Metabolic effects of amino acid mixtures and whey protein in healthy subjects: studies using glucose-equivalent drinks

Am J Clin Nutr. 2007 Apr;85(4):996-1004. doi: 10.1093/ajcn/85.4.996.


Background: Milk protein, in particular the whey fraction, has been shown to display insulinotrophic properties in healthy persons and persons with type 2 diabetes. In parallel to the hyperinsulinemia, a pronounced postprandial rise of certain amino acids and of glucose-dependent insulinotrophic polypeptide (GIP) was observed in plasma.

Objective: The objective of the study was to determine to what extent the insulinotrophic properties of whey could be simulated by specific amino acid mixtures.

Design: Twelve healthy volunteers were served drinks consisting of pure glucose (reference drink) or glucose supplemented with free amino acids or whey proteins (test drinks).

Results: A test drink with the branched-chain amino acids isoleucine, leucine, and valine resulted in significantly higher insulin responses than did the glucose reference. A drink containing glucose and leucine, isoleucine, valine, lysine, and threonine mimicked the glycemic and insulinemic responses seen after whey ingestion. With consumption of this drink, the glucose area under the curve (AUC) was 44% smaller (P < 0.05) and the insulin AUC was 31% larger (NS) than with consumption of the reference drink. With consumption of the whey drink, the AUCs were 56% smaller (glucose; P < 0.05) and 60% larger (insulin; P < 0.05), respectively, than with the reference drink. The whey drink was accompanied by an 80% greater GIP response (P < 0.05), whereas the drinks containing free amino acids did not significantly affect GIP secretion.

Conclusion: A mixture of leucine, isoleucine, valine, lysine, and threonine resulted in glycemic and insulinemic responses closely mimicking those seen after whey ingestion in the absence of an additional effect of GIP and glucagon-like peptide 1.

Publication types

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

MeSH terms

  • Adult
  • Amino Acids / blood
  • Amino Acids / metabolism*
  • Amino Acids / pharmacokinetics
  • Amino Acids, Branched-Chain / metabolism
  • Area Under Curve
  • Blood Glucose / metabolism*
  • Cross-Over Studies
  • Female
  • Gastric Inhibitory Polypeptide / metabolism
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose Tolerance Test
  • Glycemic Index
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Male
  • Milk Proteins / metabolism*
  • Milk Proteins / pharmacokinetics
  • Postprandial Period
  • Whey Proteins


  • Amino Acids
  • Amino Acids, Branched-Chain
  • Blood Glucose
  • Insulin
  • Milk Proteins
  • Whey Proteins
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1