The Effect of Whey Protein and Dietary Fibers on Risk Markers of the Metabolic Syndrome and Bone Health (MERITS)

The prevalence of overweight and lifestyle related diseases such as cardiovascular disease (CVD) and type 2 diabetes (T2D) is increasing world wide. The metabolic syndrome (MeS) is a condition characterized by abdominal obesity, high blood lipids, high blood pressure and elevated blood sugar. MeS is associated with an increased risk of developing CVD and T2D. Dietary fibers and whey protein have independently shown beneficial effects on several of these risk factors in previous studies. Whey protein is furthermore seen to show positive effects on bone turnover.

The purpose of this trial is to investigate whether an increased intake of dietary fibers and whey protein (separately or combined) over a period of 12 weeks will affect the risk markers of MeS and bone turnover in abdominally obese subjects.

A total of 80 people with abdominal obesity will be included. The design is a randomized, double blinded, controlled dietary intervention trial. Subjects are assigned to one of four experimental groups. Each group are provided with test products containing either high or low whey protein and high or low dietary fibers to replace part of their regular diet. The subjects are instructed in how to incorporate the test products in their habitual diets in order to maintain weight stability.

The primary outcome is postprandial lipaemia (PPL) - an independent risk factor of developing CVD. PPL is estimated by performing a standardized high fat meal test during which postprandial level of triglycerides is measured. The authors hypothesize that a diet of high content of whey protein and high dietary fiber during 12 weeks will induce a reduction in PPL.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Metabolic Syndrome; Type 2 Diabetes; Abdominal Obesity
• Intervention / Treatment: Other: Whey protein powder; Other: High fiber bread; Other: Maltodextrin powder; Other: Low fiber bread

Detailed Description

Please refer to summary

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital, Dep. of clinical nutrition research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Waist circumference ≥ 80 cm (women)/94 cm (men)
• Age ≥40 years

Exclusion Criteria:

