Nutrition, one-carbon metabolism and neural tube defects: A review

Nutrients

Volumn 8, Issue 11, 2016, Pages

  Li, Kelei ^a   Wahlqvist, Mark L ^a,b   Li, Duo ^a,b  

^a ZHEJIANG UNIVERSITY   (China)

^b MONASH UNIVERSITY   (Australia)

Author keywords

Alcohol; Betaine; Choline; Coffee; Folate; Neural tube defects; One carbon metabolism; Tea; Vitamin B

Indexed keywords

BETAINE; CHOLINE; CYANOCOBALAMIN; FOLIC ACID; OMEGA 3 FATTY ACID; PYRIDOXINE; RIBOFLAVIN; CARBON;

ALCOHOL CONSUMPTION; ALLELE; ASTHMA; CARBON METABOLISM; CLEFT LIP; COFFEE; DIET SUPPLEMENTATION; GENETIC POLYMORPHISM; HUMAN; LYMPHATIC LEUKEMIA; MILD COGNITIVE IMPAIRMENT; NEURAL TUBE DEFECT; PREGNANT WOMAN; PREMATURE LABOR; PSYCHOMOTOR DISORDER; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; TEA; VITAMIN SUPPLEMENTATION; WHEEZING; ANENCEPHALY; ANIMAL; DIETARY REFERENCE INTAKE; DIETARY SUPPLEMENT; FEMALE; FOLIC ACID DEFICIENCY; FORTIFIED FOOD; GENETICS; GENOTYPE ENVIRONMENT INTERACTION; MATERNAL NUTRITION; METABOLISM; NUTRITIONAL STATUS; NUTRITIONAL VALUE; PATHOPHYSIOLOGY; PREGNANCY; RISK FACTOR;

ANENCEPHALY; ANIMALS; CARBON; DIETARY SUPPLEMENTS; FEMALE; FOLIC ACID; FOLIC ACID DEFICIENCY; FOOD, FORTIFIED; GENE-ENVIRONMENT INTERACTION; HUMANS; MATERNAL NUTRITIONAL PHYSIOLOGICAL PHENOMENA; NUTRITIONAL STATUS; NUTRITIVE VALUE; PREGNANCY; RECOMMENDED DIETARY ALLOWANCES; RISK FACTORS;

EID: 84996490225     PISSN: None     EISSN: 20726643     Source Type: Journal    
DOI: 10.3390/nu8110741     Document Type: Review

References (107)

1. Mitchell, L.E. Epidemiology of Neural Tube Defects. In American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 2005; Wiley Online Library: Hoboken, NJ, USA, 2005; pp. 88–94.
2. Detrait, E.R.; George, T.M.; Etchevers, H.C.; Gilbert, J.R.; Vekemans, M.; Speer, M.C. Human neural tube defects: Developmental biology, epidemiology, and genetics. Neurotoxicol. Teratol. 2005, 27, 515–524.
3. Czeizel, A.E.; Dudas, I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N. Engl. J. Med. 1992, 327, 1832–1835.
4. Berry, R.J.; Li, Z.; Erickson, J.D.; Li, S.; Moore, C.A.; Wang, H.; Mulinare, J.; Zhao, P.; Wong, L.Y.; Gindler, J.; et al. Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative project for neural tube defect prevention. N. Engl. J. Med. 1999, 341, 1485–1490.
5. Crider, K.S.; Devine, O.; Hao, L.; Dowling, N.F.; Li, S.; Molloy, A.M.; Li, Z.; Zhu, J.; Berry, R.J. Population red blood cell folate concentrations for prevention of neural tube defects: Bayesian model. BMJ 2014, 29, g4554.
6. Liu, J.; Qi, J.; Yu, X.; Zhu, J.; Zhang, L.; Ning, Q.; Luo, X. Investigations of single nucleotide polymorphisms in folate pathway genes in Chinese families with neural tube defects. J. Neurol. Sci. 2014, 337, 61–66.
7. MRC Vitamin Study Research Group. Prevention of neural tube defects: Results of the medical research council vitamin study. Mrc vitamin study research group. Lancet 1991, 338, 131–137.
