Folate Deficiency Differential Diagnoses

1. Khan KM, Jialal I. Folic Acid Deficiency. 2022 Jan. [QxMD MEDLINE Link]. [Full Text].

2. Folic Acid. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/ncbddd/folicacid/about.html. June 15, 2022; Accessed: July 20, 2022.

3. Bailey RL, Dodd KW, Gahche JJ, Dwyer JT, McDowell MA, Yetley EA. Total folate and folic acid intake from foods and dietary supplements in the United States: 2003-2006. Am J Clin Nutr. 2010 Jan. 91(1):231-7. [QxMD MEDLINE Link].

4. Varela-Moreiras G, Murphy MM, Scott JM. Cobalamin, folic acid, and homocysteine. Nutr Rev. 2009 May. 67 Suppl 1:S69-72. [QxMD MEDLINE Link].

5. Hayden MR, Tyagi SC. Impaired Folate-Mediated One-Carbon Metabolism in Type 2 Diabetes, Late-Onset Alzheimer's Disease and Long COVID. Medicina (Kaunas). 2021 Dec 23. 58 (1):[QxMD MEDLINE Link]. [Full Text].

6. McCaddon A, Regland B. COVID-19: A methyl-group assault?. Med Hypotheses. 2021 Apr. 149:110543. [QxMD MEDLINE Link]. [Full Text].

7. Huang T, Chen Y, Yang B, Yang J, Wahlqvist ML, Li D. Meta-analysis of B vitamin supplementation on plasma homocysteine, cardiovascular and all-cause mortality. Clin Nutr. 2012 Aug. 31(4):448-54. [QxMD MEDLINE Link].

8. Huo Y, Qin X, Wang J, Sun N, Zeng Q, Xu X. Efficacy of folic acid supplementation in stroke prevention: new insight from a meta-analysis. Int J Clin Pract. 2012 Jun. 66(6):544-51. [QxMD MEDLINE Link].

9. Hankey GJ. B vitamins for stroke prevention. Stroke Vasc Neurol. 2018 Jun. 3 (2):51-58. [QxMD MEDLINE Link]. [Full Text].

10. Jain R, Manning S, Cutler AJ. Good, better, best: clinical scenarios for the use of L-methylfolate in patients with MDD. CNS Spectr. 2020 Dec. 25 (6):750-764. [QxMD MEDLINE Link]. [Full Text].

11. Surén P, Roth C, Bresnahan M, et al. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA. 2013 Feb 13. 309(6):570-7. [QxMD MEDLINE Link].

12. Correa A, Gilboa SM, Botto LD, Moore CA, Hobbs CA, Cleves MA. Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus-associated birth defects. Am J Obstet Gynecol. 2012 Mar. 206(3):218.e1-13. [QxMD MEDLINE Link].

13. Cantarella CD, Ragusa D, Giammanco M, Tosi S. Folate deficiency as predisposing factor for childhood leukaemia: a review of the literature. Genes Nutr. 2017. 12:14. [QxMD MEDLINE Link]. [Full Text].

14. Enderami A, Zarghami M, Darvishi-Khezri H. The effects and potential mechanisms of folic acid on cognitive function: a comprehensive review. Neurol Sci. 2018 Jun 23. [QxMD MEDLINE Link].

15. Ebbing M, Bonaa KH, Nygard O, Arnesen E, Ueland PM, Nordrehaug JE. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA. 2009 Nov 18. 302(19):2119-26. [QxMD MEDLINE Link].

16. Figueiredo JC, Grau MV, Haile RW, Sandler RS, Summers RW, Bresalier RS. Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst. 2009 Mar 18. 101(6):432-5. [QxMD MEDLINE Link].

17. Lubecka-Pietruszewska K, Kaufman-Szymczyk A, Stefanska B, Fabianowska-Majewska K. Folic acid enforces DNA methylation-mediated transcriptional silencing of PTEN, APC and RARbeta2 tumour suppressor genes in breast cancer. Biochem Biophys Res Commun. 2013 Jan 11. 430(2):623-8. [QxMD MEDLINE Link].

