Management of Anaemia of Chronic Disease: Beyond Iron-Only Supplementation

Chronic diseases are characterised by altered autophagy and protein metabolism disarrangement,
resulting in sarcopenia, hypoalbuminemia and hypo-haemoglobinaemia. Hypohaemoglobinaemia
is linked to a worse prognosis independent of the target organ affected by
the disease. Currently, the cornerstone of the therapy of anaemia is iron supplementation, with or
without erythropoietin for the stimulation of haematopoiesis. However, treatment strategies should
incorporate the promotion of the synthesis of heme, the principal constituent of haemoglobin (Hb)
and of many other fundamental enzymes for human metabolism. Heme synthesis is controlled by
a complex biochemical pathway. The limiting step of heme synthesis is D-amino-levulinic acid (DALA),
whose availability and synthesis require glycine and succinil-coenzyme A (CoA) as precursor
substrates. Consequently, the treatment of anaemia should not be based only on the sufficiency of iron
but, also, on the availability of all precursor molecules fundamental for heme synthesis. Therefore,
an adequate clinical therapeutic strategy should integrate a standard iron infusion and a supply of
essential amino acids and vitamins involved in heme synthesis. We reported preliminary data in a
select population of aged anaemic patients affected by congestive heart failure (CHF) and catabolic
disarrangement, who, in addition to the standard iron therapy, were treated by reinforced therapeutic
schedules also providing essential animo acids (AAs) and vitamins involved in the maintenance of
heme. Notably, such individualised therapy resulted in a significantly faster increase in the blood
concentration of haemoglobin after 30 days of treatment when compared to the nonsupplemented
standard iron therapy.