Folate deficiency

Last reviewed: 7 Jan 2023
Last updated: 10 Sep 2021



History and exam

Key diagnostic factors

  • presence of risk factors
More key diagnostic factors

Other diagnostic factors

  • prolonged diarrhoea
  • loss of appetite and weight loss
  • fatigue
  • shortness of breath
  • dizziness
  • pallor
  • headache
  • tachycardia
  • tachypnoea
  • heart murmur
  • signs of heart failure
  • signs of chronic alcohol misuse
  • signs of haemolytic anaemia
  • signs of exfoliative dermatitis
  • painful swallowing
  • petechiae
  • glossitis
  • angular stomatitis
  • neurological deficits in children
Other diagnostic factors

Risk factors

  • low dietary folate intake
  • age >65 years
  • alcohol-use disorder
  • pregnant or lactating
  • prematurity
  • intestinal malabsorptive disorders
  • use of trimethoprim, methotrexate, sulfasalazine, pyrimethamine, or anticonvulsants (e.g., phenytoin, phenobarbital)
  • infantile intake of goats' milk
  • congenital defects in folate absorption and metabolism
  • states of increased cell turnover
  • intake of special diet
  • chronic dialysis
More risk factors

Diagnostic investigations

1st investigations to order

  • peripheral blood smear
  • FBC
  • reticulocyte count
More 1st investigations to order

Investigations to consider

  • serum folate
  • red blood cell folate
  • serum vitamin B12
  • serum LDH
  • serum unconjugated bilirubin
  • serum iron panel
  • plasma or serum methylmalonic acid
  • plasma homocysteine
  • bone marrow aspirate/biopsy
More investigations to consider

Treatment algorithm


at risk of folate deficiency due to pregnancy or lactation

at risk of folate deficiency due to malabsorption disorders, chronic haemolytic disorder, or chronic dialysis

at risk of folate deficiency due to medication


acquired: macrocytosis without anaemia

acquired: macrocytic anaemia and pancytopenia

congenital folate metabolism defects

congenital folate malabsorption

congenital cerebral folate transport deficiency



Mark Koury, MD

Professor of Medicine, Emeritus (Hematology/Oncology)

Vanderbilt University Medical Center




MK declares that he has no competing interests.

Allison P. Wheeler, MD

Assistant Professor of Pathology, Microbiology, and Immunology

Assistant Professor of Pediatrics (Pediatric Hematology-Oncology)

Vanderbilt University Medical Center




APW declares that she has no competing interests.

Mohammed Sika, PhD

Research Professor of Medicine (Nephrology)

Vanderbilt University Medical Center




MS declares that he has no competing interests.


Dr Mark Koury, Dr Allison Wheeler, and Dr Mohammed Sika would like to gratefully acknowledge Dr Lakshmi V. Srivaths and Donald Mahoney Jr., previous contributors to this topic.


LVS and DM declare that they have no competing interests.

Peer reviewers

Ralph Green, MD, PhD, FRCPath

Professor and Chair

Department of Pathology and Laboratory Medicine

University of California Davis School of Medicine




RG is the author of reference(s) cited in this topic.

Jack Metz, MB, BCh, MD, DSc(Med), FRCPath, FCAP, FRCPA, FRS(SA), DSc Med(Hon Caus)

Emeritus Professor and Consultant Haematologist

Dorevitch Pathology





JM declares that he has no competing interests.

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