Background: Branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—play a fundamental role in muscle metabolism, acting as energy substrates and regulators of protein synthesis through mTOR pathway signaling. Beyond their well-established role in sports nutrition, BCAAs have been widely studied in clinical contexts such as cancer, liver cirrhosis, and cachexia due to their ability to preserve muscle mass and modulate metabolic responses in catabolic states. This article presents an integrative review of the current literature on the biochemical and physiological mechanisms of BCAAs, their therapeutic applications, and the limits of their supplementation. The paper also discusses controversies regarding the efficacy of BCAAs, their metabolic interactions with other nutrients, and the risks associated with indiscriminate use. Finally, it highlights gaps in the literature and the need for future research that prioritizes the personalization of nutritional interventions based on robust evidence. A deeper understanding of these aspects is essential to optimize the clinical and athletic use of BCAAs Material and Methods: The integrative review was conducted through a systematic search of major electronic databases—PubMed, Scopus, Web of Science, and SciELO—using keywords related to branched-chain amino acids (BCAAs) in both Portuguese and English. Included were original articles, systematic reviews, metaanalyses, and guidelines from 2000 to 2025 focusing on BCAA metabolism, sports and clinical applications, and supplementation safety and efficacy. Studies involving human interventions, relevant preclinical research, and theoretical reviews were selected. Exclusions applied to duplicates, articles without full text, and low-quality studies, with quality assessed by study design, sample size, and result clarity. Data were analyzed qualitatively to integrate biochemical mechanisms, therapeutic uses, controversies, and identify research gaps, providing a comprehensive and critical overview of current evidence. Results: This integrative review analyzed scientific studies on the metabolic, therapeutic, and ergogenic effects of branched-chain amino acids (BCAAs). It included a variety of research methods such as clinical trials, theoretical reviews, and experimental studies in animal and in vitro models. The findings highlight the complex physiological roles of BCAAs, focusing on their involvement in energy metabolism, protein synthesis, cell signaling, and their implications in diseases like cancer, type 2 diabetes, and liver disorders. Conclusion: Branched-chain amino acids (BCAAs) are key regulators of protein synthesis through the mTORC1 pathway, serve as energy sources during catabolic stress, and are involved in metabolic, liver, and cancer-related diseases. While BCAA supplementation can have ergogenic and therapeutic benefits in certain situations, its effectiveness is limited without adequate intake of other essential amino acids for optimal anabolic response. Impaired BCAA oxidation is linked to insulin resistance, obesity, and some cancers, making dietary BCAA management a potential clinical strategy. However, indiscriminate use of BCAAs can pose metabolic risks, highlighting the importance of evidence-based, individualized nutritional approaches tailored to a person’s physiological condition and treatment goals.
Costa et al. (Fri,) studied this question.