Comparison of the acute metabolic effect of different infant formulas and human milk in healthy adults: a randomized trial

Background/Objectives: Different infant formulas, varying in protein type and quantity, are available for infants who are not breastfed or are partially breastfed. Postprandial insulinemic and glycemic responses to intact vs partially hydrolyzed protein in infant formula are unclear. The objective was to compare the effect of different forms (partially hydrolyzed vs non-hydrolyzed) and levels of protein in infant formula compared with a human milk (HM) reference subgroup on insulin response in adults. Subjects/Methods: In a randomized, double-blinded, cross-over study, 35 healthy adults consumed 600 ml of three infant formulas—INTACT (intact protein, 1.87 g/100 kcal; whey/casein 70/30; 63 kcal/100 ml), PHw (partially hydrolyzed whey, 1.96 g/100 kcal; 100% whey; 63 kcal/100 ml), HPPHw (high-protein partially hydrolyzed whey, 2.79 g/100 kcal; 100% whey; 73 kcal/100 ml)—and a subgroup also consumed HM (n=11 planned; n=8 analyzed). Lipid and lactose contents were similar across products (≈5.1–5.5 g and 10.5–11.6 g/100 kcal). Venous blood was sampled fasting and up to 180 min post-ingestion for insulin, glucose, lipids, GLP-1, glucagon, and C-peptide. Results: Twenty-nine subjects (eight consuming HM) adhered to protocol. INTACT and PHw had similar postprandial insulin and glucose responses (Cmax and iAUC), not different from HM. HPPHw elicited higher postprandial insulin iAUC vs INTACT, PHw, and HM (p<0.001, p<0.001, p=0.002). HPPHw also increased glucose iAUC vs INTACT and PHw (p=0.003, p=0.001), but not vs HM (p=0.41). Conclusion: In adults, postprandial insulinemia and glycemia after INTACT and PHw were similar and close to HM, while HPPHw (with higher protein) produced greater responses. Findings require confirmation in infants. Clinical trial registration: NCT04332510.