by Aliza Becker, BA, MPS
Choline, a water-soluble nutrient that has been recognized as essential for body function and health by the United States (US) Institute of Medicine since 1998.1 First discovered in 1862 by German chemist Adolph Strecker as a novel nitrogenous chemical created when lecithin from bile was heated, further research revealed that another substance discovered three years later in the brain by German pharmacologist Oscar Liebreich, known briefly as neurine, was in fact choline as well.2 Evidence supporting choline’s role as an essential nutrient subsequently emerged in 1932 following experiments to prevent fatty liver in canines.2 Other research throughout the 1900s established choline as a component of two biologically significant molecules—phosphatidylcholine (a phospholipid and a major component of cell membranes) and acetylcholine (a neurotransmitter).2
What Does Choline Do?
Choline has been confirmed to have a number of roles in the body. Along with its part as a precursor of phosphatidylcholine, choline is also necessary for the biosynthesis of other essential components of cell membranes3 and is involved in mitochondrial function4,5 and lipid metabolism.6,7 Adequate choline in the diet is important for the formation of the brain and spinal cord in utero,6 and later helps prevent damage to the liver,3 perhaps in part by normalizing cholesterol metabolism.8 Other research indicates that choline deficiency can lead to a progressive decline in renal function.9 Additionally, choline is known to support cognitive function and memory performance,10 and it has been established that inadequate choline induces apoptosis (cell death) in different cultured cell lines, including brain and liver cells.11
According to a literature review by Moretti et al,12 choline also influences skeletal muscle by modulating fat and protein metabolism, inflammation, and autophagy. Research has reported antinociceptive effects of choline in inflammatory pain, suggesting its potential as a nonaddictive pain reliever.13
How Much Choline Do We Need?
Although choline can be endogenously synthesized in the liver by the conversion of phosphatidylethanolamine, a phospholipid, to phosphatidylcholine via the phosphatidylethanolamine N-methyltransferase pathway, the amount accumulated by this process is considered insufficient for daily needs;3 thus, additional choline must be taken in through the diet. US dietary guidelines stipulate that the adequate intake (AI) amount of choline for adults aged 19 years or older is 550mg/day for men and 425mg/day for women, with a tolerable upper limit of 3,500mg/day.1 The AI for children younger than one year of age is 125mg/day (0–6 months) to 150mg/day (6–12 months), increasing progressively with age from 200mg/day in children 1 to 3 years of age to 550mg/day in boys 14 to 18 years of age and 400mg/day in girls 14 to 18 years of age.1 However, in a narrative review of the 2018 Choline Science Summit,14 researchers cautioned that the described AI values were chosen at a point in time when dietary intakes of the nutrient across the population were unknown, and these values were informed in part by a depletion–repletion study3 of adult men who developed signs of liver damage when deficient in choline rather than by use of the traditional method of calculating an AI based on intake values observed or experimentally determined in a group of healthy individuals. The researchers noted that the food patterns recommended by the 2015–2020 Dietary Guidelines for Americans were insufficient to meet the AI for choline in most age–sex groups;14 indeed, an analysis of data from the National Health and Nutrition Examination Survey (NHANES) published in 2016 suggested that just 11 percent of American adults achieve the daily AI for choline.15
What Are Dietary Sources of Choline?
