Dietary Choline for Brain Development



Choline, or its metabolites, is required for maintaining the structural integrity and signaling function of cell membranes, for providing a pool of methyl-groups available for the methylation of biological molecules, and for cholinergic neurotransmission. This nutrient is also necessary for the export of lipids from the liver and for normal muscle cell function. Choline can be synthesized de novo in the liver, but this pathway alone does not meet human requirements for this nutrient and, therefore, choline must be derived from the diet. Symptoms of choline deficiency in humans include fat accumulation in the liver as well as liver and muscle cell damage. The developing fetus has a high demand for choline that is met by supply from the mother across the placenta. The amount of choline available to the fetus during pregnancy can have significant effects on its brain development; women with the lowest choline intake during pregnancy are more likely to have babies with neural tube defects. Animals born to mothers who were perinatally supplemented with choline show enhanced memory function, which persists throughout life without further dietary choline supplementation. In rodents, maternal dietary choline during pregnancy influences proliferation, apoptosis, migration, and differentiation of neuronal precursor cells in fetal hippocampus. These effects of choline may be mediated by epigenetic mechanisms.


Neuronal Precursor Cell MeCP2 Gene Plasma Homocysteine Concentration Choline Deficiency Muscle Cell Damage 









Very-Low-Density Lipoprotein


Adequate Intake


Upper Tolerable Limit




Phosphatidylethanolamine N-methyltransferase


Choline Dehydrogenase


Betaine Aldehyde Dehydrogenase




Betaine:Homocysteine Methyltransferase


Methionine Synthase


Cytidine Diphosphocholine


Long-Term Potential


Embryonic Day


Postnatal Day


Single-Nucleotide Polymorphism




Choline Acetyltransferase


Transforming Growth Factor-β


Deleted in Colorectal Cancer


Mitogen-Activated Protein Kinase


cAMP-Response Element-Binding Protein


Nerve Growth Factor


Histone 3

MeCP1, 2

Methyl-CpG-Binding Protein 1, 2

MBD 1–4

Methyl-CpG-Binding Domain 1–4



Much of the work discussed in this chapter was supported by grants from the National Institutes of Health (USA) (DK55865, DK56350, AG009525).


