Anabolic effects of leucine-rich whey protein, carbohydrate, and soy protein with and without β-hydroxy-β-methylbutyrate (HMB) during fasting-induced catabolism: A human randomized crossover trial

Clin Nutr. 2017 Jun;36(3):697-705. doi: 10.1016/j.clnu.2016.05.004. Epub 2016 May 25.


Background: Protein-rich beverages are widely used clinically to preserve muscle protein and improve physical performance. Beverages with high contents of leucine or its keto-metabolite β-hydroxy-β-methylbutyrate (HMB) are especially anabolic in muscle, but it is uncertain whether this also applies to catabolic conditions such as fasting and whether common or separate intracellular signaling cascades are involved.

Objective: To compare a specific leucine-rich whey protein beverage (LWH) with isocaloric carbohydrate- (CHO), soy protein (SOY), and soy protein +3 g HMB (HMB) during fasting-induced catabolic conditions.

Design: Eight healthy lean male subjects underwent four interventions (LWH, CHO, SOY, and HMB) using a randomized crossover design. Each trial included a 36 h fast and consisted of a 3 h basal fasting period and a 4 h 'sipping' period.

Results: Forearm net balances of phenylalanine (NBphe, measure of net protein loss) improved for all groups (p < 0.05), but more prominently so for LWH and HMB compared with SOY (p < 0.05). Muscle protein phosphorylation of mammalian target of rapamycin (mTOR) and its downstream targets eukaryotic translation factor 4E-binding protein 1 (4EBP1) and ribosomal S6 kinase 1 (S6) were distinctly increased during LWH consumption (p < 0.05). The ratio between autophagy protein microtubule-associated protein 1 light chain-3β II and I (LC3II/LC3I, a measure of autophagy activity) was decreased during LWH and SOY intake compared with the fasting period (p < 0.05).

Conclusion: LWH and HMB have superior anabolic effects on muscle protein kinetics after 36 h of fasting, and LWH distinctly activates the mTOR pathway. These novel findings suggest that leucine-rich whey protein and/or HMB are specifically beneficial during fasting-induced catabolic conditions.

Trial registration: NCT01840098.

Keywords: Fasting; HMB; Leucine; Protein; Soy; Whey.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Anabolic Agents / administration & dosage*
  • Body Mass Index
  • Cell Cycle Proteins
  • Cross-Over Studies
  • Dietary Carbohydrates / administration & dosage*
  • Fasting
  • Glucagon / blood
  • Humans
  • Leucine / administration & dosage*
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Ribosomal Protein S6 Kinases, 90-kDa / genetics
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism
  • Signal Transduction
  • Soybean Proteins / administration & dosage*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Valerates / administration & dosage*
  • Whey Proteins / administration & dosage*
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • Anabolic Agents
  • Cell Cycle Proteins
  • Dietary Carbohydrates
  • EIF4EBP1 protein, human
  • Phosphoproteins
  • Soybean Proteins
  • Valerates
  • Whey Proteins
  • beta-hydroxyisovaleric acid
  • Glucagon
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 90-kDa
  • TOR Serine-Threonine Kinases
  • ribosomal protein S6 kinase 1, human
  • Leucine

Associated data