An interventional study of 5-methyltetrahydrofolate (5-MTHF) and placebo group in Nonalcoholic Fatty Liver Disease, Nonalcoholic Fatty Liver Disease (NAFLD) and MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease, sponsored by Tabriz University of Medical Sciences. Not yet recruiting at 1 site in Iran. Open to participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2026-07-31.
Sponsored by Tabriz University of Medical Sciences · Not applicable, Interventional, and Treatment
To determine the effect of MTHF supplementation on serum folate and homocysteine level, metabolic, nutritional status, liver function, and PPARα and TNFα gene expression in patients with MASLD
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed non-alcoholic fatty liver disease (NAFLD), is diagnosed via liver biopsy or imaging when steatosis is present in the absence of alcohol intake or other hepatic disorders. As the liver manifestation of metabolic syndrome, it commonly coexists with obesity, diabetes, dyslipidemia, hypertension, and related conditions. Global prevalence of MASLD continues to rise.
Evidence from an earlier systematic review and meta-analysis indicated that MASLD patients had significantly lower serum folate and higher homocysteine concentrations. Folate is an essential water-soluble B vitamin that occurs in multiple chemically related forms. Food folates are mainly reduced and polyglutamated, with 5-MTHF predominating in both the diet and systemic circulation. 5-MTHF does not require reduction by DHFR and can enter the bloodstream directly for use. Reduced folates act as methyl donors in one carbon metabolism, supporting cellular proliferation, homocysteine re-methylation to methionine, nucleic acid synthesis and methylation of DNA, RNA, proteins and phospholipids.
Experimental studies have demonstrated that diet-induced hyperhomocysteinemia promotes hepatic steatosis and liver injury and folate as a key regulator of homocysteine concentration, may exert hepatoprotective effects. Evidence suggests that folate may improve hepatic lipid metabolism by activating peroxisome proliferator-activated receptor alpha (PPARα) signaling and modulate the immune response and reduce inflammatory mediators. Nevertheless, no evidence on the effects of folate on PPARα and TNFα gene expression in MASLD patients exist. Moreover, PPARα gene expression is dysregulated in MASLD and related metabolic conditions; PPARα is highly expressed in the liver, skeletal muscle and brown adipose tissue, stimulates β-oxidation and suppresses fatty-acid synthesis. Although the effect of 5-MTHF supplementation on gene expression of PPARα and TNFα in MASLD patients has not been examined, evidence showed that folate can modulate PPARα and TNFα. As folate has been shown to affect lipid metabolism and inflammation, we hypothesized that 5-MTHF supplementation might regulate PPARα and TNFα expression in MASLD patients. This randomized, double-blind, placebo-controlled clinical trial will therefore be undertaken to determine the effects of 5-MTHF supplementation on serum levels of folate and homocysteine, and gene expression of PPARα and TNFα in MASLD patients.
1,617 studies on the registry are indexed under Non-alcoholic Fatty Liver Disease; 324 are open to participants now.
This study's planned enrollment of 44 is below the median of 60 across 1,176 interventional studies indexed under Non-alcoholic Fatty Liver Disease.
Browse Non-alcoholic Fatty Liver Disease studies →Tabriz University of Medical Sciences is the lead sponsor of 15 studies on the registry; 4 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Dietary Supplement: 5-methyltetrahydrofolate (5-MTHF)
Dietary Supplement: placebo group
Patients in this group will receive 5-methyltetrahydrofolate tablets (800 mcg) once a day for 90 days. Tablets will be manufactured by Ashbal Chemi pharmaceutical company (Qfol, Ashbal Chemi Co., Tehran, Iran).
Patients in this group will receive placebo for 90 days. The placebo is corn starch/ cellulose and will be consumed once a day. Placebo tablets will be manufactured by Ashbal Chemi Co. (Tehran, Iran).
Serum folate level
Changes in serum folate level pre and post the 3-month intervention period.
Time frame: 3 months
Serum homocysteine level
Changes in serum homocysteine level pre and post the 3-month intervention period.