  1. Albright CD, Tsai AY, Mar M-H, Zeisel SH. Neurochem Res. 1998;23:751–8.PubMedCrossRefGoogle Scholar
  2. Albright CD, Tsai AY, Friedrich CB, Mar MH, Zeisel SH. Brain Res Dev Brain Res. 1999;113:13–20.PubMedCrossRefGoogle Scholar
  3. Albright CD, Mar MH, Friedrich CB, Brown EC, Zeisel SH. Dev Neurosci. 2001;23:100–6.PubMedCrossRefGoogle Scholar
  4. Albright CD, Siwek DF, Craciunescu CN, Mar MH, Kowall NW, Williams CL, Zeisel SH. Nutr Neurosci. 2003;6:129–34.PubMedCrossRefGoogle Scholar
  5. Albright CD, Mar MH, Craciunescu CN, Song J, Zeisel SH. Brain Res Dev Brain Res. 2005;159:149–54.PubMedCrossRefGoogle Scholar
  6. Blusztajn JK, Holbrook PG, Lakher M, Liscovitch M, Maire JC, Mauron C, Richardson UI, Tacconi M, Wurtman RJ. Psychopharmacol Bull. 1986;22:781–6.PubMedGoogle Scholar
  7. Blusztajn JK, Liscovitch M, Richardson UI. Proc Natl Acad Sci U.S.A. 1987;84:5474–7.PubMedCrossRefGoogle Scholar
  8. Brandner C. Brain Res. 2002;928:85–95.PubMedCrossRefGoogle Scholar
  9. Chern MK, Gage DA, Pietruszko R. Biochem Pharmacol. 2000;60:1629–37.PubMedCrossRefGoogle Scholar
  10. Chi-Shui L, Ru-Dan W. J Prot Chem. 1986;5:193–200.CrossRefGoogle Scholar
  11. Cohen EL, Wurtman RJ. Life Sci. 1975;16:1095–102.PubMedCrossRefGoogle Scholar
  12. Cooney CA, Dave AA, Wolff GL. J Nutr. 2002;132:2393S–2400S.PubMedGoogle Scholar
  13. Craciunescu CN, Albright CD, Mar MH, Song J, Zeisel SH. J Nutr. 2002;133:3614–8.Google Scholar
  14. Craciunescu CN, Johnson AR, Zeisel SH, J Nutr. 2010;140:1162–6.PubMedCrossRefGoogle Scholar
  15. da Costa KA, Gaffney CE, Fischer LM, Zeisel SH. Am J Clin Nutr. 2005;81:440–4.PubMedGoogle Scholar
  16. da Costa KA, Kozyreva OG, Song J, Galanko JA, Fischer LM, Zeisel SH. Faseb J. 2006;20:1336–44.PubMedCrossRefGoogle Scholar
  17. Davison JM, Mellott TJ, Kovacheva VP, Blusztajn JK. J Biol Chem. 2009;284:1982–9.PubMedCrossRefGoogle Scholar
  18. Eichenbaum H. Neuron. 2004;44:109–20.PubMedCrossRefGoogle Scholar
  19. Fischer LM, daCosta K, Kwock L, Stewart P, Lu T-S, Stabler S, Allen R, Zeisel S. Am J Clin Nutr. 2007;85:1275–85.PubMedGoogle Scholar
  20. Fisher MC, Zeisel SH, Mar MH, Sadler TW. Teratology. 2001;64:114–22.PubMedCrossRefGoogle Scholar
  21. Fisher MC, Zeisel SH, Mar MH, Sadler TW. Faseb J. 2002;16:619–21.PubMedGoogle Scholar
  22. Guseva MV, Hopkins DM, Scheff SW, Pauly JR. J Neurotrauma. 2008;25:975–83.PubMedCrossRefGoogle Scholar
  23. Haubrich DR, Gerber NH. Biochem Pharmacol. 1981;30:2993–3000.PubMedCrossRefGoogle Scholar
  24. Hendrich B, Bird A. Mol Cell Biol. 1998;18:6538–47.PubMedGoogle Scholar
  25. Hobbs CA, Cleves MA, Melnyk S, Zhao W, James SJ. Am J Clin Nutr. 2005;81:147–53.PubMedGoogle Scholar
  26. Holler T, Cermak J, Blusztajn J. FASEB J. 1996;10:1653–9.PubMedGoogle Scholar
  27. Holliday R, Grigg GW. Mutat Res. 1993;285:61–7.PubMedCrossRefGoogle Scholar
  28. Holmes-McNary M, Cheng WL, Mar. MH, Fussell S, Zeisel SH. Am J Clin Nutr. 1996;64:572–6.PubMedGoogle Scholar
