Metabolic impact of dietary glycine supplementation in individuals with severe obesity.

2025-10-17
Scientific reports 15(1)
- Hong Chang Tan
- Jean W Hsu
- E Shyong Tai
- Shaji Chacko
- Vieon Wu
- Paul M Yen
- Jean-Paul Kovalik
- Farook Jahoor

PubMed: 41107432
DOI: 10.1038/s41598-025-20511-x

Study Design

Type: Clinical Trial
Sample size: n = 19
Population: 19 participants with severe obesity (BMI 38.3 ± 5.3 kg/m2)
Methods: exploratory study; dietary glycine supplementation (100 mg/kg/day) for two weeks
Blinding: Open-label
Duration: two weeks
Funding: Unclear

Rigorous Journal

Glycine plays a central role in human metabolism, and an adequate supply is required for synthesizing glutathione (GSH), eliminating excess metabolites as acylglycine via the glycine conjugation detoxification pathway, and maintaining 1-carbon cycle activity. However, glycine is deficient in individuals with severe obesity, which may compromise these pathways and metabolic health. This exploratory study examines whether dietary glycine supplementation could correct glycine deficiency and impairments in glycine-dependent metabolic pathways. 19 participants with severe obesity (BMI 38.3 ± 5.3 kg/m²) were treated with dietary glycine (100 mg/kg/day) for two weeks. We found that treatment significantly increased the plasma concentration of glycine and enhanced the urinary excretion of isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine. There were no changes in body weight but significant reductions in plasma triglyceride and aminotransferases. The glutamate-serine-glycine index, an indirect marker of metabolic dysfunction-associated liver disease (MASLD), also improved. Treatment did not affect GSH but raised the plasma concentrations of serine, homocysteine, cysteine, and folate, which are 1-carbon cycle metabolites. We conclude that dietary glycine supplementation reversed obesity-associated glycine deficiency and enhanced the glycine conjugation detoxification reaction, 1-carbon cycle flux, and potentially the severity of MASLD. Glycine supplementation should be further investigated as a novel treatment for MASLD.Clinical trials registry number NCT04658134 ( https://tinyurl.com/7rthbwjb ).

Research Insights

Glycine→Improved Glutamate-Serine-Glycine Index
The glutamate-serine-glycine index, an indirect marker of metabolic dysfunction-associated liver disease (MASLD), also improved
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day
Glycine→Increased Cysteine Level
raised the plasma concentrations of serine, homocysteine, cysteine, and folate
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day
Glycine→Increased Folate Level
raised the plasma concentrations of serine, homocysteine, cysteine, and folate
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day
Glycine→Increased Glutathione Level
Treatment did not affect GSH
Effect
Neutral
Effect size
Small
Dose
100 mg/kg/day
Glycine→Increased Glycine Level
treatment significantly increased the plasma concentration of glycine
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day
Glycine→Increased Hexanoic Acid Levels
enhanced the urinary excretion of isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day
Glycine→Increased Homocysteine Level
raised the plasma concentrations of serine, homocysteine, cysteine, and folate
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day
Glycine→Increased Isovalerylglycine Level
enhanced the urinary excretion of isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day
Glycine→Increased Serine Level
raised the plasma concentrations of serine
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day
Glycine→Increased Tiglylglycine Level
enhanced the urinary excretion of isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day
Glycine→Increased Urinary Isobutyrylglycine Level
enhanced the urinary excretion of isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day
Glycine→Reduced Aminotransferase Level
significant reductions in plasma triglyceride and aminotransferases
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day
Glycine→Reduced Body Weight
There were no changes in body weight
Effect
Neutral
Effect size
Small
Dose
100 mg/kg/day
Glycine→Reduced Triglyceride Level
significant reductions in plasma triglyceride
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day