An introduction to the nutrition and metabolism of choline

Central Nervous System Agents in Medicinal Chemistry

Volumn 12, Issue 2, 2012, Pages 100-113

  Hollenbeck, Clarie B ^a  

^a SAN JOSE STATE UNIVERSITY   (United States)

Author keywords

Choline; Choline derivatives; Chronic disease; Deficiency and toxicity; Nutrition and metabolism

Indexed keywords

ACETYLCHOLINE; ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; BETAINE; CERAMIDE; CHOLINE; COBALAMIN; CYANOCOBALAMIN; DIACYLGLYCEROL; FOLIC ACID; GLYCEROPHOSPHORYLCHOLINE; HOMOCYSTEINE; LYSOPHOSPHATIDYLCHOLINE; PHOSPHATIDYLCHOLINE; PHOSPHATIDYLETHANOLAMINE METHYLTRANSFERASE; S ADENOSYLMETHIONINE; SPHINGOMYELIN; THROMBOCYTE ACTIVATING FACTOR;

ABSORPTION; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALZHEIMER DISEASE; AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; CANCER RISK; CEREAL; CORONARY ARTERY DISEASE; CYSTIC FIBROSIS; DEMENTIA; DIETARY INTAKE; DIGESTION; DISEASE ASSOCIATION; DIZZINESS; DNA METHYLATION; EGG YOLK; ENZYME LOCALIZATION; EXCRETION; FATTY LIVER; FISH; FRUIT; HUMAN; HUNTINGTON CHOREA; HYDROLYSIS; HYPOTENSION; LIPID METABOLISM; LIPID TRANSPORT; MEMORY; METHYLATION; NEURAL TUBE DEFECT; NEUROTRANSMISSION; NONALCOHOLIC FATTY LIVER; NUTRITION; OSMOSIS; RISK ASSESSMENT; SALIVATION; SENILE DEMENTIA; SIDE EFFECT; SIGNAL TRANSDUCTION; SMELLING; SOYBEAN; SWEATING; SYNCOPE; TARDIVE DYSKINESIA; UNSPECIFIED SIDE EFFECT; VEGETABLE; VITAMIN DEFICIENCY; VITAMIN METABOLISM; VITAMIN SUPPLEMENTATION; VOMITING; WHEAT GERM;

EID: 84862536855     PISSN: 18715249     EISSN: 18756166     Source Type: Journal    
DOI: 10.2174/187152412800792689     Document Type: Article

References (136)

1. Zeisel, S.H.; Blusztajn, J.K. Choline and human nutrition. Ann. Rev. Nutr., 1994, 14, 269-296.
2. Zeisel, S.H. Betaine supplementation and blood lipids: Fact or artifact? Nutr. Rev. 2006, 64, 77-79.
3. Ensminger, M.E; Ensminger, A.H. Foods and Nutrition Encyclopedia, 2nd ed.; CRC Press: Boca Raton, FL, 1994; p. 1177.
4. McCollum, E.V. A History of Nutrition: The Sequence of Ideas In Nutrition Investigation, Houghton Mifflin Company: Boston, 1957.
5. du Vigneaud, V.; Cohn, M.; Chandler, J.P.; Schenck, J.R.; Simmonds, S. The utilization of the methyl group of methionine in the biological synthesis of choline and creatine. J. Biol. Chem., 1941, 140, 625-641.
6. du Vigneaud, V.; Chandler, J.P.; Moyer, A.W.; Keppel, D.M. The effect of choline on the ability of homocysteine to replace methionine in the diet. J. Biol. Chem., 1939, 131, 57-76.
7. The Nobel Prize in Chemistry 1955. Nobelprize.org. 14 Sep 2011 http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1955/
8. du Vigneaud, V.; Ressler, C.; Swan, J.M.; Roberts, C.W.; Katsoyannis, P.G. Oxytocin: synthesis. J. Am. Chem. Soc., 1954, 76, 3115-3118.
9. Rohlfs, E.M.; Garner, S.C.; Mar, M-H.; Zeisel, S.H. Glycerophosphocholine and phosphocholine are the major choline metabolites in rat milk. J. Nutr., 1993, 123, 1762-1768.
