Rich food sources of choline include beef liver, eggs, fish, nuts, cauliflower and broccoli. Higher intake of choline is associated with a reduced risk of heart disease Folate and choline help convert the amino acid homocysteine to methionine. Therefore, a deficiency of either nutrient can result in an accumulation of homocysteine in your blood. Elevated levels of homocysteine in your blood are linked to an increased risk of heart disease and strokes Although choline may lower homocysteine levels, the association of choline intake with heart disease risk is not clear 27 , 28 , 29 , 30 , 31 , Choline may help reduce your risk of heart disease by lowering homocysteine levels.
However, the evidence is mixed. Choline is required to produce acetylcholine, a neurotransmitter that plays an important role in regulating memory , mood and intelligence Large observational studies link choline intake and blood levels to improved brain function , including better memory and processing 35 , Supplementing with 1, mg per day led to improved short- and long-term verbal memory in adults aged 50—85 who had poor memory However, other studies on healthy people and those with dementia found no effects on memory 39 , 40 , Several animal studies suggest that taking choline supplements during pregnancy may improve fetal brain development 20 , 42 , One observational study of 1, pregnant women found that choline intake had no links to mental performance in their children at 3 years of age Nevertheless, the same study determined that a higher intake during the second trimester was associated with better visual memory scores in the same children at age 7 In another study, 99 pregnant women took mg of choline per day from 18 weeks of pregnancy to three months after pregnancy.
They experienced no benefits for brain function or memory Some evidence suggests choline may play a role in the development and treatment of certain mental health disorders. One large observational study linked lower blood levels to a higher risk of anxiety — but not depression These levels are also used as an indicator for certain mood disorders, and choline supplements are sometimes used to treat bipolar disorder One study found that choline therapy improved symptoms of mania in individuals diagnosed with bipolar disorder Choline may boost memory function, improve brain development and treat anxiety and other mental disorders.
However, for most of these, the relationship is not clear and research is ongoing The study showed no association with liver disease in men or overweight women In one study , for example, women in their third trimester of pregnancy received either milligrams mg or mg of choline per day.
Those who took higher doses had reduced markers of preeclampsia. Symptoms of preeclampsia include high blood pressure , swelling, and severe headaches. One study found that choline supplementation improved lung function and reduced symptoms of fatty liver disease in 10 adult males with cystic fibrosis.
The following table lists the estimated adequate intakes AI for choline based on age, biological sex, and pregnancy and lactation status:. According to the United States Department of Agriculture , males aged 20—59 consume an average of — mg of choline per day, while females in the same age group consume around — mg per day. Although some people believe that vegetarians and vegans may be at risk of choline deficiencies, there is only mixed evidence to support this.
In fact, some of the foods with the highest choline content include soybeans, potatoes, and mushrooms. Eating a nutritious diet that focuses on whole foods should be enough to prevent deficiency. Although choline deficiencies can lead to adverse health effects, too much choline can also cause problems, including:. People can get choline from various dietary sources. Infants require lots of choline during the first few months of life, most of which they get from breast milk or fortified formula.
Dietary sources of choline include :. Some multivitamins and dietary supplements, as well as prepackaged and fortified foods, may contain choline in the form of lecithin. People can also find supplements that contain only choline. The exact amount of available choline varies, so it is vital that people read labels before taking any dietary supplements. Choline supplements are available in pharmacies, health food stores, and online.
However, the authors of one article state that different testing procedures can affect the choline concentration in blood samples. Patients requiring total parenteral nutrition At present, choline is not routinely added to commercial parenteral solutions for infants and adults [ 28 , 29 ].
The American Society for Parenteral and Enteral Nutrition recommends the routine addition of choline to adult and pediatric parenteral nutrition formulations, and calls for the development of a commercially available parenteral product that contains choline [ 28 ]. This section focuses on three conditions in which choline might play a role: cardiovascular and peripheral artery disease, neurological disorders, and NAFLD.
Choline is involved in functions that overlap with those of folate and other B vitamins. Many studies do not assess the status of all B vitamins, which can confound results and obscure the true relationship between choline and the observed outcome. Cardiovascular and peripheral artery disease Some researchers have suggested that choline might protect cardiovascular health by reducing blood pressure, altering lipid profiles, and reducing levels of plasma homocysteine [ 3 ].
Other research suggests that higher dietary choline might increase cardiovascular disease risk because some choline and other dietary ingredients, such as carnitine, are converted to trimethylamine TMA by intestinal bacteria.
The TMA is then absorbed and converted by the liver into trimethylamine-N-oxide TMAO , a substance that has been linked to a higher risk of cardiovascular disease [ 33 , 34 ].
Despite the hypothesis that choline might affect heart health, several large observational studies have found no significant associations between choline intakes and cardiovascular or peripheral artery disease risk. Similarly, a prospective study in 14, middle-aged adults in the Atherosclerosis Risk in Communities Study found that over 14 years, risk of coronary heart disease was not significantly different in the highest choline intake quartile compared to the lowest quartile [ 36 ].
