Context
The thermic effect of food (TEF) may be a therapeutic target for the prevention and treatment of obesity.

Objective
The impact of different biological and nutritional characteristics on TEF in humans was analyzed.

Data Sources
The MEDLINE/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Latin American and Caribbean Health Sciences Literature databases were searched until November 2023 without language restrictions.

Data Extraction
Clinical trials were included that offered an oral test meal to adult and elderly individuals in a fasting state and measured TEF using calorimetry. The average TEF of each group was the outcome, and the impact of the individuals' and meal characteristics on the TEF was assessed using subgroups, meta-regression, and compositional analysis.

Data Analysis
The review included 133 studies, with 321 different groups. The mean TEF at 60 minutes after the test meal was 262 (95% CI, 236-288) kcal/d and decreased over time until 240 minutes after the test meal (P < .01). Male participants, individuals with normal body mass index, meals with energy content offered according to individual requirements, and meals with a mixed degree of food processing yielded a higher TEF. The total energy content of meals was the variable most strongly associated with TEF. Compositional analysis showed that the amount of lipids in meals was the only macronutrient consistently and negatively associated with TEF.

Conclusions
The TEF is influenced by specific individuals’ and meal characteristics. Total energy content and the amount of lipids were the characteristics of the meals most consistently associated with TEF. However, due to important methodological differences between studies, it is difficult to determine how to use TEF as a potential therapeutic target against obesity.