• cobalamin;
  • cobalamin deficiency;
  • epidermal growth factor;
  • iron deficiency anaemia;
  • tumour necrosis factor-α

Abstract:Objectives:We have previously demonstrated that vitamin B12 (cobalamin)-deficient central neuropathy in the rat is associated with local overexpression of neurotoxic tumour necrosis factor (TNF)-α combined with locally decreased synthesis of neurotrophic epidermal growth factor (EGF). The aims of this study were to investigate whether a similar imbalance also occurs in the serum of adult patients with clinically confirmed cobalamin deficiency and whether it can be corrected by vitamin B12 replacement therapy. Patients and methods: We studied 34 adult patients with severe cobalamin deficiency, 12 patients with pure iron deficiency anaemia and 34 control subjects. Haematological markers of cobalamin deficiency and serum TNF-α and EGF levels were measured using commercial kits. Thirteen cobalamin-deficient patients were re-evaluated after 3 and 6 months of parenteral vitamin B12 treatment. Results: TNF-α was significantly higher (p < 0.01) and EGF significantly lower (p < 0.01) in the patients with cobalamin deficiency, but both were unchanged in patients with pure iron deficiency anaemia. In cobalamin-deficient patients the serum TNF-α levels correlated significantly with plasma total homocysteine levels (r = 0.425; p < 0.02). In the treated patients TNF-α and EGF levels normalised concomitantly with clinical and haematological disease remission. Conclusions: In humans, as in rats, cobalamin concentration appears to be correlated with the synthesis and release of TNF-α and EGF in a reciprocal manner, because cobalamin deficiency is accompanied by overproduction of TNF-α and underproduction of EGF.