10. Zeisel, S.H.; Wishnokj, S.; Blusztajn, K. Formation of methylamines from ingested choline and lecithin. Pharmacol. Exp. Ther., 1983, 225320-225324.
11. Growdon, J.H.; Hirsch, M.J.; Wurtman, R.; Weiner, W. Oral choline administration to patients with tardive dyskinesia. N. Engl. J. Med., 1977, 297, 524-527).
12. Patterson, K.Y.; Bhagwat, S.A.; Williams, J.R.; Howe, J.C.; Holden J.M. USDA database for the choline content of foods: Release two. U.S. Department of Agriculture, January 2008. http://www.nal.usda.gov/fnic/foodcomp/Data/Choline/Choln02.pdf (Accessed September 4, 2011)
13. Bremer, J.; Greenberg, D. M. Methyl transferring enzyme system of microsomes in the biosynthesis of lecithin. Biochim. Biophys. Acta, 1961, 46, 205-216.
14. Blusztajn, J.K.; Zeisel, S.H.; Wurtman R.J. Developmental changes in the activity of phosphatidylethanolamine N-methyltransferases in rat brain. Biochem. J. 1985, 232, 505-511.
15. Vance, D.E.; Li, Z.; Jacobs, R.L. Hepatic phosphatidylethanolamine N-methyltransferase, unexpected roles in animal biochemistry and physiology. J. Biol. Chem., 2007, 282, 33237-33241.
16. Mudd, S.H.; Brosnan, J.T.; Brosnan, M.E.; Jacobs, R.L.; Stabler, S.P.; Allen, R.H.; Vance, D.E.; Wagner, C. Methyl balance and transmethylation fluxes in humans. Am. J. Clin. Nutr., 2007, 85, 19-25.
17. Hollenbeck, C.B. The importance of being choline. J. Am. Diet. Assoc., 2010, 110, 1162-1165.
18. Fernández-Murray, J.P.; McMaster, C.R. Glycerophosphocholine catabolism as a new route for choline formation for phosphatidylcholine synthesis by the Kennedy Pathway. J. Biol. Chem., 2005, 280, 38290-38296.
19. Kwon, E.D.; Zablocki, K.; Jung, K.Y.; Peters, E.M.; Garcia-Perez, A.; M. B. Burg, M.B. Osmoregulation of GPC:choline phosphodiesterase in MDCK cells: Different effects of urea and NaCl. Am. J. Physiol. Cell Physiol., 1995, 269, C35-C41.
20. Bianchi, G.; Azzone, G.F. Oxidation of choline in rat liver mitochondria. J. Biol. Chem., 1964, 239, 3945-3955.
21. Weinhold, P.A.; Sanders, R. The oxidation of choline by liver slices and mitochondria during liver development in the rat. Life Sci., 1973, 13, 621-629.
22. Glunde, K.; Jie, C.; Bhujwalla, Z.M. Molecular causes of the aberrant choline phospholipid metabolism in breast cancer. Cancer Res., 2004, 74, 4270-7426.
23. Kent, C. Regulatory enzymes of phosphatidylcholine biosynthesis: a personal perspective. Biochim. Biophys. Acta - Mol. Cell Biol. Lipids, 2005, 1733, 53-66.
24. Vance, J.E.; Vance, D.E. Phospholipid biosynthesis in mammalian cells. Biochem. Cell Biol., 2004, 82, 113-128.
25. Liscovitch, M.; Ben-Av, P.; Danin, M.; Faiman, G.; Eldar, H.; Livneh E. Phospholipase D-mediated hydrolysis of phosphatidylcholine: role in cell signaling. J. Lipid Mediat., 1993, 8, 177-182.
26. Li, Z.; Vance, D.E. Phosphatidylcholine and choline homeostasis. J. Lipid Res., 2008, 49, 1187-1194.
27. Linardic, C.M.; Hannun, Y.A. Identification of a distinct pool of sphingomyelin involved in the sphingomyelin cycle. J. Biol. Chem., 1994, 269, 23530-23537.
