Investigating the Impact of Protein Supplementation from Different Sources on Advanced Glycation End Products in Older Adults in Singapore Following a Healthy Dietary Pattern.
Protein supplementation while adhering to My Healthy Plate did not significantly influence overall circulating and skin AGEs in older adults in Singapore, though differential responses were observed for specific plasma AGE markers depending on protein source.
Key Findings
Results
Overall circulating, skin, and dietary AGE levels were not significantly altered after 16 weeks of protein supplementation when participants adhered to a healthy dietary pattern.
The study used a 16-week randomized controlled trial design with 55 older adults (mean age: 66 years) in Singapore.
Three groups were compared: control (no supplementation), casein protein isolate supplementation, and soy protein isolate supplementation.
Participants followed My Healthy Plate (MHP), described as a healthy dietary pattern (HDP).
No significant changes were found in total circulating AGEs, skin AGEs, or dietary AGE intake across groups.
Results
Soy protein supplementation led to a significant increase in plasma N(6)-(1-carboxymethyl)-L-lysine (CML) compared to the other groups.
Two-way ANOVA analysis showed a significant interaction effect (pint = 0.040) for plasma CML with soy protein supplementation.
Plasma CML levels in the soy group changed from 0.72 ± 0.10 at week 0 to 0.80 ± 0.10 at week 16.
CML is a specific plasma AGE marker measured among the broader panel of AGEs assessed.
This differential response was not observed with casein supplementation or in the control group for CML.
Results
Casein protein supplementation led to a significant within-group increase in plasma pentosidine over 16 weeks.
A paired t-test showed a significant within-group increase in plasma pentosidine for the casein group (p-value = 0.045).
Plasma pentosidine levels in the casein group changed from 0.77 ± 0.06 at week 0 to 0.80 ± 0.05 at week 16.
The authors note this within-group increase 'should be interpreted with caution and requires further investigation.'
No between-group comparison for pentosidine was reported as significant.
Results
Different sources of protein supplementation resulted in differential changes in specific plasma AGE markers despite no overall AGE elevation.
Soy protein affected plasma CML while casein protein affected plasma pentosidine, suggesting source-specific AGE responses.
The authors attribute possible differential effects to 'differences in amino acid composition, digestion and metabolism.'
Other AGE markers assessed showed no significant changes in any group.
The study was registered at clinicaltrials.gov as NCT05400005.
Background
The study was designed to examine whether protein supplementation from animal-based (casein) or plant-based (soy) sources differentially affects AGE levels in older adults.
The rationale was that protein supplementation may elevate AGEs through higher dietary AGE content and increased amino acid-driven endogenous formation.
Evidence from randomized controlled trials on this topic was described as 'limited' at the time of the study.
The study population consisted of 55 older adults with a mean age of 66 years in Singapore.
The trial duration was 16 weeks.
What This Means
This research suggests that older adults who take protein supplements—whether from animal sources (casein) or plant sources (soy)—while following a balanced, healthy diet do not experience meaningful increases in their overall levels of advanced glycation end products (AGEs). AGEs are compounds that form in the body and in food, and elevated levels have been associated with aging and various health conditions. The study followed 55 Singaporean adults around age 66 for 16 weeks, comparing those who took casein supplements, soy supplements, or no supplements at all, while all participants followed dietary guidelines called My Healthy Plate.
However, this research suggests that the type of protein supplement does matter for some specific AGE markers. People taking soy protein showed a small but statistically significant increase in a specific AGE called CML in their blood, while people taking casein protein showed a small within-group increase in another marker called pentosidine. These changes were modest and did not translate into overall elevated AGE burden, and the authors caution that the pentosidine finding in particular needs further study before drawing firm conclusions.
For people interested in protein supplementation—particularly older adults who may use supplements to maintain muscle mass—this research suggests that following a healthy dietary pattern may help buffer any potential AGE-raising effects of protein supplements. The finding that different protein sources affect different specific AGE markers points to the importance of protein source in nutrition research, though the practical health significance of these small, marker-specific changes remains to be determined in future studies.
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Ting M, Mak I, Yao Y, Chng A, Khoo C, Kim J. (2026). Investigating the Impact of Protein Supplementation from Different Sources on Advanced Glycation End Products in Older Adults in Singapore Following a Healthy Dietary Pattern.. Nutrients. https://doi.org/10.3390/nu18172925