Summary
Definition
Folate is an essential vitamin present in green vegetables, legumes, and some fruits. Deficiency generally arises due to dietary deficiency, malabsorption, drugs and toxins, and increased physiological or pathological demand for folate.[1] Megaloblastic anaemia without neuropathy is the classic manifestation of folate deficiency.[Figure caption and citation for the preceding image starts]: Megaloblastic macrocytic anaemia: A. Peripheral blood smear of a patient with megaloblastic anaemia. B. Peripheral blood smear of healthy individualPhotomicrograph from Mark J. Koury, MD; used with permission [Citation ends].
History and exam
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 alcohol-use disorder
- signs of haemolytic anaemia
- signs of exfoliative dermatitis
- painful swallowing
- petechiae
- glossitis
- angular stomatitis
- neurological deficits in children
Risk factors
- low dietary folate intake
- alcohol-use disorder
- pregnant or lactating
- prematurity
- intestinal malabsorptive disorders
- use of certain drugs
- congenital defects in folate absorption and metabolism
- states of increased cell turnover
- special diet
- chronic dialysis
Diagnostic investigations
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
Treatment algorithm
Contributors
Authors
Aśok C. Antony, MD, MACP
Chancellor’s Professor of Medicine
Division of Hematology-Oncology
Department of Medicine
Indiana University School of Medicine
Indianapolis
IN
Disclosures
ACA declares that he has no competing interests.
Acknowledgements
Dr Aśok C. Antony would like to gratefully acknowledge Dr Mark Koury, Dr Allison Wheeler, Dr Mohammed Sika, Dr Lakshmi V. Srivaths, and Donald Mahoney Jr., previous contributors to this topic.
Disclosures
MK, AW, MS, 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
Sacramento
CA
Disclosures
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
Heidelberg
Victoria
Australia
Disclosures
JM declares that he has no competing interests.
Peer reviewer acknowledgements
BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.
Disclosures
Peer reviewer affiliations and disclosures pertain to the time of the review.
References
Key articles
Pfeiffer CM, Sternberg MR, Zhang M, et al. Folate status in the US population 20 y after the introduction of folic acid fortification. Am J Clin Nutr. 2019 Nov 1;110(5):1088-97.Full text Abstract
Allen LH. Causes of vitamin B12 and folate deficiency. Food Nutr Bull. 2008 Jun;29(2 suppl):S20-34. Abstract
Whitehead VM. Acquired and inherited disorders of cobalamin and folate in children. Br J Haematol. 2006 Jul;134(2):125-36.Full text Abstract
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet. 1991 Jul 20;338(8760):131-7. Abstract
Reference articles
A full list of sources referenced in this topic is available here.
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