Choline intakes also had no association with cardiovascular disease risk in a study of 16, women participating in the European Prospective Investigation into Cancer and Nutrition [ 37 ]. Additional research is needed to determine the relationship between choline intakes and cardiovascular and peripheral artery disease as well as the potential risks and benefits of choline supplementation to reduce the risk of these diseases.
In addition, because phosphatidylcholine can serve as a phospholipid precursor, it might help support the structural integrity of neurons and thus might promote cognitive function in elderly adults [ 8 ]. However, little research conducted to date supports this hypothesis, as described below. Some small randomized intervention trials have shown that choline supplements improve cognitive performance in adults [ 30 , 41 ].
However, a systematic review of 13 studies on the relationship between choline levels and neurological outcomes in adults found that choline supplements did not result in clear improvements in cognition in healthy adults [ 8 ].
A single drink [e. Although it is often benign, NAFLD can lead to steatohepatitis, fibrosis, cirrhosis, liver failure, and liver cancer [ 15 ]. Choline, especially phosphatidylcholine, is essential for transporting lipids from the liver [ 1 ].
Therefore, in choline deficiency, fat accumulates in the liver, which can result in NAFLD [ 44 , 45 ]. Data from a single large observational study support a link between choline deficiency and risk of NAFLD. Specifically, a cross-sectional study of 56, Chinese adults aged 40—75 years found an inverse relationship between dietary choline intakes and risk of NAFLD based on hour dietary recall [ 47 ].
However, choline intake was associated with NAFLD in normal-weight women only and not in those who were overweight or obese. This difference by weight status was not observed in men. Adequate choline intake is needed for proper liver function and to prevent NAFLD, but more research is needed to further clarify the role of choline in preventing or treating NAFLD [ 50 ].
High intakes of choline are associated with a fishy body odor, vomiting, excessive sweating and salivation, hypotension, and liver toxicity [ 1 , 2 ]. Choline consumption has been shown to increase production of TMAO, a substance that has been linked to a higher risk of cardiovascular disease, in a dose-dependent manner in adults.
The FNB has established ULs for choline from food and supplements based on the amounts of choline that are associated with hypotension and fishy body odor see Table 3 [ 2 ]. The ULs apply to healthy children and adults, but not to those taking high doses of choline under medical supervision.
The FNB was unable to establish ULs for infants due to the lack of data on adverse effects in this age group. The federal government's Dietary Guidelines for Americans notes that "Because foods provide an array of nutrients and other components that have benefits for health, nutritional needs should be met primarily through foods.
In some cases, fortified foods and dietary supplements are useful when it is not possible otherwise to meet needs for one or more nutrients e. For more information about building a healthy dietary pattern, refer to the Dietary Guidelines for Americans and the U. Department of Agriculture's MyPlate.
The nutrigenetics and nutrigenomics of the dietary requirement for choline. Prog Mol Biol Transl Sci ; Common genetic polymorphisms affect the human requirement for the nutrient choline. Faseb j ; Identification of new genetic polymorphisms that alter the dietary requirement for choline and vary in their distribution across ethnic and racial groups. Nutr Clin Pract ; This fact sheet by the Office of Dietary Supplements ODS provides information that should not take the place of medical advice.
We encourage you to talk to your healthcare providers doctor, registered dietitian, pharmacist, etc. Any mention in this publication of a specific product or service, or recommendation from an organization or professional society, does not represent an endorsement by ODS of that product, service, or expert advice. Updated: March 29, History of changes to this fact sheet. This is referred to as de novo synthesis of choline. The substitution of choline by serine in the synthesis of phosphatidylserine from phosphatidylcholine by phosphatidylserine synthase-1 also releases choline 4.
Because phosphatidylcholine metabolism is a source of endogenous choline, the nutrient was not initially classified as essential 1. In the US, mean dietary intakes of choline are well below the recommended AI. In a year US prospective study , including over 14, middle-aged participants, mean daily intakes of choline were mg and mg in women and men, respectively Eggs, liver, and peanuts, are especially rich in choline Major contributors to choline in the American diet are meat, poultry, fish, dairy foods, pasta, rice, and egg-based dishes Spinach, beets, wheat, and shellfish are also good sources of the choline metabolite , betaine Betaine cannot be converted back to choline but can spare some choline requirements for homocysteine remethylation 1.
Lecithin extracts, which comprise a mixture of phosphatidylcholine and other phospholipids , are often added during food processing. Lecithins in processed food have been estimated to increase the daily consumption of phosphatidylcholine by about 1. Strict vegetarians, who consume no meat, milk, or eggs, may be at risk for inadequate choline intake.
The total choline contents of some choline-containing foods are listed in milligrams mg in Table 2. For more information on the nutrient content of specific foods, search the USDA food composition website or the USDA documentation on the choline content of common foods. CDP-choline citicoline and choline salts, such as choline chloride and choline bitartrate, are available as supplements.
Therefore, a supplement containing 4, mg 4. Egg yolk lecithin is a more unlikely source of lecithin in dietary supplements. Moreover, the nature of phosphatidylcholine-containing fatty acids depends on whether lecithin is produced from vegetable, animal, or microbial sources.
