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

NCT05200468 | Completed DMC

• 1 other identifier: 3728
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity

Keywords

dietary restrictions; ketogenic diet; mitochondrial function; gut microbiota

Outcome Measures

Primary Outcomes (1)

• mitochondrial function

  Change in mitochondrial function determined by mitochondrial oxygen consumption rate in monocytes

  Baseline to 4, 5 and 8 weeks

Secondary Outcomes (14)

• gut microbiota composition

  Baseline to 4, 5 and 8 weeks

• oxidative stress markers

  Baseline to 4, 5 and 8 weeks

• body composition

  Baseline to 4, 5 and 8 weeks

• body weight

  Baseline to 4, 5 and 8 weeks

• grip strength

  Baseline to 4 and 8 weeks

Study Arms (4)

Ketogenic diet

EXPERIMENTAL

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.

Other: Ketogenic diet

Caloric restriction diet

EXPERIMENTAL

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.

Other: Caloric restriction diet

Intermittent fasting 16/8

EXPERIMENTAL

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.

Other: Intermittent fasting 16/8

habitual diet

NO INTERVENTION

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

Interventions

Ketogenic diet 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.

Ketogenic diet

Caloric restriction diet 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.

Caloric restriction diet

Intermittent fasting 16/8 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.

Intermittent fasting 16/8

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female.
• Adults between 18 and 60 years of age.
• BMI ≥ 30 and ≤ 50 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 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.

Sponsors & Collaborators

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

Study Sites (1)

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, 14080, Mexico

Location

Related Publications (12)

• 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.

  PMID: 28877457 RESULT

• 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.

  PMID: 24291541 RESULT

• 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.

  PMID: 12724520 RESULT

• 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.

  PMID: 29874567 RESULT

• 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.

  PMID: 25666556 RESULT

• 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.

  PMID: 30174308 RESULT

• 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.

  PMID: 23217257 RESULT

• 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.

  PMID: 31311141 RESULT

• 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.

  PMID: 20430626 RESULT

• 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.

  PMID: 32437658 RESULT

• 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.

  PMID: 28467922 RESULT

• 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 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Diet, Ketogenic; Caloric Restriction

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

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: OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The groups will receive the treatment simultaneously

Study Record Dates

• First Submitted: January 7, 2022
• First Posted: January 20, 2022
• Study Start: July 28, 2022
• Primary Completion: November 30, 2022
• Study Completion: March 27, 2023
• Last Updated: December 7, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)