• Significant cardiovascular, renal or endocrine disease
• History of diabetes
• ≥ 3 kg of weight gain or loss within the last 3 months
• Any change in medication within the last month
• Treatment with steroids
• Pregnancy, breastfeeding or planned pregnancy
• Psychiatric history
• Alcohol or drug addiction
• Dietary fiber supplement within the last month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HP/HF; Whey protein powder / High fiber bread	Other: Whey protein powder; 60 g of whey protein powder; Other: High fiber bread; Wheat bread with high content of dietary fibers (approximately 30 g fibers/day)
Experimental: HP/LF; Whey protein powder / Low fiber bread	Other: Maltodextrin powder; 60 g of Maltodextrin powder; Other: Low fiber bread; Wheat bread with low content of dietary fibers (approximately 10 g fibers/day)
Experimental: LP/HF; Maltodextrin powder / High fiber bread	Other: High fiber bread; Wheat bread with high content of dietary fibers (approximately 30 g fibers/day); Other: Maltodextrin powder; 60 g of Maltodextrin powder
Experimental: LP/LF; Maltodextrin powder / Low fiber bread	Other: Whey protein powder; 60 g of whey protein powder; Other: Low fiber bread; Wheat bread with low content of dietary fibers (approximately 10 g fibers/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial triglyceride response	Postprandial triglyceride response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360 min) following a high-fat meal.	Meal test: -15, 0, 60, 90, 120, 240, 360 min. Performed at baseline and at 12 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24 hours blood pressure (BP)	Arteriograph 24, TensioMed, Hungary	Performed at baseline and week 12
24 hours augmentation Index (AI)	Arteriograph 24, TensioMed, Hungary	Performed at baseline and week 12
Respiratory Exchange Ratio	Measured twice during each meal test by indirect calorimetry (hood)	Meal test: -30 and 140 min. Performed at baseline and week 12.
Body composition	Dual Energy X-ray Absorptiometry (DEXA) scan: Total body fat percentage, lean mass percentage, gynoid and android fat percentage	Performed at baseline and week 12
Postprandial apolipoprotein B48 response	Postprandial apolipoprotein response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360 min) following a high-fat meal.	Meal test: -15, 0, 60, 240, 360 min. Performed at baseline and at 12 weeks.
Glucose response during high-fat meal test	Glucose response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360 min) following a high-fat meal.	Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12
Insulin response during high-fat meal test	Insulin response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360 min) following a high-fat meal.	Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12
Glucagon response during high-fat meal test	Glukagon response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360 min) following a high-fat meal.	Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12
Glucagon-like peptide 1 (GLP-1) response during high-fat meal test	GLP-1 response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360	Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12
Glucagon-like peptide 2 (GLP-2) response during high-fat meal test	GLP-2 response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360	Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12
Glucose-dependent insulinotropic polypeptide (GIP) response during high-fat meal test	GIP response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360	Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12
Ghrelin response during high-fat meal test	Ghrelin response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360	Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12
Peptide tyrosine tyrosine (PYY) response during high-fat meal test	PYY response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360	Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12
Adiponectin response during high-fat meal test	Adiponectin response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360)	Meal test: -15, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12
Non-esterified fatty acids (NEFA) response during high-fat meal test	NEFA response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360)	Meal test: -15, 0, 60, 90, 120, 240, 360 min. Performed at baseline and week 12
Interleukin-6 (IL-6) response during high-fat meal test	IL-6 response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)	Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12
Monocyte chemoattractant protein 1 (MCP-1) response during high-fat meal test	MCP-1 response measured as fasting value and incremental Area Under the Curve (iAUC from 0 - 240 min)	Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12
RANTES (CCL5) response during high-fat meal test	CCL5 response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)	Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12
High-sensitive c-reactive protein (hs-CRP) response during high-fat meal test	hs-CRP response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)	Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12
Procollagen type 1 N-terminal propeptide (P1NP) response during high-fat meal test	P1NP response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)	Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12
C-telopeptide (CTX) response during high-fat meal test	CTX response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)	Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12
Parathyroid hormone (PTH) response during high-fat meal test	PTH response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)	Meal test: 0, 15, 30, 90, 240 min. Performed at baseline and week 12
Osteoprotegrin response during high-fat meal test	Osteoprotegrin response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)	Meal test: 0, 15, 30, 90, 240 min. Performed at baseline and week 12
Osteocalcin response during high-fat meal test	Osteocalcin response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)	Meal test: 0, 15, 30, 90, 240 min. Performed at baseline and week 12
25-dihydroxy vitamin D	Fasting value measured at baseline and week 12	Change from week 0 to week 12
Phosphate	Fasting value measured at baseline and week 12	Change from week 0 to week 12
Magnesium	Fasting value measured at baseline and week 12	Change from week 0 to week 12
Total cholesterol	Fasting value measured at baseline and week 12	Change from week 0 to week 12
Low density lipoprotein (LDL)	Fasting value measured at baseline and week 12	Change from week 0 to week 12
High density lipoprotein (HDL)	Fasting value measured at baseline and week 12	Change from week 0 to week 12
Glucose response during oral glucose tolerance test (OGTT)	Glucose measured as incremental Area Under the Curve (iAUC from -15 - 120 min)	OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12
Insulin response during oral glucose tolerance test (OGTT)	Insulin measured as incremental Area Under the Curve (iAUC from -15 - 120 min)	OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12
Glucagon response during oral glucose tolerance test (OGTT)	Glucagon measured as incremental Area Under the Curve (iAUC from -15 - 120 min)	OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12
Glucagon-like peptide 1 (GLP-1) response during oral glucose tolerance test (OGTT)	GLP-1 measured as incremental Area Under the Curve (iAUC from -15 - 120 min)	OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12
Glucagon-like peptide 2 (GLP-2) response during oral glucose tolerance test (OGTT)	GLP-2 measured as incremental Area Under the Curve (iAUC from -15 - 120 min)	OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12
Glucose-dependent insulinotropic polypeptide (GIP) response during oral glucose tolerance test (OGTT)	GIP measured as incremental Area Under the Curve (iAUC from -15 - 120 min)	OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12
Parathyroid hormone (PTH) response during oral glucose tolerance test (OGTT)	PTH measured as incremental Area Under the Curve (iAUC from 0-90 min)	OGTT: 0, 30, 90 min. Performed at baseline and week 12
C-telopeptide (CTX) response during oral glucose tolerance test (OGTT)	CTX measured as incremental Area Under the Curve (iAUC from 0-90 min)	OGTT: 0, 30, 90 min. Performed at baseline and week 12
Procollagen type 1 N-terminal propeptide (P1NP) response during oral glucose tolerance test (OGTT)	P1NP measured as incremental Area Under the Curve (iAUC from 0-90 min)	OGTT: 0, 30, 90 min. Performed at baseline and week 12
Osteoprotegrin response during oral glucose tolerance test (OGTT)	Osteoprotegrin measured as incremental Area Under the Curve (iAUC from 0-90 min)	OGTT: 0, 30, 90 min. Performed at baseline and week 12
Osteocalcin response during oral glucose tolerance test (OGTT)	Osteocalcin measured as incremental Area Under the Curve (iAUC from 0-90 min)	OGTT: 0, 30, 90 min. Performed at baseline and week 12
Waist and hip circumference.	Waist and hip circumference in cm	Change from week 0 to week 12
Body weight	Body weight in kg	Change from week 0 to week 12
Body Mass Index	kg/m2	Change from week 0 to week 12
Adipose tissue gene expression	Subcutaneous fat tissue biopsy performed at baseline and week 12 for the measurement of changes in genes related to lipid and glucose metabolism and insulin signalling.	Change from week 0 to week 12
Adipose tissue proliferation and differentiation	Subcutaneous fat tissue biopsy performed at baseline and week 12 for measuring proliferation and differentiation processes of preadipocyte stem cells into mature adipocytes, and to test the effect of diets on expanding the capacity of the subcutaneous adipose tissue to store fat.	Change from week 0 to week 12
Urinary calcium	Urinary calcium excretion measured in 24-hour urine samples collected at baseline and week 12	Change from week 0 to week 12
Urinary nitrogen	Urinary nitrogen excretion measured in 24-hour urine samples collected at baseline and week 12	Change from week 0 to week 12
Metabolomics, plasma	Non-targeted metabolomics analysis using Liquid Chromatography - Mass Spectrometry	OGTT: -15, 30, 60, 90, 120 min. Performed at baseline and week 12.
Metabolomics, urine	Non-targeted metabolomics analysis using Liquid Chromatography - Mass Spectrometry	24-hour urine collection performed at baseline and week 12.
Metabolomics, faeces	Non-targeted metabolomics analysis using Liquid Chromatography - Mass Spectrometry	Collected at baseline and week 12.
Insulin sensitivity during oral glucose tolerance test (OGTT)	Homeostasis model assessment - insulin resistance (HOMA-IR) and Matsuda Index calculated based on blood glucose and insulin measurements during OGTT	OGTT performed at baseline and week 12 (blood sampling at -15, -10, 0, 30, 60, 90, 120 min)
Appetite assessment during high-fat meal test	Visual Analog Scale (VAS) electronic questionnaire	Meal test: Questionnaire at -10, 0, 30, 60, 90, 120, 180, 240, 300, 360 min. Performed at baseline and week 12.
Microbiota	Non-targeted microbiome and metabolome analyses using high-throughput DNA sequencing on Illumina Miseq and Liquid Chromatography - Mass Spectrometry (LC-MS) metabolomics,	Faecal samples collected at baseline and week 12.

