Dietary Glycine Supplementation in Metabolic Dysfunction-associated Steatotic Liver Disease

Investigating the Effects of Dietary Glycine Supplementation in Patients With Metabolic Dysfunction-associated Steatotic Liver Disease

The purpose of this research study is to determine whether taking glycine, a naturally occurring amino acid, as a supplement improves liver health measurements in individuals with Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD).

This project will be divided into two parts. The first part will be a case-control study comparing parameters of glycine-dependent metabolic pathways between individuals with MASLD and healthy controls. The second part will be a randomized placebo-controlled trial (RCT) to evaluate the impact of 26-week dietary glycine supplementation on parameters of liver health versus 26-week placebo in patients with MASLD.

Study Overview

• Status: Not yet recruiting
• Conditions: Metabolic Dysfunction Associated Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: Glycine; Dietary supplement: Placebo

Detailed Description

This study will recruit 60 participants with MASLD and 30 healthy controls.

Following written informed consent, subjects will be screened. Eligible study subjects will return to undergo MRI scans of the abdomen to measure fat, iron, fibro-inflammation in the liver. Baseline metabolic measurements will include clinical laboratory tests, anthropometrics, body composition, resting energy expenditure, and comprehensive metabolomic profiling. Medical history, physical activity, dietary intake, and sleep quality will also be documented.

Study subjects in with MASLD will be randomized to consume either 9g/day of glycine capsules or placebo capsules for the next 26 ± 4 weeks. Subjects MASLD will be reviewed at 12 ± 4 weeks following the initiation of glycine or placebo to monitor compliance and adverse events.

The final study visit (for subjects with MASLD) will be scheduled at 26 ± 4 weeks after initiation of glycine or placebo. The study subjects will undergo metabolic measurements similar to those performed during the baseline visit.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hong Chang Tan, MD PhD; Phone Number: +65 63214658; Email: tan.hong.chang@singhealth.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

All subjects:

1. Age 21-70 years
2. Ability to provide informed consent.

MASLD group:

1. Hepatic steatosis on MRI
2. BMI of 25-50 kg/m2

Controls:

1. Absence of hepatic steatosis on MRI
2. BMI of 18.5-24.9 kg/m2
3. No chronic disease
4. No long-term medications

Exclusion Criteria:

1. Uncontrolled diabetes (HbA1c > 8%)
2. Type 1 Diabetes Mellitus
3. Clinically significant anemia (Haemoglobin < 10 g/dL)
4. Chronic liver disorders (except MASLD) such as Hepatitis B, Hepatitis C, Wilson's disease, hemochromatosis, autoimmune hepatitis, chronic cholestatic disorders, and liver cirrhosis
5. Drugs that may induce hepatic steatosis, such as methotrexate, amiodarone, tamoxifen, or Systemic steroid usage (eg. prednisolone, hydrocortisone, cortisone, dexamethasone)
6. Glomerular filtration rate (GFR < 30 ml/min)
7. Serum alanine transaminase (ALT) > 3x upper limit of normal (ULN)
8. Serum aspartate transaminase (AST) > 3x ULN
9. Liver cirrhosis
10. Significant alcohol consumption (> 20g/day for women and >30g/day for men)
11. Receiving weight loss medications or GLP-1 receptor agonists
12. Pregnancy
13. Uncontrolled thyroid disease
14. Previous bariatric surgery
15. Weight loss > 5% in the past 1 month
16. Metallic implants (including incompatible pacemakers, AICD, metallic heart valves) or other contraindications to MRI
17. Claustrophobia
18. Any factors likely to limit adherence to study protocol (e.g., dementia; alcohol or substance abuse; history of unreliability in medication taking or appointment keeping; significant concerns about participation in the study from spouse, significant other, or family members)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Microcrystalline cellulose in capsules	Dietary supplement: Placebo; Microcrystalline cellulose in identifically-looking capsules
Active Comparator: Glycine; 9g per day of glycine in capsules	Dietary supplement: Glycine; 9g/day of glycine in capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in hepatic Magnetic Resonance Imaging-Proton Density Fat Fraction and concentrations of acylglycines, glutathione, cytokines, oxidative stress markers, and 1-carbon cycle metabolites from baseline to 26 weeks	From the initiation to end of the treatment at 26 weeks
Differences in concentrations of acylglycines, glutathione, cytokines, oxidative stress markers, and 1-carbon cycle metabolites between subjects with MASLD and controls	From enrollment to the completion of baseline metabolic assessment (within 8 weeks)

Collaborators and Investigators

• Sponsor: Singapore General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Fatty liver; glycine supplements
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Amino Acids, Peptides, and Proteins; Amino Acids; Glycine
• Other Study ID Numbers: 2025-1240; CSAINV25jan-0007 (Other Identifier: NMRC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication
• IPD Sharing Time Frame: Beginning 3 months and ending 3 years after the publication of results

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No