An expert panel on the adequacy of safety data and physiological roles of dietary bovine osteopontin in infancy Provisionally Accepted

Stephen A. Fleming^1* Sarah M. Reyes² Sharon M. Donovan³ Olle Hernell⁴ Rulan Jiang⁵ Bo Lonnerdal⁵ Josef Neu⁶ Lawrence Steinman⁷ Esben S. Sørensen⁸ Christina E. West⁴ Ronald Kleinman⁹ John Wallingford¹⁰

• ¹Traverse Science, Inc., United States
• ²Independent researcher, United States
• ³Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, United States
• ⁴Department of Clinical Sciences, Pediatrics, Umeå University, Sweden
• ⁵Nutrition, University of California, Davis, United States
• ⁶Department of Pediatrics, Division of Neonatology, University of Florida, United States
• ⁷Departments of Pediatrics and of Neurology and Neurological Sciences, Interdepartmental Program in Immunology, Beckman Center for Molecular Medicine, School of Medicine, Stanford University, United States
• ⁸Department of Molecular Biology and Genetics, Aarhus University, Denmark
• ⁹Pediatrics, Massachusetts General Hospital, Harvard Medical School, United States
• ¹⁰Independent researcher, United States

Human milk, due to its unique composition, is the optimal standard for infant nutrition.Osteopontin (OPN) is abundant in human milk but not bovine milk. The addition of bovine milk osteopontin (bmOPN) to formula may replicate OPN's concentration and function in human milk.To address safety concerns, we convened an expert panel to assess the adequacy of safety data and physiological roles of dietary bmOPN in infancy. The exposure of breastfed infants to human milk OPN (hmOPN) has been well-characterized and decreases markedly over the first 6 months of lactation. Dietary bmOPN is resistant to gastric and intestinal digestion, absorbed and cleared from circulation within 8-24 h, and represents a small portion (<5%) of total plasma OPN. Label studies on hmOPN suggest that after 3 h, intact or digested OPN is absorbed into carcass (62%), small intestine (23%), stomach (5%), and small intestinal perfusate (4%), with <2% each found in the cecum, liver, brain, heart, and spleen. Although the results are heterogenous with respect to bmOPN's physiologic impact, no adverse impacts have been reported across growth, gastrointestinal, immune, or brain-related outcomes. Recombinant bovine and human forms demonstrate similar absorption in plasma as bmOPN, as well as effects on cognition and immunity.The panel recommended prioritization of trials measuring a comprehensive set of clinically relevant outcomes on immunity and cognition to confirm the safety of bmOPN over that of further research on its absorption, distribution, metabolism, and excretion. This review offers expert consensus on the adequacy of data available to assess the safety of bmOPN for use in infant formula, aiding evidence-based decisions on the formulation of infant formula.