28. Tafesse, F.G.; Ternes, P.; Holthuis, J.C.M. The multigenic sphingomyelin synthase family. J. Biol. Chem., 2006, 281, 29421-29425.
29. Longmore, W.J.; Oldenborg V.; van Golde, L.M.G. Phospholipase A2 in rat-lung microsomes: substrate specificity towards endogenous phosphatidylcholines. Biochim. Biophys. Acta, 1979, 572, 452-460.
30. Burke, J.E.; Dennis, E.A. Phospholipase A2 biochemistry. Cardiovas. Drugs Ther., 2009, 23 49-59.
31. Frenkel, R.; Maguruma, K.; Johnson, J. The biochemical role of platelet-activating factor I reproduction. Prog. Lipid Res., 1996, 35, 155-168.
32. Parthasarathy, S.; Subbaiah, P.V.; Ganguly, J. Mechanism of intestinal absorption of phosphatidylcholine in rats. Biochem. J. 1974, 140, 503-508.
33. Kwon, E.D.; Jung, K.Y.; Edsall, L.C.; Kim, H.Y.; García-Pérez, A.; Burg, M.B. Osmotic regulation of synthesis of glycerophosphocholine from phosphatidylcholine in MDCK cells. Am. J. Physiol., 1995, 268, C402-412.
34. Zablocki, K.; Millert, S.P.F.; García-Pérez, A.; Burg M.B. Accumulation of glycerophosphocholine (GPC) by renal cells: Osmotic regulation of GPC:choline phosphodiesterase. Proc. Natl. Acad. Sci., 1991, 88, 7820-7824.
35. MacIntosh, F.C.; Synthesis and storage of acetylcholine in nervous tissue. Can. J. Biochem. Physiol., 1963, 41, 2555-2571.
36. Yoshio, O. Choline acetyltransferase: The structure, distribution and pathologic changes in the central nervous system. Pathol. Intl., 1999, 49, 921-937.
37. Blusztajn J.K.; Wurtman, R.J.; Choline and cholinergic neurons. Science, 1983, 221, 614-620.
38. Kawashima, K; Fujii, T.; Basic and clinical aspects of non-neuronal acetylcholine: Overview of non-neuronal cholinergic systems and their biological significance. J. Pharmacol. Sci., 2008, 106, 167-173.
39. Fujii T.; Takada-Takatori, Y.; Kawashima, K.; Basic and clinical aspects of non-neuronal acetylcholine: Expression of an independent, non-neuronal cholinergic system in lymphocytes and its clinical significance in immunotherapy. J. Pharmacol. Sci., 2008, 106, 186-192.
40. Wessler, I.; Kirkpatrick, C.L.; Rack, K.; The cholinergic pitfall: Acetylcholine, a universal cell molecule in biological systems, including humans. Clin. Exp. Pharmacol. Physiol., 1999, 26, 198-205.
41. Nilsson, A.; Duan, R-D. Absorption and lipoprotein transport of sphingomyelin. J. Lipid Res., 2006, 47, 154-171.
42. Sheard, N.F.; Zeisel, S.H. An in vitro study of choline uptake by intestine from neonatal and adult rats. Pediatr. Res., 1986, 20, 768-772.
43. Kuczler, F.F.; Nahrwold, D.L.; Rose, R.C. Choline influx across the brush border of the guinea pig jejunum. Biochim. Biophys. Acta., 1977, 465, 131-137.
44. Sanford, P.A.; Smyth, D.H. Intestinal transport of choline in the rat and hamster. Physiology, 1971, 215, 769-778.
45. Herzberg, G.R.; Lerner, J. Intestinal absorption of choline in the chick. Biochim. Biophys. Acta, 1973, 307, 234-242.
46. Kettunen, H.; Peuranen, S.; Tiihonen, K.; Saarinen, M. Intestinal uptake of betaine in vitro and the distribution of methyl groups from betaine, choline, and methionine in the body of broiler chicks. Comparative Biochemistry and Physiology - Part A: Mol. Integr. Physiol., 2001, 128, 269-278.
47. Le Kim, D.; Betzing, H. Intestinal absorption of polyunsaturated phosphatidylcholine in the rat. Hoppe Seylers Z. Physiol. Chem., 1976, 357, 1321-31.
