What is choline?
Choline is an essential nutrient that plays a role in the synthesis of phospholipid membranes and is a source of methyl groups that are needed for many steps in metabolism. It’s also the precursor to the neurotransmitter acetylcholine. Choline has particular relevance for brain development, liver health, and skeletal muscle function. Choline is mostly found in animal foods such as eggs, milk, fish, chicken, and beef, but some plant foods also contain choline.[2]
What are choline’s main benefits?
Choline supplementation during pregnancy or early childhood has favorable effects on children’s brain function and neurodevelopment, including memory, attention, and visual-spatial learning.[3] Choline supplementation among children with fetal alcohol spectrum disorder improves memory, nonverbal intelligence, visual-spatial skills, ADHD symptoms, executive function, and white matter microstructure.[4][5][6] These effects occur primarily when choline is supplemented before the age of 5.
Higher choline intakes have been associated with a lower risk for cardiovascular events and stroke, cognitive impairment, post-stroke depression,[7] cardiovascular disease,[8] and dementia.[9] A higher intake of choline is also associated with lower levels of cardiometabolic risk factors.[10] Interestingly, a low choline intake may impair gains in strength and lean mass in response to exercise training[11][12] and reduce cognitive function.[9]
What are choline’s main drawbacks?
High/excessive intakes of choline can result in some side effects, including a fishy body odor, vomiting, excessive sweating and salivation, low blood pressure (hypotension), and liver toxicity.[1] In addition, choline consumption has been shown to increase the production of trimethylamine N-oxide (TMAO), which is associated with an increased risk of cardiovascular disease. However, some studies indicate that the amount of choline consumed in 3 eggs per day does not elevate plasma TMAO levels.[13][14][15][16][17] Some studies have associated higher choline intakes with increased atrial fibrillation risk[18] and type 2 diabetes.[19]
How does choline work?
Dietary choline is a precursor for the neurotransmitter acetylcholine (ACh), which is crucial for normal cognitive and motor function. Choline is irreversibly oxidized into betaine in the liver and kidneys. Betaine is a methyl group donor that participates in the important process of remethylating homocysteine to methionine. Choline is also a precursor for the synthesis of phosphatidylcholine, the most abundant form of phospholipid in the body.[2]
Choline is important for neural tube closure, stem cell proliferation, and apoptosis (programmed cell death) in the fetal brain during early pregnancy. The choline metabolite phosphatidylcholine is also required for packaging and exporting very-low-density lipoproteins from the liver and the secretion of bile acid salts; the disruption of this process can contribute to the accumulation of triglycerides in the liver.[20][21][22][23][24]
What are other names for Choline
- Trimethylethanolamine
- Choline Bitartrate
- DMAE
- Lecithin
- alpha-GPC
- CDP-choline
- Citicoline
Dosage information
The adequate intake (AI) for choline is 550 mg per day for men and 425 mg per day for women. The AI for choline increases during pregnancy (450 mg per day) and lactation (550 mg per day).
The tolerable upper intake level (UL) for choline from food and supplements is 3,500 mg per day for men and women. The UL is 1,000 mg per day for children 1–8 years old, 2,000 mg per day for children 9–13, and 3,000 mg per day for children 14–18 years old.[1]
Frequently asked questions
Choline is an essential nutrient that plays a role in the synthesis of phospholipid membranes and is a source of methyl groups that are needed for many steps in metabolism. It’s also the precursor to the neurotransmitter acetylcholine. Choline has particular relevance for brain development, liver health, and skeletal muscle function. Choline is mostly found in animal foods such as eggs, milk, fish, chicken, and beef, but some plant foods also contain choline.[2]
Choline is found naturally in foods in different forms, including the fat-soluble phospholipids phosphatidylcholine and sphingomyelin and the water-soluble compounds phosphocholine, glycerophosphocholine, and free choline. About half of the dietary choline consumed in the United States is in the form of phosphatidylcholine.
The main dietary sources of choline are animal-based foods such as meat, poultry, fish, dairy, and eggs, as well as some cruciferous vegetables, beans, nuts, seeds, and whole grains. The top sources of choline are beef liver (3 ounces contains 356 mg of choline), eggs (one large egg contains 147 mg of choline), beef (3 ounces contains 117 mg of choline) and soybeans (one half of a cup contains 107 mg of choline).[1]
Choline can also be obtained from dietary supplements that contain choline, choline + B vitamins, and multivitamin/multimineral products. Most tend to contain 10–250 mg of choline. The most commonly supplemented form of choline is choline bitartrate.
