Usage of whey protein may cause liver damage via inflammatory and apoptotic responses

Hum Exp Toxicol. 2015 Jul;34(7):769-79. doi: 10.1177/0960327114556787. Epub 2014 Oct 28.


The purpose of this study was to investigate the long- and short-term inflammatory and apoptotic effects of whey protein on the livers of non-exercising rats. Thirty rats were divided into three groups namely (1) control group, (2) short-term whey (WS) protein diet (252 g/kg for 5 days), and (3) long-term whey (WL) protein diet (252 g/kg for 4 weeks). Interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), and cytokeratin 18 (CK-18-M30) were assessed using enzyme-linked immunosorbent assay and immunohistochemical methods. Apoptosis was evaluated using the terminal transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method. Hepatotoxicity was evaluated by quantitation of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Based on the biochemical levels and immunohistochemical results, the highest level of IL-1β was identified in the WL group (p < 0.01). The IL-6 and TNF-α results were slightly lower in the WS group than in the control group and were highest in the WL group (p < 0.01). The CK-18-M30 and TUNEL results were highest in the WS group and exhibited medium intensity in the WL group (p < 0.01). AST results were statistically significant for all groups, while our ALT groups were particularly significant between the WL and control groups (p < 0.01). The results showed that when whey protein is used in an uninformed manner and without exercising, adverse effects on the liver may occur by increasing the apoptotic signal in the short term and increasing inflammatory markers and hepatotoxicity in the long term.

Keywords: ELISA; Whey protein; apoptosis; immunohistochemistry; inflammation; liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Apoptosis / drug effects
  • Aspartate Aminotransferases / blood
  • Cytokines / metabolism
  • Inflammation / blood
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Keratin-18 / metabolism
  • Liver / drug effects*
  • Liver / pathology
  • Male
  • Rats, Wistar
  • Whey Proteins / toxicity*


  • Cytokines
  • Keratin-18
  • Whey Proteins
  • Aspartate Aminotransferases
  • Alanine Transaminase