妊娠期母体叶酸水平与母儿结局的研究进展
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摘要
叶酸作为人体必需的B族水溶性维生素,在胚胎发育、人体生长、新陈代谢等过程中均发挥着重要作用。妊娠期母体叶酸的缺乏,可导致胎儿脊柱裂、脑脊膜膨出等神经管畸形,还会增加妊娠期高血压、早产、贫血等不良母儿结局风险,但叶酸补充过量同样可引发一些问题,如引发维生素B_(12)缺乏的神经表现。本文主要就叶酸的生理作用、评价方法、对母儿结局的影响以及关于叶酸补充的相关推荐等进行阐述。
Folic acid,as an essential B group water-soluble vitamin,plays an important role in embryo development,body growth and metabolism.Lack of folic acid in pregnant women can lead to neural tube malformations,such as spina bifida and encephalomeningocele,and adverse maternal outcomes,such as gestational hypertension,premature birth,and anemia in pregnant women and infants.Excessive folic acid supplementation can also cause problems,such as neurological manifestations of vitamin B_(12) deficiency.In this paper,the physiological role of folic acid,evaluation methods,effects on maternal and infant outcomes,and related recommendations on folic acid supplementation were discussed.
Folic acid,as an essential B group water-soluble vitamin,plays an important role in embryo development,body growth and metabolism.Lack of folic acid in pregnant women can lead to neural tube malformations,such as spina bifida and encephalomeningocele,and adverse maternal outcomes,such as gestational hypertension,premature birth,and anemia in pregnant women and infants.Excessive folic acid supplementation can also cause problems,such as neurological manifestations of vitamin B_(12) deficiency.In this paper,the physiological role of folic acid,evaluation methods,effects on maternal and infant outcomes,and related recommendations on folic acid supplementation were discussed.
引文
[1]MITCHELL H K,SNELL E E,WILLIAMS R J.The concentration of “folic acid”[J].J Am Chem Soc,1941,63:2284.
[2]LIEW S C.Folic acid and diseases-supplement it or not?[J].Rev Assoc Med Bras(1992),2016,62(1):90-100.DOI:10.1590/1806-9282.62.01.90.
[3]IMBARD A,BENOIST J F,BLOM H J.Neural tube defects,folic acid and methylation[J].Int J Environ Res Public Health,2013,10(9):4352-4389.DOI:10.3390/ijerph10094352.
[4]BAKER H,HERBERT V,FRANK O,et al.A microbiologic method for detecting folic acid deficiency in man[J].Clin Chem,1959,5(4):275-280.
[5]FAZILI Z,PFEIFFER C M,ZHANG M.Comparison of serum folate species analyzed by LC-MS/MS with total folate measured by microbiologic assay and bio-rad radioassay[J].Clin Chem,2007,53(4):781-784.DOI:10.1373/clinchem.2006.078451.
[6]FAZILI Z,PFEIFFER C M,ZHANG M,et al.Influence of 5,10-methylenetetrahydrofolate reductase polymorphism on wholeblood folate concentrations measured by LC-MS/MS,microbiologic assay,and bio-rad radioassay[J].Clin Chem,2008,54(1):197-201.DOI:10.1373/clinchem.2007.096545.
[7]ANDERSON B B,COWAN J D.Effect of light on the Lactobacillus casei microbiological assay[J].J Clin Pathol,1968,21(1):85-87.
[8]YETLEY E A,PFEIFFER C M,PHINNEY K W,et al.Biomarkers of folate status in NHANES:a roundtable summary[J].Am J Clin Nutr,2011,94(1):303S-312.DOI:10.3945/ajcn.111.013011.
[9]PFEIFFER C,SCHLEICHER R,CALDWELL K.Enclyclopedia of human nutrition[M].3rd ed.Waltham,MA:Academic Studies Press,2013:156-174.
[10]CHANARIN I.Folates and pterins.Volume 3.Nutritional,pharmacological,and physiological aspects[M].New York:John Wiley&Sons,1986:75-146.
