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Perth Haematology :: Dr Steven Ward

Vitamin B12 and Folic Acid


Vitamin B12 and Folic Acid (folate) are essential vitamins, involved in DNA synthesis. Deficiency of these causes anaemia and many other problems.


The anaemia due to Vitamin B12 or folate deficiency is termed Megaloblastic Anaemia.


  B12 Folate

Dietary source

Animal only (liver, fish, dairy)

Not fruit/veg

stable after cooking

Average diet = 7 - 30 mcg/day

Most foods (especially liver, greens, yeast).

Destroyed by cooking

Average diet = 200 - 600 mcg/day

Body Stores

2-3mg (4 years supply)

10mg (4 months supply)





Terminal ileum (small bowel). Needs Intrinisic Factor (IF) from stomach parietal cells.

Proximal jejenum (small bowel)

Causes of Deficiency

1. Reduced intake:

diet - vegan

diet, alcohol, infants, dialysis

2. Malabsorption

IF deficiency = Pernicious Anaemia; ileal disease; gastric disease; parasites; pancreatic disease GI blind loops, anticonvulsants, OCP

3. Increased Requirements

pregnancy pregnancy, lactaton, Haemolysis, cancer, exfoliative skin disorders

4. Decreased Utilisation

enzyme deficiency, N2O folate antagonists (eg MTX), enz deficiency

Haematological Features

High MCV (>120); oval macrocytes; stippling; HJB;

Low retics; ±nRBC

hyersegmented neutrophils (early); pancytopenia; High LDH; High bili

Hypercellular marrow; megaloblastic; giant metameylocytes


Parietal Cell Ab in 90% but non-specific

Intrinsic Factor Ab in 50%; specific

Low B12 level; high serum folate; low red cell folate

low serum folate; low red cell folate

± borderline B12

Special Clinical Features

Atrophic gastritis (not reversed by B12)

Ileal villus atrophy (reversible)

Neuro: SACD (see below)

Often assoc with multiple vitamin deficiencies


Vitamin B12 im 1000mcg every 3 months for life.

Prophylasctic in gastrectomy, ileal resection

oral B12 if vegan and no pathology

Folic acid 1 - 5 mg/day

Prophylactic: Pregnancy, severe haemolysis, dialysis

Avoid folate in B12 deficency - worsens neuro damage

Differential Diagnosis

Megalobastic Anaemia: rarely not due to B12 or folate

Abnormal B12/folate metabolism: congential enzyme deficiency, TCII defic, N2O, DHF reductase inhibitors (MTX), chemo (TG,  6MP, aza, 5FU)

DNA synthesis defects: orotic aciduria, drugs (cytarabine, hydroxyurea), sideroblastic anaemia, erythroleukaemia, Leish-Nyhan

Macrocytic: alcohol, liverdisease, myxoedema, retics, cytotoxics, aplastic, pregnancy, MDS, myeloma




= Sub-Acute Combined Degeneration of the spinal cord.


Due to B12 deficiency


Leads to posterior and lateral column defect and peripheral sensory neuropathy


Link to Problems of Diagnosis of B12 deficiency (pdf)