SummaryThe combined supplementation of medium-chain triglycerides (MCTs), l-leucine-rich amino acids, and cholecalciferol (vitamin D3) increase muscle strength and function in frail elderly individuals. However, their effects on cognition are unknown. We enrolled 38 elderly nursing home residents (mean age6SD, 86.664.8 y) in a 3-mo randomized, controlled, parallel group trial. The participants were randomly allocated to 3 groups: the first group received a l-leucine (1.2 g)-and cholecalciferol (20 mg)-enriched supplement with 6 g of MCT (LD1MCT); the second group received the same supplement with 6 g of long-chain triglycerides (LD1LCT); and the third group did not receive any supplements (control). Cognition was assessed at baseline and after the 3-mo intervention. The difference in changes among the groups was assessed with ANCOVA, adjusting for age and the baseline value as covariates. After 3 mo, the Mini-Mental State Examination (MMSE) score in the LD1MCT group increased by 10.6% (from 16.6 to 18.4 points, p,0.05). After 3 mo, the Nishimura geriatric rating scale for mental status (NM scale) score in the LD1MCT group increased by 30.6% (from 24.6 to 32.2 points, p,0.001), whereas that in the LD1LCT and control groups decreased by 11.2% (from 31.2 to 27.7 points, p,0.05) and 26.1% (from 27.2 to 20.1 points, p,0.001), respectively. The combined supplementation of MCTs (6 g), l-leucine-rich amino acids, and cholecalciferol may improve cognitive function in frail elderly individuals.