This short-term, randomized, placebo-controlled, investigator-initiated trial aims to establish metabolic improvements in NAFLD subjects by dietary supplementation with cofactors N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside and serine. Concomitant use of pivotal metabolic cofactors via simultaneous dietary supplementation will stimulate three different pathways to enhance hepatic β-oxidation and this study's hypothesis is that this will result in decreased amount of fat in the liver.
Name: Metabolic Cofactor Supplementation
Name: Sorbitol
Description: The change in liver fat content as well as subcutaneous abdominal and intra-abdominal fat content between the placebo and cofactor treatment arms in NAFLD patients from baseline to 2 weeks, 6 weeks and 10 weeks.
Measure: Magnetic Resonance Spectroscopy (MRS) Measurement Time: 2 weeks, 6 weeks and 10 weeksDescription: Body weight will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Measure: Change in body weight from baseline Time: 10 weeksDescription: Change in heart rate will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Measure: ECG Measurement Time: 10 weeksDescription: Systolic and Diastolic Blood Pressure will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Measure: Change in Blood Pressure from baseline Time: 10 weeksDescription: Waist and hip circumference will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Measure: Change in waist and hip circumference from baseline Time: 10 weeksDescription: Complete blood count includes number of blood cells. Complete blood count test will be performed to measure possible toxic effects of the metabolic cofactor supplementation on hematological system.
Measure: Change of complete blood count (number of blood cells) from baseline Time: 10 weeksDescription: Complete blood count includes concentration of hemoglobin. Complete blood count test will be performed to measure possible toxic effects of the metabolic cofactor supplementation on hematological system.
Measure: Change of complete blood count (hemoglobin) from baseline Time: 10 weeksDescription: Kidney function tests (creatinine, urea, uric acid) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on kidney function.
Measure: Changes in kidney function tests (creatinine, urea, uric acid) from baseline Time: 10 weeksDescription: Kidney function tests (sodium, potassium) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on kidney function.
Measure: Changes in kidney function tests (sodium, potassium) from baseline Time: 10 weeksDescription: Liver function tests (ALT, AST, GGT, ALP) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on liver function.
Measure: Changes in liver function tests [Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyl transferase (GGT), Alkaline phosphatase (ALP)] from baseline Time: 10 weeksDescription: Liver function tests (Total Bilirubin, Albumin) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on liver function.
Measure: Changes in liver function tests (Total Bilirubin, and Albumin) from baseline Time: 10 weeksDescription: Creatinine kinase (CK) level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Measure: Changes in creatinine kinase (CK) level from baseline Time: 10 weeksDescription: Blood lipid levels (total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C)) will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Measure: Changes in blood lipid levels (total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C)) from baseline Time: 2 weeks, 6 weeks and 10 weeksDescription: Blood glucose levels will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Measure: Changes in blood glucose levels from baseline Time: 10 weeksDescription: Blood insulin level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Measure: Change in blood insulin level from baseline Time: 10 weeksDescription: Thyroid-stimulating hormone (TSH) level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Measure: Change in thyroid-stimulating hormone (TSH) level from baseline Time: 10 weeksDescription: The change in gut microbiota between the placebo and the treatment arms in NAFLD patients. Feces and saliva samples will be collected to assess changes in gut microbiota. Instructions on specimen collection will be given during the first visit. Microbiota will be assessed using shot-gun metagenomic techniques.
Measure: Microbiota analysis Time: 2 weeks, 6 weeks and 10 weeksDescription: This process aiming to monitoring of adverse events of metabolic cofactor supplementation. Adverse events and serious adverse events will be monitored continuously and all adverse events that occur at any time during the study will be reported in Case Report Forms. Any symptoms of intestinal discomfort or other side effects will be carefully recorded and all study subjects will be informed to contact (by phone or text message) the investigators immediately if they experience any symptoms of discomfort or any side effects during the intervention period.
Measure: Monitoring of adverse events Time: 10 weeksAllocation: Randomized
Parallel Assignment
There is one SNP
heart failure, documented coronary artery disease, valvular heart disease) - Patients with active bronchial asthma - Patients with phenylketonuria (contraindicated for NAC) - Patients with histamine intolerance - Clinically significant TSH level outside the normal range (0.04-6 mU/L) - Known allergy for substances used in the study - Concomitant medication use: 1. Lipid-lowering drugs within 3 months 2. Oral antidiabetics given for insulin resistance of obesity (metformin, liraglutide etc.) within 3 months 3. Thiazide diuretics with a dose >25 mg/d 4. Postmenopausal estrogen therapy 5. Any medication acting on nuclear hormone receptors or inducing Cytochromes P450 (CYPs) 6. Self-administration of dietary supplements such as any vitamins, omega-3 products, or plant stanol/sterol products within 1 month 7. Treatment with medications known to cause fatty liver disease such as atypical neuroleptics, tetracycline, methotrexate or tamoxifen 8. Use of an antimicrobial agent in the 4 weeks preceding randomization - Active smokers consuming >10 cigarettes/day - Alcohol consumption over 192 grams for men and 128 grams for women per week - Patients considered as inappropriate for this study for any reason (patients unable to undergo MRI study, noncompliance etc.) - Subjects with Patatin-like phospholipase domain-containing protein 3( PNPLA3) I148M (homozygous for I148M) - Women who are pregnant, are planning pregnancy, or who are breast-feeding - Women of childbearing potential not protected by effective birth control method - Active participation in another clinical study Inclusion Criteria: - Men and women (18-70 years old) - Body mass index >27kg/m2 - Triglyceride levels ≤354 mg/dl and LDL chol ≤175 mg/dl - No history of medication use for hepatic steatosis - Increased liver fat (>5.5%) --- I148M ---
