Cysteine-rich whey protein isolate (Immunocal®) ameliorates deficits in the GFAP.HMOX1 mouse model of schizophrenia

Free Radic Biol Med. 2017 Sep;110:162-175. doi: 10.1016/j.freeradbiomed.2017.05.025. Epub 2017 Jun 8.


Schizophrenia is a neuropsychiatric disorder that features neural oxidative stress and glutathione (GSH) deficits. Oxidative stress is augmented in brain tissue of GFAP.HMOX1 transgenic mice which exhibit schizophrenia-relevant characteristics. The whey protein isolate, Immunocal® serves as a GSH precursor upon oral administration. In this study, we treated GFAP.HMOX1 transgenic mice daily with either Immunocal (33mg/ml drinking water) or equivalent concentrations of casein (control) between the ages of 5 and 6.5 months. Immunocal attenuated many of the behavioral, neurochemical and redox abnormalities observed in GFAP.HMOX1 mice. In addition to restoring GSH homeostasis in the CNS of the transgenic mice, the whey protein isolate augmented GSH reserves in the brains of wild-type animals. These results demonstrate that consumption of whey protein isolate augments GSH stores and antioxidant defenses in the healthy and diseased mammalian brain. Whey protein isolate supplementation (Immunocal) may constitute a safe and effective modality for the management of schizophrenia, an unmet clinical imperative.

Keywords: Astrocyte; Dopamine; Glutathione; Heme oxygenase-1; Immunocal; Neurodegenerative disorder; Neurodevelopmental disorder; Schizophrenia; Whey protein isolate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Behavior, Animal / drug effects
  • Cysteine / administration & dosage*
  • Dietary Supplements*
  • Disease Models, Animal
  • Gene Expression Regulation
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutathione / agonists*
  • Glutathione / metabolism
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Oxidative Stress / drug effects
  • Schizophrenia / diet therapy*
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism
  • Schizophrenia / physiopathology
  • Whey Proteins / administration & dosage*


  • Glial Fibrillary Acidic Protein
  • Membrane Proteins
  • Whey Proteins
  • glial fibrillary astrocytic protein, mouse
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Glutathione
  • Cysteine