Effect of Dietary Restrictions and Ketogenic Diet on Mitochondrial Function and Gut Microbiota in Subjects With Obesity

NCT ID: NCT05200468

Last Updated: 2023-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-28

Study Completion Date

2023-03-27

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Obesity

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

dietary restrictions ketogenic diet mitochondrial function gut microbiota

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The groups will receive the treatment simultaneously
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The person who will perform the biochemical determinations, the gut microbiota sequencing and the statistical analysis will be blinded from the intervention group by assigning each patient

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Ketogenic diet

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.

Group Type EXPERIMENTAL

Ketogenic diet

Intervention Type OTHER

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.

Caloric restriction diet

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.

Group Type EXPERIMENTAL

Caloric restriction diet

Intervention Type OTHER

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.

Intermittent fasting 16/8

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.

Group Type EXPERIMENTAL

Intermittent fasting 16/8

Intervention Type OTHER

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.

habitual diet

Participants will be advised to follow their usual diet until the end of the study.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Ketogenic diet

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.

Intervention Type OTHER

Caloric restriction diet

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.

Intervention Type OTHER

Intermittent fasting 16/8

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.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Male and female.
* Adults between 18 and 60 years of age.
* BMI ≥ 30 and ≤ 50 kg/m2.

Exclusion Criteria

* 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 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.
* Drug treatment:

* Antihypertensive drugs or treatment
* Treatment with hypoglycemic agents or insulin and antidiabetic drugs.
* Treatment with statins, fibrates or other drugs to control dyslipidemia.
* Use of antibiotics in the three months prior to the study.
* Use of steroid drugs, chemotherapy, immunosuppressants, or radiation therapy.
* Anorexigenic or that accelerate weight loss such as sibutramine or orlistat.
* Supplements with any of the functional foods used in the study.
* Probiotic, prebiotic or symbiotic supplements.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Laura A Velazquez Villegas, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, , Mexico

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Mexico

References

Explore related publications, articles, or registry entries linked to this study.

Roberts MN, Wallace MA, Tomilov AA, Zhou Z, Marcotte GR, Tran D, Perez G, Gutierrez-Casado E, Koike S, Knotts TA, Imai DM, Griffey SM, Kim K, Hagopian K, McMackin MZ, Haj FG, Baar K, Cortopassi GA, Ramsey JJ, Lopez-Dominguez JA. A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. Cell Metab. 2017 Sep 5;26(3):539-546.e5. doi: 10.1016/j.cmet.2017.08.005.

Reference Type RESULT
PMID: 28877457 (View on PubMed)

Rizza W, Veronese N, Fontana L. What are the roles of calorie restriction and diet quality in promoting healthy longevity? Ageing Res Rev. 2014 Jan;13:38-45. doi: 10.1016/j.arr.2013.11.002. Epub 2013 Nov 27.

Reference Type RESULT
PMID: 24291541 (View on PubMed)

Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, Ingram DK, Lane MA, Mattson MP. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6216-20. doi: 10.1073/pnas.1035720100. Epub 2003 Apr 30.

Reference Type RESULT
PMID: 12724520 (View on PubMed)

Cignarella F, Cantoni C, Ghezzi L, Salter A, Dorsett Y, Chen L, Phillips D, Weinstock GM, Fontana L, Cross AH, Zhou Y, Piccio L. Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota. Cell Metab. 2018 Jun 5;27(6):1222-1235.e6. doi: 10.1016/j.cmet.2018.05.006.

Reference Type RESULT
PMID: 29874567 (View on PubMed)

Vidali S, Aminzadeh S, Lambert B, Rutherford T, Sperl W, Kofler B, Feichtinger RG. Mitochondria: The ketogenic diet--A metabolism-based therapy. Int J Biochem Cell Biol. 2015 Jun;63:55-9. doi: 10.1016/j.biocel.2015.01.022. Epub 2015 Feb 7.

Reference Type RESULT
PMID: 25666556 (View on PubMed)

Fabbiano S, Suarez-Zamorano N, Chevalier C, Lazarevic V, Kieser S, Rigo D, Leo S, Veyrat-Durebex C, Gaia N, Maresca M, Merkler D, Gomez de Aguero M, Macpherson A, Schrenzel J, Trajkovski M. Functional Gut Microbiota Remodeling Contributes to the Caloric Restriction-Induced Metabolic Improvements. Cell Metab. 2018 Dec 4;28(6):907-921.e7. doi: 10.1016/j.cmet.2018.08.005. Epub 2018 Aug 30.

Reference Type RESULT
PMID: 30174308 (View on PubMed)

Lanza IR, Zabielski P, Klaus KA, Morse DM, Heppelmann CJ, Bergen HR 3rd, Dasari S, Walrand S, Short KR, Johnson ML, Robinson MM, Schimke JM, Jakaitis DR, Asmann YW, Sun Z, Nair KS. Chronic caloric restriction preserves mitochondrial function in senescence without increasing mitochondrial biogenesis. Cell Metab. 2012 Dec 5;16(6):777-88. doi: 10.1016/j.cmet.2012.11.003.

Reference Type RESULT
PMID: 23217257 (View on PubMed)

Paoli A, Mancin L, Bianco A, Thomas E, Mota JF, Piccini F. Ketogenic Diet and Microbiota: Friends or Enemies? Genes (Basel). 2019 Jul 15;10(7):534. doi: 10.3390/genes10070534.

Reference Type RESULT
PMID: 31311141 (View on PubMed)

Hamanaka RB, Chandel NS. Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci. 2010 Sep;35(9):505-13. doi: 10.1016/j.tibs.2010.04.002. Epub 2010 Apr 27.

Reference Type RESULT
PMID: 20430626 (View on PubMed)

Ang QY, Alexander M, Newman JC, Tian Y, Cai J, Upadhyay V, Turnbaugh JA, Verdin E, Hall KD, Leibel RL, Ravussin E, Rosenbaum M, Patterson AD, Turnbaugh PJ. Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells. Cell. 2020 Jun 11;181(6):1263-1275.e16. doi: 10.1016/j.cell.2020.04.027. Epub 2020 May 20.

Reference Type RESULT
PMID: 32437658 (View on PubMed)

Goodpaster BH, Sparks LM. Metabolic Flexibility in Health and Disease. Cell Metab. 2017 May 2;25(5):1027-1036. doi: 10.1016/j.cmet.2017.04.015.

Reference Type RESULT
PMID: 28467922 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39003957 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

3728

Identifier Type: -

Identifier Source: org_study_id