Postnatal Iron Supplementation with Ferrous Sulfate vs. Ferrous Bis-Glycinate Chelate: Effects on Iron Metabolism, Growth, and Central Nervous System Development in Sprague Dawley Rat Pups

Nutrients. 2021 Apr 22;13(5):1406. doi: 10.3390/nu13051406.

Abstract

Iron-fortified formulas and iron drops (both usually ferrous sulfate, FS) prevent early life iron deficiency, but may delay growth and adversely affect neurodevelopment by providing excess iron. We used a rat pup model to investigate iron status, growth, and development outcomes following daily iron supplementation (10 mg iron/kg body weight, representative of iron-fortified formula levels) with FS or an alternative, bioavailable form of iron, ferrous bis-glycinate chelate (FC). On postnatal day (PD) 2, sex-matched rat litters (n = 3 litters, 10 pups each) were randomly assigned to receive FS, FC, or vehicle control until PD 14. On PD 15, we evaluated systemic iron regulation and CNS mineral interactions and we interrogated iron loading outcomes in the hippocampus, in search of mechanisms by which iron may influence neurodevelopment. Body iron stores were elevated substantially in iron-supplemented pups. All pups gained weight normally, but brain size on PD 15 was dependent on iron source. This may have been associated with reduced hippocampal oxidative stress but was not associated with CNS mineral interactions, iron regulation, or myelination, as these were unchanged with iron supplementation. Additional studies are warranted to investigate iron form effects on neurodevelopment so that iron recommendations can be optimized for all infants.

Keywords: brain; ferrous bis-glycinate; ferrous sulfate; infant nutrition; iron supplementation.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Animals, Newborn
  • Central Nervous System / drug effects
  • Central Nervous System / growth & development*
  • Dietary Supplements*
  • Ferrous Compounds / pharmacology*
  • Gene Expression Regulation / drug effects
  • Glycine / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Homeostasis / drug effects
  • Iron / blood
  • Iron / metabolism*
  • Iron / pharmacology*
  • Iron Chelating Agents / pharmacology*
  • Myelin Sheath / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Trace Elements / analysis
  • Weight Gain / drug effects

Substances

  • Ferrous Compounds
  • Iron Chelating Agents
  • Trace Elements
  • ferrous sulfate
  • Iron
  • ferrous bisglycinate
  • Glycine