8. Daly, L.E.; Kirke, P.N.; Molloy, A.; Weir, D.G.; Scott, J.M. Folate levels and neural tube defects. Implications for prevention. JAMA 1995, 274, 1698–1702.
9. Centers for Disease Control and Prevention. Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Recomm. Rep. 1992, 41, 1–7.
10. Bestwick, J.P.; Huttly, W.J.; Morris, J.K.; Wald, N.J. Prevention of neural tube defects: A cross-sectional study of the uptake of folic acid supplementation in nearly half a million women. PLoS ONE 2014, 9.
11. Ren, A.G. Prevention of neural tube defects with folic acid: The Chinese experience. World J. Clin. Pediatr. 2015, 4, 41–44.
12. Arth, A.; Kancherla, V.; Pachon, H.; Zimmerman, S.; Johnson, Q.; Oakley, G.P., Jr. A 2015 global update on folic acid-preventable spina bifida and anencephaly. Birth Defects Res. A Clin. Mol. Teratol. 2016, 106, 520–529.
13. Santos, L.M.; Lecca, R.C.; Cortez-Escalante, J.J.; Sanchez, M.N.; Rodrigues, H.G. Prevention of neural tube defects by the fortification of flour with folic acid: A population-based retrospective study in brazil. Bull. World Health Organ. 2016, 94, 22–29.
14. Khoshnood, B.; Loane, M.; de Walle, H.; Arriola, L.; Addor, M.C.; Barisic, I.; Beres, J.; Bianchi, F.; Dias, C.; Draper, E.; et al. Long term trends in prevalence of neural tube defects in europe: Population based study. BMJ 2015, 24, h5949.
15. Wang, H.; De Steur, H.; Chen, G.; Zhang, X.; Pei, L.; Gellynck, X.; Zheng, X. Effectiveness of folic acid fortified flour for prevention of neural tube defects in a high risk region. Nutrients 2016, 8, 152.
16. Liu, Z.Z.; Zhang, J.T.; Liu, D.; Hao, Y.H.; Chang, B.M.; Xie, J.; Li, P.Z. Interaction between maternal 5,10-methylenetetrahydrofolate reductase c677t and methionine synthase a2756g gene variants to increase the risk of fetal neural tube defects in a Shanxi han population. Chin. Med. J. 2013, 126, 865–869.
17. Morales de Machin, A.; Mendez, K.; Solis, E.; Borjas de Borjas, L.; Bracho, A.; Hernandez, M.L.; Negron, A.; Delgado, W.; Sanchez, Y. c677t polymorphism of the methylentetrahydrofolate reductase gene in mothers of children affected with neural tube defects. Investig. Clin. 2015, 56, 284–295.
18. Van der Put, N.M.; Steegers-Theunissen, R.P.; Frosst, P.; Trijbels, F.J.; Eskes, T.K.; van den Heuvel, L.P.; Mariman, E.C.; den Heyer, M.; Rozen, R.; Blom, H.J. Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 1995, 346, 1070–1071.
19. Shaw, G.M.; Lu, W.; Zhu, H.; Yang, W.; Briggs, F.B.; Carmichael, S.L.; Barcellos, L.F.; Lammer, E.J.; Finnell, R.H. 118 snps of folate-related genes and risks of spina bifida and conotruncal heart defects. BMC Med. Genet. 2009, 10, 1471–2350.
20. Yan, L.; Zhao, L.; Long, Y.; Zou, P.; Ji, G.; Gu, A.; Zhao, P. Association of the maternal mthfr c677t polymorphism with susceptibility to neural tube defects in offsprings: Evidence from 25 case-control studies. PLoS ONE 2012, 7, 3.
21. Crider, K.S.; Zhu, J.H.; Hao, L.; Yang, Q.H.; Yang, T.P.; Gindler, J.; Maneval, D.R.; Quinlivan, E.P.; Li, Z.; Bailey, L.B.; et al. Mthfr 677c→t genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation. Am. J. Clin. Nutr. 2011, 93, 1365–1372.
22. Tsang, B.L.; Devine, O.J.; Cordero, A.M.; Marchetta, C.M.; Mulinare, J.; Mersereau, P.; Guo, J.; Qi, Y.P.; Berry, R.J.; Rosenthal, J.; et al. Assessing the association between the methylenetetrahydrofolate reductase (mthfr) 677c>t polymorphism and blood folate concentrations: A systematic review and meta-analysis of trials and observational studies. Am. J. Clin. Nutr. 2015, 101, 1286–1294.