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: Rigshospitalet, Denmark; University of Copenhagen; University of California, Davis; University of Aarhus
• Investigators: Principal Investigator: Søren Gregersen, MD, ph.d., Aarhus University Hospital; Study Chair: Knud Erik B. Knudsen, Professor, Department of Animal Science, University of Aarhus

Publications and helpful links

General Publications

• Fuglsang-Nielsen R, Rakvaag E, Vestergaard P, Hermansen K, Gregersen S, Starup-Linde J. The Effects of 12-Weeks Whey Protein Supplements on Markers of Bone Turnover in Adults With Abdominal Obesity - A Post Hoc Analysis. Front Endocrinol (Lausanne). 2022 Mar 29;13:832897. doi: 10.3389/fendo.2022.832897. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): June 29, 2017
• Study Completion (Actual): June 29, 2017

Study Registration Dates

• First Submitted: August 19, 2016
• First Submitted That Met QC Criteria: October 11, 2016
• First Posted (Estimate): October 13, 2016

Study Record Updates

• Last Update Posted (Actual): July 17, 2017
• Last Update Submitted That Met QC Criteria: July 13, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Metabolic syndrome; Body composition; Blood pressure; Insulin sensitivity; Whey protein; Dietary fibers; Postprandial lipaemia; Metabolic rate; Arabinoxylan; Wheat bran
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Overnutrition; Nutrition Disorders; Insulin Resistance; Hyperinsulinism; Obesity; Cardiovascular Diseases; Syndrome; Metabolic Syndrome; Obesity, Abdominal
• Other Study ID Numbers: MERITS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO