Pre-meal protein intake alters postprandial plasma metabolome in subjects with metabolic syndrome

  • Ceyda Tugba PekmezEmail author
  • Ann Bjørnshave
  • Giulia Pratico
  • Kjeld Hermansen
  • Lars Ove Dragsted
Original Contribution



We examined the effect on the postprandial plasma metabolome of protein pre-meals before a fat-rich main meal.


Two randomized, cross-over meal studies were conducted to test the dose–response effect (0 g, 10 g, 20 g) of a pre-meal with whey protein (WP) (PREMEAL I), and the effect of protein quality (10 g WP, casein, or gluten) and timing (− 15 min vs − 30 min) of the pre-meal (PREMEAL II). Participants with metabolic syndrome received one of the test meals on each test day, − 15 min (or − 30 min) prior to a standardized fat-rich breakfast. Plasma samples were collected at − 15 min (or − 30 min), 0, 120, 240 a nd 360 min and analyzed using liquid chromatography–mass spectrometry with an untargeted method.


Pre-meal WP intake elevated plasma branched-chain amino acids (BCAA), aromatic amino acids and methionine and decreased plasma LPC (16:0) and PC (32:1) levels before the main meal. Early (− 15 to 0 min) aromatic amino acids and BCAA in response to pre-meal WP partially predict the glucose and insulin response after the main meal. A pre-meal with WP altered the postprandial plasma metabolic pattern of acyl-carnitines, specific PCs, LPCs and LPEs, betaine, citric acid, linoleic acid, and β-hydroxypalmitic acid compared to no pre-meal. The casein and WP pre-meals exhibited similar postprandial amino acid responses whereas a pre-meal with gluten resulted in lower levels of plasma amino acids and its metabolites.


A pre-meal with protein affects the postprandial metabolic pattern indicating facilitated glucose and lipid disposal from plasma in participants with metabolic syndrome.


Insulin resistance Metabolites Second meal Effect biomarkers UPLC–ESI–Q-TOF–MS 



Area under the curve


Collision dissociation energies


Cardiovascular diseases


Electrospray ionization


Free fatty acids


Glucagon-like peptide-1


Homeostatic model assessment for insulin resistance


Liquid chromatography/mass spectrometry






Mass to charge ratio


Metabolic syndrome


Tandem mass spectrometry


Mass spectrometry


Principal component analysis




Partial least squares discriminant analysis


Peptide YY


Quadrupole-time of flight mass spectrometer


Area under the receiver-operator curve


Retention time


Type 2 diabetes mellitus


Ultra-performance liquid chromatography


Variable importance in projection


Whey protein



AB and KH planned and conducted the intervention studies. CTP conducted the metabolomics workflow and data analysis and drafted the manuscript. GP and LOD contributed to data analysis, identification and interpretation. LOD, CTP, AB, GP, and KH reviewed the manuscript. All the authors have read and approved the final version.


This work was supported by grants from the Danish Dairy Research Foundation and the Innovation Fund—MERITS (4105-00002B). CTP was supported by a Ph.D. grant from the Department of Nutrition, Exercise and Sports, University of Copenhagen and Hacettepe University. AB was supported by research grants from The Danish Diabetes Academy supported by the Novo Nordisk Foundation, Aarhus University and The Research Foundation of the Department of Endocrinology and Internal Medicine, Aarhus University Hospital. Protein powder was kindly provided by Arla Foods Ingredients Group P/S.

Compliance with ethical standards

Conflict of interest

CTP, GP, KH and LOD declare no conflicts of interest. AB has after termination of the study been employed at Arla Foods Ingredients Group P/S.

Supplementary material

394_2019_2039_MOESM1_ESM.docx (12.1 mb)
Supplementary material 1 (DOCX 12340 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Nutrition, Exercise and Sports, Faculty of ScienceUniversity of CopenhagenFrederiksberg CDenmark
  2. 2.Department of Nutrition and Dietetics, Faculty of Health SciencesHacettepe UniversityAnkaraTurkey
  3. 3.Department Endocrinology and Internal MedicineAarhus University HospitalAarhus NDenmark
  4. 4.Department of Clinical MedicineAarhus UniversityAarhus NDenmark
  5. 5.Danish Diabetes AcademyOdense CDenmark

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