Dietary choline exists in both water-soluble (e.g., free choline, phosphocholine, and glycerophosphocholine) and lipid (fat)-soluble (e.g., phosphatidylcholine and sphingomyelin) forms, which differ in how they are metabolized in the body following ingestion. Water-soluble forms of choline travel to the liver through portal circulation, while lipid-soluble forms first must be packaged with fatty acids and cholesterol into chylomicrons,16 which are then absorbed and transported through the lymphatic circulation.17 During a human’s infancy, most choline is consumed in the water-soluble form found in breast milk, while adults tend to obtain lipid-soluble forms of choline through diet.18 Those who consume animal-based foods are likely to take in more choline than those who consume a vegetarian or wholly plant-based diet; in particular, research indicates that those who consume eggs have nearly double the intake of choline compared to individuals who do not consume eggs.19
In an analysis of the choline concentration of 145 common foods using liquid chromatography–mass spectrometry, investigators20 reported foods with the highest total choline concentration to be as follows:
• Beef liver (418mg/100g)
• Chicken liver (290mg/100g)
• Eggs (251mg/100g)
• Wheat germ (152mg/100g)
• Bacon (125mg/100g)
• Dried soy beans (116mg/100g)
• Pork (103mg/100g)
Smaller amounts of choline may also be found in the following:
• Nuts and seeds
—Coffee (brewed from grounds, prepared with tap water (2.6mg/100g)
—Light beer (7.9g/100g).21
Both water- and lipid-soluble forms of choline are present in a few single foods (e.g., strawberries contain free choline [0.6mg/100g], glycerophosphocholine [0.9mg/100g], and phosphatidylcholine [4.2mg/100g),]21 which contribute collectively to total dietary choline concentration. Additionally, dietary betaine as a methyl donor may act as a substitute for up to 50 percent of an individual’s choline needs.22 Foods with the highest betaine concentration (mg/100g) are wheat bran (1,506mg/100g), wheat germ (1,395mg/100g), spinach (725mg/100g), pretzels (266mg/100g), shrimp (246mg/100g), and wheat bread (227mg/100g).23 The US Department of Agriculture reports that strawberries contain 0.2mg/100g of betaine;.21 however, this capacity to substitute for inadequate choline does not seem to exist among all methyl donor nutrients. For example, Zeisel et al3 documented decreased choline stores and elevated alanine aminotransferase levels (indicative of liver damage) when men were fed a diet that contained adequate methionine, folate, and vitamin B12 but inadequate choline for three weeks, while Jacob et al24 reported that choline may be co-opted to cover for inadequate folate intake, which may enhance a choline discrepancy.
Special Populations at Risk for Choline Deficiency
Though nearly 90 percent of Americans may not be achieving their daily AI for choline,15 certain populations are at even greater risk of deficiency. Foremost, in pregnant women, choline is delivered to the fetus during gestation to support brain and spinal cord development, depleting maternal choline stores.25,26 Human breast milk is rich in choline, so lactation further reduces maternal levels.27 Moreover, inadequate levels of other nutrients can further complicate nutritional status. For example, Wu et al28 reported that lower vitamin B levels correlated with lower choline levels in a population of pregnant Canadian women. In pregnant women, the AI is 450mg/day.1
Those who are physically active should also remain aware of their choline needs. Conlay et al29 suggested that athletes may deplete their choline levels by approximately 40 percent when engaging in strenuous physical activity. Other research has indicated that plasma choline concentrations after biking in triathletes who took a placebo were reduced by an average of 16.9 percent compared to those who took lecithin.30
Genetic variations can also lead to an increased susceptibility to choline deficiency.31
Many of the foods offering significant levels of dietary choline are animal products, suggesting the need for greater awareness of potential choline deficiency among those who primarily or exclusively consume a plant-based diet, although some research found no differences in total water-soluble choline concentrations among healthy lactating women who adhered to a vegan, vegetarian, or non-vegetarian diet.32
Choline and Disease
