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IRCT20100123003140N26 IRCT 2026-06-01 Tabriz University of Medical Sciences The effect of 5-methyltetrahydrofolate supplementation on the control and treatment of metabolic dysfunction–associated steatotic liver disease The effect of 5-methyltetrahydrofolate supplementation on serum folate and homocysteine level, metabolic, nutritional status, liver function, and PPARα and TNFα gene expression in patients with metabolic dysfunction–associated steatotic liver disease: a double-blind, parallel randomized controlled trial study 2026-07-23 anticipated 44 Pending https://irct.ir/trial/89552 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Used, Assignment: Parallel, Purpose: Treatment, Randomization description: At the beginning of the study and before the intervention, random assignment of individuals to intervention groups will be performed using the Stratified Block Randomization method. Initially, individuals will be placed in four strata (overweight men, obese men, overweight women, obese women) based on sex (male/female) and body mass index (overweight/obese). In each stratum, individuals will be randomly assigned to the intervention or placebo group in a 1:1 ratio using blocks of 2. Randomization will be done using the random allocation software. Given the total sample size (44 individuals), each study group (intervention or placebo) will be approximately 22 individuals. Blocking and stratification ensure that balance is maintained in each stratum, even if the number of individuals in the strata is not exactly equal, Blinding description: The present study will be conducted in a double-blind manner, meaning that the participants, the principal investigator, and the evaluators will not be aware of the content (supplement/ placebo) they receive. The appearance, color, taste, and odor of the MTHF supplement and the placebo will be similar. As a result, the study participants will not know which supplement/placebo they were taking. Also, the supplement/placebo will be coded, and a person outside the study will know the codes and the type of supplement/placebo. The evaluators will deliver the supplement/placebo to the participants based on the code labeled on them and will not know the content of each supplement. 2-3 Metabolic dysfunction–associated steatotic liver disease. Intervention 1: Intervention group: Patients in this group will receive 5-methyltetrahydrofolate tablets (800 mcg) once a day for 90 days. Tablets are manufactured by Ashbal Chemi pharmaceutical company. Intervention 2: Control group: Patients in this group will receive placebo for 90 days. The placebo is corn starch/ cellulose and will be consumed once a day. Yes - There is a plan to make this available What will be shared: The study protocol will be written and published in the form of an article. The clinical report of the study will be published in the form of an article. When: 8 months after the end of the study To whom: The data will only be available for people working in academic institutions. Conditions: To use the findings in the clinic or to write other articles, including review articles. In the case of original articles, researchers will be allowed to do so. Where to obtain: Data and documents related to the present study will be available via email from the study researcher, Dr. Bahram Pourghassem Gargari (pourghassemb@tbzmed.ac.ir/bahrampg@yahoo.com). How to obtain: After receiving the request from the person in charge of updating, the study will be provided to the researcher in consultation with the scientific officer. Comments:
public Dr. Bahram Pourghassem Gargari
Faculty of Nutrition and Food Sciences - Attar Neyshaburi St. - Golgasht St. - Tabriz
Tabriz Iran (Islamic Republic of) 5166614711 +98 41 3334 1113 pourghassemb@tbzmed.ac.ir Tabriz University of Medical Sciences scientific Dr. Bahram Pourghassem Gargari
Faculty of Nutrition and Food Sciences - Attar Neyshaburi St. - Golgasht St. - Tabriz