[11]PFEIFFER C M,ZHANG M,LACHER D A,et al.Comparison of serum and red blood cell folate microbiologic assays for national population surveys[J].J Nutr,2011,141(7):1402-1409.DOI:10.3945/jn.111.141515.
[12]BOTTO L D,YANG Q.5,10-methylenetetrahydrofolate reductase gene variants and congenital anomalies:a HuGE review[J].Am J Epidemiol,2000,151(9):862-877.
[13]WILCKEN B,BAMFORTH F,LI Z,et al.Geographical and ethnic variation of the 677C>T allele of 5,10methylenetetrahydrofolate reductase(MTHFR):findings from over 7000 newborns from 16 areas world wide[J].J Med Genet,2003,40(8):619-625.
[14]SHANE B.Folate and vitamin B_(12) metabolism:overview and interaction with riboflavin,vitamin B6,and polymorphisms[J].Food Nutr Bull,2008,29(2 Suppl):S5-19.DOI:10.1177/15648265080292S103.
[15]NZILA A,OKOMBO J,MOLLOY A M.Impact of folate supplementation on the efficacy of sulfadoxine/pyrimethamine in preventing malaria in pregnancy:the potential of5-methyltetrahydrofolate[J].J Antimicrob Chemother,2014,69(2):323-330.DOI:10.1093/jac/dkt394.
[16]SMITHELLS R W,SHEPPARD S,SCHORAH C J.Vitamin dificiencies and neural tube defects[J].Arch Dis Child,1976,51(12):944-950.
[17]HIBBARD B M,HIBBARD E D,JEFFCOATE T N.Folic acid and reproduction[J].Acta Obstet Gynecol Scand,1965,44(3):375-400.
[18]HIBBARD B M.The role of folic acid in pregnancy;with particular reference to anaemia,abruption and abortion[J].J Obstet Gynaecol Br Commonw,1964,71:529-542.
[19]SMITHELLS R W,NEVIN N C,SELLER M J,et al.Further experience of vitamin supplementation for prevention of neural tube defect recurrences[J].Lancet,1983,1(8332):1027-1031.
[20]ECONOMIDES D L,FERGUSON J,MACKENZIE I Z,et al.Folate and vitamin B_(12) concentrations in maternal and fetal blood,and amniotic fluid in second trimester pregnancies complicated by neural tube defects[J].Br J Obstet Gynaecol,1992,99(1):23-25.
[21]MURRAY C J,LOPEZ A D.Health dimensions of sex and reproduction[M].Cambridge:Harvard School of Public Health,1998:455-512.
[22]LAURENCE K M,JAMES N,MILLER M H,et al.Doubleblind randomised controlled trial of folate treatment before conception to prevent recurrence of neural-tube defects[J].Br Med J(Clin Res Ed),1981,282(6275):1509-1511.
[23]MRC Vitamin Study Research Group.Prevention of neural tube defects:Results of the medical research council vitamin study[J].Lancet,1991,338(8760):131-137.
[24]BERRY R J,LI Z,ERICKSON J D,et al.Prevention of neuraltube defects with folic acid in China.China-U.S.Collaborative project for neural tube defect prevention[J].N Engl J Med,1999,341(20):1485-1490.
[25]ROTHENBERG S P,DA COSTA M P,SEQUEIRA J M,et al.Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect[J].N Engl J Med,2004,350(2):134-142.DOI:10.1056/NEJMoa031145.
[26]BARBER R C,LAMMER E J,SHAW G M,et al.The role of folate transport and metabolism in neural tube defect risk[J].Mol Genet Metab,1999,66(1):1-9.DOI:10.1006/mgme.1998.2787.
[27]DALY L E,KIRKE P N,MOLLOY A,et al.Folate levels and neural tube defects.Implications for prevention[J].JAMA,1995,274(21):1698-1702.
