Investigating the effect of a fasting-mimicking diet and synbiotic supplementation on SIRT1 gene expression, serum IGF-1 level, insulin resistance index, and metabolic parameters in obese adults with metabolic syndrome

Determining the effect of a fasting-mimicking diet and synbiotic supplementation on SIRT1 gene expression, serum IGF-1 levels, insulin resistance index, and metabolic parameters in obese adults with metabolic syndrome

A three-arm, parallel-group, randomized, controlled clinical trial involving 186 participants. Randomization will be performed using a stratified approach with variable-sized blocks, based on gender and body mass index (BMI) categories. Outcome assessors and the data analyst will be blinded to group allocation.

This clinical trial will be conducted at the Imam Khomeini Hospital in Urmia. After screening and obtaining informed consent, participants will be randomly allocated to three groups and followed for 3 months. Outcome assessors and data analysts will be blinded to group allocation.

Major inclusion criteria before randomization: Age 18 to 55 years, both sexes, BMI greater than 30 kg/m², central obesity, and metabolic syndrome according to the International Diabetes Federation criteria. Major non-inclusion criteria before randomization: Chronic liver, kidney, or cardiovascular diseases, malignancy, inflammatory diseases or severe gastrointestinal disorders, uncontrolled thyroid disorders, pregnancy or breastfeeding, smoking or alcohol consumption, recent use of antibiotics or probiotic and prebiotic supplements, use of medications affecting metabolism, significant weight change during the previous three months

Group 1: Continuation of the usual diet, general healthy eating recommendations, and daily use of one placebo capsule for 12 weeks.Group 2: Fasting mimicking diet for 3 months, consisting of one 5 day cycle each month with continuation of the usual diet on the remaining days.Group 3: Fasting mimicking diet similar to Group 2, along with daily use of one synbiotic capsule for 12 weeks.

SIRT1 gene expression; serum IGF-1; HOMA-IR; serum insulin

Method of randomization and description of the method: Stratified block randomization with an allocation ratio of 1:1:1 and variable block sizes will be used Unit of randomization: Individual Stratification factors: Sex (female/male) and body mass index (BMI) in two strata of 30–34.9 and ≥35 kg/m² Randomization tool: The random allocation sequence will be computer-generated by an independent researcher who is not involved in the implementation of the study Generation of the random allocation sequence: For each stratum, a separate random allocation sequence will be generated using variable block sizes and an allocation ratio of 1:1:1 to the three study groups Allocation concealment: The allocation sequence will be placed in opaque, sealed, sequentially numbered envelopes, and the envelope corresponding to each participant will be opened only after eligibility criteria have been confirmed, written informed consent has been obtained, and the participant has been definitively enrolled in the study

Due to the nature of the dietary intervention, complete blinding of participants to receiving the FMD or usual diet is not feasible. However, participants will be blinded to the type of supplement received (synbiotic or placebo). The synbiotic supplement and placebo will be identical in appearance, packaging, and taste and will be provided in coded containers. The researcher responsible for implementing the intervention will be aware of the group allocation and the type of supplement received by each participant and therefore will not be blinded to group allocation. Outcome assessors and personnel responsible for data collection will be blinded to the participants’ group allocation, and information regarding group assignment will not be disclosed to them. The data analyst will also be blinded to group allocation. Data will be provided using anonymous group codes, such as A, B, and C. The group codes will remain concealed from the data analyst until completion of the primary statistical analysis.

Due to the nature of the individual-level data and confidentiality and research ethics considerations, there is no plan to share the individual-level de-identified participant data after completion of the study.