Choline is an essential nutrient.
Choline occurs as a cation that forms various salts.
It must be obtained from the diet as choline or as choline phospholipids, like phosphatidylcholine.
Humans, make choline de novo, however production is generally insufficient.
To maintain health, it must be obtained from the diet as choline or as choline phospholipids, like phosphatidylcholine.
Choline is often not classified as a vitamin, but as a nutrient with an amino acid–like metabolism.
Choline phospholipids are necessary components in cell membranes, in the membranes of cell organelles, and in very low-density lipoproteins.
Choline consumption is widespread with over-the-counter supplements and multivitamins being frequently used to promote brain and heart heath or to prevent liver damage, and choline supplementation is often advised during pregnancy to aid fetal neural development.
Foods with high calling content, like eggs or regularly consumed in the western diet.
Choline is required to produce acetylcholine, a neurotransmitter, and S-adenosylmethionine, a universal methyl donor involved in the synthesis of homocysteine.
Choline deficiency is rare in humans, and causes nonalcoholic fatty liver disease and muscle damage.
Excessive dietary choline of greater than 7.5 g/day, can cause low blood pressure, sweating, diarrhea and fish-like body odor due to trimethylamine, which forms in its metabolism.
Rich dietary sources of choline and choline phospholipids include: organ meats and egg yolks, dairy products, peanuts, certain beans, nuts, seeds and vegetables with pasta and rice.
It is a family of water-soluble quaternary ammonium compounds.
It is hygroscopic.
Aqueous solutions of choline are stable, but the compound slowly breaks down to ethylene glycol, polyethylene glycols, and trimethylamine.
Historically produced from natural sources, such as via hydrolysis of lecithin.
De novo synthesis of choline is via the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, but biosynthesis is not enough to meet human requirements.
Certain enzyme mutations and estrogen deficiency, often due to menopause, increase the dietary need for choline.
In humans, choline is absorbed from the intestines via the SLC44A1 (CTL1) membrane protein via facilitated diffusion governed by the choline concentration gradient and the electrical potential across the enterocyte membranes.
SLC44A1 has limited ability to transport choline.
Absorbed choline leaves the enterocytes via the portal vein, passes the liver and enters systemic circulation.
Gut microbes degrade the unabsorbed choline to trimethylamine, which is oxidized in the liver to trimethylamine N-oxide.
In humans, choline is transported as a free molecule in blood.
Choline–containing phospholipids and other substances, are transported in blood lipoproteins.
Blood plasma choline levels in healthy fasting adults is 7–20 micromoles per liter (μmol/l) and 10 μmol/l on average.
Levels are regulated.
Levels are elevated for about 3 hours after choline consumption.
Choline is a water-soluble ion and thus requires transporters to pass through fat-soluble cell membranes.
Sodium- (Na+) and ATP-dependent transporters have high binding affinity for choline, transport it primarily to neurons and are indirectly associated with the acetylcholine production.
The deficient function Sodium- (Na+) and ATP-dependent transporters
cause hereditary weakness in the pulmonary and other muscles in humans via acetylcholine deficiency.
Choline transporter CTL1s have moderate affinity for choline and transport it in almost all tissues, including the intestines, liver, kidneys, placenta and mitochondria.
CTL1s supply choline for phosphatidylcholine and trimethylglycine production.
CTL2s occur especially in the mitochondria in the tongue, kidneys, muscles and heart.
CTL2s are associated with the mitochondrial oxidation of choline to trimethylglycine.
CTL1s and CTL2s are not associated with the acetylcholine production, but transport choline together via the blood–brain barrier.
Only CTL2s occur on the brain side of the barrier, and remove excess choline from the neurons back to blood.
CTL1s occur only on the blood side of the barrier, but also on the membranes of astrocytes and neurons.
OCT1s and OCT2s are not associated with the acetylcholine production.
They transport choline with low affinity.
