Effects of Artificial Sweeteners on the Musculoskeletal System: A Systematic Review of Current Evidence

Background: FDA-approved artificial sweeteners (ASs) are widely used in food products due to their low-calorie content and high sweetness. However, growing evidence links them to adverse metabolic effects, including stroke and coronary heart disease. The musculoskeletal system, as a key metabolic target organ, has gradually gained attention, but the potential impact of ASs on its health remains unclear. Objective: This systematic review aims to assess the effects of ASs on bone and muscle, explore the underlying biological mechanisms and provide guidance for future research. Methods: A comprehensive literature search was conducted in PubMed, Embase, and Web of Science using relevant keywords from inception to 25 June 2025. Studies written in English, available in full text, and investigating FDA-approved ASs in relation to the musculoskeletal system were included. Two independent reviewers screened and selected the eligible studies. The findings were summarized using a narrative synthesis approach. Results: A total of 15 studies (12 preclinical, 3 clinical), covering aspartame, acesulfame potassium, sucralose, and saccharin were included from an initial pool of 662 articles identified across PubMed (168), Embase (368), and Web of Science (126). Among them, twelve studies focused on skeletal effects, four on muscles, and two on joints; three studies reported multiple outcomes. No studies investigated ligaments or tendons. Conclusions: Based on our search, this review provides a narrative synthesis of the available evidence on ASs influencing skeletal structure, development, biomechanical strength, and skeletal muscle metabolism. Potential mechanisms involve gut microbiota, oxidative stress, and signaling pathways such as SIRT1/FOXO3a and PGC-1α/UCP3. Further research is warranted to clarify these mechanisms and to assess the chronic health effects of long-term AS exposure on the musculoskeletal system in human populations.