Novel Iron-Whey Protein Microspheres Protect Gut Epithelial Cells from Iron-Related Oxidative Stress and Damage and Improve Iron Absorption in Fasting Adults

Acta Haematol. 2017;138(4):223-232. doi: 10.1159/000480632. Epub 2018 Jan 5.


Background: Iron food fortification and oral iron formulations are frequently limited by poor absorption, resulting in the widespread use of high-dose oral iron, which is poorly tolerated.

Methods: We evaluated novel iron-denatured whey protein (Iron-WP) microspheres on reactive oxygen species (ROS) and viability in gut epithelial (HT29) cells. We compared iron absorption from Iron-WP versus equimolar-dose (25 mg elemental iron) ferrous sulphate (FeSO4) in a prospective, randomised, cross-over study in fasting volunteers (n = 21 per group) dependent on relative iron depletion (a ferritin level ≤/>30 ng/mL).

Results: Iron-WP caused less ROS generation and better HT29 cell viability than equimolar FeSO4. Iron-WP also showed better absorption with a maximal 149 ± 39% increase in serum iron compared to 65 ± 14% for FeSO4 (p = 0.01). The response to both treatments was dependent on relative iron depletion, and multi-variable analysis showed that better absorption with Iron-WP was independent of baseline serum iron, ferritin, transferrin saturation, and haemoglobin in the overall group and in the sub-cohort with relative iron depletion at baseline (p < 0.01).

Conclusions: Novel Iron-WP microspheres may protect gut epithelial cells and improve the absorption of iron versus FeSO4. Further evaluation of this approach to food fortification and supplementation with iron is warranted.

Keywords: Absorption; Amorphous formulation; Clinical study; Iron; Modified release; Whey protein.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Carriers / administration & dosage
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Fasting / blood
  • Female
  • Ferritins / blood
  • Humans
  • Intestinal Absorption / drug effects
  • Iron / administration & dosage*
  • Iron / adverse effects
  • Iron Deficiencies
  • Male
  • Microspheres
  • Oxidative Stress / drug effects
  • Prospective Studies
  • Protective Agents / administration & dosage
  • Whey Proteins / administration & dosage*


  • Drug Carriers
  • Protective Agents
  • Whey Proteins
  • Ferritins
  • Iron