In particular, soybean lecithin is richer in polyunsaturated fatty acids than egg yolk lecithin The fishy body odor results from excessive production and excretion of trimethylamine, a metabolite of choline.
Disease management includes the use of choline-restricted diets in affected individuals Taking large doses of choline in the form of phosphatidylcholine lecithin does not generally result in fishy body odor, because its metabolism results in little trimethylamine. However, it is likely that these effects were caused by the salicylate, rather than the choline in the preparation This recommendation was based primarily on preventing hypotension low blood pressure , and secondarily, on preventing the fishy body odor due to increased excretion of trimethylamine.
The UL was established for generally healthy people, and the FNB noted that individuals with liver or kidney disease, Parkinson's disease , depression, or inherited trimethylaminuria might be at increased risk of adverse effects when consuming choline at levels near the UL Oral supplementation with phosphatidylcholine mg of total choline from food plus mg of supplemental phosphatidylcholine has been found to result in detectable concentrations of trimethylamine and trimethylamine N-oxide TMAO in the blood The intestinal microbiota is directly implicated in the generation of trimethylamine from dietary choline, phosphatidylcholine, and carnitine.
Trimethylamine is subsequently converted into TMAO by flavin-containing monooxygenases in the liver. However, depending on gut microbiota composition, the risk of having an adverse cardiovascular event may be lower in individuals with low vs. Elevated TMAO concentrations have been reported in subjects at increased risk of CVD, such as those with diabetes mellitus 83 or end-stage renal disease chronic kidney failure 84 , and in patients with cardiac insufficiency chronic heart failure Yet, in the latter patients, high plasma concentrations of choline, betaine, and TMAO were not associated with a poorer survival rate after five years of follow-up Finally, supplementation with choline, TMAO, or betaine was found to result in the formation of macrophage -derived foam cells in atherosclerosis-prone mice Foam cells are known to contribute to the development of atherosclerotic lesions i.
Further research is needed to understand how the composition of intestinal microbiota influences the metabolic fate of ingested choline. At present, there is no evidence that dietary choline increases the risk of cardiovascular events.
Methotrexate, a medication used in the treatment of cancer , psoriasis , and rheumatoid arthritis , inhibits the enzyme dihydrofolate reductase and therefore limits the availability of methyl groups donated from folate derivatives. Rats given methotrexate have shown evidence of diminished nutritional status of choline and greater drug adverse reactions due to liver dysfunction 11 , Thus, individuals taking methotrexate may have an increased choline requirement.
Treatments with a family of lipid -lowering drugs known as fibrates e. If the benefits of fibrate therapy are indeed mitigated by fibrate-induced betaine deficiency, the use and safety of supplementing patients with betaine would need to be considered Little is known regarding the amount of dietary choline required to promote optimum health or prevent chronic diseases in humans.
A varied diet should provide enough choline for most people, but strict vegetarians who consume no milk or eggs may be at risk of inadequate choline intake. Little is known regarding the amount of dietary choline most likely to promote optimum health or prevent chronic diseases in older adults.
Originally written in by: Jane Higdon, Ph. Updated in May by: Jane Higdon, Ph. Updated in January by: Victoria J. Drake, Ph. Updated in August by: Victoria J. Updated in January by: Barbara Delage, Ph. Reviewed in February by: Steven H. Zeisel, M. Present Knowledge in Nutrition. Ueland PM. Choline and betaine in health and disease.
J Inherit Metab Dis. Gibellini F, Smith TK. The Kennedy pathway--De novo synthesis of phosphatidylethanolamine and phosphatidylcholine. Li Z, Vance DE. Phosphatidylcholine and choline homeostasis. J Lipid Res. Secades JJ. Citicoline: pharmacological and clinical review, update. Rev Neurol. Beckmann J, Lips KS. The non-neuronal cholinergic system in health and disease. A gender-specific role for phosphatidylethanolamine N-methyltransferase-derived phosphatidylcholine in the regulation of plasma high density and very low density lipoproteins in mice.
J Biol Chem. An unexpected requirement for phosphatidylethanolamine N-methyltransferase in the secretion of very low density lipoproteins. Pellanda H. Betaine homocysteine methyltransferase BHMT -dependent remethylation pathway in human healthy and tumoral liver. Clin Chem Lab Med. Homocysteine and atherosclerosis. Curr Opin Lipidol. Zeisel SH. Modern Nutrition in Health and Disease. Nat Rev Gastroenterol Hepatol. Choline and human nutrition.
Annu Rev Nutr. Choline deficiency increases lymphocyte apoptosis and DNA damage in humans. Am J Clin Nutr. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic Biol Med. Sex and menopausal status influence human dietary requirements for the nutrient choline. Dietary choline requirements of women: effects of estrogen and genetic variation. Phosphatidylethanolamine N-methyltransferase PEMT gene expression is induced by estrogen in human and mouse primary hepatocytes.
Faseb J.
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