  29. Institute of Medicine, National Academy of Sciences USA. Choline. Dietary reference intakes for folate, thiamin, riboflavin, niacin, vitamin B12, panthothenic acid, biotin, and choline. Washington, DC: National Academy Press; 1998.Google Scholar
  30. Jacobs RL, Stead LM, Devlin C, Tabas I, Brosnan ME, Brosnan JT, Vance DE. J Biol Chem. 2005;280:28299–305.PubMedCrossRefGoogle Scholar
  31. Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J. Am J Clin Nutr. 2001;73:613–21.PubMedGoogle Scholar
  32. Johnson AR, Craciunescu CN, Guo Z, Terg Y-W, Thresher RJ, Blusztajn JK, Zeisel SH, Faseb J. 2010;24:2752–61.PubMedCrossRefGoogle Scholar
  33. Jenuwein T, Allis CD. Science. 2001;293:1074–80.PubMedCrossRefGoogle Scholar
  34. Jones JP, Meck W, Williams CL, Wilson WA, Swartzwelder HS. Brain Res Dev Brain Res. 1999;118:159–67.PubMedCrossRefGoogle Scholar
  35. Jones PA, Takai D. Science. 2001;293:1068–70.PubMedCrossRefGoogle Scholar
  36. Kohlmeier M, da Costa KA, Fischer LM, Zeisel SH. Proc Natl Acad Sci U S A. 2005;102:16025–30.PubMedCrossRefGoogle Scholar
  37. Li Q, Guo-Ross S, Lewis DV, Turner D, White AM, Wilson WA, Swartzwelder HS. J Neurophysiol. 2004;91:1545–55.PubMedCrossRefGoogle Scholar
  38. Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J. Molecular cell biology, 5th edn. New York: W.H. Freeman; 2004.Google Scholar
  39. Meck W, Williams C. Neuroreport. 1997a;8:2831–5.PubMedCrossRefGoogle Scholar
  40. Meck W, Williams C. Neuroreport. 1997b;8:3053–9.PubMedCrossRefGoogle Scholar
  41. Meck W, Williams C. Neuroreport. 1997c;8:3045–51.PubMedCrossRefGoogle Scholar
  42. Meck WH, Williams CL. Brain Res Dev Brain Res. 1999;118:51–9.PubMedCrossRefGoogle Scholar
  43. Meck WH, Williams CL. Neurosci Biobehav Rev. 2003;27:385–99.PubMedCrossRefGoogle Scholar
  44. Meck WH, Smith RA, Williams CL. Dev Psychobiol. 1988;21:339–53.PubMedCrossRefGoogle Scholar
  45. Mehedint MG, Niculescu MD, Craciunescu CN, Zeisel SH, Faseb J. 2010;24:184–95.PubMedCrossRefGoogle Scholar
  46. Mellott TJ, Williams CL, Meck WH, Blusztajn JK. Faseb J. 2004;18:545–7.PubMedGoogle Scholar
  47. Nag N, Berger-Sweeney JE. Neurobiol Dis. 2007;26:473–80.PubMedCrossRefGoogle Scholar
  48. Nag N, Mellott TJ, Berger-Sweeney JE. Brain Res. 2008;1237:101–9.PubMedCrossRefGoogle Scholar
  49. Niculescu MD, Craciunescu CN, Zeisel SH. Brain Res Mol Brain Res. 2005;134:309–22.PubMedCrossRefGoogle Scholar
  50. Niculescu MD, Yamamuro Y, Zeisel SH. J Neurochem. 2004;89:1252–9.PubMedCrossRefGoogle Scholar
  51. Niculescu MD, Craciunescu CN, Zeisel SH. Faseb J. 2006;20:43–9.PubMedCrossRefGoogle Scholar
  52. Ozarda IY, Uncu G, Ulus IH. Arch Physiol Biochem. 2002;110:393–9.CrossRefGoogle Scholar
  53. Pomfret EA, da Costa K, Zeisel SH. J Nutr Biochem. 1990;1:533–41.PubMedCrossRefGoogle Scholar
  54. Resseguie M, Song J, Niculescu M, da Costa K, Randall T, Zeisel S. FASEB J. 2007;21:2622–32.Google Scholar
  55. Robertson KD, Wolffe AP. Nat Rev Genet. 2000;1:11–9.PubMedCrossRefGoogle Scholar
  56. Sandstrom NJ, Loy R, Williams CL. Brain Res. 2002;947:9–16.PubMedCrossRefGoogle Scholar
  57. Schenk F, Brandner C. Psychobiology. 1995;23:302–13.Google Scholar
