Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial

Am J Clin Nutr. 2014 Feb;99(2):276-86. doi: 10.3945/ajcn.113.068775. Epub 2013 Nov 27.


Background: Leucine is a key amino acid involved in the regulation of skeletal muscle protein synthesis.

Objective: We assessed the effect of the supplementation of a lower-protein mixed macronutrient beverage with varying doses of leucine or a mixture of branched chain amino acids (BCAAs) on myofibrillar protein synthesis (MPS) at rest and after exercise.

Design: In a parallel group design, 40 men (21 ± 1 y) completed unilateral knee-extensor resistance exercise before the ingestion of 25 g whey protein (W25) (3.0 g leucine), 6.25 g whey protein (W6) (0.75g leucine), 6.25 g whey protein supplemented with leucine to 3.0 g total leucine (W6+Low-Leu), 6.25 g whey protein supplemented with leucine to 5.0 g total leucine (W6+High-Leu), or 6.25 g whey protein supplemented with leucine, isoleucine, and valine to 5.0 g total leucine. A primed continuous infusion of l-[ring-(13)C6] phenylalanine with serial muscle biopsies was used to measure MPS under baseline fasted and postprandial conditions in both a rested (response to feeding) and exercised (response to combined feeding and resistance exercise) leg.

Results: The area under the blood leucine curve was greatest for the W6+High-Leu group compared with the W6 and W6+Low-Leu groups (P < 0.001). In the postprandial period, rates of MPS were increased above baseline over 0-1.5 h in all treatments. Over 1.5-4.5 h, MPS remained increased above baseline after all treatments but was greatest after W25 (∼267%) and W6+High-Leu (∼220%) treatments (P = 0.002).

Conclusions: A low-protein (6.25 g) mixed macronutrient beverage can be as effective as a high-protein dose (25 g) at stimulating increased MPS rates when supplemented with a high (5.0 g total leucine) amount of leucine. These results have important implications for formulations of protein beverages designed to enhance muscle anabolism. This trial was registered at clinicaltrials.gov as NCT 1530646.

Trial registration: ClinicalTrials.gov NCT01530646.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Amino Acids, Branched-Chain / administration & dosage
  • Beverages
  • Blood Glucose / metabolism
  • Diet, Protein-Restricted*
  • Dietary Proteins / administration & dosage
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Humans
  • Insulin / blood
  • Leucine / administration & dosage*
  • Leucine / blood
  • Linear Models
  • Male
  • Milk Proteins / administration & dosage
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Myofibrils / drug effects*
  • Myofibrils / metabolism
  • Phenylalanine / administration & dosage
  • Phenylalanine / blood
  • Protein Biosynthesis / drug effects*
  • Resistance Training
  • Rest / physiology
  • Whey Proteins
  • Young Adult


  • Amino Acids, Branched-Chain
  • Blood Glucose
  • Dietary Proteins
  • Insulin
  • Milk Proteins
  • Whey Proteins
  • Phenylalanine
  • Leucine

Associated data

  • ClinicalTrials.gov/NCT01530646