Gastrointestinal issues predominate among side effects of medium-chain triglyceride consumption in humans.

INTRODUCTION: Medium-chain triglycerides (MCTs) are widely used in clinical and nutritional contexts due to their rapid metabolism and therapeutic potential. However, concerns regarding their tolerability persist, particularly with respect to gastrointestinal side effects. This systematic review examines the occurrence and characteristics of side effects following oral MCT consumption. METHODS: In accordance with the PRISMA guidelines and the Cochrane Handbook, a systematic literature search was conducted in PubMed and Web of Science. Studies reporting side effects following oral, gastric or enteral MCT administration were included. Data on study design, population characteristics, MCT formulation, dosage, and reported side effects were extracted and synthesized. Side effects were analyzed quantitatively or qualitatively in studies using non-standard reporting formats. Risk of bias was assessed using the RoB 2 tool for randomized studies and the ROBINS-I tool for non-randomized studies. RESULTS: Thirty three studies comprising 1,100 participants were included. Gastrointestinal symptoms were the most frequently reported side effects, particularly diarrhea, abdominal pain, discomfort, and nausea. While these symptoms were often described as mild, moderate to severe reactions and dropouts due to side effects were not uncommon, especially at higher doses. Substantial heterogeneity in study design, dosing strategies, and reporting practices limited comparability. Temporal aspects of side effects and long-term tolerability were insufficiently investigated, and evidence regarding the influence of MCT composition and co-administration strategies on tolerability remained inconclusive. A high proportion of studies reported industry involvement, and risk-of-bias assessment indicated that 26.3% (RoB 2)--78.6% (ROBINS-I) of the included studies were at high/serious risk of bias. CONCLUSIONS: Gastrointestinal side effects represent a consistent and clinically relevant limitation of MCT use. Standardized methodologies and targeted research are needed to better understand and mitigate these effects, thereby improving the safety and applicability of MCT-based interventions.