Assessing head injury risk and neuroprotective effect of ketone monoester supplementation in military airborne training

Warfighters face significant risk of mild traumatic brain injury (mTBI) during operations and training. We performed a double-blind, randomized, placebo-controlled trial to: (1) determine head strike (HS) incidence, during US Army Basic Airborne Course's Improved Swing Landing Trainer (ISLT) training, (2) test protective efficacy of ketone monoester (KME) supplementation, and (3) assess blood-based mTBI biomarker signatures. We enrolled 354 active-duty male and female service members randomized 1:1 to placebo (PLA) or KME; n = 318 completed ISLT and assessments (PLA = 157, 142 M/15F; KME = 161, 144 M/18F). N = 112 (35.2%; 35.7% in PLA, 34.8% in KME) experienced HS, defined as whiplash or helmet-to-ground impact. Assessments included the Automated Neuropsychological Assessment Metric (ANAM-4), SWAY balance testing, and plasma biomarkers. One ANAM-4 measure (Simple Reaction Time-Repeat; p = 0.024) and one SWAY measure (Single Leg Right; p = 0.014) demonstrated significant HS × Time × Treatment interactions, with performance decrements in HS + PLA not observed in HS + KME. Several HS × Time interactions were observed for ANAM-4 and SWAY variables, indicating HS-induced cognitive and balance decline. No relevant blood-based biomarker patterns were associated with HS or KME. Predictive modeling identified variables associated with HS risk with moderate accuracy. In conclusion, ISLT resulted in ~32% head injury incidence and KME supplementation showed limited protection of cognitive and balance without corresponding biomarker changes.