In a National Health and Nutrition Examination Survey by the US Centers for Disease Control and Prevention (CDC) data analysis, both total and dietary choline intake was inversely associated with hypertension in women, and the use of choline supplements was inversely associated with hypertension in both sexes.33 Other researchers argue that each 100-mg increase in dietary choline reduced the risk of hypertension by 17 percent in individuals younger than 55 years of age and by 21 percent in men.34 However, emerging research also reveals that higher plasma concentrations of choline and betaine are associated with an increased risk of subsequent atrial fibrillation35 and that gut microbial production of trimethylamine N-oxide (TMAO) from dietary choline is prothrombotic (i.e., blood-clot promoting).36 Although betaine and L-carnitine also help to produce TMAO, the ability of choline to do so is stronger than that of either betaine or L-carnitine.37 Higher plasma TMAO levels have been linked to increased risk of cardiovascular-associated mortality in individuals with peripheral artery disease38 and independently associated with the risk of major adverse cardiac events (including myocardial infarction, stroke, the need for revascularization, or death) over ensuing 30-day and six-month periods. TMAO also facilitates the aggregation of two proteins, amyloid-beta peptide and tau protein, which is the main pathology associated with Alzheimer’s disease.39 Finally, elevated plasma TMAO levels predict the long-term future risk for the development of chronic kidney disease; moreover, as the kidneys lose function, eliminating TMAO from the body becomes more difficult and its levels further increase.40
In cancer, a meta-analysis by Sun et al41 suggested that an increase in consumption of 100mg/day of choline plus betaine lowered the risk of cancer by 11 percent. Other researchers suggest higher intakes of total choline, with a preference toward intake of phosphatidylcholine, glycerophosphocholine, and sphingomyelin, may reduce risk of colorectal cancer;42 intake of choline and betaine, especially higher levels of betaine, may be protective against lung cancer in smokers,43 and greater intake levels of betaine, phosphocholine, and free choline may reduce all-cause and breast cancer-specific mortality rates in a dose-dependent fashion.44 However, other research suggests that the inverse association between choline intake and breast cancer risk is confined primarily to individuals with a low folate level.45
According to Richman et al,46 men in the highest quintile of choline intake (median intake, 509mg/day) had a 70-percent increased risk of lethal prostate cancer, although their post-diagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer. Such contrasting findings indicate the necessity for further research to determine the cut off between the benefits and risks of choline in cancer and other diseases.
Choline serves a number of important functions in the body, including, on the cellular level, assisting with the biosynthesis of other essential components of cell membranes,3 mitochondrial function,23,24 and lipid metabolism.25,26 Choline is also essential to developing the brain and spinal cord in utero,25 as well as to maintaining cognitive and memory function throughout life. Choline is thought to have liver- and kidney-protecting properties and help regulate cholesterol metabolism. Better clarification is needed as to exactly how much choline children and adults need for optimal functioning. The best sources of choline are animal-based. However, there are several plant-based foods that are decent sources of choline. While higher intakes of choline have been associated with reduced risk of certain types of cancers, some researchers have reported opposite findings, suggesting the need for additional research to clearly define optimal intake levels of choline among children, adults, men, and women.
Editor’s note: Please consult a qualified dietitian/nutritionist or healthcare provider regarding your optimal nutritional needs.
- Food and Nutrition Board. Institute of Medicine. Dietary reference intakes: thiamine, riboflavin, niacin, vitamin B-6, vitamin B012, pantothenic acid, biotin, and choline. Washington, DC: National Academy of Sciences;1998:390–422.
- Zeisel SH. A brief history of choline. Ann Nutr Metab. 2012;61(3):254–258.
- Zeisel SH, Da Costa KA, Franklin PD, et al. Choline, an essential nutrient for humans. FASEB J. 1991;5(7):2093–2098.
- Teodoro JS, Rolo AP, Duarte FV, et al. Differential alterations in mitochondrial function induced by a choline-deficient diet: understanding fatty liver disease progression. Mitochondrion. 2008;
- Pacelli C, Coluccia A, Grattagliano I. Dietary choline deprivation impairs rat brain mitochondrial function and behavioral phenotype. J Nutr. 2010;140(6):1072–1079.
- Michel V, Singh RK, Bakovic M. The impact of choline availability on muscle lipid metabolism. Food Funct. 2011;2(1):53–62.
- Shen J, Sun B, Yu C, Cao Y, Cai C, Yao J. Choline and methionine regulate lipid metabolism via the AMPK signaling pathway in hepatocytes exposed to high concentrations of nonesterified fatty acids. J Cell Biochem. 2020;121(8–9):3667–3678.
- Montes de Oca M, Perazzo JC, Monserrat AJ, Arrizurieta de Muchnik EE. Acute renal failure induced by choline deficiency: structural-functional correlations. Nephron. 1980;26(1):41–48.
- Rajabi AL, Castro GSF, da Silva RP, et al. Choline supplementation protects against liver damage by normalizing cholesterol metabolism in Pemt/Ldlr knockout mice fed a high-fat diet. J Nutr. 2014;144(3):252–257.
- Blusztajn JK, Slack BE, Mellott TJ. Neuroprotective actions of dietary choline. Nutrients. 2017;9(8):815.
