Adaptation in iron absorption: iron supplementation reduces nonheme-iron but not heme-iron absorption from food

Am J Clin Nutr. 2000 Oct;72(4):982-9. doi: 10.1093/ajcn/72.4.982.


Background: Results of cross-sectional studies suggest that in healthy people, iron absorption adapts to meet physiologic needs and stabilize iron stores, but this has not been adequately tested in longitudinal studies.

Objective: We tested whether heme- and nonheme-iron absorption decrease in response to increased iron intake and whether iron stores reach a steady state.

Design: In a randomized, placebo-controlled trial, heme- and nonheme-iron absorption by healthy men and women (n = 57) were measured before and after 12 wk of supplementation with 50 mg Fe/d as ferrous sulfate. Serum and fecal ferritin were measured during supplementation and for 6 mo thereafter.

Results: Initially, both heme- and nonheme-iron absorption were inversely associated with serum ferritin concentration. Volunteers who took iron supplements, even those with serum ferritin <21 microg/L (n = 5), adapted to absorb less nonheme iron (3.2% at week 12 compared with 5.0% at week 0, P: < 0.001) but not less heme iron from a beef-based meal. Serum ferritin concentration was slightly but significantly higher after iron supplementation than after placebo (difference = 13 microg/L). This higher ferritin concentration persisted for >/=6 mo after supplementation, except in subjects with low iron stores, whose serum ferritin returned to baseline within 3 mo. Fecal ferritin excretion increased 2.5-fold (P: < 0.05) during supplementation.

Conclusions: Healthy individuals, even those with low iron stores, had reduced nonheme-iron absorption from food in response to iron supplementation. Despite this partial adaptation, iron stores were greater after iron supplementation than after placebo and this difference was sustained, except in individuals with the lowest iron stores.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / physiology*
  • Adult
  • Dietary Supplements*
  • Enzyme-Linked Immunosorbent Assay
  • Feces / chemistry
  • Female
  • Ferritins / analysis
  • Hematocrit
  • Heme / metabolism
  • Hemoglobins / analysis
  • Humans
  • Intestinal Absorption / physiology*
  • Iron / analysis
  • Iron / blood
  • Iron / physiology*
  • Iron Radioisotopes / analysis
  • Iron Radioisotopes / blood
  • Iron, Dietary / administration & dosage
  • Iron, Dietary / pharmacokinetics*
  • Male
  • Middle Aged
  • Receptors, Transferrin / blood
  • Scintillation Counting
  • Statistics, Nonparametric
  • Transferrin / analysis


  • Hemoglobins
  • Iron Radioisotopes
  • Iron, Dietary
  • Receptors, Transferrin
  • Transferrin
  • Heme
  • Ferritins
  • Iron