48. Cheng, W-L.; Holmes-McNary, M.Q.; Mar, M.H.; Lien, E.L.; Zeisel, S.H. Bioavailability of choline and choline esters from milk in rat pups. J. Nutr. Biochem., 1996, 7, 457-464.
49. Zeisel, S.H.; Growdon, F.H.; Wurtman, R.J.; Magil, S.G.; Logue, M. Normal plasma choline responses to ingested lecithin. Neurology, 1980, 30, 1226-1229.
50. Zeisel, S.H. Dietary choline biochemistry, physiology, and pharmacology. Ann. Rev., 1981, 1, 195-121.
51. van Rossum G.D.V.; Boyd C.A.R. Sodium-dependent and - independent choline uptake by type II epithelial cells from rat lung. J. Membr. Biol., 1998, 162, 147-156.
52. Leventer, S.M.; Rowell, P.P. Investigations of the rate-limiting step in the synthesis of acetylcholine by the human placenta. Placenta, 1984, 5, 261-270.
53. Chao C.K.; Pomfret, E.A.; Zeisel, S.H. Uptake of choline by rat mammary-gland epithelial cells. Biochem. J., 1988, 254, 33-38.
54. Caudill, M.A. Pre-and postnatal health: Evidence of increased choline needs. J. Am. Diet. Assoc., 2010, 110, 1198-1206
55. Zeisel, S.H.; Stanbury, J.B.; Wurtman, R.J.; Brigida, M.; Fierro, B.R. Choline content of mothers' milk in Ecuador and Boston. N. Engl. J. Med., 1982, 306, 175-176.
56. Michel, V.; Yuan, Z.; Ramsubir, S.; Bakovic, M. Choline transport for phospholipid synthesis. Exp. Biol. Med., 2006, 231, 490-504.
57. Deves, R.; Krupker, R.M. The binding and translocation steps in transport as related to substrate structure: A study of choline carrier of erythrocytes. Biochim. Biophys. Acta, 1979, 557, 468-485.
58. Simon J.R.; Atweh, S.; Kuhar, M.J. Sodium-dependent, high affinity choline uptake: A regulatory step in the synthesis of acetylcholine. J. Neurochem., 1976, 26, 909-922.
59. Grassl, S.M. Choline transport in human placental brush-border membrane vesicles. Biochim. Biophys. Acta, 1994, 1194, 203-213.
60. Zeisel, S.H. Choline deficiency. J. Nutr. Biochem., 1990, 1, 332-349.
61. Nagan, N.; Zoeller, R. A. Plasmalogens: Biosynthesis and functions. Prog. Lipid Res., 2001, 40, 199-229.
62. Katz-Brull, R.; Degani, H. Kinetics of choline transport and phosphorylation in human breast cancer cells: NMR application of the zero trans method. Anticancer Res., 1996, 16, 1375-1380.
63. Pomfret, E.A.; da Costa, K.A.; Schurman, L.L.; Zeisel, S.H. Measurement of choline and choline metabolite concentrations using high-pressure liquid chromatography and gas chromatography-mass spectrometry. Anal. Biochem., 1989, 180, 85-90.
64. Zhang, P.; Jenkins, G.M.; Hannun, Y.A.; Obeid L.M. Expression of neutral sphingomyelinase identifies a distinct pool of sphingomyelin involved in apoptosis. J. Biol. Chem., 1997, 272, 9609-9612.
65. Sciorra, V.A.; Morris, A.J. Sequential actions of phospholipase D and phosphatidic acid phosphohydrolase 2b generate diglyceride in mammalian cells. Mol. Biol. Cell, 1999, 10, 3863-3876.
66. Exton, J.H. Phosphatidylcholine breakdown and signal transduction. Biochim. Biophys. Acta, 1994, 1212, 26-42.
67. Merrill, A.H.; Liotta, D.C.; Riley, R.E. Bioactive properties of sphingosine and structurally related compounds. In: Handbook of Lipid Research; R.M. Bell, Ed.; Plenum Press: New York, 1996; Vol.8, Lipid Second Messengers, pp. 201-237.
