Doguer · Comprehensive Physiology 2018 · narrative review · n=?

Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver.

Cited 165 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review of mechanistic and physiological studies without new human data

PubMed 30215866 · doi:10.1002/cphy.c170045 · record verified 2026-08-29

What was done

This narrative review synthesized literature on the molecular and physiological interactions between iron and copper metabolism in the mammalian intestine and liver. It examined the absorption and transport of both minerals, tissue redistribution during deficiency states, and regulatory mechanisms involving hypoxia-inducible factor-2alpha (HIF2alpha), ceruloplasmin, and hepcidin across health and disease states.

What was found

The abstract presents no quantitative data, effect sizes, or sample statistics. Qualitatively, iron deficiency promotes copper redistribution to enterocytes of the upper small bowel, liver, and circulation. Copper supports enterocyte iron transport, stimulates hepatic ceruloplasmin synthesis, and modulates the DNA-binding activity of HIF factors as well as hepcidin regulation. Conversely, iron-loading conditions such as hereditary hemochromatosis or high-dose iron supplementation can lead to copper depletion.

Why it matters

These mechanistic relationships highlight the bidirectional coupling of essential trace minerals and raise clinical awareness that routine high-dose iron supplementation or genetic iron overload may precipitate copper deficiency.

Limits

The paper is a non-systematic narrative review providing no quantitative pooling or study counts in the abstract. Much of the underlying molecular evidence derives from animal models and in vitro systems rather than controlled human clinical studies.

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