PMID- 31531707 OWN - NLM STAT- MEDLINE DCOM- 20210525 LR - 20210525 IS - 1436-6215 (Electronic) IS - 1436-6207 (Print) IS - 1436-6207 (Linking) VI - 59 IP - 6 DP - 2020 Sep TI - Co-ingestion of whey protein hydrolysate with milk minerals rich in calcium potently stimulates glucagon-like peptide-1 secretion: an RCT in healthy adults. PG - 2449-2462 LID - 10.1007/s00394-019-02092-4 [doi] AB - 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. FAU - Chen, Yung-Chih AU - Chen YC AD - Department for Health, University of Bath, Bath, BA2 7AY, UK. AD - Department of Physical Education, National Taiwan Normal University, Taipei, Taiwan. FAU - Smith, Harry A AU - Smith HA AD - Department for Health, University of Bath, Bath, BA2 7AY, UK. FAU - Hengist, Aaron AU - Hengist A AD - Department for Health, University of Bath, Bath, BA2 7AY, UK. FAU - Chrzanowski-Smith, Oliver J AU - Chrzanowski-Smith OJ AD - Department for Health, University of Bath, Bath, BA2 7AY, UK. FAU - Mikkelsen, Ulla Ramer AU - Mikkelsen UR AD - Arla Foods Ingredients Group P/S, Viby J, Denmark. FAU - Carroll, Harriet A AU - Carroll HA AD - Department for Health, University of Bath, Bath, BA2 7AY, UK. AD - Rowett Institute, University of Aberdeen, Aberdeen, UK. FAU - Betts, James A AU - Betts JA AD - Department for Health, University of Bath, Bath, BA2 7AY, UK. FAU - Thompson, Dylan AU - Thompson D AD - Department for Health, University of Bath, Bath, BA2 7AY, UK. FAU - Saunders, John AU - Saunders J AD - Department for Health, University of Bath, Bath, BA2 7AY, UK. AD - Royal United Hospitals Bath NHS Foundation Trust, Bath, UK. FAU - Gonzalez, Javier T AU - Gonzalez JT AUID- ORCID: 0000-0002-9939-0074 AD - Department for Health, University of Bath, Bath, BA2 7AY, UK. J.T.Gonzalez@bath.ac.uk. LA - eng SI - ClinicalTrials.gov/NCT03232034 SI - ClinicalTrials.gov/NCT03370497 SI - ClinicalTrials.gov/NCT03370484 PT - Journal Article PT - Randomized Controlled Trial DEP - 20190917 PL - Germany TA - Eur J Nutr JT - European journal of nutrition JID - 100888704 RN - 0 (Minerals) RN - 0 (Protein Hydrolysates) RN - 0 (Whey Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - SY7Q814VUP (Calcium) SB - IM MH - Adult MH - Animals MH - Calcium/*pharmacology MH - Cross-Over Studies MH - Double-Blind Method MH - Eating MH - Glucagon-Like Peptide 1/*metabolism MH - Humans MH - Milk/*chemistry MH - Minerals/pharmacology MH - Postprandial Period MH - Protein Hydrolysates/*chemistry/*pharmacology MH - Whey Proteins/*chemistry MH - Young Adult PMC - PMC7413905 OTO - NOTNLM OT - Calcium OT - Gastric inhibitory polypeptide OT - Incretins OT - Metabolism OT - Peptide tyrosine tyrosine OT - Postprandial OT - Protein COIS- 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. EDAT- 2019/09/19 06:00 MHDA- 2021/05/26 06:00 PMCR- 2019/09/17 CRDT- 2019/09/19 06:00 PHST- 2019/02/26 00:00 [received] PHST- 2019/09/11 00:00 [accepted] PHST- 2019/09/19 06:00 [pubmed] PHST- 2021/05/26 06:00 [medline] PHST- 2019/09/19 06:00 [entrez] PHST- 2019/09/17 00:00 [pmc-release] AID - 10.1007/s00394-019-02092-4 [pii] AID - 2092 [pii] AID - 10.1007/s00394-019-02092-4 [doi] PST - ppublish SO - Eur J Nutr. 2020 Sep;59(6):2449-2462. doi: 10.1007/s00394-019-02092-4. Epub 2019 Sep 17.