OCT1s transport choline primarily in the liver and kidneys
OCT2s in kidneys and the brain.
Choline is stored in the cell membranes and organelles as phospholipids, and inside cells as phosphatidylcholines and glycerophosphocholines.
Daily dietary free choline supplementation for 28 days significantly raises fasting TMAO levels and increases platelet aggregation.
The daily consumption of eggs or phosphatidylcholine containing an equivalent total choline content to the free choline, fails to increase TMAO or platelet aggregation.
The form of choline in dietary nutrients differentially contributes to gut microbiome depended TMAO generation and systemic TMAO levels.
Very little choline is excreted into the urine.
Its most notable function is as a synthetic precursor for other essential cell components and signalling molecules, such as phospholipids that form cell membranes, the neurotransmitter acetylcholine, and the osmoregulator trimethylglycine.
Trimethylglycine in turn serves as a source of methyl groups by participating in the biosynthesis of S-adenosylmethionine.
Choline is transformed to phospholipids: Phosphatidylcholines and sphingomyelins.
These are found in all cell membranes and the membranes of most cell organelles.
Phosphatidylcholines are structurally important part of the cell membranes, comprising 40–50% of their phospholipids.
Choline phospholipids form lipid rafts in the cell membranes along with cholesterol, which are centers for receptors and receptor signal transduction enzymes.
Phosphatidylcholines are needed for the synthesis of VLDLs: 70–95% of their phospholipids are phosphatidylcholines.
Choline is required for the synthesis of pulmonary surfactant, a mixture consisting mostly of phosphatidylcholines.
The surfactant is responsible for lung elasticity, that is for lung tissue’s ability to contract and expand.
A deficiency of phosphatidylcholines in the lung tissues has been linked to acute respiratory distress syndrome.
Phosphatidylcholines are excreted into bile and work together with the intestinal absorption of lipids.
Choline is needed to produce acetylcholine, the neurotransmitter which plays a necessary role in muscle contraction, memory and neural development.
Diets deficient in choline are associated with the development of fatty liver, liver damage, and muscle damage.
Neurons store choline in the form of phospholipids in their cell membranes for the production of acetylcholine.
Choline deficiency thus leads to elevated homocysteine levels.
Choline occurs in foods as a free molecule and in the form of phospholipids, especially as phosphatidylcholines.
Choline is highest in organ meats and egg yolks.
Rich dietary sources of choline and choline phospholipids include organ meats and egg yolks, dairy products, peanuts, certain beans, nuts, seeds and vegetables with pasta and rice also contributing to choline intake in the American diet.
It is found to a lesser degree in non-organ meats, grains, vegetables, fruit and dairy products.
Cooking oils and other food fats have about 5 mg/100 g of total choline.
Food labels express the amount of choline in a serving as a percentage of daily value (%DV) based on the adequate intake of 550 mg/day.
Breast milk is rich in choline, corresponds to about 120 mg of choline per day for the baby.
Breast milk levels vary with the choline intake of the mother.
Infant formulas vary in the amount of choline added.
Trimethylglycine is a functional metabolite of choline.
It substitutes for choline nutritionally: High amounts of trimethylglycine occur in wheat bran (1,339 mg/100 g), toasted wheat germ (1,240 mg/100 g) and spinach (600–645 mg/100 g).
Choline content of foods (mg/100 g).