68. Munder, P.G.; Modolell, M.; Andreesen, R.; Weltzien, H.U.; Westphal, O. Lysophosphatidylcholine (lysolecithin) and its synthetic analogues. Immunomodulating and other biologic effects. Springer Semi Immunopathol., 1979, 203, 187-203.
69. Mehta, D. Lysophosphatidylcholine an enigmatic lysolipid. Am. J. Physiol. Lung Cell Mol. Physiol., 2005, 28, L174-L175
70. Muir, L.V.; Born, E.; Mathur, S.N.; Field, F.J. Lysophosphatidylcholine increases 3-Hydroxy-3-methylglutarylcoenzyme A reductase gene expression in CaCo-2 cells. Gastroenterology, 1996, 110, 1068-1076
71. Montrucchio, G.; Alloatti, G.; Camussi, G. Role of plateletactivating factor in cardiovascular pathophysiology. Physiol. Rev., 2000, 80, 1669-1699.
72. Benveniste, J. Platelet-activating factor, a new mediator of anaphylaxis and immune complex deposition from rabbit and human basophils. Nature, 1974, 249, 581-582.
73. Fésüs, L.; Csaba, B.; Muszbek, L. Platelet activating factor, the trigger of haemostatic alterations in rat anaphylaxis. Clin. Exp. Immunol., 1977, 27, 512-515.
74. Thompson, D.; Pepys, M.B.; Wood, S.P. The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure, 1999, 7, 169-177.
75. Lovell, T.M.; Woods, R.J.; Butlin, D.J.; Brayley, K.J.; Manyonda, I.T.; Jarvis, J.; Howell, S.; Lowry, P.J. Identification of a novel mammalian post-translational modification, phosphocholine, on placental secretory polypeptides. J. Mol. Endocrinol., 2007, 39, 189-198.
76. Lombardi, B.; Pani, P.; Schlunk, F.F. Choline-deficiency fatty liver: Impaired release of hepatic triglycerides. J. Lipid Res., 1968, 9, 437-446.
77. Takahashi, Y.; Mizunuma, T.; Kishino Y. Effects of choline deficiency and phosphatidylcholine on fat absorption in rats. J. Nutr. Sci. Vitaminol. (Tokyo), 1982, 28, 139-147.
78. Yao, Z.; Vance, D.E. The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. J. Biol. Chem., 1988, 263, 2998-3004.
79. Abdelmalek, M.F.; Angulo, P.; Jorgensen, R.A.; Sylvestre, P.B.; Lindor, K.D. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: Results of a pilot study. Am. J. Gastroenterol., 2001, 96, 2711-2717.
80. Fischer, L.M.; da Costa, K.A.; Kwock, L.; Stewart, P.W.; Lu, T.S.; Stabler, S.P.; Allen, R.H.; Zeisel, S.H. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am. J. Clin. Nutr., 2007, 85, 1275-1285.
81. Leventer, S.M.; Rowell, P.P.; Clark, M.J. The effect of choline acetyltransferase inhibition on acetylcholine synthesis and release in term human placenta. JPET, 1982, 222, 301-305.
82. Sastry B.V. Human placental cholinergic system. Biochem. Pharmacol., 1997, 53, 1577-1586.
83. Wessler, I.; Kirkpatrick, C.J. Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans. Br. J. Pharmacol., 2008, 154, 1558-1571.
84. Cohen, E.L.; Wurtman, R.J. Brain acetylcholine: Increase after systematic choline administration. Life Sci., 1975, 16, 1095-1102.
85. Blusztajn, J.K.; Holbrook, P.G.; Lakher, M.; Liscovitch, M.; Maire, J.C.; Mauron, C.; Richardson, U.I.; Tacconi, M.; Wurtman, R.J. Autocannibalism of membrane choline-phospholipids: Physiology and pathology. Psychopharmacol. Bull., 1986, 22, 781-786.
86. Wecker, L. The synthesis and release of acetylcholine by depolarized hippocampal slices is increased by increased choline available in vitro prior to stimulation. J. Neurochem., 1991, 57, 1119-1127.
