Genistein Stimulates Insulin Sensitivity Through Gut Microbiota

NCT04105023 | Completed DMC

• 1 other identifier: 1099
• Study Type: interventional
• Target: 45
• Locations: 0 countries
• Sites: N/A

Brief Summary

There is evidence that genistein present in soy can improve insulin resistance in rodents and humans with metabolic syndrome (MetS). However, it is not known if this improvement is associated with changes in the gut microbiota. In the present study, the investigators show that the consumption of genistein for 2 months could have an effect on insulin resistance in subjects with MetS. This effect will be accompanied by a modification of the gut microbiota taxonomy. As a consequence, there will be a reduction in metabolic endotoxemia accompanied by an increase in AMP-activated protein kinase (AMPK) phosphorylation and the expression of genes of fatty acid oxidation in skeletal muscle.

Conditions

Metabolic Syndrome; Obesity

Keywords

genistein; gut microbiota; AMPK; fatty acid oxidation

Outcome Measures

Primary Outcomes (1)

• intestinal microbiota

  Measurement of gut microbiota by sequencing using the Illumina platform

  Baseline to 2 month

Secondary Outcomes (9)

• glucose metabolism profile

  Baseline to 2 month

• Glucose metabolism profile

  Baseline to 2 month

• Triglycerides

  Baseline to 2 month

• Total Cholesterol

  Baseline to 2 month

• LDL cholesterol

  Baseline to 2 month

Study Arms (2)

genistein

EXPERIMENTAL

Genistein capsules of 25 mg each, 50mg/day

Dietary Supplement: genistein

placebo

PLACEBO COMPARATOR

Maltodextrin capsules, administered orally once every 12 hours

Dietary Supplement: Placebo

Interventions

genistein DIETARY_SUPPLEMENT

Administered orally once every 12 hours

genistein

Placebo DIETARY_SUPPLEMENT

Administered orally once every 12 hours

placebo

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults (men and women) between the ages of 18 and 50.
• Patients with obesity (BMI ≥ 30 and ≤ 40 kg / m2) and with insulin resistance (HOMA - IR Index ≥ 2.5).
• Mexican mestizos (parents and grandparents born in Mexico).
• Patients who can read and write.

You may not qualify if:

• Patients with any type of diabetes.
• Patients with kidney disease diagnosed by a medical or with creatinine\> 1.3 mg / dL for men and \> 1.1 mg / dL for women and / or BUN\> 20 mg / dL.
• Patients with acquired diseases that produce obesity and diabetes secondarily.
• Patients who have suffered a cardiovascular event.
• Patients with weight loss \> 3 kg in the last 3 months.
• Patients with any catabolic diseases.
• Gravidity status
• Positive smoking
• Treatment with any medication

Sponsors & Collaborators

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead
• National Council of Science and Technology, Mexico: collaborator

Related Publications (4)

• Guevara-Cruz M, Flores-Lopez AG, Aguilar-Lopez M, Sanchez-Tapia M, Medina-Vera I, Diaz D, Tovar AR, Torres N. Improvement of Lipoprotein Profile and Metabolic Endotoxemia by a Lifestyle Intervention That Modifies the Gut Microbiota in Subjects With Metabolic Syndrome. J Am Heart Assoc. 2019 Sep 3;8(17):e012401. doi: 10.1161/JAHA.119.012401. Epub 2019 Aug 27.

  PMID: 31451009 BACKGROUND

• Palacios-Gonzalez B, Vargas-Castillo A, Velazquez-Villegas LA, Vasquez-Reyes S, Lopez P, Noriega LG, Aleman G, Tovar-Palacio C, Torre-Villalvazo I, Yang LJ, Zarain-Herzberg A, Torres N, Tovar AR. Genistein increases the thermogenic program of subcutaneous WAT and increases energy expenditure in mice. J Nutr Biochem. 2019 Jun;68:59-68. doi: 10.1016/j.jnutbio.2019.03.012. Epub 2019 Mar 29.

  PMID: 31030168 BACKGROUND

• Lopez P, Sanchez M, Perez-Cruz C, Velazquez-Villegas LA, Syeda T, Aguilar-Lopez M, Rocha-Viggiano AK, Del Carmen Silva-Lucero M, Torre-Villalvazo I, Noriega LG, Torres N, Tovar AR. Long-Term Genistein Consumption Modifies Gut Microbiota, Improving Glucose Metabolism, Metabolic Endotoxemia, and Cognitive Function in Mice Fed a High-Fat Diet. Mol Nutr Food Res. 2018 Aug;62(16):e1800313. doi: 10.1002/mnfr.201800313. Epub 2018 Jul 29.

  PMID: 29979819 BACKGROUND

• Medina-Vera I, Sanchez-Tapia M, Noriega-Lopez L, Granados-Portillo O, Guevara-Cruz M, Flores-Lopez A, Avila-Nava A, Fernandez ML, Tovar AR, Torres N. A dietary intervention with functional foods reduces metabolic endotoxaemia and attenuates biochemical abnormalities by modifying faecal microbiota in people with type 2 diabetes. Diabetes Metab. 2019 Apr;45(2):122-131. doi: 10.1016/j.diabet.2018.09.004. Epub 2018 Sep 25.

  PMID: 30266575 BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome; Obesity

Interventions

Genistein

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Isoflavones; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The interventions with genistein and placebo were identically encapsulated in appearance, both the researcher and the participant did not know what type of maneuver was assigned. The bottle with the capsules was distributed by a person outside the study who was the same one who performed the randomization. Study staff and participants were blinded during the assignment and execution of the interventions in the study. the capsules delivered to the participants were 2 per day, the capsules had the same color and appearance
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lab Director and Senior Scientist of the department of nutrition physiology

Model Details: These individuals were advised to consume the recommended diet for subjects with MetS according to the guidelines of the ATPIII. Patients were randomly distributed to consume a) placebo treatment or b) genistein capsules (50 mg/day). The participants were followed for 2 months

Study Record Dates

• First Submitted: September 20, 2019
• First Posted: September 26, 2019
• Study Start: September 15, 2013
• Primary Completion: December 15, 2017
• Study Completion: December 1, 2018
• Last Updated: September 26, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share