Microbiota in Dietary Approach to Obesity

Ketone Bodies and Gut Microbiota Role in the Dietetic Approach of Obesity

Main aim: Study the anthropometric, metabolic, cardiovascular and neurocognitive and gut microbiota changes of different approaches for the weight reduction that increase the ketone bodies in a different proportion in relation to the classic hypocaloric diet.

Objective 1: Study the effect of hypocaloric diets that increase the ketone bodies on gut microbiota and its relationship with anthropometric changes and of the Brown adipose tissue, Objective 2: with the metabolic and inflammatory changes, Objective 3: on the cardiovascular system, Objective 4: on the neurocognition, Objective 5: if they are associated to epigenetic changes that may explain the changes found in the other objectives. Objective 6: Determine the safety of the diets that increase the ketone bodies compared to the classic hypocaloric diet, Objective 7: if the effects of the different dietary approaches are maintained during the medium time, and Objective 8: Verify in experimental models (microbiota transplants from humans with different diets to germ-free mice, ketosis dietary models, and ketone bodies administration) the causality of the gut microbiota of these findings.

Methodology: Model 1: Dietary intervention in humans with 4 types of diet with a different increase of the ketone bodies: classic hypocaloric diet (DH); diet with 8h of feeding and 16h of starving in periods of 24h (D16); diet with intermittent caloric restriction (DA); and normal in protein and low in carbohydrates hypocaloric ketogenic diet (DC).

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Standard hypocaloric die; Other: Intermittent fasting 16/8 (early fasting); Other: Intermittent fasting 16/8 (late fasting); Other: Alternate-day fasting; Other: Ketogenic diet

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Malaga, Spain, 29010
    • Virgen de la Victoria Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Obesity (BMI≥30-45 kg/m2)

Exclusion Criteria:

• Type 2 diabetes mellitus
• Patients with major cardiovascular events in the 6 months prior to the study beginning.
• Previous or current history of inflammatory disease.
• Active infectious disease.
• The refusal of the patient to participate in the study
• Consumption of probiotics or prebiotics
• Antibiotic therapy in the 3 months prior to the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard hypocaloric diet; Mediterranean diet based on olive oil as main fat and regular consumption of vegetables (2 daily rations), fruits 3 daily rations), legumes (3 weekly rations), fish (3 weekly rations), with low consumption of red meat and meat products (less than twice a week), dairy foods (less than once a week) and no sweets, pastries or sugary drinks. Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein distributed in at least 4 meals (breakfast, lunch, afternoon snack and dinner).	Other: Standard hypocaloric die; Standard hypocaloric diet
Experimental: Intermittent fasting 16/8 (early fasting); Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 12 am. to 8 pm.), maintaining 16 fasting hours (from 8 pm. to 12 am. the following day).	Other: Intermittent fasting 16/8 (early fasting); Intermittent fasting 16/8 (early fasting)
Experimental: Intermittent fasting 16/8 (late fasting); Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 8 am. to 4 pm.), maintaining 16 fasting hours (from 4 pm. to 8 am. the following day).	Other: Intermittent fasting 16/8 (late fasting); Intermittent fasting 16/8 (late fasting)
Experimental: Alternate-day fasting; In this diet subjects alternate norm caloric diet during 24 h (according to Harris-Benedict equation) and a diet including only 25% of caloric requirements the following 24 h (this day diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein).	Other: Alternate-day fasting; Alternate-day fasting
Experimental: Ketogenic diet; Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein.	Other: Ketogenic diet; Ketogenic diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gut microbiota composition	To evaluate changes in gut microbiota composition from baseline using different strategies for weight loss which increase ketone bodies in comparison to a standard hypocaloric diet. Change from baseline in 16S rRNA amplicons of fecal community DNA at 3 months and 6 months	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in weight	To analyze the effect of hypocaloric diets which increase ketone bodies on anthropometric parameters in comparison to a standard hypocaloric diet	Baseline, 12 weeks
Changes in body mass index.	To analyze the effect of hypocaloric diets which increase ketone bodies on body mass index in comparison to a standard hypocaloric diet	Baseline, 12 weeks
Changes in waist circumference.	To analyze the effect of hypocaloric diets which increase ketone bodies on the waist circumference in comparison to a standard hypocaloric diet	Baseline, 12 weeks
Changes in body composition.	To analyze the effect of hypocaloric diets which increase ketone bodies on anthropometric parameters in comparison to a standard hypocaloric diet measured by bioelectrical impedance analysis	Baseline, 12 weeks
Changes in brown adipose tissue.	To analyze the effect of hypocaloric diets which increase ketone bodies on brown adipose tissue in comparison to a standard hypocaloric diet, measured by Positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET).	Baseline, 12 weeks
Changes in uncoupling protein 1 (UCP1)	To analyze the effect of hypocaloric diets which increase ketone bodies on brown adipose tissue UCP1 in comparison to a standard hypocaloric diet using a sample of subcutaneous white adipose tissue assessed by mRNA qPCR.	Baseline, 12 weeks
Changes in physical activity.	To analyze the effect of hypocaloric diets which increase ketone bodies on physical activity in comparison to a standard hypocaloric diet measured by accelerometry	Baseline, 12 weeks
Changes in blood pressure	To analyze the effect of hypocaloric diets which increase ketone bodies over the cardiovascular system in comparison to a standard hypocaloric diet based on blood pressure	Baseline, 12 weeks
Changes in the punctuation in neurocognitive test	To analyze the effect of hypocaloric diets which increase ketone bodies on neurocognition, in comparison to a standard hypocaloric diet, measured by neurocognitive test	Baseline, 12 weeks
Changes in heart rate	To analyze the effect of hypocaloric diets which increase ketone bodies on heart function measured by heart rate in comparison to a standard hypocaloric diet, measured by Holter.	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Investigators: Principal Investigator: Francisco J. Tinahones, PhD, Instituto de Investigación Biomédica de Málaga

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2020
• Primary Completion (Actual): June 9, 2022
• Study Completion (Actual): June 22, 2022

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: June 26, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: July 5, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Microbiota; Ketosis
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: ISCIII CP18/01160

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No