Cellular mechanisms in the regulation of iron absorption by the human intestine: studies in patients with iron deficiency before and after treatment.

An in vitro method for measuring initial rates of iron uptake by mucosal biopsies of human duodenum was used to study control mechanisms for iron absorption. Within the physiological range of intraluminal concentrations (18--450 mumol/l) iron influx has many features of active, carrier-mediated transport. In biopsies form six patients with iron deficiency anaemia, uptake rates were increased 2--3-fold at the higher concentrations, when compared with normal controls (P less than 0.01) and overall were related inversely to serum transferrin saturation. Uptake was examined in four anaemic patients before and after therapy: the enhanced uptake fell to normal after repletion with iron, but was not reduced in two patients treated initially by red cell transfusion alone. Total mucosal iron in the anaemic patients was significantly lower at 58+/-7 nmol/mg protein, compared with 129+/-25 nmol/mg in normal subjects (P less than 0.05). In the serial studies, iron therapy for 6 weeks corrected the anaemia but did not restore mucosal iron levels to normal, even though uptake had fallen to control values. The experiments indicate that iron deficiency reversibly induces brush border iron carriers, and suggest that in man initial entry into the enterocyte rather than cellular retention of iron is a major regulatory step in the control of iron absorption.