Biochemical responses to high-protein diet in rats and metabolic adaptations

Abstract

A high-protein diet is defined as protein intake exceeding 25% of total energy or greater than 1.6 g/kg body weight daily levels increasingly common in athletic and weight-loss populations. This research investigated metabolic adaptations to chronic high-protein feeding in Wistar rats over 12 weeks. Animals were assigned to control (14% protein), moderate-protein (28% protein), or high-protein (42% protein) diets with isocaloric adjustments. Serum biochemistry, organ weights, hepatic enzyme activities, and renal function markers were assessed at weeks 4, 8, and 12. High-protein feeding significantly increased liver weight by 28.7% and kidney weight by 18.4% compared to controls. Serum urea rose by 62.3% and creatinine by 47.8% in the high-protein group, indicating enhanced nitrogen metabolism. Hepatic aminotransferase activities increased proportionally to protein intake, with ALT showing 48.6% elevation at 12 weeks. Despite these metabolic adaptations, histopathological examination revealed no evidence of organ damage. These findings suggest that healthy rats can tolerate substantial protein excess through adaptive mechanisms, though the safety margins for extended high-protein consumption require further investigation.