People who are severely obese often have lower levels of the amino acid, glycine, compared to people of healthy weight, as their body typically cannot synthesise enough glycine to meet the metabolic demand. Glycine is essential for detoxification, antioxidant protection, and energy metabolism.
In severely obese people, low glycine levels may accelerate oxidative stress, resulting in a higher risk of developing certain diseases such as type 2 diabetes mellitus, and Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD), a condition caused by excessive fat in the liver.
Hence, researchers wanted to study if glycine supplementation can correct glycine deficiency in individuals with severe obesity, and study its impact on the metabolic pathways that are dependent on glycine availability.
The findings were published in Scientific reports.
Study design
The single-arm clinical trial was conducted at the Singapore General Hospital’s weight management clinic, and involved 19 adults with severe obesity (BMI 38.3 ± 5.3 kg/m2).
While some participants had hypertension or high cholesterol, all were otherwise healthy with no existing liver diseases, diabetes and not on any weight loss medication.
Participants were asked to maintain their usual dietary habits, and given two weeks of glycine supplement at 100 mg/kg/day. The supplement was manufactured by NOW Foods.
Researchers measured plasma amino acid levels, metabolic markers, and took anthropometric measurements at baseline and after two weeks.
Key findings
Researchers found that glycine supplementation significantly increased plasma glycine plasma levels by 49.2 ± 29.4 µmol/L at the end of the study.
“We demonstrated that treatment with glycine supplements at 100 mg/kg/day (four times the amount of the participants’ dietary glycine intake) for two weeks raised plasma glycine concentration by 35%,” they wrote.
Other amino acids including serine, cysteine folate, and homocysteine also increased. These amino acids are involved in the one-carbon metabolism cycle, which supports essential processes such as methylation, antioxidant function, and cell growth.
Since the liver is a major site of one-carbon metabolism and this process is often disrupted in MASLD, the findings suggest that glycine may help improve liver function through enhanced one-carbon metabolism.
“(The one-carbon metabolism reaction) occur primarily in the liver, and the associated improvement in MASLD markers suggests glycine supplements could be developed as a low-risk, cost-effective treatment for (non-alcoholic fatty liver disease),” the authors said.
There was a significant increase in the urinary excretion of acylglycines which are by-products of amino acid and fat metabolism, suggesting improved detoxification activity.
Improving liver health
In addition, participants recorded significantly lower levels of blood triglycerides and liver enzymes (alanine transaminase and aspartate transaminase), as well as improvements in the glutamate-serine-glycine (GSG) index.
These measures are known markers of MASLD and fibrosis risk, suggesting that glycine supplementation may help reduce liver fat and inflammation.
There were no significant changes in body weight, blood pressure, cholesterol. Glycine supplementation also did not significantly affect glycaemic control, with no changes to HbA1C, fasting glucose, fasting insulin, and insulin resistance.
The researchers concluded, “we found that dietary glycine supplements corrected obesity-associated glycine deficiency, increased urine acylglycine excretion, and plasma metabolites associated with one-carbon metabolism”.
These findings suggest that glycine could be a safe, low-cost therapeutic option for improving liver health in people with severe obesity, although larger and longer clinical trials are needed to confirm glycine’s potential in treating MASLD.
Source: Scientific reports, 15(1), 36433. doi:10.1038/s41598-025-20511-x.“Metabolic impact of dietary glycine supplementation in individuals with severe obesity.” Authors: Tan, H. C. et al.
