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

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 ).