Essential Amino Acids and Protein Synthesis: Insights into Maximizing the Muscle and Whole-Body Response to Feeding

Nutrients. 2020 Dec 2;12(12):3717. doi: 10.3390/nu12123717.


Ingesting protein-containing supplements and foods provides essential amino acids (EAA) necessary to increase muscle and whole-body protein synthesis (WBPS). Large variations exist in the EAA composition of supplements and foods, ranging from free-form amino acids to whole protein foods. We sought to investigate how changes in peripheral EAA after ingesting various protein and free amino acid formats altered muscle and whole-body protein synthesis. Data were compiled from four previous studies that used primed, constant infusions of L-(ring-2H5)-phenylalanine and L-(3,3-2H2)-tyrosine to determine fractional synthetic rate of muscle protein (FSR), WBPS, and circulating EAA concentrations. Stepwise regression indicated that max EAA concentration (EAACmax; R2 = 0.524, p < 0.001), EAACmax (R2 = 0.341, p < 0.001), and change in EAA concentration (ΔEAA; R = 0.345, p < 0.001) were the strongest predictors for postprandial FSR, Δ (change from post absorptive to postprandial) FSR, and ΔWBPS, respectively. Within our dataset, the stepwise regression equation indicated that a 100% increase in peripheral EAA concentrations increases FSR by ~34%. Further, we observed significant (p < 0.05) positive (R = 0.420-0.724) correlations between the plasma EAA area under the curve above baseline, EAACmax, ΔEAA, and rate to EAACmax to postprandial FSR, ΔFSR, and ΔWBPS. Taken together our results indicate that across a large variety of EAA/protein-containing formats and food, large increases in peripheral EAA concentrations are required to drive a robust increase in muscle and whole-body protein synthesis.

Keywords: aging; amino acid kinetics; anabolism; essential amino acids; muscle protein synthesis; nutrition; protein; protein quality; whole body protein synthesis.

MeSH terms

  • Aging / physiology
  • Amino Acids / metabolism
  • Amino Acids / pharmacokinetics
  • Amino Acids, Essential / biosynthesis*
  • Amino Acids, Essential / pharmacology*
  • Dietary Supplements
  • Eating
  • Food
  • Humans
  • Kinetics
  • Male
  • Metabolism
  • Muscle Proteins / biosynthesis*
  • Muscle Proteins / pharmacokinetics*
  • Muscle, Skeletal / metabolism
  • Phenylalanine
  • Postprandial Period
  • Protein Biosynthesis*
  • Whey Proteins


  • Amino Acids
  • Amino Acids, Essential
  • Muscle Proteins
  • Whey Proteins
  • Phenylalanine