87. Finkelstein, J.D. Methionine metabolism in mammals. J. Nutr. Biochem., 1990, 1, 228-237.
88. Selhub J, Seyoum E; Pomfret, E.A.; Zeisel, S.H. Effects of choline deficiency and methotrexate treatment upon liver folate content and distribution. Cancer Res., 1991, 51, 16-21.
89. Varela-Moreiras, G.; Ragel, C.; de Miguelsanz, J.P. Choline deficiency and methotrexate treatment induces marked but reversible changes in hepatic folate concentrations, serum homocysteine and DNA methylation rates in rats. J. Am. Coll. Nutr., 1995, 14, 480-485.
90. Burg, M.B.; Ferraris, J.D.; Intracellular organic osmolytes: Function and regulation. J. Biol. Chem., 2008, 283, 7309-7313.
91. Kempson, S.A.; Montrose M.H. Osmotic regulation of renal betaine transport: transcription and beyond. Pflugers Archiv. - Eur. J. Physiol., 2004, 449, 227-234.
92. Bligh, J. The role of the liver and kidneys in the maintenance of the level of free choline in the plasma. J. Physiol., 1953, 120, 53-62
93. Acara, M.; Rennick, B. Regulation of plasma choline by the renal tubule bidirectional transport of choline. Am. J. Physiol., 1973, 225, 1123-1128.
94. Lever, M.; Sizeland, P.C.B.; Bason, L.M.; Hayman, C.M.; Chambers, S.T. Glycine betaine and proline betaine in human blood and urine. Biochim. Biophys. Acta, 1994, 1200, 259-264.
95. Food and Nutrition Board, National Research Council. Recommended Dietary Allowances, 7th ed. Washington, DC: National Academy of Sciences; 1968.
96. National Academy of Sciences, Food and Nutrition Board, Institute of Medicine. Choline. In: Dietary Reference Intakes Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. National Academy Press: Washington, D.C.; 1998, pp. 390-422.
97. Zeisel, S.H.; daCosta, K.A.; Franklin, P.D.; Alexander, E.A.; Lamont, J.T.; Sheard, N.F.; Beiser, A. Choline, an essential nutrient for humans. FASEB J., 1991, 5, 2093-2098.
98. Buchman, A.L.; Dubin, M.; Moukarzei, A.; Jenden, D.J.; Roch, M.; Rice, K.M.; Gornbein, J.; Ament, M.E. Choline deficiency: A cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology, 1995, 22, 1399-1403.
99. Buchman AL, Dubin M, Jenden D, Moukarzel A, Roch MH, Rice K, Gornbein J, Ament ME, Eckhert CD. Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. Gastroenterology, 1992, 102, 1363.
100. Lieber, C.S.; Robins, S.J.; Li, J.; deCarli, L.M.; Mak, K.M.; Fasuolo, L.J.M.; Leo, M.A. Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterology, 1994, 106, 152-159.
101. Ji, C; Kaplowitz, N. Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice. Gastroenterology, 2003, 14, 1488-1499.
102. Song, Z; Deaciuc, I; Shou, Z; Song, M; Chen, C; Hill, D; McClain, C.J. Involvement of AMP-activated protein kinase in beneficial effects of betaine on high-sucrose diet-induced hepatic steatosis. Am. J. Physiol. Gastrointest. Liver Physiol., 2007, G894-G902.
103. Niebergall, L.J; Jacobs, R.L; Chaba, T; Vance, D.E. Phosphatidylcholine protects against steatosis in mice by not nonalcoholic steatohepatitis. Biochimica et Biophysica Acta 2011, 1811, 1177-1185.
104. da Costa, KA.; Badea, M.; Fischer, L.M.; Zeisel, S.H. Elevated serum creatine phosphokinase in choline-deficient humans: mechanistic studies in C2C12 mouse myoblasts. Am. J. Clin. Nutr., 2004, 80, 163-170.
105. da Costa, K.A.; Niculescu, M.D.; Craciunescu, C.N.; Fischer, L.M.; Zeisel, S.H. Choline deficiency increases lymphocyte apoptosis and DNA damage in humans. Am. J. Clin. Nutr., 2006, 84, 88-94.
