggested that mothers delivering before full term may not have adequate mammary development, and may not reach full mammary development by the time they begin producing mature milk. It is possible that choline content may be lower in preterm mothers because of this effect. However, Lucas et al. did find significant improvement at 18 months and at 7.5–8 years of age in IQ score among preterm infants that were fed breast milk via tube in comparison to those that were not fed breast milk, suggesting that even if the mammary gland may be "immature" breast milk produced by it still has benefit. Additionally, preterm infants fed formula prepared for term infants had lower mental performance than those fed formula prepared specifically for preterm infants, but this effect was diminished between preterm infants fed donated breast milk and those fed preterm formula. Further supporting this, Lucas et al. also found that of the factors examined, consumption of mothers' milk was the most significantly related to later IQ performance.

Additionally, a meta-analysis by Anderson et al. found that low-birth-weigh infants derived more benefit from breast feeding, (in terms of IQ score later in life) than did normal weight infants also being breast fed. Drane and Logemann summarize their meta-analysis of 24 studies by stating "an advantage in IQ to breast-fed infants of the order of five points for term infants and eight points for low birth weight infants [was observed]. Arguably, increases in IQ of these magnitudes would have relatively subtle impact at an individual level. However, the potential impact at a population level must also be considered."

Differences Between Breast milk and Formula

Human milk is very rich in choline, however, formulas derived from other sources, particularly soy, have lower total choline concentrations than human milk, (and also lack other important nutrients, such as long chain polyunsatureated fatty acids, sialylated oligosaccharides, thyroid-stimulating hormone, neurotensin, nerve growth factor, and the enzymes lysozume and peroxidase). Bovine milk and bovine-derived formulas had similar or higher glycerophosphocholine to human milk and soy derived formulas had lower glycerophosphocholine content. Phosphatidylcholine and sphingomyelin concentrations were similar between bovine formulas and human milk, but soy-derived infant formulas had more phosphatidylcholine than human or bovine sources. Soy-derived formulas had less sphingomyelin than human milk, (a concern, since sphingomyelin is used for producing myelin, which insulates neurons). Free choline concentrations in mature human milk were 30-80% lower than that found in bovine milk or formulas. Mature human milk also has lower free choline than colostrum-transitional human milk. Phosphocholine is particularly abundant in human milk. Overall, formulas, milks, and breast milk appear to provide different amounts and forms of choline, and Holmes-McNary et al. suggests "This may have consequences for the relative balance between use of choline as a methyl donor (via betaine), acetylcholine precursor (via choline), or phospholipid precursor (via phosphocholine and phosphatidylcholine)". This is supported by Ilcol et al.'s observations that serum free choline concentrations were lower in formula-fed infants than in breast-fed infants.

More broad interpretations of breast milk consumption versus formula use have also been investigated - though some researchers in the field feel that meta-analysis of the problem should be treated with skepticism, given the multitude of factors that impact cognitive development in humans. Uauy & Peirano, in their editorial for the American Journal of Clinical Nutrition state: "The magnitude of the effect of breast-feeding on IQ is somewhat lower than that of anemia and lead burden. Yet feeding mode is an intervention that affects the whole population, thus, the net effect of improving IQ by 3 points may be similar if not larger than that of gaining 6 points in 5-10% of the children.". Additionally, they go on to summarize that "The burden of proof should be placed on those who propose that feeding formula from a bottle can equal feeding milk from the breast." There is some science behind this proposal. Lucas et al., after adjusting for social and educational factors on development, still found that preterm children consuming breast milk via tube performed over half a standard deviation higher on IQ tests at 7.5–8 years of age than their cohorts that did not receive breast milk. Previously he had also found an improvement in cognitive development as early as 18 months in preterm infants consuming breast milk versus those not consuming breast milk.

The argument has been made that the increased IQ and developmental performance exhibited by breastfed infants stems from interaction between the mother and child as well as, or without any additional input from, the actual milk. Drane and Logemann suggest that lactation increases oxytocin and prolactin production, generating feelings of well-being in the mother and encouraging nurturing behavior. This may lead to better mother-child relationships and that may in turn generate improved neural performance. Additionally, social class and maternal education are highly correlated with type of infant feeding, (formula vs. breastfeeding), while also being correlated to observed cognitive performance. Lucas et al., however, refutes the assumption that fluid breast milk itself has no or minimal beneficial function on cognitive performance later in life. They report an increase in IQ between preterm infants, (and later 7.5-8 yr old children), provided with breast milk and those not provided with breast milk via nasogastric tube, without any interaction between mother and offspring and with controlling for social and educational factors.

Current Consumption Levels by Lactating and Pregnant Women

Shaw et al. found that 25% of pregnant women studied in California had observed intakes of less than half the estimated daily choline intake for women.

Choline Synthesis and Metabolism in the Infant

Impact in Neonates to 5 years

DNA methylation and Choline in Breast milk

Cognitive Performance and Choline in Breast milk

A meta-analysis on breastfeeding and cognitive development indicated that breast feeding was associated with higher scores for cognitive development than formula use. Additionally, the longer the duration of breastfeeding the greater the cognitive developmental benefit in offspring and this benefit was evident early in development and sustained up to 15 years of age, (the last time point at which IQ was measured in the meta-analysis). In addition to IQ performance, breastfed children had more rapid maturation of visual functions and appeared to acquire motor skills at an earlier age. Researchers in the meta-analysis also suggested that breastfed children had fewer emotional or behavioral problems and exhibited fewer minor neurological problems later in life. As previously stated, choline is necessary for neural development and is higher in breast milk than in formula, and therefore choline may be playing a role in the higher performance of breastfed infants. However, in the meta-analysis under discussion, the author attributed increased cognitive performance to presence of long-chain polyunsaturated fatty acids (LCPUFAs) such as docosahexaenoic acid and arachidonic acid, which are lipid components within the brain, rather than choline. They state that the difference between formula and breastfed infants is derived from a lack of these LCPUFAs in infant formulas available in the United States, (data was not provided for formula sources from other countries). Since choline also plays a role in brain development, and differences in choline are present between breast milk and formula, it seems possible that choline could also be playing a role in observed IQ score improvement in breastfed offspring.

Long Term Memory Preservation and Memory Performances as a Result of Fetal Choline Consumption

For more information on this topic, search for this review on www.pubmed.com: Caudill, MA. Pre- and postnatal health: evidence of increased choline needs.J Am Diet Assoc. 2010 Aug;110(8):1198-206.

External links

  • Choline, Linus Pauling Institute
  • Choline, Kyoto Encyclopedia of Genes and Genomes
The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK