Soy Protein Intake and the Metabolic Syndrome

Study Overview
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Brief Summary
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Soy protein has a high biological value, and contains several potential health-related nutritional factors, i.e. its amino acids pattern, biological active peptides and non-protein compounds such as isoflavones. In the field of obesity and blood lipids soy protein is well-studied and appreciated; it improves circulating blood lipids and is associated with weight reduction. The effect of soy on insulin resistance, glucose homeostasis and the metabolic syndrome is less frequently studied. However, several molecular mechanisms of action of soy protein make it a promising approach.

Detailed Description
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Objective: The primary objective of the present study is to evaluate the effect of a high soy protein diet on insulin resistance and glycemic control in participants with characteristics of the metabolic syndrome. Secondly, the present study will evaluate whether reduced low-grade inflammation is a possible mechanism underlying the improvement in insulin resistance and glucose homeostasis. Finally, it will be assessed whether soy protein has beneficial effects on components of the metabolic syndrome, such as cardio-metabolic risk factors, blood lipid profile, blood pressure and endothelial function, fat storage in the liver and gene-expression in subcutaneous abdominal adipose tissue. Study design: Single-blind, cross-over strictly-controlled dietary intervention.

Official Title
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Soy Protein Intake and the Metabolic Syndrome: Reducing Inflammation to Improve Insulin Resistance and Glucose Homeostasis

Conditions
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Metabolic Syndrome X

Intervention / Treatment
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* Other: Soy protein diet
* Other: Control diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women 45-70 years No menstrual cycle for ≥1 year Stable body weight for ≥6 months (no weight gain/loss > 3 kg) Stable exercise habits during the last 6 months, and not participating in any vigorous exercise program Central obesity: waist circumference ≥80 cm Plus any one of the following four factors: Raised triglyceride level: ≥1.7 mmol/L; Reduced high-density lipoprotein (HDL) cholesterol: <1.29 mmol/L Raised blood pressure: systolic blood pressure ≥135 mmHg or diastolic BP ≥85 mmHg or use of blood pressure lowering medication Raised fasting plasma glucose ≥ 5.6 mmol/L Exclusion Criteria: (Undiagnosed) Diabetes - but not impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) as evaluated by an oral glucose tolerance test at screening Active hearth disease, i.e. history of myocardial infarction, stroke or angina pectoris Active or a history of thyroid disease Cancer or other malignancies in the past 5 years Two sided ovariectomy Drug use knowing to interfere with objectives of the study oral corticosteroids, lipid-lowering drugs (statins) anti-conceptive use (such as the pill or IUD) hormone replacement therapy long-term antibiotics use Habitual intake of soy foods (>1 soy food per week) Isoflavone supplements Vegetarian Following, or have recently followed a (weight-loss) diet Allergic to soy or dairy products Smoking Consuming more than 14 glasses of alcohol per week Donated or intended to donate blood 2 months before till two months after the study Participation in another biomedical study within 1 month before the first screening visit Not willing to be informed if deviations are found in blood samples Contraindications to MRI scanning

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Soy protein diet<br>High mixed protein diet (20 en%) with 25gr of soy protein per day | Other: Soy protein diet<br>* 4 weeks high protein diet (20 en%) with 25gr of soy protein per day<br>|
| Active Comparator: Control diet<br>High mixed protein diet (20 en%) | Other: Control diet<br>* 4 weeks high mixed protein diet (20 en%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Insulin sensitivity is measured with an intravenous glucose tolerance test (IVGTT). | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adipose tissue gene expression | Adipose tissue samples will be collected for subsequent gene expression analysis. | 4 weeks | 
| Blood lipids | Circulating triglycerides, free fatty acids (FFA), and HDL and total cholesterol will be measured in fasted blood samples, LDL will be calculated. | 4 weeks | 
| Inflammation markers and adipokines | For low-grade inflammation interleukins, tumor necrosis factor-α, C-reactive protein and adipokines will be measured in fasting blood samples. Furthermore, peripheral blood mononuclear cells (PBMC's) will be collected to measure expression of genes involved in lipid handling and inflammation. | 4 weeks | 
| Cardio-metabolic risk factors | Blood pressure and macro vascular regional arterial stiffness will be assessed by Pulse Wave Analysis (PWA). Besides PWA, we will also measure markers for endothelial function in fasting blood samples. | 4 weeks | 
| Hepatic lipid content | Hepatic lipid content The lipid content in liver will be quantified by proton magnetic resonance spectroscopy (1H -MRS) | 4 weeks |