Reasoning GP · Algorithm · 1-page summary
Low folate in adults
For: adults with a low serum folate or suspected folate deficiency in primary care, including pregnancy, preconception and methotrexate. Not for: B12 deficiency with normal folate (use the vitamin B12 deficiency algorithm) or macrocytosis with normal folate (use the macrocytosis algorithm).
Core rule: check B12 before (or alongside) folic acid. Folic acid can correct the blood count while B12 nerve damage carries on.
0Stop — act today — before anything else
- Unstable, septic, actively bleeding, confused or unable to travel safely → 999
- Severe or symptomatic anaemia, pancytopenia with infection or bleeding, suspected acute leukaemia/MDS, rapidly falling counts → Same-day hospital / haematology
- Gait disturbance, loss of proprioception, weakness, cognitive or visual change (possible subacute combined degeneration) → take FBC, B12/active B12 and folate, then start B12 Same-day + urgent neurology/haematology advice. Never folic acid alone.
- Confusion, ataxia, ophthalmoplegia (Wernicke) or severe malnutrition → Same-day emergency hospital; suspected Wernicke's → immediate transfer, parenteral thiamine first if available (oral not adequate); never delay it for glucose.
1Triage — B12 first, then the context
| Situation | Action |
|---|---|
| B12 low, borderline or unknown | Treat B12 first (IM hydroxocobalamin), then folate, or both together. |
| Pregnant, NICE high risk | Folic acid 5 mg daily now; do not wait for the result. Check B12. |
| On methotrexate | Folic acid 5 mg once weekly co-prescribed? If not, add it now. |
| Diet / alcohol, B12 normal | Folic acid 5 mg daily + treat the cause (block 5). |
| Haemolysis, dialysis | Long-term folic acid per haematology / renal-unit protocol. |
2Screen — serious causes
- Methotrexate + mouth ulcers, cytopenia or macrocytosis: withhold if significant cytopenia, severe mucositis, suspected sepsis, renal or significant LFT deterioration; FBC, LFTs, U&E → specialist / acute team Same-day. Folinic acid is specialist-led.
- Pregnant + severe anaemia, significant vomiting/dehydration, neurological disease or another obstetric concern → Same-day maternity. Low folate alone and well → primary care.
- Chronic haemolysis + sudden Hb fall, rising bilirubin/LDH, low reticulocytes (aplastic crisis, marrow disease) → Urgent haematology
- Refeeding risk (BMI <16, little or no intake >10 days, >15% weight loss in 3–6 months) → thiamine before feeding (CG32), dietitian.
3Assess
☐ FBC, MCV, reticulocytes; film if macrocytosis or cytopenias ☐ Serum folate ☐ B12 or active B12 before folic acid ☐ Anti-tTG IgA + total IgA, while eating gluten ☐ LFTs + GGT, ferritin; TFTs if macrocytosis unexplained ☐ Diet, AUDIT-C, medicines, pregnancy plans, haemolysis, bowel surgery
Not routine: red-cell folate, homocysteine, methylmalonic acid.
4Classify — find the cause
- Diet / alcohol (commonest) — older people living alone, eating disorders, alcohol.
- Coeliac disease — iron + folate deficiency together; the MCV can look normal → anti-tTG; positive → gastroenterology.
- Increased demand — pregnancy, lactation, haemolysis, exfoliative skin disease, malignancy, dialysis.
- Medicines — methotrexate, trimethoprim, sulfasalazine, phenytoin, carbamazepine, phenobarbital, primidone.
- B12 + folate together → treat B12 first, or both at once.
- Uncertain / poor response → reconsider B12, iron, haemolysis, alcohol, thyroid, MDS, adherence.
5Treat today — doses: NICE/SPC, BNF, local formulary
- Deficiency: folic acid 5 mg daily; 4 months suits many adults, longer if malabsorption or haemolysis continues.
- Preconception to 12 weeks: 400 micrograms daily. 5 mg daily if previous NTD pregnancy, personal/family NTD history, type 1 or 2 diabetes, sickle cell/thalassaemia, some anti-epileptic or HIV medicines. BMI alone does not need 5 mg (NG247).
- Methotrexate: folic acid 5 mg once weekly on a different day, for as long as methotrexate continues.
- Anti-epileptics: review folate with neurology if pregnant or planning; never stop them abruptly. Valproate → Pregnancy Prevention Programme.
6Refer routinely
- Gastroenterology: positive coeliac serology, suspected malabsorption. Dietitian: severe or multiple deficiencies, eating disorder, new coeliac disease.
- Recheck FBC at about 4–8 weeks if anaemic or macrocytic; do not recheck serum folate on treatment.
7Never reassure by
- A rising Hb or falling MCV on folic acid — B12 nerve damage can still progress.
- A normal MCV — combined iron and folate deficiency can hide it.
- A normal serum folate after a recent good diet — it reflects the last few days.
- Folic acid in someone taking valproate — it does not remove the risk to a baby.
- Methotrexate prescribed without weekly folic acid.
- A negative coeliac test done on a gluten-free diet.
8Safety-net — say it, then document it
999 “Call 999 if you collapse, become confused, are bleeding heavily, or are very unwell with a fever.” Same day “Contact us today if you get numbness, tingling, unsteady walking, weakness, memory or eyesight changes, unusual bruising or bleeding, or — on methotrexate — mouth ulcers or fever.” Book the FBC recheck with a date.
✓Safe to manage in primary care only if — all five, documented
No block 0–2 row applies; no neurological symptoms
B12 checked (or treated) before folic acid
Cause sought: diet, alcohol, coeliac, medicines
Dose matched: pregnancy, methotrexate, haemolysis
FBC recheck dated; safety-net given
Summary of the full Reasoning GP low folate algorithm, which holds causes, coeliac and refeeding management, lifestyle advice and evidence. Sources: NICE NG239, NG247, NG20, NG3, CG32; BSR and SPS methotrexate guidance; BSH cobalamin and folate (2014); MHRA valproate Pregnancy Prevention Programme and metformin–B12 (2022); local methotrexate shared-care protocol. Clinical reference — follow local pathways and check doses: NICE/SPC, BNF.