Effect of hydrolyzed milk proteins and postbiotic Lacticaseibacillus rhamnosus GG on inflammatory responses in conscripts: A randomized double-blind pilot trial.

BACKGROUND: Low-grade inflammation (LGI) and increased infection susceptibility are common under sustained stress. We investigated whether daily consumption of hydrolyzed milk protein (HMP), alone or combined with heat-killed Lacticaseibacillus rhamnosus GG (HK-LGG), reduces LGI in healthy young Finnish conscripts, with serum high-sensitivity C-reactive protein (hs-CRP) as the primary outcome. Secondary outcomes included additional inflammatory biomarkers (calprotectin, haptoglobin, suPAR), sick days, stress, fitness, and recovery metrics. METHODS: In this eight-week randomized, double-blinded, placebo-controlled pilot trial, 160 conscripts (157 male) received milk beverages containing either maltodextrin (Control; 9.5g protein; n=53), HMP (19.5g protein; n=53), or HMP (19.3g protein; n=54) with HK-LGG (2×109 cells) daily, administered in two 250ml portions. We assessed the following factors: fasting serum markers of LGI, anthropometrics, smartwatch-based activity, recovery, fitness test metrics, self-reported sick days, and stress and fatigue questionnaire scores. RESULTS: Between-group differences in changes over the intervention period were observed for hs-CRP (p=0.02) and calprotectin (p=0.04). Over time the increase in hs-CRP from baseline was lower in the HMP vs HMP+HK-LGG group (ratio of geometric means 0.45; 95% CI 0.21-0.95; p= 0.03), whereas post hoc comparisons for calprotectin showed no between-group differences. No differences were observed between the treatment groups in haptoglobin (p = 0.53) or suPAR (p = 0.14). Infection prevalence was highest in the HMP+HK-LGG group (60.5%) compared with the HMP group (34.1%; p = 0.045), whereas the Control group (45.2%) did not differ from either group. The interventions did not impact body weight, activity, recovery, or fitness test outcomes. CONCLUSION: HMP may help stabilize immune responses during physical and infectious stress in conscripts, although these effects did not extend to fitness or recovery outcomes. The potential postbiotic HK-LGG showed no additional benefit when combined with HMP, calling for further evaluation of its efficacy in high stress and infection risk populations. REGISTRATION NUMBER OF CLINICAL TRIAL: NCT06355089 (https://www. CLINICALTRIALS: gov/study/NCT06355089; registered on March 21, 2024).