Intermittent bolus feeding promotes greater lean growth than continuous feeding in a neonatal piglet model

Am J Clin Nutr. 2018 Oct 1;108(4):830-841. doi: 10.1093/ajcn/nqy133.


Background: Orogastric tube feeding is indicated in neonates with an impaired ability to ingest food normally and can be administered with an intermittent bolus or continuous feeding schedule.

Objectives: The objectives were to 1) compare the long-term effect of continuous with intermittent feeding on growth using the newborn pig as a model, 2) determine whether feeding frequency alters lean tissue and fat mass gain, and 3) identify the signaling mechanisms by which protein deposition is controlled in skeletal muscle in response to feeding frequency.

Design: Neonatal pigs were fed the same amount of a balanced formula by orogastric tube either as an intermittent bolus meal every 4 h (INT) or as a continuous infusion (CON). Body composition was assessed at the start and end of the study by dual-energy X-ray absorptiometry, and hormone and substrate profiles, muscle mass, protein synthesis, and indexes of nutrient and insulin signaling were measured after 21 d.

Results: Body weight, lean mass, spine length, and skeletal muscle mass were greater in the INT group than in the CON group. Skeletal muscle fractional protein synthesis rates were greater in the INT group after a meal than in the CON group and were associated with higher circulating branched-chain amino acid and insulin concentrations. Skeletal muscle protein kinase B (PKB) and ribosomal protein S6 kinase phosphorylation and eukaryotic initiation factor (eIF) 4E-eIF4G complex formation were higher, whereas eIF2α phosphorylation was lower in the INT group than in the CON group, indicating enhanced activation of insulin and amino acid signaling to translation initiation.

Conclusions: These results suggest that when neonates are fed the same amounts of nutrients as intermittent meals rather than continuously there is greater lean growth. This response can be ascribed, in part, to the pulsatile pattern of amino acids, insulin, or both induced by INT, which enables the responsiveness of anabolic pathways to feeding to be sustained chronically in skeletal muscle.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipose Tissue / metabolism
  • Amino Acids / blood
  • Animals
  • Animals, Newborn / growth & development
  • Body Composition / physiology*
  • Body Fluid Compartments / metabolism
  • Body Fluid Compartments / physiology*
  • Energy Intake
  • Eukaryotic Initiation Factor-2 / metabolism
  • Eukaryotic Initiation Factor-4E / metabolism
  • Feeding Behavior / physiology*
  • Female
  • Humans
  • Infant, Newborn
  • Insulin / blood
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology*
  • Protein Biosynthesis*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Ribosomal Protein S6 Kinases / metabolism
  • Signal Transduction
  • Spine / growth & development
  • Swine
  • Weight Gain / physiology*


  • Amino Acids
  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factor-4E
  • Insulin
  • Muscle Proteins
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases