Duodenal ascorbate and ferric reductase in human iron deficiency

Area of Science:

• Human physiology
• Nutritional science
• Gastroenterology

Background:

• Iron absorption is crucial for health, with the initial step involving ferric iron reduction to ferrous iron.
• This reduction is catalyzed by duodenal ferric reductase, an enzyme critical for dietary iron uptake.
• While animal studies suggest a link between iron deficiency, reductase activity, and ascorbate, this relationship in humans remained unclear.

Purpose of the Study:

• To investigate the relationship between ferric reductase activity in human duodenal biopsy specimens and ascorbate concentrations.
• To compare these levels between iron-replete and iron-deficient individuals.

Main Methods:

• Adults undergoing upper gastrointestinal endoscopy provided overnight-fasted duodenal biopsy specimens.
• Ferric reductase activity was measured using nitroblue tetrazolium assay.
• Ascorbate levels were quantified in both duodenal biopsy specimens and plasma samples.

Main Results:

• Iron-deficient subjects exhibited significantly higher duodenal ferric reductase activity compared to controls.
• Ascorbate concentrations were elevated in both duodenal biopsy specimens and plasma of iron-deficient individuals.
• Manipulating ascorbate levels in vitro demonstrated a complex regulatory role in reductase activity.

Conclusions:

• Human iron deficiency is associated with increased duodenal ascorbate concentrations.
• This elevation in ascorbate likely contributes to the increased duodenal ferric reductase activity observed in iron deficiency.
• The findings highlight ascorbate as a potential substrate influencing duodenal cytochrome b reductase 1 activity and iron absorption.