heart failure, documented coronary artery disease, valvular heart disease) - Patients with active bronchial asthma - Patients with phenylketonuria (contraindicated for NAC) - Patients with histamine intolerance - Clinically significant TSH level outside the normal range (0.04-6 mU/L) - Known allergy for substances used in the study - Concomitant medication use: 1. Lipid-lowering drugs within 3 months 2. Oral antidiabetics given for insulin resistance of obesity (metformin, liraglutide etc.) within 3 months 3. Thiazide diuretics with a dose >25 mg/d 4. Postmenopausal estrogen therapy 5. Any medication acting on nuclear hormone receptors or inducing Cytochromes P450 (CYPs) 6. Self-administration of dietary supplements such as any vitamins, omega-3 products, or plant stanol/sterol products within 1 month 7. Treatment with medications known to cause fatty liver disease such as atypical neuroleptics, tetracycline, methotrexate or tamoxifen 8. Use of an antimicrobial agent in the 4 weeks preceding randomization - Active smokers consuming >10 cigarettes/day - Alcohol consumption over 192 grams for men and 128 grams for women per week - Patients considered as inappropriate for this study for any reason (patients unable to undergo MRI study, noncompliance etc.) - Subjects with Patatin-like phospholipase domain-containing protein 3( PNPLA3) I148M (homozygous for I148M) - Women who are pregnant, are planning pregnancy, or who are breast-feeding - Women of childbearing potential not protected by effective birth control method - Active participation in another clinical study Inclusion Criteria: - Men and women (18-70 years old) - Body mass index >27kg/m2 - Triglyceride levels ≤354 mg/dl and LDL chol ≤175 mg/dl - No history of medication use for hepatic steatosis - Increased liver fat (>5.5%) --- I148M --- --- I148M ---
heart failure, documented coronary artery disease, valvular heart disease) - Patients with active bronchial asthma - Patients with phenylketonuria (contraindicated for NAC) - Patients with histamine intolerance - Clinically significant TSH level outside the normal range (0.04-6 mU/L) - Known allergy for substances used in the study - Concomitant medication use: 1. Lipid-lowering drugs within 3 months 2. Oral antidiabetics given for insulin resistance of obesity (metformin, liraglutide etc.) within 3 months 3. Thiazide diuretics with a dose >25 mg/d 4. Postmenopausal estrogen therapy 5. Any medication acting on nuclear hormone receptors or inducing Cytochromes P450 (CYPs) 6. Self-administration of dietary supplements such as any vitamins, omega-3 products, or plant stanol/sterol products within 1 month 7. Treatment with medications known to cause fatty liver disease such as atypical neuroleptics, tetracycline, methotrexate or tamoxifen 8. Use of an antimicrobial agent in the 4 weeks preceding randomization - Active smokers consuming >10 cigarettes/day - Alcohol consumption over 192 grams for men and 128 grams for women per week - Patients considered as inappropriate for this study for any reason (patients unable to undergo MRI study, noncompliance etc.) - Subjects with Patatin-like phospholipase domain-containing protein 3( PNPLA3) I148M (homozygous for I148M) - Women who are pregnant, are planning pregnancy, or who are breast-feeding - Women of childbearing potential not protected by effective birth control method - Active participation in another clinical study Non-alcoholic Fatty Liver Disease (NAFLD) Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease In this study, investigators aim to lower liver fat content in obese patients with NAFLD by increasing the hepatic levels of pivotal metabolic cofactors via simultaneous dietary supplementation of serine, L-carnitine, N-acetylcysteine (NAC) and nicotinamide riboside (NR). --- I148M ---
heart failure, documented coronary artery disease, valvular heart disease) - Patients with active bronchial asthma - Patients with phenylketonuria (contraindicated for NAC) - Patients with histamine intolerance - Clinically significant TSH level outside the normal range (0.04-6 mU/L) - Known allergy for substances used in the study - Concomitant medication use: 1. Lipid-lowering drugs within 3 months 2. Oral antidiabetics given for insulin resistance of obesity (metformin, liraglutide etc.) within 3 months 3. Thiazide diuretics with a dose >25 mg/d 4. Postmenopausal estrogen therapy 5. Any medication acting on nuclear hormone receptors or inducing Cytochromes P450 (CYPs) 6. Self-administration of dietary supplements such as any vitamins, omega-3 products, or plant stanol/sterol products within 1 month 7. Treatment with medications known to cause fatty liver disease such as atypical neuroleptics, tetracycline, methotrexate or tamoxifen 8. Use of an antimicrobial agent in the 4 weeks preceding randomization - Active smokers consuming >10 cigarettes/day - Alcohol consumption over 192 grams for men and 128 grams for women per week - Patients considered as inappropriate for this study for any reason (patients unable to undergo MRI study, noncompliance etc.) - Subjects with Patatin-like phospholipase domain-containing protein 3( PNPLA3) I148M (homozygous for I148M) - Women who are pregnant, are planning pregnancy, or who are breast-feeding - Women of childbearing potential not protected by effective birth control method - Active participation in another clinical study Non-alcoholic Fatty Liver Disease (NAFLD) Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease In this study, investigators aim to lower liver fat content in obese patients with NAFLD by increasing the hepatic levels of pivotal metabolic cofactors via simultaneous dietary supplementation of serine, L-carnitine, N-acetylcysteine (NAC) and nicotinamide riboside (NR). --- I148M --- --- I148M ---