23. Van der Put, N.M.; Gabreels, F.; Stevens, E.M.; Smeitink, J.A.; Trijbels, F.J.; Eskes, T.K.; van den Heuvel, L.P.; Blom, H.J. A second common mutation in the methylenetetrahydrofolate reductase gene: An additional risk factor for neural-tube defects? Am. J. Hum. Genet. 1998, 62, 1044–1051.
24. De Marco, P.; Calevo, M.G.; Moroni, A.; Arata, L.; Merello, E.; Finnell, R.H.; Zhu, H.; Andreussi, L.; Cama, A.; Capra, V. Study of mthfr and ms polymorphisms as risk factors for ntd in the italian population. J. Hum. Genet. 2002, 47, 319–324.
25. Stegmann, K.; Ziegler, A.; Ngo, E.T.; Kohlschmidt, N.; Schroter, B.; Ermert, A.; Koch, M.C. Linkage disequilibrium of mthfr genotypes 677c/t-1298a/c in the german population and association studies in probands with neural tube defects(ntd). Am. J. Med. Genet. 1999, 87, 23–29.
26. Barber, R.; Shalat, S.; Hendricks, K.; Joggerst, B.; Larsen, R.; Suarez, L.; Finnell, R. Investigation of folate pathway gene polymorphisms and the incidence of neural tube defects in a texas hispanic population. Mol. Genet. Metab. 2000, 70, 45–52.
27. Volcik, K.A.; Blanton, S.H.; Tyerman, G.H.; Jong, S.T.; Rott, E.J.; Page, T.Z.; Romaine, N.K.; Northrup, H. Methylenetetrahydrofolate reductase and spina bifida: Evaluation of level of defect and maternal genotypic risk in hispanics. Am. J. Med. Genet. 2000, 95, 21–27.
28. Wang, Y.; Liu, Y.; Ji, W.; Qin, H.; Wu, H.; Xu, D.; Turtuohut, T.; Wang, Z. Variants in mthfr gene and neural tube defects susceptibility in China. Metab. Brain Dis. 2015, 30, 1017–1026.
29. Wang, Y.; Liu, Y.; Ji, W.; Qin, H.; Wu, H.; Xu, D.; Tukebai, T.; Wang, Z. Analysis of mtr and mtrr polymorphisms for neural tube defects risk association. Medicine 2015, 94, 1367.
30. Sliwerska, E.; Szpecht-Potocka, A. Mutations of MTHFR, MTR, MTRR genes as high risk factors for neural tube defects. Med. Wieku Rozwoj 2002, 6, 371–382.
31. Boyles, A.L.; Billups, A.V.; Deak, K.L.; Siegel, D.G.; Mehltretter, L.; Slifer, S.H.; Bassuk, A.G.; Kessler, J.A.; Reed, M.C.; Nijhout, H.F.; et al. Neural tube defects and folate pathway genes: Family-based association tests of gene-gene and gene-environment interactions. Environ. Health Perspect. 2006, 114, 1547–1552.
32. Richter, B.; Stegmann, K.; Roper, B.; Boddeker, I.; Ngo, E.T.; Koch, M.C. Interaction of folate and homocysteine pathway genotypes evaluated in susceptibility to neural tube defects (ntd) in a german population. J. Hum. Genet. 2001, 46, 105–109.
33. Candito, M.; Rivet, R.; Herbeth, B.; Boisson, C.; Rudigoz, R.C.; Luton, D.; Journel, H.; Oury, J.F.; Roux, F.; Saura, R.; et al. Nutritional and genetic determinants of vitamin B and homocysteine metabolisms in neural tube defects: A multicenter case-control study. Am. J. Med. Genet. A 2008, 1, 1128–1133.
34. Yadav, U.; Kumar, P.; Yadav, S.K.; Mishra, O.P.; Rai, V. Polymorphisms in folate metabolism genes as maternal risk factor for neural tube defects: An updated meta-analysis. Metab. Brain Dis. 2015, 30, 7–24.