  58. Shaw GM, Carmichael SL, Yang W, Selvin S, Schaffer DM. Am J Epidemiol. 2004;160:102–9.PubMedCrossRefGoogle Scholar
  59. Shaw GM, Carmichael SL, Laurent C, Rasmussen SA. Epidemiology. 2006;17:285–91.PubMedCrossRefGoogle Scholar
  60. Shelnutt KP, Kauwell GP, Chapman CM, Gregory JF, 3rd, Maneval DR, Browdy AA, Theriaque DW, Bailey LB. J Nutr. 2003;133:4107–11.PubMedGoogle Scholar
  61. Shields DJ, Lingrell S, Agellon LB, Brosnan JT, Vance DE. J Biol Chem. 2005;280:27339–44.PubMedCrossRefGoogle Scholar
  62. Sweiry JH, Page KR, Dacke CG, Abramovich DR, Yudilevich DL. J Devel Physiol. 1986;8:435–45.Google Scholar
  63. Sweiry JH, Yudilevich DL. J Physiol. 1985;366:251–66.PubMedGoogle Scholar
  64. Thomas JD, La Fiette MH, Quinn VR, Riley EP. Neurotoxicol Teratol. 2000;22:703–11.PubMedCrossRefGoogle Scholar
  65. Thomas JD, Biane JS, O’Bryan KA, O’Neill TM, Dominguez HD. Behav Neurosci. 2007;121:120–30.PubMedCrossRefGoogle Scholar
  66. Ulus IH, Wurtman RJ, Mauron C, Blusztajn JK. Brain Res. 1989;484:217–27.PubMedCrossRefGoogle Scholar
  67. USDA, Nutrient Data Laboratory and Agricultural Research Service. United States Department of Agriculture Database for the Choline Content of Common Foods, Release 2. 6232, 2008.
  68. Varela-Moreiras G, Ragel C, Perez de Miguelsanz J. J Amer Coll Nutr. 1995;14:480–5.Google Scholar
  69. Walkey CJ, Yu L, Agellon LB, Vance DE. J Biol Chem. 1998;273:27043–6.PubMedCrossRefGoogle Scholar
  70. Waterland RA, Jirtle RL. Mol Cell Biol. 2003;23:5293–300.PubMedCrossRefGoogle Scholar
  71. Watkins D, Ru M, Hwang HY, Kim CD, Murray A, Philip NS, Kim W, Legakis H, Wai T, Hilton JF, Ge B, Dore C, Hosack A, Wilson A, Gravel RA, Shane B, Hudson TJ, Rosenblatt DS. Am J Hum Genet. 2002;71:143–53.PubMedCrossRefGoogle Scholar
  72. Wecker L. J Neurochem. 1991;57:1119–27.PubMedCrossRefGoogle Scholar
  73. Weisberg IS, Jacques PF, Selhub J, Bostom AG, Chen Z, Curtis Ellison R, Eckfeldt JH, Rozen R. Atherosclerosis. 2001;156:409–15.PubMedCrossRefGoogle Scholar
  74. Wolff GL, Kodell RL, Moore SR, Cooney CA. Faseb J. 1998;12:949–57.PubMedGoogle Scholar
  75. Wong-Goodrich SJ, Mellott TJ, Glenn MJ, Blusztajn JK, Williams CL. Neurobiol Dis. 2008;30:255–69.PubMedCrossRefGoogle Scholar
  76. Xu X, Gammon MD, Zeisel SH, Lee YL, Wetmur JG, Teitelbaum SL, Bradshaw PT, Neugut AI, Santella RM, Chen J. Faseb J. 2008;22:2045–52.PubMedCrossRefGoogle Scholar
  77. Yang Y, Liu Z, Cermak JM, Tandon P, Sarkisian MR, Stafstrom CE, Neill JC, Blusztajn JK, Holmes GL. J Neurosci. 2000;20:RC109.Google Scholar
  78. Zeisel SH. Annu Rev Nutr. 2006;26:229–50.PubMedCrossRefGoogle Scholar
  79. Zeisel SH, Wurtman RJ. Biochem J. 1981;198:565–70.PubMedGoogle Scholar
  80. Zeisel SH, Stanbury JB, Wurtman RJ, Brigida M, Fierro BR. New Engl J Med. 1982;306:175–6.PubMedGoogle Scholar
  81. Zeisel SH, Mar M-H, Zhou Z-W, da Costa K-A. J Nutr. 1995;125:3049–54.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Nutrition Research InstituteUniversity of North Carolina at Chapel HillKannapolisUSA

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