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.

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.

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