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Choline

Choline is found in a wide variety of foods, yet many children, pregnant and lactation women have low intake. Prenatal supplements often do not contain adequate choline.

How it works

  • In pregnancy, choline is important for brain and spinal cord development of the infant [1] Involved in creating, breaking down, and transporting fats2-4 (required for VLDL synthesis and release from the liver) [2,3]

  • Supports neurotransmitter production (e.g., acetylcholine) [2-4]

  • Supports cell membranes (phospholipids) [2-4]

  • Works with other B vitamins (e.g., folate, B12) to make DNA and amino acids [3]

  • Involved in cell-to-cell communication [2]

  • Supports numerous reactions in the body, including those that regulate homocysteine [2,3] Betaine (a metabolite of choline) helps kidneys regulate water and osmotic stress [2-4]

​The body makes choline, but not enough to meet the demands of the body. Thus, choline is considered a vitamin-like substance. [2] Choline is widely distributed in food. [2,4]

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  • Soybeans, soy products (tofu, soymilk)

  • Peanuts, peanut butter

  • Wheat germ

  • Cruciferous veggies (broccoli, cabbage, Brussels sprouts)

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Animal sources of choline:  eggs, fish, chicken

Sources of nutrient

Bioavailability

No estimates are available on the absorption potentials of the different forms of choline in humans. [2]

Recommended daily amount

Daily upper limits

Measures of adequate status

There are no specific or sensitive indicators of choline deficiency.  

 

Plasma choline concentrations are affected by dietary intake (but do not accurately reflect intake [3)] and can vary 2 to 4-fold after meals or supplements, respectively. [2] Fasting plasma choline varies from 7 to 20 micromoles/L* (averages around 10 micromoles/L*) but may not decline even with a lack of dietary intake for more than a week. [2] (*Values may vary due to the assay used.)  

 

Plasma phosphatidylcholine concentrations decrease with choline deficiency but also are influenced by factors that change lipoprotein levels. [2]

Deficiency signs and symptoms

  • Liver steatosis, liver damage, and NAFLD (due to lack of VLDL formation and release[3]) with severe deficiency [2-4]

  • Muscle damage (with severe/prolonged deficiency) [3,4]

  • Lowered LDL (due to lack of VLDL formation and release in severe/prolonged deficiency) [3]

  • Increased creatinine phosphokinase, aspartate and alanine aminotransferases (in severe/prolonged deficiency) [2,3]

Examples of nutrient-rich foods

  • Persons consuming a mostly to fully plant-based diet without sufficient amounts of choline-rich food [3]

  • Pregnant and breastfeeding women as requirements are higher [1]

  • Infants aged 6 to 12 months, adolescents, and pregnant and breastfeeding women in the US tend to under-consume choline [1]

  • Persons with low folate status, intake, or genetic variants that reduce folate metabolism due to the irreversible conversion of choline to its metabolite betaine for methyl donation [3,4]

  • Individuals with certain medical conditions, such as cystic fibrosis, may have increased choline losses [4]

Populations at risk for deficiency

  • Fishy odor (typically with high-dose supplements except for lecithin [2]) [2-4]

  • Sweating, salivation, low blood pressure, vomiting, liver toxicity with excessive use of high-dose supplements [2-4] (e.g., 7500 mg or more [3])

Toxicity signs and prevention

The content provided is for informational purposes only and may not be an exhaustive list of potential interactions.

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  • ​Chloramphenicol – limited evidence suggests it may interfere with red blood cell response to supplemental B12 in some patients. [2] Proton pump inhibitors (e.g., omeprazole) – may interfere with acidic needs of food-based B12 to be absorbed. [2,8]

  • Although the impact on B12 status is conflicting, prolonged use of these drugs may influence B12 levels. [2]

  • H2 receptor antagonists (e.g., Zantac) – may interfere with the absorption of food-based B12. [2,8]

  • Metformin may reduce serum B12 levels by causing B12 to accumulate in the liver.[8] For example, randomized controlled trials of patients taking metformin for an average of 4.3 years had a ~20% decrease in B12 levels and a 7% increased risk of B12 deficiency compared to placebo. [2]

  • Phenformin may reduce B12 levels when used over long periods of time. [9]

  • Oral contraceptives may reduce vitamin B12 binding capacity in serum, and serum B12 levels in oral contraceptive users have been reported to be lower than in non-users; however, mechanisms are not fully understood. [22]

  • Chronic exposure to the anesthetic gas, nitrous oxide, can cause a functional B12 deficiency. [8] ​​

Potential drug-nutrient interactions

Notes

Although intake varies widely, only 11% of the U.S. population is estimated to meet adequate choline recommendations. [4]

​

Requirements for dietary choline are influenced by the demand for methyl-donors in metabolic reactions of folate, vitamin B12, and methionine (an amino acid). [2] For example, low folate levels can increase the demand for betaine, a metabolite of choline, as a methyl donor. [3]

 

Many prenatal vitamins do not contain choline, [1] and those that do typically have low amounts (25 – 50 mg [4])

 

Relationships between choline deficiency during pregnancy and the risk of neural tube defects (NTDs) have been inconsistent in studies; it is unknown if pre-conceptual supplementation of choline provides benefits against NTDs.[3] ​

 

Emerging evidence suggests choline plays a role in placental health and corticotropin-releasing hormone during pregnancy [4]

 

Estrogen stimulates the endogenous production of phosphatidylcholine [2,3] ​

 

Higher intake in the maternal diet can increase breast milk concentrations [4] ​

 

There is no convincing evidence that high choline or betaine intake may lower homocysteine for cardiovascular benefits. [3]

 

Free choline in the blood is shuttled across the blood-brain barrier by specific carrier transporters at a rate that is proportional to blood concentrations; the transporters are particularly efficient in neonates. [2]

 

Choline is part of lecithin, used as an emulsifier used in food processing; lecithin can contribute to choline intake in the diet[2-4] and has been used to treat high cholesterol. [2]

 

Betaine, a metabolite of choline, cannot be converted back to choline in the body, but dietary intake of betaine (e.g., beets, spinach, wheat) can donate methyl groups sparing choline from being used. [3,4]

 

Animal models suggest high TMAO (a choline metabolite) production from the gut may be linked with cardiovascular disease, diabetes, and chronic kidney disease; [3] however, gut interactions with food or supplemental choline in humans remain unknown. [3,4]

 

There is no evidence that dietary choline increases the risk of cardiovascular disease.[3] 

1. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th Edition. December 2020. Available at https://DietaryGuidelines.gov.

 

2. Institute of Medicine 1998. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: The National Academies Press. https://doi.org/10.17226/6015.

 

3. Choline Linus Pauling Institute Micronutrient Information Center, Oregon State University. Updated Feb 2015. Accessed Sept 2020. https://lpi.oregonstate.edu/mic/vitamins/choline

 

4. Zeisel SH, Klatt KC, Caudill MA. Choline. Adv Nutr; 2018;9:58–60.

 

5. FoodData Central Database. United States Department of Agriculture. Accessed Oct 2021. https://fdc.nal.usda.gov.

References

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