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Nutritional Supplement

Folic Acid

Folic acid is a B vitamin needed for cell replication and growth. Folic acid helps form building blocks of DNA, the body’s genetic information, and building blocks of RNA, needed for protein synthesis in all cells. Therefore, rapidly growing tissues, such as those of a fetus, and rapidly regenerating cells, like red blood cells and immune cells, have a high need for folic acid. Folic acid deficiency results in a form of anemia that responds quickly to folic acid supplementation.

References

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12. Folsom AR, Nieto FJ, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins. Circulation 1998;98:204-10.

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27. Folsom AR, Nieto FJ, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins. Circulation 1998;98:204-10.

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32. Lobo A, Naso A, Arheart K, et al. Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12. Am J Cardiol 1999;83:821-5.

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34. Carrero JJ, Lopez-Huertas E, Salmeron LM, et al. Daily supplementation with (n-3) PUFAs, oleic acid, folic acid, and vitamins B-6 and E increases pain-free walking distance and improves risk factors in men with peripheral vascular disease. J Nutr2005;135:1393-9.

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38. Perry IJ. Homocysteine, hypertension and stroke. J Hum Hypertens 1999;13:289-93 [review].

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40. Ubbink JB, Vermaak WJH, ven der Merwe A, et al. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994;124:1927-33.

41. Manson JB, Miller JW. The effects of vitamin B12, B6, and folate on blood homocysteine levels. Ann NY Acad Sci 1992;669:197-204 [review].

42. Wang X, Qin X, Demirtas H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 2007;369:1876-82.

43. MRC Vitamin Study Research Group. Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. Lancet 1991;338:131-7.

44. Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327:1832-5.

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46. Moore KL. Formulation of the trilaminar embryo. In: The Developing Human. Philadelphia, PA: WB Saunders Co., 1988:55-64.

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48. Truswell AS. ABC of nutrition. Nutrition for pregnancy. Br Med J 1985;291:263-6.

49. Scholl TO, Hediger ML, Schall JI, et al. Dietary and serum folate: their influence on the outcome of pregnancy. Am J Clin Nutr 1996;63:520-5.

50. MRC Vitamin Study Research Group. Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. Lancet 1991;338:131-7.

51. Tamura T, Goldenberg RL, Johnston KE, et al. Serum concentrations of zinc, folate, vitamins A and E, and proteins, and their relationships to pregnancy outcome. Acta Obstet Gynecol Scand Suppl 1997;165:63-70.

52. Tamura T, Goldenberg RL, Freeberg LE, et al. Maternal serum folate and zinc concentrations and their relationships to pregnancy outcome. Am J Clin Nutr 1992;56:365-70.

53. Goldenberg RL, Tamura T, Cliver SP, et al. Serum folate and fetal growth retardation: a matter of compliance? Obstet Gynecol 1992;795 (Pt 1):719-22.

54. Neggers YH, Goldenberg RL, Tamura T, et al. The relationship between maternal dietary intake and infant birthweight. Acta Obstet Gynecol Scand Suppl 1997;165:71-5.

55. Frelut ML, de Courcy GP, Christides JP, et al. Relationship between maternal folate status and foetal hypotrophy in a population with a good socio-economical level. Int J Vitam Nutr Res 1995;65:267-71.

56. Ek J. Plasma and red cell folate in mothers and infants in normal pregnancies. Relation to birth weight. Acta Obstet Gynecol Scand 1982;61:17-20.

57. Malinow MR, Rajkovic A, Duell PB, et al. The relationship between maternal and neonatal umbilical cord plasma homocyst(e)ine suggests a potential role for maternal homocyst(e)ine in fetal metabolism. Am J Obstet Gynecol 1998;178:228-33.

58. Burke G, Robinson K, Refsum H, et al. Intrauterine growth retardation, perinatal death, and maternal homocysteine levels. N Engl J Med 1992;326:69-70 [letter].

59. Iyengar L, Rajalakshmi K. Effect of folic acid supplement on birth weights of infants. Am J Obstet Gynecol 1975;122:332-6.

60. Rolschau J, Date J, Kristoffersen K. Folic acid supplement and intrauterine growth. Acta Obstet Gynecol Scand 1979;58:343-6.

61. Blot I, Papiernik E, Kaltwasser JP, et al. Influence of routine administration of folic acid and iron during pregnancy. Gynecol Obstet Invest 1981;12:294-304.

62. Baumslag N, Edelstein T, Metz J. Reduction of incidence of prematurity by folic acid supplementation in pregnancy. Br Med J 1970;1:16-7.

63. Fleming AF, Martin JD, Hahnel R, Westlake AJ. Effects of iron and folic acid antenatal supplements on maternal haematology and fetal wellbeing. Med J Aust 1974;2:429-36.