35. De Marco, P.; Merello, E.; Calevo, M.G.; Mascelli, S.; Raso, A.; Cama, A.; Capra, V. Evaluation of a methylenetetrahydrofolate-dehydrogenase 1958g>a polymorphism for neural tube defect risk. J. Hum. Genet. 2006, 51, 98–103.
36. Etheredge, A.J.; Finnell, R.H.; Carmichael, S.L.; Lammer, E.J.; Zhu, H.; Mitchell, L.E.; Shaw, G.M. Maternal and infant gene-folate interactions and the risk of neural tube defects. Am. J. Med. Genet. A 2012, 10, 17.
37. Jiang, J.; Zhang, Y.; Wei, L.; Sun, Z.; Liu, Z. Association between mthfd1 g1958a polymorphism and neural tube defects susceptibility: A meta-analysis. PLoS ONE 2014, 9.
38. Meng, J.; Han, L.; Zhuang, B. Association between mthfd1 polymorphisms and neural tube defect susceptibility. J. Neurol. Sci. 2015, 348, 188–194.
39. Parle-McDermott, A.; Pangilinan, F.; O’Brien, K.K.; Mills, J.L.; Magee, A.M.; Troendle, J.; Sutton, M.; Scott, J.M.; Kirke, P.N.; Molloy, A.M.; et al. A common variant in mthfd1l is associated with neural tube defects and mrna splicing efficiency. Hum. Mutat. 2009, 30, 1650–1656.
40. Pangilinan, F.; Molloy, A.M.; Mills, J.L.; Troendle, J.F.; Parle-McDermott, A.; Signore, C.; O’Leary, V.B.; Chines, P.; Seay, J.M.; Geiler-Samerotte, K.; et al. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects. BMC Med. Genet. 2012, 13, 62.
41. Wu, J.; Bao, Y.; Lu, X.; Wu, L.; Zhang, T.; Guo, J.; Yang, J. Polymorphisms in mthfd1 gene and susceptibility to neural tube defects: A case-control study in a Chinese han population with relatively low folate levels. Med. Sci. Monit. 2015, 21, 2630–2637.
42. Guo, J.; Xie, H.; Wang, J.; Zhao, H.; Wang, F.; Liu, C.; Wang, L.; Lu, X.; Bao, Y.; Zou, J.; et al. The maternal folate hydrolase gene polymorphism is associated with neural tube defects in a high-risk Chinese population. Genes Nutr. 2013, 8, 191–197.
43. Pei, L.J.; Zhu, H.P.; Li, Z.W.; Zhang, W.; Ren, A.G.; Zhu, J.H.; Li, Z. Interaction between maternal periconceptional supplementation of folic acid and reduced folate carrier gene polymorphism of neural tube defects. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2005, 22, 284–287.
44. Zhang, T.; Lou, J.; Zhong, R.; Wu, J.; Zou, L.; Sun, Y.; Lu, X.; Liu, L.; Miao, X.; Xiong, G. Genetic variants in the folate pathway and the risk of neural tube defects: A meta-analysis of the published literature. PLoS ONE 2013, 8, e59570.
45. Piao, W.; Guo, J.; Bao, Y.; Wang, F.; Zhang, T.; Huo, J.; Zhang, K. Analysis of polymorphisms of genes associated with folate-mediated one-carbon metabolism and neural tube defects in Chinese han population. Birth Defects Res. A Clin. Mol. Teratol. 2016, 106, 232–239.
46. Hao, L.; Ma, J.; Zhu, J.; Stampfer, M.J.; Tian, Y.; Willett, W.C.; Li, Z. High prevalence of hyperhomocysteinemia in Chinese adults is associated with low folate, vitamin B-12, and vitamin B-6 status. J. Nutr. 2007, 137, 407–413.
47. Gu, Q.; Li, Y.; Cui, Z.L.; Luo, X.P. Homocysteine, folate, vitamin B12 and B6 in mothers of children with neural tube defects in Xinjiang, China. Acta Paediatr. 2012, 101, 1651–2227.
48. Zhang, T.; Xin, R.; Gu, X.; Wang, F.; Pei, L.; Lin, L.; Chen, G.; Wu, J.; Zheng, X. Maternal serum vitamin B12, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China. Public Health Nutr. 2009, 12, 680–686.
