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.

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.

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)

All IPD that underlie results in a publication

Beginning 3 months and ending 3 years after the publication of results