Background Fructose consumption has significantly increased in recent years and is associated with hepatic oxidative stress, playing a major role in metabolic diseases such as metabolic‐associated fatty liver disease (MAFLD). This systematic review aimed to summarize how excessive fructose consumption causes liver injury through oxidative stress, leading to lipid accumulation in hepatic cells. Methods PubMed, Scopus, and Web of Science databases were systematically searched (2019–2024) for preclinical studies using fructose‐only diets. Criteria were applied to identify relevant studies. The primary outcome was hepatic oxidative stress, and the secondary outcomes included weight, metabolic markers, liver function, and histopathology changes. Two reviewers assessed bias risk using SYRCLE. Results Among 517 studies screened, 26 met the inclusion criteria. Most studies had unclear bias risk due to poor reporting. Low‐dose fructose intake (10%) over 8–12 weeks induced hepatic oxidative stress, indicated by elevated malondialdehyde (MDA) in 53.8% of cases, increased reactive oxygen species (ROS) in 19.2%, and reduced antioxidant defenses, including glutathione (GSH), GSH peroxidase (GSH‐Px), and superoxide dismutase (SOD) in 38.5%. Four studies showed early upregulation of antioxidant responses (11.5%), suggesting initial adaptation. Prolonged fructose exposure (up to 36 weeks) caused sustained liver injury due to overwhelming defenses and increased oxidative stress. Most studies also reported metabolic disturbances, liver dysfunction, and lipid accumulation. Conclusion This systematic review showed that excessive fructose consumption induces liver injury through oxidative stress, which then triggers subsequent processes like inflammation. Overconsumption led to uncontrolled hepatic metabolism, increasing lipid synthesis, metabolic overload, overproduction of ROS, impairment of antioxidant defenses, and histopathological changes.
Arifin et al. (2026) studied this question.