106. Albright, C.D.; Lui, R.; Bethea, T.C.; da Costa, K.A.; Salganik, R.I.; Zeisel, S.H. Choline deficiency induces apoptosis in SV40-immortalized CWSV-1 rat hepatocytes in culture. FASEB J., 1996, 10, 510-516.
107. Holmes-McNary, M.; Baldwin, J.; Zeisel, S.H. Opposing Regulation of Choline Deficiency-induced Apoptosis by p53 and Nuclear Factor kappa B. J. Biol. Chem., 2001, 276, 41197-41204.
108. Zeisel, S.H.; da Costa, K.A.; Youssef, M.; Hensey, S. Conversion of dietary choline to trimethylamine and dimethylamine in rats: Dose-response relationship. J. Nutr., 1989, 119, 800-804.
109. Shaw, G.M.; Carmichael, S.L.; Yang, W.; Selvin, S.; Schaffer, D.M. Periconceptional dietary intake of choline and betaine and neural tube defect in offspring. Am. J. Epidemiol., 2004, 160, 102-109.
110. Shaw, G.M.; Finnell, R.H.; Blom, H.J.; Carmichael, S.L.; Vollset, S.E.; Yang, W.; Ueland, P.M. Choline and risk of neural tube defects in a folate fortified population. Epidemiology., 2009, 20, 714-719.
111. Welch, G.N.; Loscalzo, J. Homocysteine and atherothrombosis. N. Engl. J. Med., 1998, 338, 1042-1050.
112. Bonaa, K.H.; Njolstad, I.; Ueland, P.M.; Schirmer, H.; Tverdal, A.; Steigen, T.; Wang, H.; Nordrehaug, J.E.; Arnesen, E.; Rasmussen, K. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N. Engl. J. Med., 2006, 354, 1578-1588.
113. Lonn, E.; Yusuf, S.; Arnold, M.J.; Sheridan, P.; Pogue, J.; Micks, M.; McQueen, M.J.; Probstfield, J.; Fodor, G.; Held, C.; Genest, J. Homocysteine lowering with folic acid and B vitamins in vascular disease. N. Engl. J. Med., 2006, 354, 1567-1577.
114. Toole, J.F.; Malinow, M.R.; Chambless, L.E.; Spence, J.D.; Pettigrew, L.C.; Howard, V.J.; Sides, E.G.; Wang, C.H.; Stampfer, M. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: The Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA, 2004, 291, 565-575.
115. Bidulescu, A.; Chambless, L.E.; Siega-Riz, A.M.; Zeisel, S.H.; Heiss, G. Usual choline and betaine dietary intake and incident coronary heart disease: Atherosclerosis Risk In Communities (ARIC) study. BMC Cardiovas. Disord., 2007, 7, 20. Available at: http://www.biomedcentral.com/1471-2261/7/20 (Accessed September 4, 2011)
116. Dalmeijer, G.W.; Olthof, M.R.; Verhoef, P.; Bots, M.L.; van der Schouw, Y.T. Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women. Eur. J. Clin. Nutr., 2008, 63, 386-394.
117. Schwab, U.; Alfthan, G.; Aro, A.; Uusitupa, M.; Long-term effect of betaine on risk factors associated with the metabolic syndrome in healthy subjects. Eur. J. Clin. Nutr., 2011, 65, 70-76.
118. Cho, E.; Holmes, M.D.; Hankinson, S.E.; Willett, W.C. Nutrients involved in one-carbon metabolism and risk of breast cancer among premenopausal women. Cancer Epidemiol. Biomarkers Prev., 2007, 16, 2787-2790.
119. Cho, E.; Holmes, M.D.; Hankinson, S.E.; Willett, W.C. Choline and betaine intake and risk of breast cancer among postmenopausal women. Br. J. Cancer, 2010, 102, 489-494.
120. Lee, J.E.; Giovannucci, E.; Fuchs, C.S.; Willett, W.C.; Zeisel, S.H.; Cho, E. Choline and betaine intake and the risk of colorectal cancer in men. Cancer Epidemiol. Biomarkers Prev., 2010, 19, 884-887.
