Folate testing and management

What's New

This piece of guidance is new

These guidelines are being issued to provide nationally agreed advice for Scotland on appropriate requesting and interpretation of serum folate deficiency.

Serum folate testing is often performed indiscriminately as part of routine screening and can lead to unnecessary diagnostic and management quandries.

Red cell folate is no longer available routinely.

Folate deficiency: Folate is present in leafy vegetables and fruit but is destroyed by overcooking. It is not stored in the body and so mild dietary deficiency is very common. Folate and iron are absorbed in the jejunum so combined deficiency is very suggestive of Coeliac disease or inflammatory bowel disease. The most useful investigation is dietary history.

Causes of Low Serum Folate Levels:
  • Insufficient/Poor diet
  • Malabsorption syndromes
  • Pregnancy
  • Dialysis
  • Anti-convulsants
  • Drug treatment (colestyramine, sulfasalazine, methotrexate)
  • Increased cell turnover (haemolysis, haemoglobinopathy, exfoliative skin disease)
Indications for serum folate testing

Macrocytosis (MCV greater than 104.1 on sample processed within 24 hours) +with or without: anaemia, cytopenias, malabsorption syndromes/ Coeliac/ Sprue/ Crohn’s/ Ulcerative colitis (UC), pre-dialysis testing, folate supplement therapy

Serum Folate Results
Abnormal results out with laboratory reference normal ranges are reported as either low (less than 3.5 nanogram/mL) or borderline/indeterminate (3.5 to 5.5 nanogram/mL), although both will have an ‘L’ against the result.  A low serum folate result should be taken as suggestive of deficiency rather than as a highly sensitive diagnostic test.  Additional interpretative guidance is given in the set comments and a clinical assessment of the whole picture is required before making a treatment decision.   

Cautions for serum folate testing interpretation
  1. Tiredness is NOT an indication for testing; Please check FBC first.
  2. Low or borderline serum folate levels may represent true deficiency or may be secondary to acute illness. Consider full clinical context, other haematological parameters (haemolysis, unexplained anaemia, raised MCV) and evidence of any underlying causes (see above).
  3. Falsely reduced serum folate levels can occur in patients with anorexia, acute alcohol consumption, normal pregnancy (if on supplementation then no indication for testing unless poor diet, suspected malabsorption, hyperemesis or new macrocytic anaemia) and during anti-convulsant therapy. Therapy indicated if co-existing anaemia, known poor oral intake or other symptoms suggestive of deficiency.
  4. Results should be considered within the full clinical context, and in conjunction with any concurrent B12 deficiency results.
  5. Lower folate levels are seen in patients taking the combined oral contraceptive pill/ HRT. These levels are generally not clinically significant. Testing should NOT be undertaken in these situations unless one of the indications above is also present.
Treatment

Folic acid

Folate-deficient megaloblastic anaemia

For Adult - 5 mg daily for 4 months (until term in pregnant women), doses up to 15 mg daily may be required in malabsorption states.

Prophylaxis in chronic haemolytic states

For Adult - 5 mg every 1 to 7 days, frequency dependent on underlying disease.

Prophylaxis of folate deficiency in dialysis

For Adult - 5 mg every 1 to 7 days.

Patients with vitamin B12 deficiency should not be treated with folic acid unless administered with adequate amounts of hydroxocobalamin, as it can mask the condition but the subacute irreversible damage to the nervous system will continue. The deficiency can be due to undiagnosed megaloblastic anaemia including in infancy, pernicious anaemia or macrocytic anaemia of unknown aethiology or other cause of cobalamin deficiency, including lifelong vegetarians.

References
  1. BSH Guidelines for the diagnosis and treatment of cobalamin and folate disorders. BJH, 2014, 166, 496-513
  2. Haematology and Transfusion Scotland draft guideline for folate testing.
Glossary
Abbreviation Meaning
FBC Full blood count
HRT Hormone replacement therapy
UC Ulcerative colitis
MCV Mean corpuscular volume
Editorial Information

Last reviewed: 06 February 2020

Next review: 28 February 2023

Author(s): Consultant Haematologist

Approved By: TAM subgroup of ADTC

Reviewer Name(s): Consultant Haematologist

Document Id: TAM441