64. Fletcher J, Gurr A, Fellingham FR, et al. The value of folic acid supplements in pregnancy. J Obstet Gynaecol Br Commonw 1971;78:781-5.

65. Giles PF, Harcourt AG, Whiteside MG. The effect of prescribing folic acid during pregnancy on birth-weight and duration of pregnancy. A double-blind trial. Med J Aust 1971;2:17-21.

66. Sutterlin M, Bussen S, Ruppert D, Steck T. Serum levels of folate and cobalamin in women with recurrent spontaneous abortion. Hum Reprod 1997;12:2292-6.

67. Wouters MG, Boers GH, Blom HJ, et al. Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril 1993;60:820-5.

68. Steegers-Theunissen RP, Boers GH, Blom HJ, et al. Hyperhomocysteinaemia and recurrent spontaneous abortion or abruptio placentae. Lancet 1992;339:1122-3 [letter].

69. Quere I, Bellet H, Hoffet M, et al. A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages. Fertil Steril 1998;69:152-4.

70. Quere I, Mercier E, Bellet H, et al. Vitamin supplementation and pregnancy outcome in women with recurrent early pregnancy loss and hyperhomocysteinemia. Fertil Steril 2001;75:823-5.

71. Pietrzik K, Prinz R, Reusch K, et al. Folate status and pregnancy outcome. Ann N Y Acad Sci 1992;669:371-3.

72. Neiger R, Wise C, Contag SA, et al. First trimester bleeding and pregnancy outcome in gravidas with normal and low folate levels. Am J Perinatol 1993;10:460-2.

73. Neela J, Raman L. The relationship between maternal nutritional status and spontaneous abortion. Natl Med J India 1997;10:15-6.

74. Botto LD, Mulinare J, Erickson JD. Occurrence of congenital heart defects in relation to maternal mulitivitamin use. Am J Epidemiol 2000;151:878-84.

75. Czeizel AE. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet 1996;62:179-83.

76. Leeda M, Riyazi N, de Vries JI, et al. Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. Am J Obstet Gynecol 1998;179:135-9.

77. Powers RW, Evans RW, Majors AK, et al. Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation. Am J Obstet Gynecol 1998;179:1605-11.

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79. Laivuori H, Kaaja R, Turpeinen U, et al. Plasma homocysteine levels elevated and inversely related to insulin sensitivity in preeclampsia. Obstet Gynecol 1999;93:489-93.

80. Sorensen TK, Malinow MR, Williams MA, et al. Elevated second-trimester serum homocyst(e)ine levels and subsequent risk of preeclampsia. Gynecol Obstet Invest 1999;48:98-103.

81. Ray JG, Laskin CA. Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: A systematic review. Placenta 1999;20:519-29 [review].

82. Roberts JM. Endothelial dysfunction in preeclampsia. Semin Reprod Endocrinol 1998;16:5-15.

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86. Taylor RN, de Groot CJ, Cho YK, Lim KH. Circulating factors as markers and mediators of endothelial cell dysfunction in preeclampsia. Semin Reprod Endocrinol 1998;16:17-31.

87. Wachstein M, Graffeo LW. Influence of Vitamin B6 on the incidence of preeclampsia. Obstet Gynecol 1956;8:177-80.

88. Nisenson A. Treatment of seborrheic dermatitis with biotin and vitamin B complex. J Pediatr 1972;81:630-1 [letter].

89. Callaghan TJ. The effect of folic acid on seborrheic dermatitis. Cutis 1967;3:583-8.

90. Schreiner AW, Rockwell E, Vilter RW. A local defect in the metabolism of pyridoxine in the skin of persons with seborrheic dermatitis of the “sicca” type. J Invest Derm 1952;19:95-6.

91. Andrews GC, Post CF, Domnkos AN. Seborrheic dermatitis: supplemental treatment with vitamin B12. NY State Med J 1950;50:1921-5.

92. Christen WG, Glynn RJ, Chew EY, et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study. Arch Intern Med 2009;169:335-41.

93. Durga J, van Boxtel MPJ, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 2007;369:208-16.

94. Kang JH, Cook N, Manson J, Buring JE, Albert CM, Grodstein F. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr 2008;88:1602-10.)

95. Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One 2010;5(9):e12244.

96. Walker JG, Batterham PJ, Mackinnon AJ, et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms - the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr 2012;95:194-203.

97. Clarke R, Smith D, Jobst KA, et al. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998;55:1449-55.

98. Snowdon DA, Tully CL, Smith CD, et al. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study. Am J Clin Nutr 2000;71:993-8.

