Metabolic Impact on the Mitochondria-gut Microbiota Axis of Failure to Follow Restrictive Dietary Interventions in Subjects Living With Obesity

NCT06782009 | Completed DMC

• 1 other identifier: 4952
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 2

Brief Summary

Nutritional interventions with dietary restrictions have become highly popular for promoting weight and body fat loss; In addition, they are largely associated with the improvement and preservation of mitochondrial function as well as the changes they generate in the composition of the gut microbiota and microbial metabolites. During obesity, mitochondrial dysfunction in monocytes can increase low-grade inflammation and contribute to alterations in various metabolic tissues. There have been many studies that have been dedicated to describing the benefits and mechanisms of the use of restrictive interventions, but few have focused on further monitoring and evaluating the metabolic changes that occur due to the lack of follow-up of the use of these interventions, where subjects resume eating patterns with energy overload. behavior that happens in the vast majority of patients, so keeping mitochondria in good condition is a key aspect of maintaining health. The present project aims to study the metabolic changes that are generated by the lack of follow-up of restrictive dietary interventions, focusing on the effects produced in mitochondrial function evaluated in monocytes isolated from peripheral blood and the impact that the composition of the intestinal microbiota is generated from the metabolites produced, affecting as a consequence the inflammatory state of the host. A randomized controlled clinical trial will be carried out where the selected participants will be assigned by lottery to one of the 3 nutritional interventions for 8 weeks, then the participants will be followed up at 8, 16 and 24 weeks after the intervention has ended. Anthropometric and biochemical parameters, resting energy expenditure, blood pressure, oxidative stress markers, metabolomics, gut microbiota composition, and mitochondrial function will be evaluated during follow-up.

Conditions

Obesity

Keywords

dietary restrictions; intermittent fasting; mitochondrial function; gut microbiota; ketogenic diet

Outcome Measures

Primary Outcomes (1)

• Mitochondrial function

  Change in mitochondrial function determined by measuring the oxygen consumption rate (OCR) in isolated monocytes

  baseline to 8, 16, 24 and 32 weeks

Secondary Outcomes (20)

• Gut microbiota composition

  baseline to 8, 16 and 32 weeks

• Body weight measurement

  baseline to 8, 16, 24 and 32 weeks

• Glucose concentration

  baseline to 8, 16, 24 and 32 weeks

• Cholesterol concentration

  baseline to 8, 16, 24 and 32 weeks

• HDL cholesterol concentration

  baseline to 8, 16, 24 and 32 weeks

Study Arms (3)

Calorie Restriction

EXPERIMENTAL

Participants will be provided with a food menu guide for fifteen days with a 30% energy restriction (kcal) according to their usual diet, with a macronutrient distribution of 20-30% protein, 50-60% carbohydrates and 20-30% fat.

Other: Calorie restriction

Intermittent fasting 16/8

EXPERIMENTAL

Participants will be provided with a food menu guide for fifteen days with an energy intake according to the energy expenditure determined by indirect calorimetry with normal distribution of macronutrients. Intermittent fasting will be used with a time-restricted model of 16:8. For 16 hours, they will not be able to eat or drink calories. In the other 8 hours, they need to adhere to the energy-restricted diet.

Other: Intermittent fasting 16/8

Ketogenic diet

EXPERIMENTAL

Participants will be provided with a food menu guide for 15 days with an energy intake according to the energy expenditure determined by indirect calorimetry, with the following distribution of macronutrients: 20-25% protein, 5-10% carbohydrates, 70-80% fat.

Other: Ketogenic diet

Interventions

Calorie restriction OTHER

Participants will be provided with a food menu guide for fifteen days with a 30% energy restriction (kcal) according to their usual diet, with a macronutrient distribution of 20-30% protein, 50-60% carbohydrates and 20-30% fat.