49. Dang, S.; Yan, H.; Zeng, L.; Wang, Q.; Li, Q.; Xiao, S.; Fan, X. The status of vitamin B12 and folate among Chinese women: A population-based cross-sectional study in northwest China. PLoS ONE 2014, 9.
50. Gaber, K.R.; Farag, M.K.; Soliman, S.E.; El-Bassyouni, H.T.; El-Kamah, G. Maternal vitamin B12 and the risk of fetal neural tube defects in egyptian patients. Clin. Lab. 2007, 53, 69–75.
51. Molloy, A.M.; Kirke, P.N.; Troendle, J.F.; Burke, H.; Sutton, M.; Brody, L.C.; Scott, J.M.; Mills, J.L. Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification. Pediatrics 2009, 123, 917–923.
52. Nasri, K.; Ben Fradj, M.K.; Touati, A.; Aloui, M.; Ben Jemaa, N.; Masmoudi, A.; Elmay, M.V.; Omar, S.; Feki, M.; Kaabechi, N.; et al. Association of maternal homocysteine and vitamins status with the risk of neural tube defects in tunisia: A case-control study. Birth Defects Res. A Clin. Mol. Teratol. 2015, 103, 1011–1020.
53. Ray, J.G.; Wyatt, P.R.; Thompson, M.D.; Vermeulen, M.J.; Meier, C.; Wong, P.Y.; Farrell, S.A.; Cole, D.E. Vitamin B12 and the risk of neural tube defects in a folic-acid-fortified population. Epidemiology 2007, 18, 362–366.
54. Thompson, M.D.; Cole, D.E.; Ray, J.G. Vitamin B-12 and neural tube defects: The canadian experience. Am. J. Clin. Nutr. 2009, 89, 30.
55. Franke, B.; Vermeulen, S.H.; Steegers-Theunissen, R.P.; Coenen, M.J.; Schijvenaars, M.M.; Scheffer, H.; den Heijer, M.; Blom, H.J. An association study of 45 folate-related genes in spina bifida: Involvement of cubilin (cubn) and trna aspartic acid methyltransferase 1 (trdmt1). Birth Defects Res. A Clin. Mol. Teratol. 2009, 85, 216–226.
56. Hustad, S.; Ueland, P.M.; Vollset, S.E.; Zhang, Y.; Bjorke-Monsen, A.L.; Schneede, J. Riboflavin as a determinant of plasma total homocysteine: Effect modification by the methylenetetrahydrofolate reductase c677t polymorphism. Clin. Chem. 2000, 46, 1065–1071.
57. McNulty, H.; Dowey le, R.C.; Strain, J.J.; Dunne, A.; Ward, M.; Molloy, A.M.; McAnena, L.B.; Hughes, J.P.; Hannon-Fletcher, M.; Scott, J.M. Riboflavin lowers homocysteine in individuals homozygous for the mthfr 677c→t polymorphism. Circulation 2006, 113, 74–80.
58. Moat, S.J.; Ashfield-Watt, P.A.; Powers, H.J.; Newcombe, R.G.; McDowell, I.F. Effect of riboflavin status on the homocysteine-lowering effect of folate in relation to the mthfr (c677t) genotype. Clin. Chem. 2003, 49, 295–302.
59. Smithells, R.W.; Sheppard, S.; Schorah, C.J.; Seller, M.J.; Nevin, N.C.; Harris, R.; Read, A.P.; Fielding, D.W. Apparent prevention of neural tube defects by periconceptional vitamin supplementation. Arch. Dis. Child. 1981, 56, 911–918.
60. Haberg, S.E.; London, S.J.; Stigum, H.; Nafstad, P.; Nystad, W. Folic acid supplements in pregnancy and early childhood respiratory health. Arch. Dis. Child. 2009, 94, 180–184.
61. Yang, L.; Jiang, L.; Bi, M.; Jia, X.; Wang, Y.; He, C.; Yao, Y.; Wang, J.; Wang, Z. High dose of maternal folic acid supplementation is associated to infant asthma. Food Chem. Toxicol. 2015, 75, 88–93.
62. Rozendaal, A.M.; van Essen, A.J.; te Meerman, G.J.; Bakker, M.K.; van der Biezen, J.J.; Goorhuis-Brouwer, S.M.; Vermeij-Keers, C.; de Walle, H.E. Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the northern netherlands: A population based case-control study. Eur. J. Epidemiol. 2013, 28, 875–887.