Bacon, cooked124.89
Bean, snap 13.46
Beef, trim-cut, cooked78.15
Beetroot 6.01
Beef liver, pan fried418.22
Broccoli 40.06
Chicken, roasted, with skin65.83
Brussels sprout 40.61
Chicken, roasted, no skin78.74
Cabbage 15.45
Chicken liver290.03
Carrot 8.79
Cod, atlantic83.63
Cauliflower 39.10
Ground beef, 75–85% lean, broiled79.32–82.35
Sweetcorn, yellow 21.95
Pork loin cooked102.76
Cucumber 5.95
Shrimp, canned70.60
Lettuce, iceberg 6.70
Lettuce, romaine 9.92
Butter, salted18.77
Pea 27.51
Cheese16.50–27.21
Sauerkraut 10.39
Cottage cheese18.42
Spinach 22.08
Milk, whole/skimmed 14.29–16.40
Sweet potato 13.11
Sour cream20.33
Tomato 6.74
Yogurt, plain15.20
Zucchini 9.36
Grains Fruits
Oat bran, raw58.57
Apple 3.44
Oats, plain7.42
Avocado 14.18
Rice, white2.08
Banana 9.76
Rice, brown9.22
Blueberry 6.04
Wheat bran74.39
Cantaloupe 7.58
Wheat germ, toasted152.08
Grape 7.53
Others Grapefruit 5.63
Bean, navy26.93
Orange 8.3
Egg, hen251.00
Peach 6.10
Olive oil0.29
Pear 5.11
Peanut52.47
Prune 9.66
Soybean, raw115.87
Strawberry 5.65
Tofu, soft27.37
Watermelon 4.07
Food Milligrams (mg) per serving Percent DV*
Egg, hard boiled, 1 large egg 147 27%
Beef top round, 3 oz (85 g) 117 21%
Soybeans,, 1⁄2 cup 107 19%
Chicken breast, roasted, 3 oz (85 g) 72 13%
Beef, ground, 93% lean meat, broiled, 3 oz (85 g) 72 13%
Cod, Atlantic, cooked, dry heat, 3 oz (85 g) 71 13%
Mushrooms, shiitake, cooked, 1⁄2 cup pieces 58 11%
Potatoes, red, baked, flesh and skin, 1 large potato 57 10%
Wheat germ, toasted, 1 oz (28 g) 51 9%
Beans, kidney, canned, 1⁄2 cup 45 8%
Quinoa, cooked, 1 cup 43 8%
Milk, 1% fat, 1 cup 43 8%
Yogurt, vanilla, nonfat, 1 cup 38 7%
Brussels sprouts, boiled, 1⁄2 cup 32 6%
Broccoli, chopped, boiled, drained, 1⁄2 cup 31 6%
Cottage cheese, nonfat, 1 cup 26 5%
Tuna, white, canned in water, drained in solids, 3 oz (85 g) 25 5%
Peanuts, dry roasted, 1⁄4 cup 24 4%
Cauliflower, 1 in (2.5 cm) pieces, boiled, drained, 1⁄2 cup 24 4%
Peas, green, boiled, 1⁄2 cup 24 4%
Sunflower seeds, oil roasted, 1⁄4 cup 19 3%
Rice, brown, long-grain, cooked, 1 cup 19 3%
Bread, pita, whole wheat, 1 large (6+1⁄2 in or 17 cm diameter) 17 3%
Cabbage, boiled, 1⁄2 cup 15 3%
Tangerine (mandarin orange), sections, 1⁄2 cup 10 2%
Beans, snap, raw, 1⁄2 cup 8 1%
Kiwifruit, raw, 1⁄2 cup sliced 7 1%
Carrots, raw, chopped, 1⁄2 cup 6 1%
Apples, raw, with skin, quartered or chopped, 1⁄2 cup 2 0%
The DV for choline is 550 mg for adults and children age 4 years and older.
While daily dietary free choline supplementation significantly raises TMAO levels in plasma and urine, and increases platelet aggregation.
The daily consumption of eggs containing an equivalent total choline content to the free choline, failed to increase TMAO or platelet aggregation.
Choline recommendations (mg/day)
Infants and children
0–6 months125
7–12 months150
1–3 years200
4–6 years250
7–8 years250
9–10 years 250
11–13 years375
Males
14 years 340 550
15–18 years 400
19+ years 400 550 3,500
Females
14 years 340
15–18 years400
19+ y400
If pregnant480
If breastfeeding520
Symptomatic choline deficiency is rare in humans, as most people obtain sufficient amounts of it from the diet and are able to biosynthesize limited amounts of it.