Time frame: 3 months
Expression of PPARα and TNFα genes
Changes in expression of PPARα and TNFα genes pre and post the 3-month intervention period.
Time frame: 3 months
Liver biochemical parameters (ALT (alanine aminotransferase), AST (aspartate aminotransferase), and GGT (gamma-glutamyl transferase)
Changes in ALT, AST, and GGT pre and post the 3-month intervention period.
Time frame: 3 months
The fibrosis-4 (FIB-4) index
Changes in FIB-4 index pre and post the 3-month intervention period. The Fibrosis-4 (FIB-4) index will be calculated using the following formula: FIB-4 = (Age \[years\] × AST \[U/L\]) / (Platelet count \[10⁹/L\] × √ALT \[U/L\]). FIB-4 values \>1.3, indicate a greater likelihood of liver fibrosis.
Time frame: 3 months
Quality of life using SF-36 (36-Item Short Form Health Survey) questionnaires
Changes in quality-of-life pre and post the 3-month intervention period. Health-related quality of life will be assessed using the validated 36-Item Short Form Health Survey (SF-36). The questionnaire evaluates eight health domains: physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. Scores for each domain will be transformed to a 0-100 scale according to the standard scoring algorithm, with higher scores indicating better health-related quality of life.
Time frame: 3 months
Lipid profile (triglycerides, total cholesterol, LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol))
Changes in lipid profile (triglycerides, total cholesterol, LDL-C, HDL-C) pre and post the 3-month intervention period.
Time frame: 3 monhs
Fasting blood glucose
Changes in fasting blood glucose pre and post the 3-month intervention period.
Time frame: 3 months
Fasting serum insulin
Changes in fasting serum insulin pre and post the 3-month intervention period.
Time frame: 3 months
QUICKI (quantitative insulin sensitivity check index)
Changes in QUICKI pre and post the 3-month intervention period. The quantitative insulin sensitivity check index (QUICKI) will be calculated as 1/\[log(fasting insulin \[µU/mL\]) + log(fasting glucose \[mg/dL\])\], higher values indicating greater insulin sensitivity.
Time frame: 3 months
HOMA-IR (homeostatic model assessment of insulin resistance
Changes in HOMA-IR pre and post the 3-month intervention period. Insulin resistance will be assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), calculated as fasting insulin (µU/mL) × fasting glucose (mg/dL) / 405, higher values indicating greater insulin resistance.
Time frame: 3 months
Weight
Changes in weight pre and post the 3-month intervention period.
Time frame: 3 months
Body Mass Index (BMI)
Changes in BMI pre and post the 3-month intervention period. Body mass index (BMI) will be calculated as weight (kg) divided by the square of height (m²) and expressed as kg/m².
Time frame: 3 months
Waist circumference
Changes in waist circumference pre and post the 3-month intervention period.
Time frame: 3 months
Waist-to-hip ratio (WHR)
Changes in WHR pre and post the 3-month intervention period. Waist-to-hip ratio (WHR) will be calculated by dividing waist circumference by hip circumference.
Time frame: 3 months
Body composition (fat-free mass)
Changes in fat-free mass (%) pre and post the 3-month intervention period. Body composition will be determined using a bioelectrical impedance analyzer.
Time frame: 3 months
Body composition (fat mass)
Changes in fat mass (%) pre and post the 3-month intervention period. Body composition will be determined using a bioelectrical impedance analyzer.
Time frame: 3 months
Plan to share: Yes
No publications or documents are linked to this record.
Start is estimated for Sep 2026; primary completion for Aug 2027, 11 months later.
Of 357 non-industry interventional studies with no phase under Non-alcoholic Fatty Liver Disease, half reached primary completion within 26 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 51. This study's planned 11 months is below that.
Counting every sponsor, half of 385 studies reached it within 26 months; a quarter within 12 and three quarters within 50.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Levomefolic acid
Non-alcoholic Fatty Liver Disease →
Tabriz University of Medical Sciences