NPF Science Update: Choline
Posted Thursday, July 12, 2012

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Choline: Little Know Nutrient Essential for Life

By Robert M. Levy, MD

Almost all mammal cells contain choline. Choline is required for production of phospholipids (major components of cell membranes), production of the neurotransmitter acetylcholine, and is required for brain development and neural tube closure. Dietary choline occurs free or bound to phospholipids, but can be synthesized by the human body assuming the required precursor molecules (building blocks) are available. Human cells have an absolute requirement for choline without which they die.

Adequate intake level (AI) for women is 450 mg each day, and up to 550 mg during pregnancy and lactation. The level in neonates is 3-6 times higher than maternal blood. Current data suggest that most pregnant and lactating women do not achieve the AI and most prenatal vitamins do not contain choline. Human milk contains about 160-210 mg choline/l, a level that falls toward the end of pregnancy, presumably because of increased need of the developing fetus. The AI for infants in the first 6 months of life is about 25 mg/day rising to 150 mg/day for months 6-12. Animals fed choline deficient diets during pregnancy may have offspring with growth retardation and developmental abnormalities of bone, kidneys and other organs. 

Choline metabolism is intimately connected to levels of folate and vitamin B12. Choline deficiency is associated with neural tube defects in humans. Women in the lowest 25% of choline intake have approximately a 4-fold greater risk of having a child with a neural tube defect than choline replete women. Animal experiments have shown that choline can reverse some of the effects of developmental folate deficiency. Several genetic defects affecting choline synthesis have been identified and it is thought that more than half the population carry at least one of the genetic variations. These people are at greater risk for choline deficiency in the absence of adequate dietary intake. This may be of particular importance in pregnancy where inadequate maternal and fetal levels of choline may affect neurological development. 

Choline and brain development

Many studies have shown that improved cognitive and special function induced by choline supplementation in the fetal and neonatal stages persists into adulthood. Conversely, prenatal choline deficiency is associated with effects in learning and memory that persist throughout life. Studies in rats suggest that adequate choline intake early in life may decrease or delay the onset of memory deficits in older animals. For example, using magnetic resonance spectroscopy, choline levels were found to be decreased in selected brain areas in infants with fetal alcohol spectrum disorders (FASD). Similar results were found in teenagers and young adults with FASD. This is compatible with prior animal work in which choline was able to prevent many of the effects of prenatally administered alcohol even after alcohol induced brain damage and, possibly—although to a lesser extent—even when administered in the postnatal period.

The timing of supplement administration appears to be important and coincides with the time of peak development of learning and memory centers in the brain. At present it is not known if the effects of pre/perinatal choline are due to an augmentation of the number of neural cells, their number of connections, alteration in their organization, changes in membrane content or configurations, metabolic enhancement, or a phenomenon called metabolic imprinting. It seems most likely, however, that the underlying mechanism for the lifelong behavioral and cognitive effects of choline begin with modification of existing DNA, altered gene expression and changes in neural progenitor cells and neural organization that occur in prenatal learning, memory and visual centers in the brain beginning in the prenatal period and continuing until about age 3-4 years. 

In summary, choline is an essential, but little known nutrient, especially important for maintenance of neurologic and metabolic health. Maternal requirements increase significantly during pregnancy and lactation. Care should be taken to choose prenatal and postnatal vitamin preparation containing choline supplementation.

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Story Source: Robert M. Levy, MD, is the Director of Clinical Development at Primus Pharmaceuticals. Dr. Levy is Board Certified in Rheumatology and Internal Medicine and was in private practice in the State of Washington for 30 years. He was the founder and president of the Olympia Arthritis Clinic and Olympia Osteoporosis Center, and the Medical Director of South Sound Clinical Research Center. Dr. Levy received his MD from the University of Chicago School of Medicine and completed his rheumatology fellowship at the Scripps Clinic & Research Foundation.

References: Astley SJ, Richards T, Aylward EH, et al. Magnetic resonance spectroscopy outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders. Magn Reson Imaging. 2009.27:760-8.

Bremer J, Greenberg D. Methyl transferring enzyme system of microsomes in the biosynthesis of lecithin (phosphatidycholine). Biochim Biophys Acta. 1961. 16:205-16.

Caudill MA, Pre- and postnatal health: evidence of increased choline needs. J Am Diet Assoc. 2010.110:1198-206.

Craciunesco CN, Johnson AR, Zeisel SH. Dietary choline reveres some, but not all, effects of folate deficiency on neurogenesis and apoptosis in fetal mouse brain. J Nutr. 2010.140:1162-6.

da Costa KA, Kozyreva OG, Song J, et al. Common genetic polymorphisms have major effects on the human requirement for the nutrient choline. FASEB J. 2004.20:1336-44.

Fagerlund A. Heikkinen S, Autti-Ramo I. et al. Brain metabolic alterations in adolescents and young adults with fetal alcohol spectrum disorders. Alcohol Clin Exp Res. 2006.30:2097-104. 

Food and Nutrition Board: Institute of medicine, National Academy of Sciences. Dietary reference intake for Thiamine, riboflavin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin and choline. Wash. DC. National Academy Press. 1988.

Meck WH, Smith RA, Williams CL. Pre- and postnatal choline supplementation produces long term facilitation of special memory. Dev Psychobiol. 1988.21:339-53.

Meck WH, Smith RA, Williams CL. Organizational changes in cholinergic activity and enhanced visuospacial memory as a function of choline administered prenatally or postnatally or both. Behav Neurosci. 1989.103:1234-41.

Meck WH, Williams CL. Characterization of the facilitative effects of perinatal choline supplementation on timing and temporal memory. Neuroreport. 1997.8: 2831-5.

Meck WH, Williams CL. Metabolic imprinting of choline by its availability during gestation: implications for memory and attentional processing across the lifespan. Neurosci Biobehav Rev. 2003.27:385-99.

Ryan SH, Williams JK, Thomas JD. Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: Effects of varying the timing of choline administration. Brain Res. 2008.1237:91-100.

Shaw GM, Carmichael SL, Yang W, et al. Periconceptual dietary intake of choline and betaine and neural tube defects in offspring. Am j Epidem. 2004.160:102-9.

Schenk F, Brandner C. Indirect effects of peri- and postnatal choline treatment on place learning abilities in the rat. Psychobiol. 1995.23:302-13.

Thomas JD, Garrison M, O’Neill TM. Perinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats. Neurotoxicol Teratol. 2004.26:35-45.

Tees RC. The influences of sex, rearing environment and neonatal choline dietary supplementation on spacial and non-spacial learning and memory in adult rats. Dev Psychobiol. 1999. 35:328-42.

Yen CL, Mar MH, Meefer RB, et al. Choline deficiency induces apoptosis in primary cultures of fetal neurons. FASEB J. 2001.15:1704-10.

Zeisel SH, Blusztajn JK. Choline and human nutrition. Ann Rev Nutr. 1994.14:269-96.

Zeisel SH. The fetal origins of memory: the role of dietary choline in optimal brain development. J Pediatr. 2006a.149 (5 suppl) S131-6.

Zeisel SH, Niculescu MD. Perinatal choline influences brain structure and function. Nutr Rev. 2006b.64:197-203.

Zeisel SH. Choline:critical role during fetal development and dietary requirements in adults. Ann Rev Nutr. 2006c.26:229-50.


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