63. Sengpiel, V.; Bacelis, J.; Myhre, R.; Myking, S.; Devold Pay, A.S.; Haugen, M.; Brantsaeter, A.L.; Meltzer, H.M.; Nilsen, R.M.; Magnus, P.; et al. Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: A prospective observational cohort study. BMC Pregnancy Childbirth 2014, 14, 014–0375.
64. Valera-Gran, D.; Garcia de la Hera, M.; Navarrete-Munoz, E.M.; Fernandez-Somoano, A.; Tardon, A.; Julvez, J.; Forns, J.; Lertxundi, N.; Ibarluzea, J.M.; Murcia, M.; et al. Folic acid supplements during pregnancy and child psychomotor development after the first year of life. JAMA Pediatr. 2014, 168, 3.
65. Tolarova, M.; Harris, J. Reduced recurrence of orofacial clefts after periconceptional supplementation with high-dose folic acid and multivitamins. Teratology 1995, 51, 71–78.
66. Li, Z.; Ye, R.; Zhang, L.; Li, H.; Liu, J.; Ren, A. Periconceptional folic acid supplementation and the risk of preterm births in China: A large prospective cohort study. Int. J. Epidemiol. 2014, 43, 1132–1139.
67. McGarel, C.; Pentieva, K.; Strain, J.J.; McNulty, H. Emerging roles for folate and related B-vitamins in brain health across the lifecycle. Proc. Nutr. Soc. 2015, 74, 46–55.
68. Quinlivan, E.P.; Gregory, J.F., 3rd. Effect of food fortification on folic acid intake in the united states. Am. J. Clin. Nutr. 2003, 77, 221–225.
69. Kelly, P.; McPartlin, J.; Goggins, M.; Weir, D.G.; Scott, J.M. Unmetabolized folic acid in serum: Acute studies in subjects consuming fortified food and supplements. Am. J. Clin. Nutr. 1997, 65, 1790–1795.
70. Plumptre, L.; Masih, S.P.; Ly, A.; Aufreiter, S.; Sohn, K.J.; Croxford, R.; Lausman, A.Y.; Berger, H.; O’Connor, D.L.; Kim, Y.I. High concentrations of folate and unmetabolized folic acid in a cohort of pregnant canadian women and umbilical cord blood. Am. J. Clin. Nutr. 2015, 102, 848–857.
71. Pentieva, K.; Selhub, J.; Paul, L.; Molloy, A.M.; McNulty, B.; Ward, M.; Marshall, B.; Dornan, J.; Reilly, R.; Parle-McDermott, A.; et al. Evidence from a randomized trial that exposure to supplemental folic acid at recommended levels during pregnancy does not lead to increased unmetabolized folic acid concentrations in maternal or cord blood. J. Nutr. 2016, 146, 494–500.
72. Bailey, H.D.; Miller, M.; Langridge, A.; de Klerk, N.H.; van Bockxmeer, F.M.; Attia, J.; Scott, R.J.; Armstrong, B.K.; Milne, E. Maternal dietary intake of folate and vitamins B6 and B12 during pregnancy and the risk of childhood acute lymphoblastic leukemia. Nutr. Cancer 2012, 64, 1122–1130.
73. Katan, M.B. How much vitamin B6 is toxic? Ned. Tijdschr. Geneeskd. 2005, 149, 2545–2546.
74. Rogovik, A.L.; Vohra, S.; Goldman, R.D. Safety considerations and potential interactions of vitamins: Should vitamins be considered drugs? Ann. Pharmacother. 2010, 44, 311–324.
75. Chu, D.-M.; Wahlqvist, M.L.; Chang, H.-Y.; Yeh, N.-H. Choline and betaine food sources and intakes in taiwanese. Asia Pac. J. Clin. Nutr. 2012, 21, 547–557.
76. Zeisel, S.H.; da Costa, K.A. Choline: An essential nutrient for public health. Nutr. Rev. 2009, 67, 615–623.
77. Steenge, G.R.; Verhoef, P.; Katan, M.B. Betaine supplementation lowers plasma homocysteine in healthy men and women. J. Nutr. 2003, 133, 1291–1295.
