Effect of Fenugreek Seed Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion

A randomized, double-blind, placebo controlled clinical trial will be conducted in 28 patients with metabolic syndrome according to the criteria of the International Diabetes Federation. Patients will be assigned to two different arms: one group will receive fenugreek seed extract (1500 mg/day) or a matched placebo for 12 weeks.

At the beginning and end of the intervention, the following measurements will be taken: body weight, body mass index, waist circumference, body fat percentage, systolic blood pressure, diastolic blood pressure, glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein, insulin, creatinine, uric acid, alanine aminotransferase, and aspartate aminotransferase. In addition, insulin sensitivity and insulin secretion will be calculated. Written informed consent will be obtained from all volunteers.

• Fenugreek seed (Dietary supplement), also known as Trigonella foenum-graecum: Fenugreek seed: 1500 mg per day for 12 weeks
• Placebo (Other), also known as Calcined magnesia: Placebo: Calcined magnesia 1500 mg per day for 12 weeks

Primary outcomes

• Waist Circumference (WC) [Baseline to week 12 (end of intervention)]: Waist Circumference (WC) is evaluated at baseline and after 12 weeks with a flexible tape in the midpoint between the lowest rib and the iliac crest
• Systolic Blood Pressure (SBP) [Baseline to week 12 (end of intervention)]: Systolic Blood Pressure (SBP) is measured at baseline and after 12 weeks with a digital sphygmomanometer
• Diastolic Blood Pressure (DBP) [Baseline to week 12 (end of intervention)]: Diastolic Blood Pressure (DBP) is measured at baseline and after 12 weeks with a digital sphygmomanometer
• High Density Lipoprotein Cholesterol (HDL-c) [Baseline to week 12 (end of intervention)]: High Density Lipoprotein Cholestero (HDL-c) is evaluated at baseline and after 12 weeks with enzymatic/colorimetric techniques
• Triglycerides (TG) [Baseline to week 12 (end of intervention)]: Triglycerides (TG) are evaluated at baseline and after 12 weeks with enzymatic/colorimetric techniques
• Fasting Plasma Glucose (FPG) [Baseline to week 12 (end of intervention)]: Fasting Plasma Glucose (FPG) is evaluated at baseline and after 12 weeks with enzymatic/colorimetric techniques
• Insulin Sensitivity (IS) [Baseline to week 12 (end of intervention)]: Insulin Sensitivity (IS) will be calculated at baseline and week 12 with Matsuda index to get insulin sensitivity
• Total Insulin Secretion (TIS) [Baseline to week 12 (end of intervention)]: Total Insulin Secretion (TIS) will be calculated at baseline and week 12. It is the result of the ratio between the AUC of insulin in a 2-h OGTT and the AUC of glucose in a 2-h OGTT. It allows estimating the proportion of total insulin secretion in relation to plasma glucose concentration.
• First Phase of Insulin Secretion (FPIS) [Baseline to week 12 (end of intervention)]: The First Phase if Insulin Secretion (FPIS) will be calculated at baseline and week 12 with Stumvoll index to get first phase of insulin secretion

Secondary outcomes

• Body Weight (BW) [Baseline to week 12 (end of intervention)]: Body Weight (BW) is evaluated at baseline and after 12 weeks with an inbody 270
• Body Mass Index (BMI) [Baseline to week 12 (end of intervention)]: Body Mass Index (BMI) is calculated at baseline and after 12 weeks with the Quetelet index formula
• Body Fat Percentage (BF%) [Baseline to week 12 (end of intervention)]: Body Fat Percentage (BF%) will be measured at baseline and week 12 with a bioimpedance analysis
• Total Cholesterol (TC) [Baseline to week 12 (end of intervention)]: Total Cholesterol (TC) is evaluated at baseline and after 12 weeks with enzymatic/colorimetric techniques
• Low Density Lipoprotein Cholesterol (LDL-c) [Baseline to week 12 (end of intervention)]: Low Density Lipoprotein Cholesterol (LDL-c) level will be calculated at baseline and week 12 with Friedewald formula to get LDL-c level
• Very Low Density Lipoprotein (VLDL) [Baseline to week 12 (end of intervention)]: Very Low Density Lipoprotein (VLDL) is calculated at baseline and after 12 weeks as triglycerides/5
• Aspartate Aminotransferase (AST) [Baseline to week 12 (end of intervention)]: Aspartate Aminotransferase (AST) is evaluated at baseline and after 12 weeks with enzymatic/colorimetric techniques
• Alanine Aminotransferase (ALT) [Baseline to week 12 (end of intervention)]: Alanine Aminotransferase (ALT) is evaluated at baseline and after 12 weeks with enzymatic/colorimetric techniques
• Creatinine [Baseline to week 12 (end of intervention)]: Creatinine is evaluated at baseline and after 12 weeks with enzymatic/colorimetric techniques
• Uric Acid (UA) [Baseline to week 12 (end of intervention)]: Uric Acid (UA) is evaluated at baseline and after 12 weeks with enzymatic-colorimetric techniques
• Adverse Events (AE) [Baseline to week 12 (end of intervention)]: Adverse Events (AE) of fenugreek seed or placebo will be identified by clinical evaluation from baseline week to week 12 with continuous surveillance

Sex: All, ages: 30 Years to 60 Years

Inclusion Criteria:

* Men and women between 30 and 60 years old.
* Diagnosis of Metabolic Syndrome (MS) according to the International Diabetes Federation (IDF) criteria.

Waist circumference ≥90 cm in men and ≥80 cm in women, plus the presence of two or more of the following criteria:

* Fasting glucose ≥100 mg/dL or previous diagnosis of type 2 diabetes.
* Systolic Blood Pressure ≥130 mmHg.
* Diastolic Blood Pressure ≥85 mmHg.
* Triglycerides ≥150 mg/dL.
* HDL cholesterol <40 mg/dL in men and <50 mg/dL in women.

  * Body Mass Index between 25.0 and 34.9 kg/m².
  * Stable weight during the 3 months prior to the start of the study (weight variation less than 10%).
  * Not receiving pharmacological treatment for any component of MS, insulin sensitivity, and/or insulin secretion.
  * Signed informed consent form.

Non-Inclusion Criteria:

* Suspected or confirmed pregnancy.
* Breastfeeding period.
* Fasting glucose ≥126 mg/dL.
* LDL cholesterol ≥155 mg/dL.
* Triglycerides ≥500 mg/dL.
* Systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg.
* Use of medications and/or supplements known to influence the study variables.
* History of kidney, thyroid, liver disease, or ischemic heart disease.
* Active smoker.
* Not using an effective and stable contraceptive method.

Exclusion Criteria:

* Voluntary withdrawal of informed consent.
* Treatment adherence ≤80%.
* Occurrence of a serious adverse event.
* Loss to follow-up.

• Marisol Cortez Navarrete, PhD, Principal investigator, Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara