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

Study Overview
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Brief Summary
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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.

Detailed Description
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Please refer to summary

Official Title
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The Effect of Whey Protein and Dietary Fibers on Risk Markers of the Metabolic Syndrome and Bone Health

Conditions
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Abdominal Obesity, Metabolic Syndrome, Type 2 Diabetes, Cardiovascular Disease

Intervention / Treatment
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* Other: Whey protein powder
* Other: Maltodextrin powder
* Other: High fiber bread
* Other: Low fiber bread


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Whey protein, Dietary fibers, Wheat bran, Arabinoxylan, Postprandial lipaemia, Body composition, Blood pressure, Metabolic rate, Insulin sensitivity, Metabolic syndrome