Effect of Dietary Restrictions and Ketogenic Diet on Mitochondrial Function and Gut Microbiota in Subjects With Obesity
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional

Summary: 
      The benefits of nutritional interventions with dietary restrictions are associated with
      improvement and preservation of mitochondrial function. Evidence suggests that dietary
      restrictions, including modifications in caloric intake (caloric restriction), or in the
      timing of food intake (e.g., intermittent fasting), play an important role in stimulating
      cell and mitochondrial autophagy, favoring the elimination of old and dysfunctional
      mitochondria. In addition to the observed effects on mitochondrial function, there is
      evidence that intermittent fasting, caloric restriction, and the ketogenic diet also generate
      changes in gut microbiota and microbial metabolite composition. The main aim of this study is
      to evaluate the effect of intermittent fasting, caloric restriction and ketogenic diet on
      mitochondrial function determined by respirometry in monocytes, modulated by the gut
      microbiota in subjects with obesity. An open randomized controlled clinical trial will be
      conducted with 80 participants divided by a draw in 4 nutritional interventions groups for 1
      month, each for 20 participants, then participants will receive 550 mg of rifaximin and will
      finish the study with the assigned nutritional intervention for another month of follow-up.
      Knowledge of these dynamics will allow us to explore and understand the relationship between
      metabolites from the gut microbiota and their effect on mitochondrial function associated
      with the dietary interventions mentioned above.
    

Detailed description: 
      The study consists of an open-label randomized controlled clinical trial. Selected subjects
      will be randomized to one of 4 dietary intervention groups for 1 month with energy intake
      according to the resting energy expenditure obtained by indirect calorimetry.

      The intervention groups will be as follows; a) ketogenic diet, b) caloric restriction diet,
      c) intermittent fasting diet and, d) usual diet.

        1. Ketogenic diet: A dietary recommendation will be given which will be isocaloric
           according to the resting energy expenditure obtained by indirect calorimetry, containing
           the following macronutrient distribution: 25% protein, 10% carbohydrates, 65% fat.

        2. Caloric restriction diet: A dietary recommendation will be given according to their
           usual diet, 500 kcal will be restricted, containing the following macronutrient
           distribution: 25-35% protein, 45-55% carbohydrates, 20-30% fat.

        3. Intermittent fasting 16/8: Participants will have the same diet as the participants from
           the caloric restriction diet group, with the difference that intermittent fasting will
           be employed, with a time-restricted pattern of 16:8. During 16 hours; for example, from
           04.00 pm to 08.00 am or from 05.00 pm to 09.00 am (fasting hours) participants will be
           fasted and no calories can be eaten or drunk. But participants in the fasting hours can
           drink water, unsweetened tea, unsweetened coffee and mineral water. In the other 8
           hours, participants need to adhere to the energy restriction diet.

        4. Usual diet: Participants will not be recommended any diet, participants will be referred
           to follow their usual diet until the end of the study.

      After one month of the assigned intervention, the antibiotic rifaximin will be prescribed to
      the participants in doses of 550mg, twice a day for 7 days. After the 7 days with the
      antibiotic, participants will complete another month with the dietary intervention according
      to the group that the participants were initially randomized.

      Participants will be required to complete food logs (2 on weekdays and 1 for weekends) during
      each week in order to monitor adherence to the dietary plan. For this, a nutritionist will
      teach them how to complete the food log, where participants must record the type, quantity
      and place where the food was consumed at each feeding time. Also, 2 phone calls will be made
      each week to evaluate adherence to treatment. The adherence will be determined with the % of
      adherence to the dietary treatment as obtained in the analysis of the food logs. Similarly,
      urine ketone concentration will be determined to measure adherence to the ketogenic diet. A
      logbook will be provided by the investigator to the participants to record the consumption of
      the medication, which should be filled out daily by the participant.
    

Intervention name(s): Ketogenic diet; Caloric restriction diet; Intermittent fasting 16/8
Intervention type(s): Other; Other; Other
Intervention description(s): Weekly menus will be delivered according to diet with the following macronutrient distribution: 25% protein, 10% carbohydrate, 65% fat. Participants will receive a 30-day food menu guide.; Weekly menus will be provided according to their usual diet with 500 kcal restriction with the following macronutrient distribution 25-35% protein, 45-55% carbohydrates, 20-30% fat. Participants will receive a 30-day food menu guide.; Calorie-restricted menus will be provided with a 16:8 time-restricted feeding. The feeding window will be 8 hours with a fasting time of 16 hours (04.00 pm- 08.00 am or 05.00 pm - 09.00 am), during the fasting window participants will only be allowed to drink water, unsweetened tea, mineral water and coffee without added sugar. Participants will receive a 30-day food menu guide.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The groups will receive the treatment simultaneously
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: dietary restrictions; ketogenic diet; mitochondrial function; gut microbiota