Approach Considerations

The dosage of folic acid needed to prevent or reverse folic acid deficiency varies with the clinical circumstances, as follows^[49]:

Folate-deficient megaloblastic anemia due to dietary insufficiency or antiepileptic drugs: 5 mg/day for 4 months
Malabsorption: Up to 15 mg/day for 4 months
Chronic hemolytic states and kidney dialysis: for prophylaxis, 5 mg daily to weekly, depending on the patient's diet and rate of hemolysis

Referral to a dietician may be indicated to ensure that the patient has appropriate dietary intake of folic acid. Fruits, vegetables, and fortified foods constitute the primary dietary source of folic acid.^[2]

Recommended intakes as published by the Food and Nutrition Board (FNB) at the Institute of Medicine (IOM) of the National Academies^[21] are as follows (RDA=recommended daily allowance, DFE=dietary folate equivalents, UL=tolerable upper level):

Adults and teenagers aged 14-19 years (male or female): RDA, 400 mcg DFE; UL, 1000 mcg DFE
Pregnant females: RDA, 600 mcg DFE; UL, 1000 mcg DFE
Lactating females: RDA, 500 mcg DFE; UL, 1000 mcg DFE

Because of variable absorption rates, an approximation of total folate intake in a day can be calculated as follows:

Grams of DFEs provided = grams of food folate + 1.7 × (grams of folic acid supplementation)

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. Because major teratogenic effects from folate deficiency occur 3-4 weeks after conception and many pregnancies are unplanned, women of reproductive age should ensure that they are receiving 400 μg daily, in addition to consuming food with folate from a varied diet. The US Centers for Disease Control and Prevention (CDC) recommends that women who have had a pregnancy affected by a neural tube defect consume 4000 μg of folic acid each day 1 month before becoming pregnant and through the first 3 months of pregnancy. ^[2]

Medication

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Media Gallery

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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Author

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.

Coauthor(s)

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.

Specialty Editor Board

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.

Chief Editor

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.

Additional Contributors

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.

Acknowledgements

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.

Folate Deficiency Treatment & Management

Approach Considerations

Prevention

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