99. Joosten E, Lesaffre E, Riezler R, et al. Is metabolic evidence for vitamin B-12 and folate deficiency more frequent in elderly patients with Alzheimer's disease? J Gastroenterol 1997;52A:M76-M79.

100. Ebly EM, Schaefer JP, Campbell NR, Hogan DB. Folate status, vascular disease and cognition in elderly Canadians. Age Ageing 1998;27:485-91.

101. Lashner BA, Heidenreich PA, Su GL, et al. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. Gastroenterology 1989;97:255-9.

102. Lashner BA. Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis. J Cancer Res Clin Oncol 1993;119:549-54.

103. Lashner BA, Provencher KS, Seidner DL, et al. The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. Gastroenterology 1997;112:29-32.

104. Kim YI, Salomon RN, Graeme-Cooke F, et al. Dietary folate protects against the development of macroscopic colonic neoplasia in a dose responsive manner in rats. Gut 1996;39:732-40.

105. Elsbord L, Larsen L. Folate deficiency in chronic inflammatory bowel disease. Scand J Gastroenterol 1979;14:1019-24.

106. Halsted CH, Gandhi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative colitis. N Engl J Med 1981;317:1513-7.

107. Kaltsky AL, Armstrong MA, Friedman GD, Hiatt RA. The relations of alcoholic beverage use to colon and rectal cancer. Am J Epidemiol 1988;128:1007-15.

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110. Solomons NW, Rosenberg IH, Sandstead HH. Zinc nutrition in celiac sprue. Am J Clin Nutr 1976;29:371-5.

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112. Hallert C, Astrom J, Walan A. Reversal of psychopathology in adult celiac disease with the aid of pyridoxine (vitamin B6). Scand J Gastroenterol 1983;18:299-304.

113. Hallert C, Svensson M, Tholstrup J, Hultberg B. Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet. Aliment Pharmacol Ther 2009;29:811-6.

114. Imes S, Plinchbeck BR, Dinwoodie A, et al. Iron, folate, vitamin B-12, zinc, and copper status in out-patients with Crohn's disease: effect of diet counseling. J Am Dietet Assoc 1987;87:928-30.

115. Sandstead HH. Zinc deficiency in Crohn's disease. Nutr Rev 1982;40:109-12.

116. Driscoll RH Jr, Meredith SC, Sitrin M, et al. Vitamin D deficiency and bone disease in patients with Crohn's disease. Gastroenterology 1982;83:1252-8.

117. Haffejee IE. Effect of oral folate on duration of acute infantile diarrhoea. Lancet 1988;2:334-5 [letter].

118. Ashraf H, Rahman MM, Fuchs GJ, Mahalanabis D. Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial. Acta Pædiatr 1998;87:1113-5.

119. Truswell AS. ABC of nutrition. Nutrition for pregnancy. Br Med J 1985;291:263-6.

120. Scholl TO, Hediger ML, Schall JI, et al. Dietary and serum folate: their influence on the outcome of pregnancy. Am J Clin Nutr 1996;63:520-5.

121. MRC Vitamin Study Research Group. Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. Lancet 1991;338:131-7.

122. Tamura T, Goldenberg RL, Johnston KE, et al. Serum concentrations of zinc, folate, vitamins A and E, and proteins, and their relationships to pregnancy outcome. Acta Obstet Gynecol Scand Suppl 1997;165:63-70.

123. Tamura T, Goldenberg RL, Freeberg LE, et al. Maternal serum folate and zinc concentrations and their relationships to pregnancy outcome. Am J Clin Nutr 1992;56:365-70.

124. Goldenberg RL, Tamura T, Cliver SP, et al. Serum folate and fetal growth retardation: a matter of compliance? Obstet Gynecol 1992;795 (Pt 1):719-22.

125. Neggers YH, Goldenberg RL, Tamura T, et al. The relationship between maternal dietary intake and infant birthweight. Acta Obstet Gynecol Scand Suppl 1997;165:71-5.

126. Frelut ML, de Courcy GP, Christides JP, et al. Relationship between maternal folate status and foetal hypotrophy in a population with a good socio-economical level. Int J Vitam Nutr Res 1995;65:267-71.

127. Ek J. Plasma and red cell folate in mothers and infants in normal pregnancies. Relation to birth weight. Acta Obstet Gynecol Scand 1982;61:17-20.

128. Malinow MR, Rajkovic A, Duell PB, et al. The relationship between maternal and neonatal umbilical cord plasma homocyst(e)ine suggests a potential role for maternal homocyst(e)ine in fetal metabolism. Am J Obstet Gynecol 1998;178:228-33.

