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Whey protein (WP) is widely utilized to support muscle strength, but WP alone is insufficient to achieve desired muscle synthesis. Here, a simple and effective piperine (Pip)\u2010WP synergistic supplementation system was developed. A nanoemulsion with high interfacial\u2010volume WP layer, designated as WP(Pip), was prepared with 10\u00a0wt.% WP and Pip loaded in the oil phase. Compared with the single dose of WP and Pip, the co\u2010delivered system of WP(Pip) combined with major WP can increase in vivo WP and Pip absorption,\u00a0with increase of 6.10% and 890%, respectively. The mechanism of Pip for WP hydrolysate absorption is investigated in a Caco\u20102 monolayer model. Pip enhances WPH bioavailability by reversibly modulating epithelial tight junctions. Increased circulating free amino acids, together with Pip, synergistically activate mTOR signaling pathway in skeletal muscle through direct and indirect regulation. This promotes efficient utilization of absorbed WP for muscle protein synthesis and improves exercise performance. Meanwhile, the WP(Pip) co\u2010supplementary system mitigates muscle fatigue and damage in healthy mice and in a dexamethasone\u2010induced sarcopenia model, respectively. These findings suggest a strategy to enhance protein absorption and translate dietary protein intake into muscle\u2010building outcomes, with potential nutritional and clinical relevance.<\/jats:p>","DOI":"10.1002\/advs.202522455","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:33:09Z","timestamp":1774528389000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Enhanced Whey Protein Oral Bioavailability and Muscle Anabolism Ability by a Simple and Effective Piperine\u2010Whey Protein Synergistic Codelivery System"],"prefix":"10.1002","volume":"13","author":[{"given":"Qing","family":"Yue","sequence":"first","affiliation":[{"name":"Research Center of Food Colloids and Delivery of Functionality College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiwen","family":"Wu","sequence":"additional","affiliation":[{"name":"Research Center of Food Colloids and Delivery of Functionality College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wei","sequence":"additional","affiliation":[{"name":"Beijing Competitor Sports Science &amp; Tech. 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