[28]DE WALS P,TAIROU F,VAN ALLEN M I,et al.Reduction in neural-tube defects after folic acid fortification in Canada[J].N En gl J Med,2 0 0 7,3 57(2):13 5-1 42.DOI:10.1056/NEJMoa067103.
[29]RAY J G,MEIER C,VERMEULEN M J,et al.Association of neural tube defects and folic acid food fortification in Canada[J].Lancet,2002,360(9350):2047-2048.DOI:10.1016/S0140-6736(02)11994-5.
[30]CHANARIN I,MACGIBBON B M,O'SULLIVAN W J,et al.Folic-acid deficiency in pregnancy the pathogenesis of megaloblastic an?mia of pregnancy[J].Lancet,1959,274(7104):634-639.
[31]F U J I W A R A T,M O R I S A K I N,H O N D A Y,e t a l.Chemicals,nutrition,and autism spectrum disorder:a minireview[J].Front Neurosci,2016,10:174.DOI:10.3389/fnins.2016.00174.
[32]ROTH C,MAGNUS P,SCHJ?LBERG S,et al.Folic acid supplements in pregnancy and severe language delay in children[J].JAMA,2011,306(14):1566-1573.DOI:10.1001/jama.2011.1433.
[33]SCHMIDT R J,TANCREDI D J,OZONOFF S,et al.Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE(Childhood Autism Risks from Genetics and Environment)case-control study[J].Am J Clin Nutr,2012,96(1):80-89.DOI:10.3945/ajcn.110.004416.
[34]SUREN P,ROTH C,BRESNAHAN M,et al.Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children[J].JAMA,2013,309(6):570-577.DOI:10.1001/jama.2012.155925.
[35]BRAUN J M,FROEHLICH T,KALKBRENNER A,et al.Brief report:are autistic-behaviors in children related to prenatal vitamin use and maternal whole blood folate concentrations?[J].J Autism Dev Disord,2014,44(10):2602-2607.DOI:10.1007/s10803-014-2114-x.
[36]NEGGERS Y.The relationship between folic acid and risk of autism spectrum disorders[J].Healthcare(Basel),2014,2(4):429-444.DOI:10.3390/healthcare2040429.
[37]KOSTI R I,PANAGIOTAKOS D B.The epidemic of obesity in children and adolescents in the world[J].Cent Eur J Public Health,2006,14(4):151-159.
[38]WANG G,HU F B,MISTRY K B,et al.Association between maternal prepregnancy body mass index and plasma folate concentrations with child METABOLIC health[J].JAMAPediatr,2016,170(8):e160845.DOI:10.1001/jamapediatr ics.2016.0845.
[39]HUANG T,HU X,KHAN N,et al.Effect of polyunsaturated fatty acids on homocysteine metabolism through regulating the gene expressions involved in methionine metabolism[J].Sci World J,2013,2013:931626.DOI:10.1155/2013/931626.
[40]ZAPPACOSTA B,MASTROIACOVO P,PERSICHILIS,et al.Homocysteine lowering by folate-rich diet or pharmacological supplementations in subjects with moderate hyperhomocysteinemia[J].Nutrients,2013,5(5):1531-1543.DOI:10.3390/nu5051531.
[41]CHAKRABORTY P,GOSWAMI S K,RAJANI S,et al.Recurrent pregnancy loss in polycystic ovary syndrome:role of hyperhomocysteinemia and insulin resistance[J].PLoS One,2013,8(5):e64446.DOI:10.1371/journal.pone.0064446.
[42]LI H C,HOU L,TAN H,et al.The homocysteine levels of prenatal,pregnancy and post-natal and its clinical significance[J].Int J Lab Med,2011,32(19):2295-2296.
[43]AGAMANOLIS D P,CHESTER E M,VICTOR M,et al.Neuropathology of experimental vitamin B_(12) deficiency in monkeys[J].Neurology,1976,26(10):905-914.
