Co-ingestion of whey protein hydrolysate with milk minerals rich in calcium potently stimulates glucagon-like peptide-1 secretion: an RCT in healthy adults

Yung-Chih Chen, Harry A Smith, Aaron Hengist, Oliver J Chrzanowski-Smith, Ulla Ramer Mikkelsen, Harriet A Carroll, James A Betts, Dylan Thompson, John Saunders, Javier T Gonzalez, Yung-Chih Chen, Harry A Smith, Aaron Hengist, Oliver J Chrzanowski-Smith, Ulla Ramer Mikkelsen, Harriet A Carroll, James A Betts, Dylan Thompson, John Saunders, Javier T Gonzalez

Abstract

Purpose: To examine whether calcium type and co-ingestion with protein alter gut hormone availability.

Methods: Healthy adults aged 26 ± 7 years (mean ± SD) completed three randomized, double-blind, crossover studies. In all studies, arterialized blood was sampled postprandially over 120 min to determine GLP-1, GIP and PYY responses, alongside appetite ratings, energy expenditure and blood pressure. In study 1 (n = 20), three treatments matched for total calcium content (1058 mg) were compared: calcium citrate (CALCITR); milk minerals rich in calcium (MILK MINERALS); and milk minerals rich in calcium plus co-ingestion of 50 g whey protein hydrolysate (MILK MINERALS + PROTEIN). In study 2 (n = 6), 50 g whey protein hydrolysate (PROTEIN) was compared to MILK MINERALS + PROTEIN. In study 3 (n = 6), MILK MINERALS was compared to the vehicle of ingestion (water plus sucralose; CONTROL).

Results: MILK MINERALS + PROTEIN increased GLP-1 incremental area under the curve (iAUC) by ~ ninefold (43.7 ± 11.1 pmol L-1 120 min; p < 0.001) versus both CALCITR and MILK MINERALS, with no difference detected between CALCITR (6.6 ± 3.7 pmol L-1 120 min) and MILK MINERALS (5.3 ± 3.5 pmol L-1 120 min; p > 0.999). MILK MINERALS + PROTEIN produced a GLP-1 iAUC ~ 25% greater than PROTEIN (p = 0.024; mean difference: 9.1 ± 6.9 pmol L-1 120 min), whereas the difference between MILK MINERALS versus CONTROL was small and non-significant (p = 0.098; mean difference: 4.2 ± 5.1 pmol L-1 120 min).

Conclusions: When ingested alone, milk minerals rich in calcium do not increase GLP-1 secretion compared to calcium citrate. Co-ingesting high-dose whey protein hydrolysate with milk minerals rich in calcium increases postprandial GLP-1 concentrations to some of the highest physiological levels ever reported. Registered at ClinicalTrials.gov: NCT03232034, NCT03370484, NCT03370497.

Keywords: Calcium; Gastric inhibitory polypeptide; Incretins; Metabolism; Peptide tyrosine tyrosine; Postprandial; Protein.

Conflict of interest statement

Y.C.C., H.A.S., A.H., O.C.S., D.T., and J.S. have no conflicts of interest to declare. U.R.M. is an employee of Arla Foods Ingredients who produce and sell milk minerals enriched in calcium and whey protein hydrolysate. H.A.C. has accepted conference fees from Danone Nutricia and received research funding from the European Hydration Institute. J.A.B. has received research funding from GlaxoSmithKline Nutritional Healthcare R&D, Lucozade Ribena Suntory and Kelloggs, has acted as a consultant for Lucozade Ribena Suntory and PepsiCo and is a scientific advisor to the International Life Sciences Institute (ILSI) Europe Task Force on Energy Balance. J.T.G. has received research funding from Arla Foods Ingredients, Lucozade Ribena Suntory, The Rank Prize Funds, The European Society for Clinical Nutrition and Metabolism (ESPEN), and Kenniscentrum Suiker and Voeding, and has acted as a consultant for Lucozade Ribena Suntory and PepsiCo.

Figures

Fig. 1
Fig. 1
Plasma GLP-1 concentrations (a) and time-average incremental area under the curve (iAUC) values for plasma GLP-1 (b), GIP (c) and PYY (d) following ingestion of calcium citrate, milk minerals rich in calcium (MILK MINERALS) and MILK MINERALS plus whey protein hydrolysate (MILK MINERALS + PROTEIN) in healthy men and women. Data are means ± 95% CI, n = 20 for all data other than PYY, which are n = 16. GLP-1 glucagon-like peptide-1, GIP glucose-dependent insulinotropic polypeptide, PYY peptide tyrosine tyrosine. bSignificant difference between MILK MINERALS + PROTEIN and MILK MINERALS; cSignificant difference between MILK MINERALS + PROTEIN and CITRATE (p ≤ 0.05)
Fig. 2
Fig. 2
Energy expenditure (a), respiratory exchange ratio (b), plasma glucose concentrations (c) and time-average postprandial area under the curve (AUC) values for appetite (d) following ingestion of calcium citrate, milk minerals rich in calcium (MILK MINERALS) and MILK MINERALS plus whey protein hydrolysate (MILK MINERALS + PROTEIN) in healthy men and women. Data are means ± 95% CI, n = 20. aSignificant difference between CITRATE and MILK MINERALS; bSignificant difference between MILK MINERALS + PROTEIN and MILK MINERALS; cSignificant difference between MILK MINERALS + PROTEIN and CITRATE (p ≤ 0.05)
Fig. 3
Fig. 3
Systolic (a) and diastolic (b) blood pressure following ingestion of calcium citrate, milk minerals rich in calcium (MILK MINERALS) and MILK MINERALS plus whey protein hydrolysate (MILK MINERALS + PROTEIN) in healthy men and women. Data are means ± 95% CI, n = 20
Fig. 4
Fig. 4
Plasma GLP-1 concentrations (a) and time-average incremental area under the curve (iAUC) values for plasma GLP-1 (b), GIP (c) and PYY (d) following ingestion of whey protein hydrolysate in the presence (MILK MINERALS + PROTEIN) and absence (PROTEIN) of milk minerals rich in calcium in healthy men and women. Data are means ± 95% CI, n = 6. GLP-1 glucagon-like peptide-1, GIP glucose-dependent insulinotropic polypeptide, PYY peptide tyrosine tyrosine. *Significant difference between treatments (p ≤ 0.05)
Fig. 5
Fig. 5
Plasma GLP-1 concentrations (a) and time-average incremental area under the curve (iAUC) values for plasma GLP-1 (b), GIP (c) and PYY (d) following ingestion of milk minerals rich in calcium (MILK MINERALS) or the vehicle of ingestion (CONTROL; 500 mL water plus 80 mg sucralose) in healthy men and women. Data are means ± 95% CI, n = 6. GLP-1 glucagon-like peptide-1, GIP glucose-dependent insulinotropic polypeptide, PYY peptide tyrosine tyrosine

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