18. Hirsch S, Sanchez H, Albala C, de la Maza MP, Barrera G, Leiva L. Colon cancer in Chile before and after the start of the flour fortification program with folic acid. Eur J Gastroenterol Hepatol. 2009 Apr. 21(4):436-9. [QxMD MEDLINE Link].

19. Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007 Jul. 16(7):1325-9. [QxMD MEDLINE Link].

20. Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007 Jun 6. 297(21):2351-9. [QxMD MEDLINE Link].

21. Institute of Medicine. Food and Nutrition Board. Dietary reference intakes: thiamine, riboflavin, niacin, vitamin B6, folate, vitamin b12, pantothenic acid, biotin and choline. Washington DC: National Academy Press; 1998.

22. Pfeiffer CM, Caudill SP, Gunter EW, Osterloh J, Sampson EJ. Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999-2000. Am J Clin Nutr. 2005 Aug. 82(2):442-50. [QxMD MEDLINE Link].

23. Pieroth R, Paver S, Day S, Lammersfeld C. Folate and Its Impact on Cancer Risk. Curr Nutr Rep. 2018 Sep. 7 (3):70-84. [QxMD MEDLINE Link].

24. Matejcic M, de Batlle J, Ricci C, Biessy C, Perrier F, et al. Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort. Int J Cancer. 2017 Mar 15. 140 (6):1246-1259. [QxMD MEDLINE Link].

25. European Surveillance of Congenital Anomalies. Folic Acid. eurocat-network.eu. Available at http://www.eurocat-network.eu/preventionandriskfactors/folicacid. Accessed: September 14, 2018.

26. Noor RA, Abioye AI, Ulenga N, Msham S, Kaishozi G, Gunaratna NS, et al. Large -scale wheat flour folic acid fortification program increases plasma folate levels among women of reproductive age in urban Tanzania. PLoS One. 2017. 12 (8):e0182099. [QxMD MEDLINE Link]. [Full Text].

27. Casey GJ, Phuc TQ, Macgregor L, et al. A free weekly iron-folic acid supplementation and regular deworming program is associated with improved hemoglobin and iron status indicators in Vietnamese women. BMC Public Health. 2009 Jul 24. 9:261. [QxMD MEDLINE Link]. [Full Text].

28. Chang JY, Wang YP, Wu YC, Cheng SJ, Chen HM, Sun A. Hematinic deficiencies and anemia statuses in oral mucosal disease patients with folic acid deficiency. J Formos Med Assoc. 2015 Sep. 114 (9):806-12. [QxMD MEDLINE Link].

29. Genest JJ Jr, McNamara JR, Salem DN, Wilson PW, Schaefer EJ, Malinow MR. Plasma homocyst(e)ine levels in men with premature coronary artery disease. J Am Coll Cardiol. 1990 Nov. 16(5):1114-9. [QxMD MEDLINE Link].

30. Coull BM, Malinow MR, Beamer N, Sexton G, Nordt F, de Garmo P. Elevated plasma homocyst(e)ine concentration as a possible independent risk factor for stroke. Stroke. 1990 Apr. 21(4):572-6. [QxMD MEDLINE Link].

31. Wang G, Mao JM, Wang X, Zhang FC. Effect of homocysteine on plaque formation and oxidative stress in patients with acute coronary syndromes. Chin Med J (Engl). 2004 Nov. 117(11):1650-4.

32. Bokhari SW, Bokhari ZW, Zell JA, Lee DW, Faxon DP. Plasma homocysteine levels and the left ventricular systolic function in coronary artery disease patients. Coron Artery Dis. 2005 May. 16(3):153-61. [QxMD MEDLINE Link].

33. Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006 Apr 13. 354(15):1567-77. [QxMD MEDLINE Link].

34. Bonaa KH, Njolstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006 Apr 13. 354(15):1578-88. [QxMD MEDLINE Link].

35. 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 Sep. 20(7):519-29. [QxMD MEDLINE Link].

36. Wolff T, Witkop CT, Miller T, Syed SB. Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2009 May 5. 150(9):632-9. [QxMD MEDLINE Link].

37. Honein MA, Paulozzi LJ, Mathews TJ, Erickson JD, Wong LY. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA. 2001 Jun 20. 285(23):2981-6. [QxMD MEDLINE Link].

