Dairy Lipids, Proteins, and the Metabolic Syndrome - DairyHealth

Study Overview
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Brief Summary
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Dairy food contains a large amount of long-chain saturated fat, which traditionally has been linked to increased risk of cardiovascular disease (CVD). However, recent data indicates a more neutral role. Milk fat contains large amounts of medium-chain saturated fatty acids (MC-SFA), which may have beneficial effects on human health. In addition, milk proteins and in particular whey proteins have been shown to have a beneficial effect on glucose disposal as well as anti-inflammatory properties. Therefore dairy products have a potential role in the treatment of the metabolic abnormalities of metabolic syndrome (MeS). However, human data from intervention studies are lacking. Aims of this project is to explore and understand the influence on human health of both medium-chain saturated fatty acids from milk fat and bioactive milk proteins per se as well as their interaction and potential positive synergy on the MeS. The investigators hypothesize that whey protein and medium-chain saturated fatty acids improve insulin sensitivity, postprandial lipid metabolism, blood pressure and inflammatory stress in humans and that they possess preventive effects on the risk of developing CVD and type 2 diabetes mellitus (T2DM). A total of 64 people with MeS or abdominal obesity will be included. The design is a randomized double-blinded, controlled parallel diet-intervention trial. Subjects are assigned one of four experimental diets for 12 weeks. The diets consist of either a diet with low levels of MC-SFA + whey protein (LF + whey), a diet high in MC-SFA + whey protein (HF + whey), a diet high in MC-SFA + casein protein (HF + casein) or a diets with low levels of MC-SFA + casein protein (LF + casein). The subjects are advised how to integrate the test foods in their habitual diet, which also continues unchanged. The subjects' energy intake is matched so they are kept weight stable throughout the study.

Detailed Description
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See above.

Official Title
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Dairy Lipids, Proteins, and the Metabolic Syndrome - DairyHealth

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

Intervention / Treatment
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* Dietary Supplement: High content of MC-SFA
* Dietary Supplement: Whey
* Dietary Supplement: Low content of MC-SFA
* Dietary Supplement: Casein


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metabolic syndrome Central obesity (Waist: female ≥ 80 cm; male ≥ 94 cm) with two or more of the following Fasting triglyceride > 1.7 mmol/l HDL-cholesterol; male < 1.03 mmol/l, female < 1.29 mmol/l BP ≥ 130/85 Fasting plasma glucose ≥ 5,6 mmol/l (but not diabetes) Or abdominal obesity (Waist: female ≥ 80 cm; male ≥ 94 cm) Exclusion Criteria: Significant cardiovascular, renal or endocrine disease Psychiatric history Treatment with steroids Alcohol- or drug-addiction Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fat rich in MC-SFA<br>63 gram milk fat with high content of MC-SFA (C6-C12=8.5 g) incorporated in rolls, muffin and as butter. | Dietary Supplement: High content of MC-SFA<br>* 12 weeks dietary intervention<br>|
| Experimental: Fat low on MC-SFA<br>63 gram milkfat with low content of MC-SFA (C6-C12=6.9 g) incorporated in rolls, muffin and as butter | Dietary Supplement: Low content of MC-SFA<br>* 12 weeks dietary intervention<br>|
| Experimental: Casein protein<br>60 gram casein protein (Miprodan 30) ingested twice daily with 600 ml water. | Dietary Supplement: Casein<br>* 12 weeks dietary intervention<br>|
| Experimental: Whey protein<br>60 gram whey protein (Lacprodan DI-9224) ingested twice daily with 600 ml water. | Dietary Supplement: Whey<br>* 12 weeks dietary intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial triglyceride response | Compare the changes in mean difference of 6 hours incremental area under the curve (iAUC) (week 12 - week 0) between the groups and the intervention components. | Change from week 0 to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 hour blood pressure (BP) | Spacelabs, model 90207/90217, USA | Change from week 0 to week 12 | 
| Indirect calorimetry | Measured 2 times during meal test. | Change from week 0 to week 12 | 
| Dexa-scan (body composition) | Total body fat percentage, lean mass, gynoid, and android fat percentage, and total body weight. | Change from week 0 to week 12 | 
| Weight |  | Change from week 0 to week 12 | 
| Biomarkers in blood samples | Glucose, insulin, glucagon, HbA1c. free fatty acids, Lipid profile (total-cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride). Inflammations markers (interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1RA), interleukin-1 beta (IL-1b), high sensitive c-reactive protein (hs-CRP), adiponectin, monocyte chemoattractant protein-1 (MCP-1), Rantes (CCL5)). Incretins (GLP-1, GIP). Nutrigenomics. Metabolomics. Proteomics. | Change from week 0 to week 12 | 
| Waist and hip circumference |  | Change from week 0 to week 12 | 
| Fat tissue biopsy | Fat tissue gene expression. Twice during meal test. | Change from week 0 to week 12 | 
| Biomarkers in urine | Nutrigenomics and metabolomics | Change from week 0 to week 12 | 
| Glucose tolerance | Oral glucose tolerance test (OGTT) (with insulin and glucose measurement at time -15 min, -10 min, 0 min, 30 min, 60 min, and 120 min). Hereby calculating the homeostatic model assessment of insulin resistance (HOMA-IR) and the Matsuda index. | Change from week 0 to week 12 | 
| Dietary compliance | 3-day food diary. | Change from week 0 to week 12 | 
| Postprandial apolipoprotein-48 (apoB-48), 6 hour | Meal test, blood samples at time 0,2,4 and 6 hours. | Change from week 0 to week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Medium chain fatty acids, Saturated fatty acids, Whey protein, Casein protein, Metabolic syndrome, Type 2 diabetes, Cardiovascular disease, Dairy products, Dietary intervention