Folic Acid Deficiency Follow-up

  • Author: Angela Gentili, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Dec 1, 2011
 

Further Outpatient Care

Treat the underlying disease or condition causing folic acid deficiency.

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Deterrence/Prevention

  • Patients whose folic acid deficiency is related to dietary factors should be counseled to include green vegetables and fruit in their diet.
  • Prophylactic treatment of pregnant patients and patients with chronic hemolytic anemias can prevent folic acid deficiency due to the increased requirement for folate in these conditions.
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Complications

  • Megaloblastic anemia
  • Leukopenia
  • Thrombocytopenia
  • Angular stomatitis
  • Glossitis
  • Nausea and vomiting
  • Diarrhea
  • Hyperpigmentation
  • Low-grade fever
  • Elevated serum homocysteine
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Patient Education

  • Educate patients regarding proper nutrition, including eating fruits and vegetables.
  • Educate patients regarding the need to reduce alcohol ingestion.
  • Discuss the need to take folic acid supplementation.

Medical/legal pitfalls

  • Failure to provide folic acid supplementation to pregnant females may lead to spontaneous abortion and fetal abnormalities, including neural tube defects and increased risk of severe language delay in the child.
  • Providing only folic acid supplementation to a patient who has cobalamin deficiency may lead to development of irreversible neuropathies.
  • No randomized clinical trial has proven the efficacy of lowering the homocysteine concentration to improve cognition or to lower the incidence of cardiovascular disease (CVD). Until new evidence is available, clinicians should not promise patients that folate supplementation will improve cognition or decrease cardiovascular risk.
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Contributor Information and Disclosures
Author

Angela Gentili, MD  Director of Geriatrics Fellowship Program, Associate Professor, Department of Internal Medicine, Virginia Commonwealth University Health System and McGuire Veterans Affairs Medical Center

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

Disclosure: Nothing to disclose.

Coauthor(s)

Muhammad Vohra, MD  Assistant Professor, Department of Internal Medicine, Hamdard University Hospital, Pakistan

Muhammad Vohra, MD is a member of the following medical societies: American Geriatrics Society

Disclosure: Nothing to disclose.

Subir Vij, MD, MPH  Assistant Professor, Department of Medicine, Eastern Virginia Medical School; Medical Director, Portsmouth Community Health Center

Subir Vij, MD, MPH is a member of the following medical societies: American College of Physician Executives, American College of Physicians, and American Medical Association

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 and Phi Beta Kappa

Disclosure: Nothing to disclose.

Waleed Siddiqi, MD  Fellow in Geriatrics, Department of Internal Medicine, Division of General Internal Medicine/Primary Care, Medical College of Virginia

Waleed Siddiqi, MD is a member of the following medical societies: American College of Physicians and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

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: Novartis Honoraria Speaking and teaching

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

Disclosure: Medscape Salary Employment

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, and Southwest Oncology Group

Disclosure: No financial interests None None

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, 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 College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

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

References

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

  2. 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. Aug 2005;82(2):442-50. [Medline].

  3. McDowell MA, Lacher DA, Pfeiffer CM, Mulinare J, Picciano MF, Rader JI, et al. Blood folate levels: the latest NHANES results. NCHS Data Brief. May 2008;1-8. [Medline].

  4. 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. Jul 24 2009;9:261. [Medline]. [Full Text].

  5. Lawrence MA, Chai W, Kara R, Rosenberg IH, Scott J, Tedstone A. Examination of selected national policies towards mandatory folic acid fortification. Nutr Rev. May 2009;67 Suppl 1:S73-8. [Medline].

  6. Genest JJ, Jr, McNamara JR, Salem DN, et al. Plasma homocyst(e)ine levels in men with premature coronary artery disease. J Am Coll Cardiol. Nov 1990;16(5):1114-9. [Medline].

  7. Coull BM, Malinow MR, Beamer N, et al. Elevated plasma homocyst(e)ine concentration as a possible independent risk factor for stroke. Stroke. Apr 1990;21(4):572-6. [Medline].

  8. 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). Nov 2004;117(11):1650-4.

  9. 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. May 2005;16(3):153-61. [Medline].

  10. [Best Evidence] Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. Apr 13 2006;354(15):1567-77. [Medline].

  11. [Best Evidence] Bønaa KH, Njølstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. Apr 13 2006;354(15):1578-88. [Medline].

  12. 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. Sep 1999;20(7):519-29. [Medline].

  13. 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. May 5 2009;150(9):632-9. [Medline].

  14. Honein MA, Paulozzi LJ, Mathews TJ, et al. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA. Jun 20 2001;285(23):2981-6. [Medline].

