Introduction: Understanding sex-based differences in nutrient utilization is critical for optimizing sports nutrition. This study investigates the in vitro digestibility of bovine milk and oat-based milk alternatives, exploring the impact of sex on protein breakdown to inform gender-specific nutritional strategies.

Methods: A semi-dynamic in vitro digestion model was used to simulate male and female physiological conditions. Bovine milk and oat drink, along with their protein powder counterparts, were subjected to gastric and intestinal digestion. Proteolytic trajectories, peptide generation, and free amino acid (FAA) release were analyzed via LC-MS proteomic analyses and SDS-PAGE.

Results: Significant sex-based differences in protein clotting and breakdown were observed. Females exhibited higher efficiency in oat protein digestion, while males showed improved bovine milk protein digestion. Male gastric conditions liberated bioactive peptides with antimicrobial, DPP-IV inhibitory (dipeptidyl peptidase IV, involved in blood sugar regulation), and cholesterol-regulating activities from milk proteins. In females, gastric conditions led to the release of an osteoanabolic peptide, which is potentially beneficial given women's higher risk of osteoporosis (affecting ~20% of women >50 years). FAA analysis indicated that women produced more FAA from oats, especially essential amino acids such as leucine (important for muscle protein synthesis), while men yielded more from milk proteins.

Conclusion: Sex significantly influences protein digestibility, impacting bioactive peptide release and FAA bioaccessibility. These findings suggest that gender-specific nutritional strategies, tailoring protein sources to optimize digestibility and harness the benefits of sex-specific peptide release, could enhance athletic performance and overall health. This research underscores the importance of considering biological sex in the design of future food products and dietary recommendations.