Saccharin sodium powder

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.

Abstract licence: CC BY

Nonsugar sweeteners (NSSs) are added to foods and beverages to provide sweetness in place of sugar while reducing the total caloric content. Reducing sugar intake, and corresponding calories, may decrease the risk of diabetes and other health conditions associated with obesity (e.g., cancer). Numerous observational epidemiology studies have evaluated the effect of NSSs on cancer risk, sometimes focusing on a specific NSS or a specific cancer, other times focusing on all NSSs or all cancers. We conducted a systematic review of epidemiology studies of NSS intake (of all types in aggregate and individually) and the risks of all types of cancer published through Fall 2024 [preregistered with Open Science Framework (https://osf.io/gc8v6)]. We considered how major study quality concerns might have impacted the interpretation of individual study results, as well as the evidence as a whole. We identified 90 studies of acesulfame potassium (ace-K), aspartame, cyclamate, saccharin, sucralose, or nonspecific NSSs in aggregate [e.g., diet sodas, artificially sweetened beverages], and 17 specific types of cancer. We found no consistent associations between any NSS or NSSs in aggregate and any cancer overall, and no evidence for dose-response. NSS intake information was always self-reported, rendering exposure misclassification an ongoing challenge in all studies, and recall bias remains a significant possibility in all case-control studies. Many studies also did not fully account for potential confounders. Experimental animal and mechanistic evidence for NSSs does not support human-relevant carcinogenicity or any biologically plausible mechanisms by which NSSs could cause genotoxicity or cancer in humans. Overall, the epidemiology evidence does not support associations between any NSS and any cancer type.

Abstract licence: CC BY