Choline is produced endogenously in the liver (as phosphatidylcholine), but the amount we make isn’t sufficient to meet our body’s needs. Therefore, it’s essential to obtain choline from the diet and/or supplements. According to some estimates, adults in the United States only consume between 278 and 402 mg of choline per day, which falls below the adequate intake (AI) for choline.[25] Despite having lower-than-recommended dietary intakes of choline, most adults don’t appear to be choline-deficient, possibly due to the contribution from endogenous choline production.
The liver is the primary site for choline synthesis. Choline synthesis is catalyzed by the enzyme phosphatidylethanolamine N-methyltransferase (PEMT), which synthesizes phosphatidylcholine by methylating phosphatidylethanolamine using the methyl donor S-adenosyl-L-methionine (SAMe).
Choline supplementation during pregnancy or early childhood has favorable effects on children’s brain function and neurodevelopment, including memory, attention, and visual-spatial learning.[3] Choline supplementation among children with fetal alcohol spectrum disorder improves memory, nonverbal intelligence, visual-spatial skills, ADHD symptoms, executive function, and white matter microstructure.[4][5][6] These effects occur primarily when choline is supplemented before the age of 5.
Higher choline intakes have been associated with a lower risk for cardiovascular events and stroke, cognitive impairment, post-stroke depression,[7] cardiovascular disease,[8] and dementia.[9] A higher intake of choline is also associated with lower levels of cardiometabolic risk factors.[10] Interestingly, a low choline intake may impair gains in strength and lean mass in response to exercise training[11][12] and reduce cognitive function.[9]
Choline deficiency can lead to muscle damage, liver damage, and nonalcoholic fatty liver disease. However, clinically evident choline deficiency is very rare, likely due to the contribution of the body’s endogenous choline production.
Choline intakes tend to be below the adequate intake for children and adults, who average an intake of 256 mg per day and 278–402 mg per day, respectively.[25]
Worldwide choline intakes have been estimated to be 284–468 mg per day for men and 263–374 mg per day for women. In the United States and Canada, adult intakes range from 260–396 mg per day and 292–372 mg per day, respectively.[2] The United States National Institutes of Health consider adequate intake to be 550 mg/day for men and 425 mg/day for women.[1]
Pregnant and lactating women need more choline. During pregnancy, choline demand rises due to its role in neural tube formation, brain development, and lipoprotein synthesis. There’s also evidence that choline may prevent neural tube defects, improve offspring cognitive development, and promote maternal well-being.[26] Most (90%–95%) pregnant women consume less than the adequate intake (AI) for choline,[27] and prenatal supplements typically don’t contain choline. Women who do not supplement with folic acid, those who have a low vitamin B12 status, or those who have a common variant in the enzyme methylenetetrahydrofolate dehydrogenase are the most at risk for having an inadequate choline status.[26]
Dietary choline requirements are lower in premenopausal women because estrogen induces the enzyme phosphatidylethanolamine N-methyltransferase (PEMT), which synthesizes phosphatidylcholine. However, women who have a genetic mutation in PEMT have less estrogen-induced choline synthesis and therefore higher choline requirements.[28]
Finally, adults and infants receiving total parenteral (intravenous) nutrition may need to be supplemented with choline because choline is not routinely added to these solutions. Long-term parenteral nutrition has been shown to reduce plasma choline concentrations in adults and infants and is associated with the development of fatty liver and impaired liver function.[29] These changes can be attenuated by providing intravenous choline.[30][31]
High/excessive intakes of choline can result in some side effects, including a fishy body odor, vomiting, excessive sweating and salivation, low blood pressure (hypotension), and liver toxicity.[1] In addition, choline consumption has been shown to increase the production of trimethylamine N-oxide (TMAO), which is associated with an increased risk of cardiovascular disease. However, some studies indicate that the amount of choline consumed in 3 eggs per day does not elevate plasma TMAO levels.[13][14][15][16][17] Some studies have associated higher choline intakes with increased atrial fibrillation risk[18] and type 2 diabetes.[19]
Dietary choline undergoes anaerobic metabolism by gut microbes to form trimethylamine (TMA) which is then oxidized by liver enzymes to form trimethylamine N-oxide (TMAO), a newly recognized risk marker for cardiovascular disease.[32]
