CHOLINE

Choline, a dietary component of many foods, is part of several major phospholipids (including phosphatidylcholine - also called lecithin) that are critical for normal membrane structure and function. The major precursor of betaine, it is used by the kidney to maintain water balance and by the liver as a source of methyl-groups for methionine formation. Also, choline is used to produce the important neurotransmitter acetylcholine. In the body choline is mainly found in phospholipids, such as lecithin (phosphatidylcholine) and sphingomyelin. The outer leaflet of plasma membrane is rich in these choline-phospholipids whereas the inner leaflet is dominated by phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. Phosphatidylcholine, the predominant phospholipid (>50%) in most mammalian membranes, not only contributes to the structure of the membrane bilayer, but products of receptor-mediated lecithin hydrolysis also serve as important second messengers in signal cascades that control cell growth and gene expression. Disaturated phosphatidylcholine is the primary active component of surfactant in the lung; a deficiency of surfactant in the neonate leads to respiratory distress syndrome in premature infants.

The metabolism of choline, methionine, and methyl-folate are closely interrelated; the metabolic pathways intersect at the formation of methionine from homocysteine. Some choline can be formed from methionine (through the methylation of phosphatidylethanolamine by phosphatidylethanolamine N-methyltransferase using S-adenosylmethionine as the methyl donor). This can provide some of the choline required by humans.

There are a number of mechanisms that ensure the developing fetus and the infant receive adequate amounts of choline. Like other nutrients, large amounts of choline are delivered to the fetus across the placenta. This depletes maternal stores of choline. Human milk is an especially good source of choline.

Deficiencies: Although each of the above functions is absolutely vital for the maintenance of normal cellular and organ functions, it has been difficult to identify choline-deficiency syndromes in humans. The Institute of Medicine noted that "Healthy males with normal folate and vitamin B12 status fed a choline deficient diet have diminished plasma choline and phosphatidylcholine concentrations, and develop liver damage. For these humans, de novo synthesis of choline was not adequate to meet the demand for the nutrient." Patients fed by total parenteral nutrition sometimes develop fatty liver, abnormal liver function tests, and low plasma choline and phosphatidylcholine concentrations. This is in part due to an impaired capacity to de novo synthesize choline. In some of these patients, these abnormalities resolve when they are treated with a dietary source of choline.

Diet recommendations: Based on the limited human data that is currently available, the Institute of Medicine, National Academy of Sciences USA, recommended that humans consume choline. They set an adequate intake (AI) level for choline of 550 mg/day for men and 425 mg/day for women. For children, the AI was proportionately adjusted for body size.

Food sources: Choline and choline esters can be found in significant amounts in many foods consumed by humans; some of the choline is added during processing (especially in the preparation of infant formula). Little reference information exists on the relative choline content of foods, but we estimate the average choline dietary intake (as choline and choline esters) of the adult human to be more than 500 mg/day. Orally ingested choline (e.g., as hydrochloride salt) may be degraded by intestinal bacteria and cause a fishy body odor; this does not occur when lecithin is eaten.

Clinical uses: Amino acid-glucose solutions used in total parenteral nutrition of humans lack choline. The lipid emulsions that deliver extra calories and essential fatty acids during parenteral nutrition contain choline in the form of lecithin (20% emulsion contains 13.2 mmol/L). Humans treated with parenteral nutrition required 1-1.7 mmol of choline-containing phospholipid/day during the first week of parenteral nutrition therapy to maintain plasma choline levels.

There are no established approaches to determine nutritional status for choline. Plasma choline and phosphatidylcholine concentrations fall when humans are fed a choline-deficient diet or after strenuous, prolonged physical activity, such as running a marathon. Even in severe deficiency, plasma choline concentrations do not fall below 50% of normal. Measurement of serum alanine aminotransferase activity, which rises approximately 1 week after the feeding a choline-deficient diet, may prove beneficial in assessment of choline nutritional status.

Toxicity: Large oral doses of choline or phosphatidylcholine may be associated with hypotension, sweating, salivation and diarrhea. Large doses of choline can cause a fishy body odor. The Tolerable Upper Limit for adults has been set at 3.5 g/day of choline.

For further information:

Buchman, A. L., Dubin, M. D., Moukarzel, A. A., Jenden, D. J., Roch, M., Rice, K. M. & Gornbein, J. (1995) Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology 22(5): 1399-1403.

Zeisel, S. (1997) Choline: essential for brain development and function. Adv. Pediatr. 44: 263-295.

Committee on the Scientific Evaluation of Dietary Reference Intakes, Institute of Medicine. (1998) Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic acid, Biotin, and Choline. National Academy Press, Washington, DC.

Prepared By:

Raj Chawla, Ph.D.
Professor, Internal Medicine, Clinical Nutrition,
and Toxicology
University of Kentucky Medical Center
MN 644 UKMC,
Lexington, KY 40536-0084
Phone: 606-323-6206
FAX: 606-323-1020
Email: rkchaw0@pop.uky.edu

Steven H. Zeisel, M.D., Ph.D.
Professor and Chairman of Nutrition
Professor of Pediatrics
School of Public Health and School of Medicine
The University of North Carolina
Chapel Hill, NC 27599-7400 USA
Phone: 919-966-7218
FAX: 919-966-7216
Email: steven_zeisel@unc.edu