Medium Chain Triglycerides induce mild ketosis and may improve cognition in Alzheimer's disease. A systematic review and meta-analysis of human studies

Introduction/aim: The brain in Alzheimer's disease shows glucose hypometabolism but may utilize ketones for energy production. Ketone levels can potentially be boosted through oral intake of Medium Chain Triglycerides (MCTs). The aim of this meta-analysis is to investigate the effect of MCTs on peripheral ketone levels and cognitive performance in patients with mild cognitive impairment and Alzheimer's disease. Methods: Medline, Scopus and Web of Science were searched for literature up to March 1, 2019. Meta-analyses were performed by implementing continuous random-effects models and outcomes were reported as weighted Mean Differences (MDs) or Standardized Mean Differences (SMDs). Results: Twelve records (422 participants) were included. Meta-analysis of RCTs showed that, compared with placebo, MCTs elevated beta-hydroxybutyrate [MD = 0.355; 95 % CI (0.286, 0.424), I-2 = 0 %], showed a trend towards cognitive improvement on ADAS-Cog [MD = -0.539; 95% CI (-1.239, -0.161), I-2 = 0 %], and significantly improved cognition on a combined measure (ADAS-Cog with MMSE) [SMD = 0.289; 95 % CI (-0.551, -0.027), I-2 = 0 %]. Conclusions: In this meta-analysis, we demonstrated that MCTs can induce mild ketosis and may improve cognition in patients with mild cognitive impairment and Alzheimer's disease. However, risk of bias of existing studies necessitates future trials.