- Yen C-LE, Mar M-H, Craciunescu CN, et al. Deficiency in methionine, tryptophan, isoleucine, or choline induces apoptosis in cultured cells. J Nutr. 2002;132(7):1840–1847.
- Moretti A, Paoletta M, Liguori S, et al. Choline: an essential nutrient for skeletal muscle. Nutrients. 2020;12(7):2144.
- Wang Y, Su D-M, Wang R-H, et al. Antinociceptive effects of choline against acute and inflammatory pain. Neuroscience. 2005;132(1):49–56.
- Wallace TC, Blusztajn JK, Caudill MA, et al. Choline: the underconsumed and underappreciated essential nutrient. Nutr Today. 2018;53(6):240–253.
- Wallace TC , Fulgoni VL. Assessment of total choline intakes in the United States. J Am Coll Nutr. 2016;35(2):108–112.
- Rahmany S, Jialal I. Biochemistry, Chylomicron. [Updated 2021 Jul 22]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021.
- Zeissel SH. Dietary choline: biochemistry, physiology, and pharmacology. Annu Rev Nutr. 1981;1:95–121.
- Holmes-McNary MQ, Cheng WL, Mar MH, et al. Choline and choline esters in human and rat milk and in infant formulas. Am J Clin Nutr. 1996;64(4):572–576.
- Wallace TC, Fulgoni VL. Usual choline intakes are associated with egg and protein food consumption in the United States. Nutrients. 2017;9(8):839.
- Zeisel SH, Mar M-H, Howe JC, Holden JM. Concentrations of choline-containing compounds and betaine in common foods. J Nutr. 2003;133(5):1302–1307.
- Agricultural Research Service. US Department of Agriculture. USDA database for the choline content of common foods. Release 2. https://www.ars.usda.gov/ARSUserFiles/80400525/data/choline/choln02.pdf. Accessed 14 Dec 2021.
- Dilger RN, Garrow TA, Baker DH. Betaine can partially spare choline in chicks but only when added to diets containing a minimal level of choline. J Nutr. 2007;137(10):
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- Jacob RA, Jenden DJ, Allman-Farinelli MA, Swendseid ME. Folate nutriture alters choline status of women and men fed low choline diets. J Nutr. 1999;129(3):712–717.
- Sweiry JH, Page KR, Dacke CG, et al. Evidence of saturable uptake mechanisms at maternal and fetal sides of the perfused human placenta by rapid paired-tracer dilution: studies with calcium and choline. J Dev Physiol. 1986;8(6):435–445.
- Shaw GM, Carmichael SL, Yang W, et al. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol. 2004;160(2):
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- Wu BT, Innis SM, Mulder KA, et al. Low plasma vitamin B-12 is associated with a lower pregnancy-associated rise in plasma free choline in Canadian pregnant women and lower postnatal growth rates in their male infants. Am J Clin Nutr. 2013;98(5):1209–1217.
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- da Costa K-A, Kozyreva OG, Song J, et al. Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J. 2006;20(9):1336–1344.
- Perrin MT, Pawlak R, Allen LH, Hampel D. Total water-soluble choline concentration does not differ in milk from vegan, vegetarian, and nonvegetarian lactating women. J Nutr. 2020;150(3):512–517.
- Taesuwan S, Vermeylen F, Caudill MA, Cassano PA. Relation of choline intake with blood pressure in the National Health and Nutrition Examination Survey 2007–2010. Am J Clin Nutr. 2019;109(3):648–655.
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- Zuo H, Svingen GFT, Tell GS, et al. Plasma concentrations and dietary intakes of choline and betaine in association with atrial fibrillation risk: results from 3 prospective cohorts with different health profiles. J Am Heart Assoc. 2018;7(8):e008190.
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- Yu Z-L, Xhang L-Y, Jiang X-M, et al. Effects of dietary choline, betaine, and L-carnitine on the generation of trimethylamine-N-oxide in healthy mice. J Food Sci. 2020;85(7):
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About the Author
Ms. Becker is the managing editor of The Journal of Innovations in Cardiac Rhythm Management. She also works as a freelance editor and as a teaching assistant for the George Washington University’s Master of Professional Studies in Publishing program.