[44]VAN DER WESTHUYZEN J,CANTRILL R C,FERNANDES-COSTA F,et al.Effect of a vitamin B-12-deficient diet on lipid and fatty acid composition of spinal cord myelin in the fruit bat[J].J Nutr,1983,113(3):531-537.DOI:10.1093/jn/113.3.531.
[45]BATES P J,COETZEE G A,VAN DER WESTHUYZEN D R.The degradation of endogenous and exogenous proteins in cultured smooth muscle cells[J].Biochim Biophys Acta,1982,719(2):377-387.
[46]COLE B F,BARON J A,SANDIER R S,et al.Folic acid for the prevention of colorectal adenomas:a randomized clinical trial[J].JAMA,2007,297(21):2351-2359.DOI:10.1001/jama.297.21.2351.
[47]MASON J B,DICKSTEIN A,JACQUES P F,et al.A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles:a hypothesis[J].Cancer Epidemiol Biomarkers Prev,2007,16(7):1325-1329.DOI:10.1158/1055-9965.EPI-07-0329.
[48]GIOVANNUCCI E,STAMPFER M J,COIDITZ G A,et al.Muitivitamin use,folate,and colon cancer in women in the Nurses'Health Study[J].Ann Intern Med,1998,129(7):517-524.
[49]MAYNE S T,RISCH H A,DUBROW R,et al.Nutrient intake and risk of subtypes of esophageal and gastric cancer[J].Cancer Epidemiol Biomarkers Prev,2001,10(10):1055-1062.
[50]SHRUBSOLE M J,JIN F,DAI Q,et al.Dietary folate intake and breast cancer risk:results from the Shanghai Breast Cancer Study[J].Cancer Res,2001,61(19):7136-7141.
[51]LARSSON S C,GIOVANNUCCI E,WOLK A.Folate intake,MTHFR polymorphisms,and risk of esophageal,gastric,and pancreatic cancer:a meta-analysis[J].Gastroenterology,2 0 0 6,1 3 1(4):1 2 7 1-1 2 8 3.D O I:1 0.1 0 5 3/j.gastro.2006.08.010.
[52]LARSSON S C,GIOVANNUCCI E,WOLK A.A prospective study of dietary folate intake and risk of colorectal cancer:modification by caffeine intake and cigarette smoking[J].Cancer Epidemiol Biomarkers Prev,2005,14(3):740-743.DOI:10.1158/1055-9965.EPI-04-0581.
[53]KIM Y I.Folate and colorectal cancer:an evidence-based critical review[J].Mol Nutr Food Res,2007,51(3):267-292.DOI:10.1002/mnfr.200600191.
[54]STOLZENBERG-SOLOMON R Z,CHANG S C,LEITZMANN MF,et al.Folate intake,alcohol use,and postmenopausal breast cancer risk in the prostate,lung,colorectal,and ovarian cancer screening trial[J].Am J Clin Nutr,2006,83(4):895-904.DOI:10.1093/ajcn/83.4.895.
[2]LIEW S C.Folic acid and diseases-supplement it or not?[J].Rev Assoc Med Bras(1992),2016,62(1):90-100.DOI:10.1590/1806-9282.62.01.90.
[3]IMBARD A,BENOIST J F,BLOM H J.Neural tube defects,folic acid and methylation[J].Int J Environ Res Public Health,2013,10(9):4352-4389.DOI:10.3390/ijerph10094352.
[4]BAKER H,HERBERT V,FRANK O,et al.A microbiologic method for detecting folic acid deficiency in man[J].Clin Chem,1959,5(4):275-280.
[5]FAZILI Z,PFEIFFER C M,ZHANG M.Comparison of serum folate species analyzed by LC-MS/MS with total folate measured by microbiologic assay and bio-rad radioassay[J].Clin Chem,2007,53(4):781-784.DOI:10.1373/clinchem.2006.078451.