121. Cho, E.; Willett, W.C.; Colditz, G.A.; Fuch, C.S.; Wu, K.; Chan, A.T.; Zeisel, S.H.; Giovannucci, E.L. Dietary choline and betaine and the risk of distal colorectal adenoma in women. J. Natl. Cancer Inst., 2007, 99, 1224-1231.
122. Rylett, R.J.; Ball, M.J.; Colhuon, E.H. Evidence for high affinity choline transport in synaptosomes prepared from hippocampus and neocortex of patients with Alzheimer's disease. Brain Res., 1983, 289, 169-175.
123. Perry, E.K.; Gibson, P.H.; Blessed, G.; Perry, R.H.; Tomlinson, B.E. Neurotransmitter enzyme abnormalities in senile dementia-cholineacetyltransferase and glutamic-acid decarboxlyase activities in necropsy brain-tissue. J. Neurol. Sci., 1977, 34, 247-265.
124. Nilsson, L.; Nordberg, A.; Hardy, J.; Wester, P.; Winblad, B. Physostigmine restores [3H]-acetylcholine efflux from Alzheimer brain slices to normal level. J. Neural. Transm., 1986, 67, 275-285.
125. Drachman, D.A.; Leavitt, J. Human memory and the cholinergic system. Arch. Neurol., 1974, 30, 113-121.
126. Higgins, J.P.; Flicker, L. Lecithin for dementia and cognitive impairment. Cochrane Database Syst. Rev., 2003, 3, CD001015.
127. Wells, K.; Farooqui A.A.; Liss, L.; Horrocks, L.A. Neural membrane phospholipids in Alzheimer's disease. Neurochem. Res., 1995, 20, 1329-1333.
128. Mulder, C.; Wahlund, L.O.; Teerlink, T.; Bloomberg, M.; Veerhuis R.; van Kamp, G.J.; Scheltens, P.; Scheffer, P.G. J. Decreased lysophosphatidylcholine / phosphatidycholine ratio in cerebrospinal fluid in Alzheimer disease. Neural. Transm., 2003, 110, 949-955.
129. Grimm, M.O.W.; Grösgen, S.; Riemenschneider, M.; Tanila, H.; Grimm, H.S.; Hartmann, T. From brain to food: Analysis of phosphatidylcholins, lysophosphatidylcholins and phosphatidylcholin-plasmalogens derivates in Alzheimer's disease human post mortem brains and mice model vi mass spectrometry. J. Chromatogr. A., 2011, 1218, 7713-7722.
130. Nitsch R.M.; Blusztajn, J.K.; Pittas, A.G.; Slack, B.E.; Growdon, J.H.; Wurtman, J.R. Proc. Natl. Acad. Sci., 1992, 89, 1671-1675.
131. Igarshi, M.; Ma, K.; Gao, F.; Kim, H-W.; Papoport, S.I.; Rao, J.S. Disturbed choline plasmalogen and phospholipid fatty acid concentrations in Alzheimer disease prefrontal cortex. J. Alzheimer's Dis., 2011, 24, 507-517.
132. Kristidis, P.; Bozon, D.; Corey, M. Genetic determination of exocrine pancreatic function in cystic fibrosis. Am. J. Hum. Genet., 1992, 50, 1178-1184.
133. Matel, J.L.; Mills, C.E. Nutrition in cystic fibrosis. Semin. Resprir. Crit. Care, 2009, 30, 579-586.
134. Chen, A.H.; Innis, S.M.; Davidson, A.G.; James, S.J. Phosphatidylcholine, and lysophosphatidylcholine excretion is increased in children with cystic fibrosis and is associated with increased homocysteine S-adenosylhomocysteine, and Sadenosylmethionine. Am. J. Clin. Nutr., 2005, 81, 686-691.
135. Innis, S.M.; Davidson, G.F. Cystic fibrosis and nutrition: Linking phospholipids and essential fatty acids with thiol metabolism. Annu. Rev. Nutr., 2008, 28, 55-72.
136. Innis, S.M.; Davidson, G.F.; Bay, B.N.; Slack, P.J.; Hasman, D. Plasma choline depletion is associated with decreased peripheral blood leukocyte acetylcholine in children with cystic fibrosis. Am. J. Clin. Nutr., 2011, 93, 564-568.