Tabriz Iran (Islamic Republic of) 5166614711 +98 41 3334 1113 pourghassemb@tbzmed.ac.ir Tabriz University of Medical Sciences Iran (Islamic Republic of) Adults (male and female) in the age range of 18-55 years Having a body mass index of 25-35 kg/m2 With diagnosis of metabolic dysfunction–associated steatotic liver disease (MASLD) based on liver ultrasound by a gastroenterologist Willing to participate in the study 18 years 55 years Both Regular use of nonsteroidal anti-inflammatory drugs, antibiotics, steroids (excluding topical and inhaled drugs), metformin, colchicine, hormonal drugs such as high doses of estrogen within the past 3 months, use of chemical or herbal weight loss drugs and use of hepatotoxic drugs such as phenytoin, amiodarone, levothyroxine, lithium, statins, blood pressure drugs, lipid-lowering drugs, use of multivitamin-mineral supplements, folate, antioxidants such as vitamin E and omega-3 supplements Diagnosed pathological conditions affecting the liver such as viral hepatitis, acute or chronic liver failure, cholestasis, liver transplantation Having hemochromatosis, Wilson disease, Alpha-1 antitrypsin, diabetes, heart failure, renal, intestinal, thyroid dysfunction, biliary disease, PCOS, autoimmune diseases and malabsorption diseases such as Crohn's, the presence of any diagnosed neoplasia or malignancy, having symptoms of infectious or inflammatory disease Acute systemic disease, cystic fibrosis, history of gastrointestinal surgery within the past year, irritable bowel syndrome, celiac disease Pregnancy, breastfeeding, menopause History of alcohol and tobacco use K76.0 Fatty (change of) liver, not elsewhere classified Treatment - Other Placebo Intervention group: Patients in this group will receive 5-methyltetrahydrofolate tablets (800 mcg) once a day for 90 days. Tablets are manufactured by Ashbal Chemi pharmaceutical company. Control group: Patients in this group will receive placebo for 90 days. The placebo is corn starch/ cellulose and will be consumed once a day. Serum level of folate. Timepoint: Before and after the intervention. Method of measurement: ELISA assay. Serum level of homocysteine. Timepoint: Before and after the intervention. Method of measurement: Enzymatic method. PPARα gene expression. Timepoint: Before and after the intervention. Method of measurement: Real-time PCR assay. TNFα gene expression. Timepoint: Before and after the intervention. Method of measurement: Real-time PCR assay. Liver fibrosis (FIB-4 Score). Timepoint: Before and after the intervention. Method of measurement: Formula: FIB-4 Score = (Age × AST) / (Platelet count × √ALT) (age in years, ALT and AST in U/L, and platelet count in 109/L). Alanine transaminase. Timepoint: Before and after the intervention. Method of measurement: IFCC (International Federation for Clinical Chemistry) method. Aspartate aminotransferase. Timepoint: Before and after the intervention. Method of measurement: IFCC (International Federation for Clinical Chemistry) method. Gamma-glutamyl transferase. Timepoint: Before and after the intervention. Method of measurement: Enzymatic method. Fasting blood glucose. Timepoint: Before and after the intervention. Method of measurement: Enzymatic method. Fasting serum insulin. Timepoint: Before and after the intervention. Method of measurement: ELISA assay. Insulin resistance (HOMA-IR). Timepoint: Before and after the intervention. Method of measurement: Formula: HOMA-IR = (fasting insulin (mU/L) × fasting glucose (mg/dL))/405. Insulin sensitivity (QUICKI). Timepoint: Before and after the intervention. Method of measurement: Formula: QUICKI= 1/[log fasting insulin (μU/mL)+log fasting glucose (mg/dL)]. Serum lipid profiles (HDL-C، LDL-C، TC و TG). Timepoint: Before and after the intervention. Method of measurement: Enzymatic methods for TC,TG and HDL-C and for LDL-C : Freidwald’s formula: LDL-C = TC- HDL-C - (TG/5). Nutritional status (calorie and nutrients intake). Timepoint: Before and after the intervention. Method of measurement: Food record questionnaire. Anthropometric index (weight, height, body mass index, waist circumference and waist to hip ratio). Timepoint: Before and after intervention. Method of measurement: Digital scale for weight, measurement tape for height, waist and hip circumference, body mass index with formula (weight(kg)/square height (m)). Body composition. Timepoint: Before and after intervention. Method of measurement: Bioelectrical impedance analysis. Quality of life. Timepoint: Before and after intervention. Method of measurement: Questionnaire. Adverse events. Timepoint: Before and after intervention. Method of measurement: Questionnaire. Tabriz University of Medical Sciences Approved 2026-04-27 Ethics committee of Tabriz University of Medical Sciences No 2 Central Building, Tabriz University of Medical Sciences, Golgasht Street, Tabriz Tabriz East Azarbaijan Iran (Islamic Republic of)