Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates - A Substudy

PLoS One. 2015 Sep 14;10(9):e0137183. doi: 10.1371/journal.pone.0137183. eCollection 2015.


Background: Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates.

Objective: To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake.

Methods: A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans.

Results: After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03), synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042±0.01 vs 0.045±0.01%/h;P = 0.620).

Conclusions: In the overnight fasted state, adaptation to a low-protein intake (0.4 g/kg/d) does not result in a more negative whole-body protein balance and does not lower basal muscle protein synthesis rates when compared to a high-protein intake.

Trial registration: NCT01551238.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diet, Protein-Restricted*
  • Dietary Proteins / administration & dosage*
  • Dietary Proteins / metabolism
  • Fasting / blood
  • Female
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Male
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism*
  • Nitrogen / metabolism
  • Phenylalanine / blood
  • Protein Biosynthesis
  • Tyrosine / blood
  • Young Adult


  • Dietary Proteins
  • Insulin
  • Muscle Proteins
  • Tyrosine
  • Phenylalanine
  • Glucose
  • Nitrogen

Associated data


Grants and funding

This work was supported by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 266408. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.