Symptomatic deficiency
causes muscle damage and non-alcoholic fatty liver disease, which may develop into cirrhosis.
Estrogen production predisposes individuals to deficiency along with low dietary choline intake.
Women before menopause have lower dietary need for choline than men.
due to women’s higher estrogen production.
Without estrogen therapy, the choline needs of post-menopausal women are similar to men’s.
In choline deficiency, the availability of phosphatidylcholines in the liver are decreased, and these are needed for formation of VLDLs: VLDL-mediated fatty acid transport out of the liver decreases leading to fat accumulation in the liver.
Excessive doses of choline can have adverse effects: Daily 8–20 g doses of choline cause low blood pressure, nausea, diarrhea and fish-like body odor.
The odor is due to trimethylamine (TMA) formed by the gut microbes from the unabsorbed choline.
TMA is oxidized in the liver to trimethylamine N-oxide (TMAO).
Elevated levels of TMA and TMAO in the body have been linked to increased risk of atherosclerosis and mortality.
Choline intake has not been shown to increase the risk of dying from cardiovascular diseases.
Low maternal intake of choline leads to significantly increase the risk of neural tube defects (NTDs) in newborns.
Folate deficiency also causes NTDs: Choline and folate, interacting with vitamin B12, act as methyl donors to homocysteine to form methionine, which can then go on to form SAM (S-adenosylmethionine).
Disturbed methylation via SAM could be responsible for the relation between folate and NTDs.
Choline deficiency can cause fatty liver, which may be associated with increased risk of cancer and cardiovascular diseases.
Pregnancy and lactation markedly increase demand for choline.
Maternal stores of choline are depleted during pregnancy and lactation.
The placenta accumulates choline by pumping choline into the tissue, where it is then stored, mostly as acetylcholine.
Choline concentrations in amniotic fluid can be ten times higher than in maternal blood.
Choline is a substrate for building cellular membranes in fetal and maternal tissue expansion.
Human brain growth is most rapid during the third trimester of pregnancy and continues to be rapid to approximately five years of age.
During brain development the demand is high for sphingomyelin, which is made from phosphatidylcholine, and thus from choline.
Sphingomyelin is used to myelinate nerve fibers.
Choline is also used in the production of the neurotransmitter acetylcholine, which can influence the structure and organization of brain regions, neurogenesis, myelination, and synapse formation.
Acetylcholine present in the placenta and may help control cell proliferation and differentiation and parturition.
Choline uptake to the brain is controlled by a low-affinity transporter located at the blood–brain barrier.
Transport occurs when plasma choline concentrations increase above 14 μmol/l, which can occur during a spike in choline concentration after consuming choline-rich foods.
Neurons acquire choline by both high- and low-affinity transporters.
Choline is stored as membrane-bound phosphatidylcholine, which can be used for acetylcholine neurotransmitter synthesis later.
Acetylcholine is formed as needed, travels across the synapse, and transmits the signal to the following neuron.
Subsequently, acetylcholinesterase degrades it, and the free choline is taken up by a high-affinity transporter into the neuron again.
Choline chloride and choline bitartrate are used in dietary supplements.
Certain choline salts supplement animal feeds.
Some salts are also used as industrial chemicals.
Choline theophyllinate and choline salicylate are used as medicines,
like methacholine and carbachol.
Radiolabeled cholines, are used in medical imaging.
Rarely, symptomatic choline deficiency causes nonalcoholic fatty liver disease and muscle damage.
Excessive consumption of choline is considered greater than 7.5 g/day.
Excessive consumption of choline can cause hypotension, sweating, diarrhea and fish-like body odor (due to ).
Rich dietary sources of choline and choline phospholipids include organ meats and egg yolks, dairy products, peanuts, certain beans, nuts, seeds and vegetables with pasta and rice also contributing to choline intake in the American diet.