Long-term intake of a high-protein diet with or without potassium citrate modulates acid-base metabolism, but not bone status, in male rats

J Nutr. 2008 Apr;138(4):718-24. doi: 10.1093/jn/138.4.718.


High dietary protein intake generates endogenous acid production, which may adversely affect bone health. Alkaline potassium citrate (Kcit)(2) may contribute to the neutralization of the protein-induced metabolic acidosis. We investigated the impact of 2 levels of protein intake and Kcit supplementation on acid-base metabolism and bone status in rats. Two-month-old Wistar male rats were randomly assigned to 4 groups (n = 30 per group). Two groups received a normal-protein content (13%) (NP) or a high-protein (HP) content diet (26%) for 19 mo. The 2 other groups received identical diets supplemented with Kcit (3.60%) (NPKcit and HPKcit). Rats were pair-fed based on the ad libitum intake of the HP group. At 9, 16, and 21 mo of age, 10 rats of each group were killed. The HP diet induced a metabolic acidosis characterized by hypercalciuria, hypermagnesuria, and hypocitraturia at all ages. Kcit supplementation neutralized this effect, as evidenced by decreased urinary calcium and magnesium excretion by the HPKcit rats. Femoral bone mineral density, biomechanical properties, bone metabolism biomarkers (osteocalcin and deoxypyridinoline), and plasma insulin-like growth factor 1 levels were not affected by the different diets. Nevertheless, at 21 mo of age, calcium retention was reduced in the HP group. This study suggests that lifelong excess of dietary protein results in low-grade metabolic acidosis without affecting the skeleton, which may be protected by an adequate calcium supply.

MeSH terms

  • Acid-Base Equilibrium / drug effects*
  • Animals
  • Anions / urine
  • Biomarkers
  • Biomechanical Phenomena
  • Body Weight
  • Bone Density / drug effects*
  • Calcium / metabolism
  • Cations / urine
  • Dietary Proteins / administration & dosage*
  • Dietary Proteins / pharmacology*
  • Dietary Supplements
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Male
  • Potassium Citrate / administration & dosage*
  • Potassium Citrate / pharmacology*
  • Rats
  • Rats, Wistar


  • Anions
  • Biomarkers
  • Cations
  • Dietary Proteins
  • Potassium Citrate
  • Calcium