B12 and Folate Deficiency
A deficiency of either B12 or folate stalls DNA synthesis in every dividing cell, so red cell precursors keep growing but cannot divide, producing large, immature megaloblasts, while B12 deficiency alone also strips myelin, adding neurological disease that folate cannot fix and may make worse.
In a nutshell
B12 and folate are both needed for DNA synthesis, so lack of either produces megaloblastic macrocytic anaemia. Only B12 also maintains myelin, so only B12 deficiency causes subacute combined degeneration of the cord, which is why B12 must be treated before or with folate.
Classic presentation
An insidious presentation of fatigue and pallor with a macrocytic anaemia on FBC, and in B12 deficiency, peripheral paraesthesiae or an unsteady gait alongside it.
Key points
- Both deficiencies share one mechanism (impaired DNA synthesis), producing macrocytosis and hypersegmented neutrophils.
- Only B12 deficiency causes neurological disease, because only B12 is needed for the methylmalonyl-CoA reaction that maintains myelin.
- Giving folic acid without checking or replacing B12 can correct the blood count while allowing neurological damage to progress: always treat B12 first or alongside folate.
- Pernicious anaemia (autoimmune loss of intrinsic factor) is the classic cause of B12 deficiency in non-vegans; test intrinsic factor antibodies.
- Folate has weeks of body stores and is diet-dependent; B12 has years of stores and depends on intrinsic factor and ileal absorption: this explains their different causes.
First-line investigation
FBC and blood film to identify the megaloblastic picture, followed by serum B12 and folate levels to determine which is deficient.
First-line management
Replace B12 (intramuscular hydroxocobalamin) before or alongside folic acid, never folate alone when B12 status is unknown or low.
Exam traps
- A stem describing macrocytic anaemia plus peripheral neuropathy or ataxia is B12 deficiency, not folate deficiency: folate never causes neurological disease.
- Never select 'start folic acid' as the sole answer when B12 has not been checked: this is a classic exam trap for precipitating or worsening cord disease.
- Macrocytosis is not always megaloblastic: alcohol excess, hypothyroidism and liver disease also raise MCV, so confirm with B12/folate levels and film findings.
Educational content pending clinical review. Not medical advice.