Calorie Restriction

Intermittent fasting 16/8 OTHER

Participants will be provided with a food menu guide for fifteen days with an energy intake according to the energy expenditure determined by indirect calorimetry with normal distribution of macronutrients. Intermittent fasting will be used with a time-restricted model of 16:8. For 16 hours, they will not be able to eat or drink calories. In the other 8 hours, they need to adhere to the energy-restricted diet.

Intermittent fasting 16/8

Ketogenic diet OTHER

Participants will be provided with a food menu guide for 15 days with an energy intake according to the energy expenditure determined by indirect calorimetry, with the following distribution of macronutrients: 20-25% protein, 5-10% carbohydrates, 70-80% fat.

Ketogenic diet

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female.
• Adults \>18 years of age.
• BMI ≥ 30 kg/m2

You may not qualify if:

• Patients with any type of diabetes.
• Patients with high blood pressure.
• Patients with acquired diseases secondarily producing obesity and diabetes.
• Patients who have suffered a cardiovascular event.
• Patients who at the screening visit presented glucose values greater than 126 mg/dL, triglycerides greater than 350 mg/dL, cholesterol greater than 300mg/dL and/or creatinine greater than 1.2 mg/dL in men and greater than 1 mg/dL in women.
• Patients with gastrointestinal diseases.
• Weight loss \> 3 kg in the last 3 months.
• Catabolic diseases such as cancer and acquired immunodeficiency syndrome.
• Pregnancy status.
• Positive smoking.
• History of major surgery requiring general or regional anesthesia, respiratory support, and involving a recovery time longer than 2 weeks, such as surgeries of the abdomen (bowel resection), chest, head, and neck.
• Diagnosis of Anxiety and Depression as Determined by the HADS Scale
• Drug treatment:
• Antihypertensive drugs or treatment
• Treatment with hypoglycemic agents or insulin and antidiabetic drugs.

Sponsors & Collaborators

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead

Study Sites (2)

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, Tlalpan, 14080, Mexico

Location

Departamento de Fisiología de la Nutrición. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, 14080, Mexico

Location

Related Publications (2)

• Guevara-Cruz M, Hernandez-Gomez KG, Condado-Huerta C, Gonzalez-Salazar LE, Pena-Flores AK, Pichardo-Ontiveros E, Serralde-Zuniga AE, Sanchez-Tapia M, Maya O, Medina-Vera I, Noriega LG, Lopez-Barradas A, Rodriguez-Lima O, Mata I, Olin-Sandoval V, Torres N, Tovar AR, Velazquez-Villegas LA. Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial. Clin Nutr. 2024 Aug;43(8):1914-1928. doi: 10.1016/j.clnu.2024.06.036. Epub 2024 Jul 5.

  PMID: 39003957 BACKGROUND

• Guevara-Cruz M, Hernandez-Gomez KG, Condado-Huerta C, Gonzalez-Salazar LE, Pena-Flores AK, Pichardo-Ontiveros E, Serralde-Zuniga AE, Sanchez-Tapia M, Maya O, Medina-Vera I, Noriega LG, Lopez-Barradas A, Rodriguez-Lima O, Mata I, Olin-Sandoval V, Torres N, Tovar AR, Velazquez-Villegas LA. Reply - Letter to the editor- enhancing understanding of dietary interventions in obesity: Insights and recommendations for future research. Clin Nutr. 2024 Sep;43(9):2211-2213. doi: 10.1016/j.clnu.2024.08.006. Epub 2024 Aug 13. No abstract available.

  PMID: 39173436 BACKGROUND

MeSH Terms

Conditions

Obesity; Intermittent Fasting

Interventions

Caloric Restriction; Diet, Ketogenic

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fasting; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Diet, Carbohydrate-Restricted

Study Officials

• Laura A Velazquez Villegas, PhD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Double single
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigadora en Ciencias Medicas

Model Details: The groups will receive the treatment simultaneously

Study Record Dates

• First Submitted: January 8, 2025
• First Posted: January 17, 2025
• Study Start: April 8, 2023
• Primary Completion: December 8, 2025
• Study Completion: December 8, 2025
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (2)