78. Fisher, M.C.; Zeisel, S.H.; Mar, M.H.; Sadler, T.W. Perturbations in choline metabolism cause neural tube defects in mouse embryos in vitro. FASEB J. 2002, 16, 619–621.
79. Shaw, G.M.; Carmichael, S.L.; Yang, W.; Selvin, S.; Schaffer, D.M. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am. J. Epidemiol. 2004, 160, 102–109.
80. Wang, Z.; Klipfell, E.; Bennett, B.J.; Koeth, R.; Levison, B.S.; Dugar, B.; Feldstein, A.E.; Britt, E.B.; Fu, X.; Chung, Y.M.; et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011, 472, 57–63.
81. Sanders, L.M.; Zeisel, S.H. Choline: Dietary requirements and role in brain development. Nutr. Today 2007, 42, 181–186.
82. Ye, R.; Ren, A.; Zhang, L.; Li, Z.; Liu, J.; Pei, L.; Zheng, X. Tea drinking as a risk factor for neural tube defects in northern China. Epidemiology 2011, 22, 491–496.
83. Correa, A.; Stolley, A.; Liu, Y. Prenatal tea consumption and risks of anencephaly and spina bifida. Ann. Epidemiol. 2000, 10, 476–477.
84. Yazdy, M.M.; Tinker, S.C.; Mitchell, A.A.; Demmer, L.A.; Werler, M.M. Maternal tea consumption during early pregnancy and the risk of spina bifida. Birth Defects Res. Part A Clin. Mol. Teratol. 2012, 94, 756–761.
85. Augustin, K.; Frank, J.; Augustin, S.; Langguth, P.; Ohrvik, V.; Witthoft, C.M.; Rimbach, G.; Wolffram, S. Greeen tea extracts lower serum folates in rats at very high dietary concentrations only and do not affect plasma folates in a human pilot study. J. Physiol. Pharmacol. 2009, 60, 103–108.
86. Shiraishi, M.; Haruna, M.; Matsuzaki, M.; Ota, E.; Murayama, R.; Murashima, S. Association between the serum folate levels and tea consumption during pregnancy. Biosci. Trends 2010, 4, 225–230.
87. Liu, J.; Wang, L.; Fu, Y.; Li, Z.; Zhang, Y.; Zhang, L.; Jin, L.; Ye, R.; Ren, A. Association between maternal comt gene polymorphisms and fetal neural tube defects risk in a Chinese population. Birth Defects Res. A Clin. Mol. Teratol. 2014, 100, 22–29.
88. Navarro-Peran, E.; Cabezas-Herrera, J.; Campo, L.S.; Rodriguez-Lopez, J.N. Effects of folate cycle disruption by the green tea polyphenol epigallocatechin-3-gallate. Int. J. Biochem. Cell Biol. 2007, 39, 2215–2225.
89. De Marco, P.; Merello, E.; Calevo, M.G.; Mascelli, S.; Pastorino, D.; Crocetti, L.; De Biasio, P.; Piatelli, G.; Cama, A.; Capra, V. Maternal periconceptional factors affect the risk of spina bifida-affected pregnancies: An italian case-control study. Childs Nerv. Syst. 2011, 27, 1073–1081.
90. Cravo, M.L.; Gloria, L.M.; Selhub, J.; Nadeau, M.R.; Camilo, M.E.; Resende, M.P.; Cardoso, J.N.; Leitao, C.N.; Mira, F.C. Hyperhomocysteinemia in chronic alcoholism: Correlation with folate, vitamin B-12, and vitamin B-6 status. Am. J. Clin. Nutr. 1996, 63, 220–224.
91. Stickel, F.; Choi, S.W.; Kim, Y.I.; Bagley, P.J.; Seitz, H.K.; Russell, R.M.; Selhub, J.; Mason, J.B. Effect of chronic alcohol consumption on total plasma homocysteine level in rats. Alcohol. Clin. Exp. Res. 2000, 24, 259–264.
92. Murillo-Fuentes, M.L.; Artillo, R.; Ubeda, N.; Varela-Moreiras, G.; Murillo, M.L.; Carreras, O. Hepatic s-adenosylmethionine after maternal alcohol exposure on offspring rats. Addict. Biol. 2005, 10, 139–144.