However, several dietary sources of choline (e.g., eggs) actually contain phosphatidylcholine, which may not have the same TMAO-elevating effects as choline (as choline bitartrate or other forms). For example, multiple studies have shown that eating up to 3 eggs per day (about 400 mg of choline) elevates plasma choline levels but does not increase TMAO.[13][33][14][15][16][17] On the other hand, TMAO levels increase up to 3-fold following the intake of 600 mg of choline bitartrate.[34] Adding choline to the diet from beef (3–6 ounces as part of a Dietary Approaches to Stop Hypertension diet) increases plasma choline by 10% and TMAO levels by 27% in older adults with obesity.[35]
Differences in gut microbiota may explain individual differences in TMAO production following choline intake. For example, high TMAO producers had more abundant lineages of Clostridium and Ruminococcaceae and Lachnospiraceae compared to low TMAO producers.[34]
Overall, because phosphatidylcholine is the major form of choline in food and phosphatidylcholine doesn’t appear to elevate TMAO levels, there’s no reason to avoid phosphatidylcholine over fears of its TMAO-elevating effects. Furthermore, meta-analyses have found no association between dietary choline/betaine intake and the risk of cardiovascular disease outcomes (e.g., coronary artery disease or stroke).[36]
Dietary choline is a precursor for the neurotransmitter acetylcholine (ACh), which is crucial for normal cognitive and motor function. Choline is irreversibly oxidized into betaine in the liver and kidneys. Betaine is a methyl group donor that participates in the important process of remethylating homocysteine to methionine. Choline is also a precursor for the synthesis of phosphatidylcholine, the most abundant form of phospholipid in the body.[2]
Choline is important for neural tube closure, stem cell proliferation, and apoptosis (programmed cell death) in the fetal brain during early pregnancy. The choline metabolite phosphatidylcholine is also required for packaging and exporting very-low-density lipoproteins from the liver and the secretion of bile acid salts; the disruption of this process can contribute to the accumulation of triglycerides in the liver.[20][21][22][23][24]
During pregnancy, the demand for choline increases due to its essential role in neural tube formation, brain development, lipoprotein synthesis, liver function, and lipid metabolism. Large amounts of choline are delivered to the developing fetus across the placenta — the concentration of choline in amniotic fluid may be up to 10 times greater than in maternal blood.[37] The delivery of choline to the fetus depletes maternal choline levels, as does lactation. As such, it’s crucial for pregnant and lactating women to maintain high levels of choline while breastfeeding to avoid depleting their choline stores.
Low maternal choline intakes or plasma choline levels are associated with an up to 2.4-fold greater risk for neural tube defects.[3] Intervention studies have shown that higher maternal choline intakes (550 to 1,000 mg per day) during the second half of pregnancy and the early postnatal period are safe and have favorable effects on the offspring’s memory, attention, and visual-spatial learning.[3] Choline is also associated with better maternal health and well-being.[26]
For this reason, the adequate intake (AI) for choline is 450 mg per day for pregnant women and 550 mg per day for lactating women — or 6%–30% higher than the AI for non-pregnant women.
Among women of childbearing age, choline intake from food sources ranges from 244 to 443 mg per day. Women in Europe report an average choline intake of 291 (France) to 374 (Sweden) mg per day, while women in the United States get an estimated 250–443 mg per day, and Australian women have an average choline intake of 244 mg per day. Less than 5% of Australian women had a choline intake that reached or exceeded the AI of 425 mg per day.[38]
Most pregnant women consume below the AI for choline, with average estimated intakes of 190–383 mg per day. Choline intakes for pregnant women in the United States range from 281 to 332 mg per day and are similar among women from Canada (306–383 mg per day), the United Kingdom (338 mg per day), Australia (51 mg per day), Belgium (274–280 mg per day), China (255 mg per day), Jamaica (279 mg per day), New Zealand (310 mg per day), and Latvia (336 mg per day). Lower levels of choline intake have been reported for pregnant women in Bangladesh (190 mg per day). There’s little evidence to indicate that choline intake changes across trimesters of pregnancy or when choline from supplements is included.[38] Choline intake during lactation has been less well characterized but has been reported to be in the range of 257 to 346 mg per day.
In summary, with little exception, few women of childbearing age or who are pregnant/lactating appear to consume enough choline despite its critical relevance for fetal growth and development.
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