Importance of melatonin and its supplementation in the treatment of obesity, inflammatory processes, non-alcoholic hepatic steatosis, and hepatocellular carcinoma: a systematic review

Introduction: There are more than 2.3 billion overweight and obese people in the world. One of the important neurohormones responsible for adipose tissue metabolism is melatonin (N-acetyl-5-methoxytryptamine) (MEL), which can modulate inflammatory processes by eliminating nitric oxide, reducing synthesis or inhibiting other pro-inflammatory mediators, including tumor necrosis factor-alpha (TNF-a), interleukin 6 (IL-6) and interleukin 8 (IL-8). Objective: It was to highlight the main considerations and clinical evidence of the importance of melatonin and its supplementation in the treatment of obesity, inflammatory processes, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Methods: The systematic review rules of the PRISMA Platform were followed. The search was carried out from May to July 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 115 articles were found. A total of 28 articles were evaluated and 25 were included in this systematic review. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 18 studies with a high risk of bias and 25 studies that did not meet the GRADE. Most studies presented homogeneity in their results, with X2=85.7%>50%. It was concluded that obesity-related inflammation is related to a state of oxidative stress with high production of reactive oxygen species. Melatonin has been highlighted for its antioxidant and anti-inflammatory properties. The high prevalence of obesity in the world population also confers an increased risk for the development of non-alcoholic fatty liver disease (NAFLD), as well as other liver diseases including hepatocellular carcinoma (HCC). Studies involving drug and molecular therapies are proposed to control the progression of these diseases. It is necessary to perform a molecular analysis involving epigenetic, biochemical, and inflammatory aspects related to melatonin supplementation, clarifying the effect of melatonin supplementation on obesity and liver diseases, including NAFLD and HCC. Thus, it is highlighted that the antioxidant and anti-inflammatory effect of melatonin is essential as a synergistic agent in weight loss and as prophylaxis and/or treatment of liver diseases.