[6]FAZILI Z,PFEIFFER C M,ZHANG M,et al.Influence of 5,10-methylenetetrahydrofolate reductase polymorphism on wholeblood folate concentrations measured by LC-MS/MS,microbiologic assay,and bio-rad radioassay[J].Clin Chem,2008,54(1):197-201.DOI:10.1373/clinchem.2007.096545.
[7]ANDERSON B B,COWAN J D.Effect of light on the Lactobacillus casei microbiological assay[J].J Clin Pathol,1968,21(1):85-87.
[8]YETLEY E A,PFEIFFER C M,PHINNEY K W,et al.Biomarkers of folate status in NHANES:a roundtable summary[J].Am J Clin Nutr,2011,94(1):303S-312.DOI:10.3945/ajcn.111.013011.
[9]PFEIFFER C,SCHLEICHER R,CALDWELL K.Enclyclopedia of human nutrition[M].3rd ed.Waltham,MA:Academic Studies Press,2013:156-174.
[10]CHANARIN I.Folates and pterins.Volume 3.Nutritional,pharmacological,and physiological aspects[M].New York:John Wiley&Sons,1986:75-146.
[11]PFEIFFER C M,ZHANG M,LACHER D A,et al.Comparison of serum and red blood cell folate microbiologic assays for national population surveys[J].J Nutr,2011,141(7):1402-1409.DOI:10.3945/jn.111.141515.
[12]BOTTO L D,YANG Q.5,10-methylenetetrahydrofolate reductase gene variants and congenital anomalies:a HuGE review[J].Am J Epidemiol,2000,151(9):862-877.
[13]WILCKEN B,BAMFORTH F,LI Z,et al.Geographical and ethnic variation of the 677C>T allele of 5,10methylenetetrahydrofolate reductase(MTHFR):findings from over 7000 newborns from 16 areas world wide[J].J Med Genet,2003,40(8):619-625.
[14]SHANE B.Folate and vitamin B_(12) metabolism:overview and interaction with riboflavin,vitamin B6,and polymorphisms[J].Food Nutr Bull,2008,29(2 Suppl):S5-19.DOI:10.1177/15648265080292S103.
[15]NZILA A,OKOMBO J,MOLLOY A M.Impact of folate supplementation on the efficacy of sulfadoxine/pyrimethamine in preventing malaria in pregnancy:the potential of5-methyltetrahydrofolate[J].J Antimicrob Chemother,2014,69(2):323-330.DOI:10.1093/jac/dkt394.
[16]SMITHELLS R W,SHEPPARD S,SCHORAH C J.Vitamin dificiencies and neural tube defects[J].Arch Dis Child,1976,51(12):944-950.
[17]HIBBARD B M,HIBBARD E D,JEFFCOATE T N.Folic acid and reproduction[J].Acta Obstet Gynecol Scand,1965,44(3):375-400.
[18]HIBBARD B M.The role of folic acid in pregnancy;with particular reference to anaemia,abruption and abortion[J].J Obstet Gynaecol Br Commonw,1964,71:529-542.
[19]SMITHELLS R W,NEVIN N C,SELLER M J,et al.Further experience of vitamin supplementation for prevention of neural tube defect recurrences[J].Lancet,1983,1(8332):1027-1031.
[20]ECONOMIDES D L,FERGUSON J,MACKENZIE I Z,et al.Folate and vitamin B_(12) concentrations in maternal and fetal blood,and amniotic fluid in second trimester pregnancies complicated by neural tube defects[J].Br J Obstet Gynaecol,1992,99(1):23-25.
[21]MURRAY C J,LOPEZ A D.Health dimensions of sex and reproduction[M].Cambridge:Harvard School of Public Health,1998:455-512.
[22]LAURENCE K M,JAMES N,MILLER M H,et al.Doubleblind randomised controlled trial of folate treatment before conception to prevent recurrence of neural-tube defects[J].Br Med J(Clin Res Ed),1981,282(6275):1509-1511.