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

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

  17. 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. Apr 1 1997;94(7):3290-5. [Medline].

  18. 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. Jan 1997;65(1):46-52. [Medline].

  19. Kado DM, Karlamangla AS, Huang MH, Troen A, Rowe JW, Selhub J. 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. Feb 2005;118(2):161-7. [Medline].

  20. 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. Mar-Apr 2005;40(2):129-38. [Medline].

  21. 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. Jun 29 2006;354(26):2764-72. [Medline].

  22. Daly S, Cotter A, Molloy AE, Scott J. Homocysteine and folic acid: implications for pregnancy. Semin Vasc Med. May 2005;5(2):190-200. [Medline].

  23. Faeh D, Chiolero A, Paccaud F. Homocysteine as a risk factor for cardiovascular disease: should we (still) worry about?. Swiss Med Wkly. Dec 2 2006;136(47-48):745-56. [Medline].

  24. Fakhrzadeh H, Ghotbi S, Pourebrahim R, Nouri M, Heshmat R, Bandarian F. Total plasma homocysteine, folate, and vitamin B12 status in healthy Iranian adults: the Tehran homocysteine survey (2003-2004)/a cross-sectional population based study. BMC Public Health. 2006;6:29. [Medline].

  25. Green R, Jacobsen DW. Clinical Implication of Hyperhomocysteinemia. In: Bailey LB, ed. Folate in Health and Disease. New York, NY: Marcel Dekker; 1995:75-122.

  26. Heimburger DC, Krumdieck CL, Alexander CB. Localized folic acid deficiency and bronchial metaplasia in smokers: hypothesis and preliminary report. Nutrition. 1987;3:54-60.

  27. Herbert V. Development of Human Folate Deficiency. In: Picciano MF, Stokstool ELR, Gregory, JF, eds. Folic Acid Metabolism in Health and Disease (Contemporary Issues in Clinical Nutrition). 13. New York, NY: 1990:195-210.

  28. Horne DW, Briggs WT, Wagner C. Transport of 5-methyltetrahydrofolic acid and folic acid in freshly isolated hepatocytes. J Biol Chem. May 25 1978;253(10):3529-35. [Medline].

  29. Kuo HK, Sorond FA, Chen JH, Hashmi A, Milberg WP, Lipsitz LA. The role of homocysteine in multisystem age-related problems: a systematic review. J Gerontol A Biol Sci Med Sci. Sep 2005;60(9):1190-201. [Medline].

  30. Lindenbaum J, Allen RH. Clinical Spectrum and Diagnosis of Folate Deficiency. In: Bailey LB, ed. Folate in Health and Disease. 1995. New York, NY: Marcel Dekker, Inc; 1995:43-73.

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

  32. Pietrzik KF, Thorand B. Folate economy in pregnancy. Nutrition. Nov-Dec 1997;13(11-12):975-7. [Medline].

  33. Stokstad EL, Chan MM, Watson JE, Brody T. Nutritional interactions of vitamin B12, folic acid, and thyroxine. Ann N Y Acad Sci. 1980;355:119-29. [Medline].

  34. Troen A, Rosenberg I. Homocysteine and cognitive function. Semin Vasc Med. May 2005;5(2):209-14. [Medline].

  35. Tulliez M, Diebold J. [Embedding of hematopoietic organs in epoxy resin for histopathological study. Technic and value]. Morphol Embryol (Bucur). Jan-Mar 1979;25(1):39-45. [Medline].

  36. Webster SGP. Absorption of Nutrients in Old Age. In: Wiley, ed. Principles and Practice of Geriatric Medicine. Sussex, England: John Wiley and Sons Ltd; 1991:407-415.

 
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The chemical structure of folic acid and amethopterin (methotrexate), a folic acid antagonist, shows the similarity of structure.
The transformation of formiminoglutamic acid to glutamic acid is dependent upon both vitamin B-12 and tetrahydrofolate. In contrast, the transformation of homocysteine to methionine is a vitamin B-12–dependent reaction.
Both folic acid and vitamin B-12 participate in the synthesis of DNA and RNA.
Histologically, the megaloblastosis caused by folic acid deficiency cannot be differentiated from that observed with vitamin B-12 deficiency.
Peripheral smear of blood in a patient with pernicious anemia. Macrocytes are observed and some of the red blood cells show ovalocytosis. A 6-lobed polymorphonuclear leucocyte is present.
Bone marrow aspirate from a patient with untreated pernicious anemia. Megaloblastic maturation of erythroid precursors is shown. Two megaloblasts occupy the center of the slide with a megaloblastic normoblast above.
 
 
 
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