AI-Optimized Whey Protein Peptides Achieve 89% ACE Inhibition and Lower Blood Pressure in Rats

The AI-optimized multienzyme combination MC5 achieved 89.08% ACE inhibition at 1 mg/mL, significantly outperforming single-enzyme hydrolysis. After simulated digestion, ACE inhibition decreased by only 6.87%. In hypertensive rats, MC5 reduced systolic blood pressure to 125 mmHg and diastolic to 89 mmHg. The treatment significantly lowered TNF-α and IL-6, increased SOD, GSH-Px, GR, and CAT activity, reduced serum renin (1.25-fold) and ET-1 (1.04-fold), and increased NO content 3.15-fold. Four potent peptides were identified: LPEW, LKPTPEGDL, LNYW, and LLL.

Large language models were used to predict optimal multienzyme combinations for whey protein hydrolysis. The best combination (MC5) was validated through in vitro ACE inhibition assays and simulated gastrointestinal digestion stability testing. In vivo efficacy was assessed in spontaneously hypertensive rats, measuring blood pressure, inflammatory markers, antioxidant enzymes, renin, ET-1, and NO. Molecular docking identified the most potent individual peptide sequences and their ACE binding modes.

This study bridges AI, food science, and cardiovascular health. By using deep learning to optimize enzyme combinations, the researchers achieved ACE inhibition levels (89%) approaching pharmaceutical-grade potency from a common food protein. The critical addition of in vivo data — showing actual blood pressure reduction in rats — elevates this beyond typical in vitro peptide studies. The digestion stability finding (only 6.87% loss) addresses a major concern with food-derived bioactive peptides.

This study exemplifies the convergence of AI-driven drug discovery with functional food development. Using large language models to optimize bioactive peptide production from commodity food proteins could revolutionize how we develop dietary interventions for chronic diseases. The combination of high ACE inhibition, digestion stability, and confirmed in vivo efficacy places these whey peptides among the most promising food-derived antihypertensive candidates reported to date.

The in vivo study was conducted in spontaneously hypertensive rats, which may not fully represent human hypertension. Specific rat numbers per group and treatment duration were not detailed. Human clinical trials are needed. The four identified peptides need individual testing to confirm their contribution to the overall effect. Manufacturing scale-up and cost-effectiveness were not addressed. The LLM methodology details were not fully described.