Investigating the Impact of Protein Supplementation from Different Sources on Advanced Glycation End Products in Older Adults in Singapore Following a Healthy Dietary Pattern.

Background/Objectives: Protein supplementation may elevate advanced glycation end products (AGEs) through higher dietary AGE (dAGE) content and increase amino acid-driven endogenous formation. Protein supplementation from different sources may differentially affect AGE levels, possibly through differences in amino acid composition, digestion and metabolism, but evidence from randomized controlled trials (RCTs) remains limited. This study aimed to examine the effect of protein supplementation from either casein (animal-based) or soy (plant-based) protein isolates on circulating, skin, and dAGE levels in older adults following a healthy dietary pattern (HDP). Methods: In this 16-week RCT, 55 older adults (mean age: 66 years old) in Singapore were assigned either to control (no supplementation), casein protein isolate supplementation, or soy protein isolate supplementation. This study was registered at clinicaltrials.gov as NCT05400005. Results and Discussion: Overall, there were no alterations in dietary, skin and total circulating AGE levels after protein supplementation when adhering to an HDP such as My Healthy Plate (MHP). However, different sources of protein supplementation resulted in differential changes in specific plasma AGE markers. Two-way ANOVA analysis showed that soy protein supplementation led to a significant increase in plasma N(6)-(1-carboxymethyl)-L-lysine (CML) compared to the other groups (week 0: 0.72 ± 0.10, week 16: 0.80 ± 0.10, pint = 0.040), while a paired t-test showed that casein protein supplementation led to a significant within-group increase in plasma pentosidine (week 0: 0.77 ± 0.06, week 16: 0.80 ± 0.05, p-value = 0.045). Other AGEs showed no significant changes. Conclusions: Protein supplementation while adhering to MHP did not significantly influence overall circulating and skin AGEs in older adults in Singapore. A differential response was observed only for plasma CML levels with soy protein supplementation, whereas the within-group increase in plasma pentosidine following casein supplementation should be interpreted with caution and requires further investigation.