38. Roth C, Magnus P, Schjolberg S, et al. Folic acid supplements in pregnancy and severe language delay in children. JAMA. 2011 Oct 12. 306(14):1566-73. [QxMD MEDLINE Link].

39. Gatof D, Ahnen D. Primary prevention of colorectal cancer: diet and drugs. Gastroenterol Clin North Am. 2002 Jun. 31(2):587-623, xi. [QxMD MEDLINE Link].

40. Blount BC, Mack MM, Wehr CM, et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci U S A. 1997 Apr 1. 94(7):3290-5. [QxMD MEDLINE Link]. [Full Text].

41. Kim YI, Pogribny IP, Basnakian AG, et al. Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumor suppressor gene. Am J Clin Nutr. 1997 Jan. 65(1):46-52. [QxMD MEDLINE Link].

42. Burr NE, Hull MA, Subramanian V. Folic Acid Supplementation May Reduce Colorectal Cancer Risk in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. J Clin Gastroenterol. 2017 Mar. 51 (3):247-253. [QxMD MEDLINE Link].

43. Nutrition classics. Transactions of the Association of American Physicians, volume 75, 1962, pages 307-320. Experimental nutritional folate deficiency in man. by Victor Herbert. Nutr Rev. 1982 Aug. 40 (8):246-8. [QxMD MEDLINE Link].

44. Kado DM, Karlamangla AS, Huang MH, et al. Homocysteine versus the vitamins folate, B6, and B12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging. Am J Med. 2005 Feb. 118(2):161-7. [QxMD MEDLINE Link].

45. Adunsky A, Arinzon Z, Fidelman Z, Krasniansky I, Arad M, Gepstein R. Plasma homocysteine levels and cognitive status in long-term stay geriatric patients: a cross-sectional study. Arch Gerontol Geriatr. 2005 Mar-Apr. 40(2):129-38. [QxMD MEDLINE Link].

46. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006 Jun 29. 354(26):2764-72. [QxMD MEDLINE Link].

47. Braun KV, Voortman T, Kiefte-de Jong JC, Jaddoe VW, Hofman A, Franco OH, et al. Dietary Intakes of Folic Acid and Methionine in Early Childhood Are Associated with Body Composition at School Age. J Nutr. 2015 Sep. 145 (9):2123-9. [QxMD MEDLINE Link].

48. Reynolds EH. The neurology of folic acid deficiency. Handb Clin Neurol. 2014. 120:927-43. [QxMD MEDLINE Link].

49. [Guideline] Devalia V, Hamilton MS, Molloy AM, British Committee for Standards in Haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014 Aug. 166 (4):496-513. [QxMD MEDLINE Link]. [Full Text].

Katherine Coffey-Vega, MD Fellow, Department of Internal Medicine, Division of Geriatrics, Virginia Commonwealth University School of Medicine

Katherine Coffey-Vega, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Angela Gentili, MD Director of Geriatric Medicine Fellowship Program, Professor of Internal Medicine, Division of Geriatric Medicine, Virginia Commonwealth University Health System and McGuire Veterans Affairs Medical Center, Richmond, VA

Angela Gentili, MD is a member of the following medical societies: Virginia Geriatrics Society, American Geriatrics Society

Disclosure: Nothing to disclose.

Muhammad I Vohra, MD Geriatrician, Lucy Corr Life Care

Muhammad I Vohra, MD is a member of the following medical societies: American College of Physicians, American Geriatrics Society, Medical Society of Virginia, Virginia Geriatrics Society

Disclosure: Nothing to disclose.

David Kuan-Hua Chen, MD Consulting Staff, Department of Neurology, Michael E DeBakey Veterans Affairs Medical Center

David Kuan-Hua Chen, MD is a member of the following medical societies: Alpha Omega Alpha, Phi Beta Kappa

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Pradyumna D Phatak, MBBS, MD Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor Ahmed Mosalem, MD, to the development and writing of this article.

The authors and editors of Medscape Reference also gratefully acknowledge the contributions of previous coauthors Subir Vij, MD, MPH and Waleed Siddiqi, MD to the development and writing of this article.

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