Association between artificial sweeteners and cancer risk: an umbrella meta-analyses study

Artificial sweeteners (AS) are widely used as sugar substitutes, particularly among individuals with metabolic disorders. Although AS are approved by regulatory authorities, concerns regarding their potential association with cancer risk persist due to inconsistent findings across studies. This umbrella review aimed to comprehensively synthesize evidence from published meta-analyses evaluating the association between AS consumption and cancer risk. A systematic search of PubMed, Web of Science, and Scopus was conducted to identify meta-analyses examining the association between AS consumption and cancer outcomes in human populations. Data synthesis was performed using random-effects models, and evidence certainty was evaluated using the GRADE framework. Sensitivity analyses, prediction intervals, and publication bias assessments were conducted when applicable. Overall AS consumption was not significantly associated with breast cancer (OR = 0.99, 95% CI 0.92–1.08, P = 0.99), colorectal cancer (CRC) (OR = 0.90, 95% CI 0.76–1.05, P = 0.18), pancreatic cancer (OR = 1.04, 95% CI 0.93–1.17, P = 0.44), gastric cancer (OR = 0.93, 95% CI 0.63–1.36, P = 0.71), or bladder cancer (OR = 1.19, 95% CI 0.75–1.88, P = 0.44). Dose-specific analyses showed no significant associations between AS consumption and breast cancer across low-dose (OR = 1.00, 95% CI 0.95–1.06, P = 0.83), moderate-dose (OR = 0.97, 95% CI 0.94–1.01, P = 0.21), or high-dose categories (OR = 0.88, 95% CI 0.73–1.06, P = 0.18). For CRC, low-dose AS consumption was associated with a reduced risk (OR = 0.87, 95% CI 0.76–0.99, P = 0.04; GRADE: low), whereas moderate-dose (OR = 1.11, 95% CI 0.92–1.33, P = 0.25) and high-dose AS consumption (OR = 0.89, 95% CI 0.79–1.00, P = 0.05) showed no significant associations with CRC risk. Based on the GRADE framework, the certainty of evidence was rated as low for breast cancer, CRC, and pancreatic cancer, very low for bladder cancer, and not assessable for gastric cancer due to the limited number of studies. Although no significant cancer risks were identified, the overall strength of the evidence was weak. More well-designed, high-quality studies are necessary to further explore and clarify the long-term impact of AS on cancer risk. Additionally, there is insufficient evidence available to assess the effects of AS on other cancer types, and further research is needed in this area.