Protein glycation compromises the bioavailability of milk protein-derived lysine in vivo in healthy adult males: a double-blind randomized cross-over trial

BACKGROUND: Industrial processing and storage of milk products can strongly increase protein glycation level. Previously, we have reported that ingestion of highly glycated milk protein attenuates the post-prandial rise in plasma lysine concentrations when compared to the ingestion of an equivalent amount of milk protein with a low glycation level. Whether the attenuated increase in plasma lysine availability is attributed to compromised protein digestion and subsequent lysine absorption remains to be established.

OBJECTIVE: The present study combined stable isotope methodology with the ingestion of, specifically produced, intrinsically labeled protein to assess protein digestion and amino acid absorption following ingestion of milk protein with a high versus low glycation level in vivo in humans.

METHODS: 15 recreationally active, healthy young males participated in this double-blinded, randomized cross-over study. Subjects ingested 40 g intrinsically L-[1-13C]-lysine-labeled milk protein with either a low (3%) or high (50%) glycation level. Continuous intravenous infusion of L-[4,4,5,5-2H4]-lysine was combined with frequent blood sample collection during a 6-h post-prandial period to evaluate dietary protein-derived lysine release into the circulation.

RESULTS: Post-prandial plasma lysine concentrations were lower following the ingestion of milk protein with a high versus low glycation level (time*treatment effect: P=0.002; ƞ2=0.214), resulting in a 23 mmol·L-1·360 min-1 [95%-CI:13-32] lower incremental area under the curve (0±12 vs 23±11 mmol·L-1·360 min-1, respectively, P<0.001). The post-prandial release of milk protein-derived lysine into the circulation was attenuated following ingestion of the protein with the high versus low glycation level (time*treatment effect: P<0.001; ƞ2=0.640) and was 31% [95%-CI:26-36] lower over the full 6-h post-prandial period (18±4 vs 49±10% of the ingested lysine, respectively, P<0.001).

CONCLUSIONS: A high level of milk protein glycation strongly reduces post-prandial plasma lysine availability in vivo in humans. Industrial processing and storage of (milk) protein products can strongly modulate protein bioavailability and, as such, lower the nutritional value of a protein source. This trial was registered at www.

CLINICALTRIALS: gov as NCT05479916: https://clinicaltrials.gov/study/NCT05479916.