[23]MRC Vitamin Study Research Group.Prevention of neural tube defects:Results of the medical research council vitamin study[J].Lancet,1991,338(8760):131-137.
[24]BERRY R J,LI Z,ERICKSON J D,et al.Prevention of neuraltube defects with folic acid in China.China-U.S.Collaborative project for neural tube defect prevention[J].N Engl J Med,1999,341(20):1485-1490.
[25]ROTHENBERG S P,DA COSTA M P,SEQUEIRA J M,et al.Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect[J].N Engl J Med,2004,350(2):134-142.DOI:10.1056/NEJMoa031145.
[26]BARBER R C,LAMMER E J,SHAW G M,et al.The role of folate transport and metabolism in neural tube defect risk[J].Mol Genet Metab,1999,66(1):1-9.DOI:10.1006/mgme.1998.2787.
[27]DALY L E,KIRKE P N,MOLLOY A,et al.Folate levels and neural tube defects.Implications for prevention[J].JAMA,1995,274(21):1698-1702.
[28]DE WALS P,TAIROU F,VAN ALLEN M I,et al.Reduction in neural-tube defects after folic acid fortification in Canada[J].N En gl J Med,2 0 0 7,3 57(2):13 5-1 42.DOI:10.1056/NEJMoa067103.
[29]RAY J G,MEIER C,VERMEULEN M J,et al.Association of neural tube defects and folic acid food fortification in Canada[J].Lancet,2002,360(9350):2047-2048.DOI:10.1016/S0140-6736(02)11994-5.
[30]CHANARIN I,MACGIBBON B M,O'SULLIVAN W J,et al.Folic-acid deficiency in pregnancy the pathogenesis of megaloblastic an?mia of pregnancy[J].Lancet,1959,274(7104):634-639.
[31]F U J I W A R A T,M O R I S A K I N,H O N D A Y,e t a l.Chemicals,nutrition,and autism spectrum disorder:a minireview[J].Front Neurosci,2016,10:174.DOI:10.3389/fnins.2016.00174.
[32]ROTH C,MAGNUS P,SCHJ?LBERG S,et al.Folic acid supplements in pregnancy and severe language delay in children[J].JAMA,2011,306(14):1566-1573.DOI:10.1001/jama.2011.1433.
[33]SCHMIDT R J,TANCREDI D J,OZONOFF S,et al.Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE(Childhood Autism Risks from Genetics and Environment)case-control study[J].Am J Clin Nutr,2012,96(1):80-89.DOI:10.3945/ajcn.110.004416.
[34]SUREN P,ROTH C,BRESNAHAN M,et al.Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children[J].JAMA,2013,309(6):570-577.DOI:10.1001/jama.2012.155925.
[35]BRAUN J M,FROEHLICH T,KALKBRENNER A,et al.Brief report:are autistic-behaviors in children related to prenatal vitamin use and maternal whole blood folate concentrations?[J].J Autism Dev Disord,2014,44(10):2602-2607.DOI:10.1007/s10803-014-2114-x.
[36]NEGGERS Y.The relationship between folic acid and risk of autism spectrum disorders[J].Healthcare(Basel),2014,2(4):429-444.DOI:10.3390/healthcare2040429.
[37]KOSTI R I,PANAGIOTAKOS D B.The epidemic of obesity in children and adolescents in the world[J].Cent Eur J Public Health,2006,14(4):151-159.
[38]WANG G,HU F B,MISTRY K B,et al.Association between maternal prepregnancy body mass index and plasma folate concentrations with child METABOLIC health[J].JAMAPediatr,2016,170(8):e160845.DOI:10.1001/jamapediatr ics.2016.0845.
[39]HUANG T,HU X,KHAN N,et al.Effect of polyunsaturated fatty acids on homocysteine metabolism through regulating the gene expressions involved in methionine metabolism[J].Sci World J,2013,2013:931626.DOI:10.1155/2013/931626.