93. Barak, A.J.; Beckenhauer, H.C.; Junnila, M.; Tuma, D.J. Dietary betaine promotes generation of hepatic s-adenosylmethionine and protects the liver from ethanol-induced fatty infiltration. Alcohol. Clin. Exp. Res. 1993, 17, 552–555.
94. Shiraishi, M.; Haruna, M.; Matsuzaki, M.; Ota, E.; Murayama, R.; Sasaki, S.; Yeo, S.; Murashima, S. Relationship between plasma total homocysteine level and dietary caffeine and vitamin B6 intakes in pregnant women. Nurs. Health Sci. 2014, 16, 164–170.
95. Ubbink, J.B.; Delport, R.; Becker, P.J.; Bissbort, S. Evidence of a theophylline-induced vitamin B6 deficiency caused by noncompetitive inhibition of pyridoxal kinase. J. Lab. Clin. Med. 1989, 113, 15–22.
96. Ubbink, J.B.; Delport, R.; Bissbort, S.; Vermaak, W.J.; Becker, P.J. Relationship between vitamin B-6 status and elevated pyridoxal kinase levels induced by theophylline therapy in humans. J. Nutr. 1990, 120, 1352–1359.
97. Huang, T.; Li, K.; Asimi, S.; Chen, Q.; Li, D. Effect of vitamin B-12 and n-3 polyunsaturated fatty acids on plasma homocysteine, ferritin, c-reaction protein, and other cardiovascular risk factors: A randomized controlled trial. Asia Pac. J. Clin. Nutr. 2015, 24, 403–411.
98. Huang, T.; Yu, X.; Shou, T.; Wahlqvist, M.L.; Li, D. Associations of plasma phospholipid fatty acids with plasma homocysteine in Chinese vegetarians. Br. J. Nutr. 2013, 109, 1688–1694.
99. Huang, T.; Asimi, S.; Lou, D.; Li, D. Plasma phospholipid polyunsaturated fatty acids and homocysteine in Chinese type 2 diabetes patients. Asia Pac. J. Clin. Nutr. 2012, 21, 394–399.
100. Dawson, S.L.; Bowe, S.J.; Crowe, T.C. A combination of omega-3 fatty acids, folic acid and b-group vitamins is superior at lowering homocysteine than omega-3 alone: A meta-analysis. Nutr. Res. 2016, 36, 499–508.
101. Huang, T.; Hu, X.; Khan, N.; Yang, J.; Li, D. Effect of polyunsaturated fatty acids on homocysteine metabolism through regulating the gene expressions involved in methionine metabolism. Sci. World J. 2013, 23, 931626.
102. Detopoulou, P.; Papamikos, V. Gastrointestinal bleeding after high intake of omega-3 fatty acids, cortisone and antibiotic therapy: A case study. Int. J. Sport Nutr. Exerc. Metab. 2014, 24, 253–257.
103. Wachira, J.K.; Larson, M.K.; Harris, W.S. N-3 fatty acids affect haemostasis but do not increase the risk of bleeding: Clinical observations and mechanistic insights. Br. J. Nutr. 2014, 111, 1652–1662.
104. Meredith, D.S.; Kepler, C.K.; Huang, R.C.; Hirsch, B.; Nguyen, J.; Farmer, J.C.; Girardi, F.P.; O’Leary, P.F.; Cammisa, F.P. The effect of omega-3 fatty-acid supplements on perioperative bleeding following posterior spinal arthrodesis. Eur. Spine J. 2012, 21, 2659–2663.
105. Salisbury, A.C.; Harris, W.S.; Amin, A.P.; Reid, K.J.; O’Keefe, J.H., Jr.; Spertus, J.A. Relation between red blood cell omega-3 fatty acid index and bleeding during acute myocardial infarction. Am. J. Cardiol. 2012, 109, 13–18.
106. Finnegan, Y.E.; Minihane, A.M.; Leigh-Firbank, E.C.; Kew, S.; Meijer, G.W.; Muggli, R.; Calder, P.C.; Williams, C.M. Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of ldl to oxidative modification in moderately hyperlipidemic subjects. Am. J. Clin. Nutr. 2003, 77, 783–795.
107. Mori, T.A.; Woodman, R.J.; Burke, V.; Puddey, I.B.; Croft, K.D.; Beilin, L.J. Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Free Radic. Biol. Med. 2003, 35, 772–781.