129. Burke G, Robinson K, Refsum H, et al. Intrauterine growth retardation, perinatal death, and maternal homocysteine levels. N Engl J Med 1992;326:69-70 [letter].

130. Iyengar L, Rajalakshmi K. Effect of folic acid supplement on birth weights of infants. Am J Obstet Gynecol 1975;122:332-6.

131. Rolschau J, Date J, Kristoffersen K. Folic acid supplement and intrauterine growth. Acta Obstet Gynecol Scand 1979;58:343-6.

132. Blot I, Papiernik E, Kaltwasser JP, et al. Influence of routine administration of folic acid and iron during pregnancy. Gynecol Obstet Invest 1981;12:294-304.

133. Baumslag N, Edelstein T, Metz J. Reduction of incidence of prematurity by folic acid supplementation in pregnancy. Br Med J 1970;1:16-7.

134. Fleming AF, Martin JD, Hahnel R, Westlake AJ. Effects of iron and folic acid antenatal supplements on maternal haematology and fetal wellbeing. Med J Aust 1974;2:429-36.

135. Fletcher J, Gurr A, Fellingham FR, et al. The value of folic acid supplements in pregnancy. J Obstet Gynaecol Br Commonw 1971;78:781-5.

136. Giles PF, Harcourt AG, Whiteside MG. The effect of prescribing folic acid during pregnancy on birth-weight and duration of pregnancy. A double-blind trial. Med J Aust 1971;2:17-21.

137. Sutterlin M, Bussen S, Ruppert D, Steck T. Serum levels of folate and cobalamin in women with recurrent spontaneous abortion. Hum Reprod 1997;12:2292-6.

138. Wouters MG, Boers GH, Blom HJ, et al. Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril 1993;60:820-5.

139. Steegers-Theunissen RP, Boers GH, Blom HJ, et al. Hyperhomocysteinaemia and recurrent spontaneous abortion or abruptio placentae. Lancet 1992;339:1122-3 [letter].

140. Quere I, Bellet H, Hoffet M, et al. A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages. Fertil Steril 1998;69:152-4.

141. Quere I, Mercier E, Bellet H, et al. Vitamin supplementation and pregnancy outcome in women with recurrent early pregnancy loss and hyperhomocysteinemia. Fertil Steril 2001;75:823-5.

142. Pietrzik K, Prinz R, Reusch K, et al. Folate status and pregnancy outcome. Ann N Y Acad Sci 1992;669:371-3.

143. Neiger R, Wise C, Contag SA, et al. First trimester bleeding and pregnancy outcome in gravidas with normal and low folate levels. Am J Perinatol 1993;10:460-2.

144. Neela J, Raman L. The relationship between maternal nutritional status and spontaneous abortion. Natl Med J India 1997;10:15-6.

145. Botto LD, Mulinare J, Erickson JD. Occurrence of congenital heart defects in relation to maternal mulitivitamin use. Am J Epidemiol 2000;151:878-84.

146. Czeizel AE. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet 1996;62:179-83.

147. Butterworth CE Jr, Hatch KD, Gore H, et al. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr 1982;35:73-82.

148. Zarcone R, Bellini P, Carfora E, et al. Folic acid and cervix dysplasia. Minerva Ginecol 1996;48:397-400.

149. Butterworth CE, Hatch KD, Soong S-J, et al. Oral folic acid supplementation for cervical dysplasia: A clinical intervention trial. Am J Obstet Gynecol 1992;166:803-9.

150. Butterworth CE Jr, Hatch KD, Macaluso M, et al. Folate deficiency and cervical dysplasia. JAMA 1992;267:528-33.

151. Piyathilake CJ, Macaluso M, Brill I, et al. Lower red blood cell folate enhances the HPV-16-associated risk of cervical intraepithelial neoplasia. Nutrition 2007;23:203-10.

152. Rohan TE, Jain MG, Howe GR, Miller AB. Dietary folate consumption and breast cancer risk. J Natl Cancer Inst 2000;92:266-9.

153. Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA 1999;281:1632-7.

154. Durga J, van Boxtel MPJ, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 2007;369:208-16.

155. Kang JH, Cook N, Manson J, Buring JE, Albert CM, Grodstein F. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr 2008;88:1602-10.)

156. Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One 2010;5(9):e12244.

157. Walker JG, Batterham PJ, Mackinnon AJ, et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms - the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr 2012;95:194-203.

158. Botiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutr Rev 1996;54:382-90 [review].

159. Fine EJ, Soria ED. Myths about vitamin B12 deficiency. Southern Med J 1991;84:1475-81.

160. Hasanah CI, Khan UA, Musalmah M, Razali SM. Reduced red-cell folate in mania. J Affect Disord 1997;46:95-9.

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The information presented by Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2019.