[40]ZAPPACOSTA B,MASTROIACOVO P,PERSICHILIS,et al.Homocysteine lowering by folate-rich diet or pharmacological supplementations in subjects with moderate hyperhomocysteinemia[J].Nutrients,2013,5(5):1531-1543.DOI:10.3390/nu5051531.
[41]CHAKRABORTY P,GOSWAMI S K,RAJANI S,et al.Recurrent pregnancy loss in polycystic ovary syndrome:role of hyperhomocysteinemia and insulin resistance[J].PLoS One,2013,8(5):e64446.DOI:10.1371/journal.pone.0064446.
[42]LI H C,HOU L,TAN H,et al.The homocysteine levels of prenatal,pregnancy and post-natal and its clinical significance[J].Int J Lab Med,2011,32(19):2295-2296.
[43]AGAMANOLIS D P,CHESTER E M,VICTOR M,et al.Neuropathology of experimental vitamin B_(12) deficiency in monkeys[J].Neurology,1976,26(10):905-914.
[44]VAN DER WESTHUYZEN J,CANTRILL R C,FERNANDES-COSTA F,et al.Effect of a vitamin B-12-deficient diet on lipid and fatty acid composition of spinal cord myelin in the fruit bat[J].J Nutr,1983,113(3):531-537.DOI:10.1093/jn/113.3.531.
[45]BATES P J,COETZEE G A,VAN DER WESTHUYZEN D R.The degradation of endogenous and exogenous proteins in cultured smooth muscle cells[J].Biochim Biophys Acta,1982,719(2):377-387.
[46]COLE B F,BARON J A,SANDIER R S,et al.Folic acid for the prevention of colorectal adenomas:a randomized clinical trial[J].JAMA,2007,297(21):2351-2359.DOI:10.1001/jama.297.21.2351.
[47]MASON J B,DICKSTEIN A,JACQUES P F,et al.A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles:a hypothesis[J].Cancer Epidemiol Biomarkers Prev,2007,16(7):1325-1329.DOI:10.1158/1055-9965.EPI-07-0329.
[48]GIOVANNUCCI E,STAMPFER M J,COIDITZ G A,et al.Muitivitamin use,folate,and colon cancer in women in the Nurses'Health Study[J].Ann Intern Med,1998,129(7):517-524.
[49]MAYNE S T,RISCH H A,DUBROW R,et al.Nutrient intake and risk of subtypes of esophageal and gastric cancer[J].Cancer Epidemiol Biomarkers Prev,2001,10(10):1055-1062.
[50]SHRUBSOLE M J,JIN F,DAI Q,et al.Dietary folate intake and breast cancer risk:results from the Shanghai Breast Cancer Study[J].Cancer Res,2001,61(19):7136-7141.
[51]LARSSON S C,GIOVANNUCCI E,WOLK A.Folate intake,MTHFR polymorphisms,and risk of esophageal,gastric,and pancreatic cancer:a meta-analysis[J].Gastroenterology,2 0 0 6,1 3 1(4):1 2 7 1-1 2 8 3.D O I:1 0.1 0 5 3/j.gastro.2006.08.010.
[52]LARSSON S C,GIOVANNUCCI E,WOLK A.A prospective study of dietary folate intake and risk of colorectal cancer:modification by caffeine intake and cigarette smoking[J].Cancer Epidemiol Biomarkers Prev,2005,14(3):740-743.DOI:10.1158/1055-9965.EPI-04-0581.
[53]KIM Y I.Folate and colorectal cancer:an evidence-based critical review[J].Mol Nutr Food Res,2007,51(3):267-292.DOI:10.1002/mnfr.200600191.
[54]STOLZENBERG-SOLOMON R Z,CHANG S C,LEITZMANN MF,et al.Folate intake,alcohol use,and postmenopausal breast cancer risk in the prostate,lung,colorectal,and ovarian cancer screening trial[J].Am J Clin Nutr,2006,83(4):895-904.DOI:10.1093/ajcn/83.4.895.