The effects of aspartame on glucose, insulin and appetite-regulating hormone responses in humans: Systematic review and meta-analyses.

Abstract

BACKGROUND: Aspartame (L-α-aspartyl-L-phenylalanine methyl ester) has been implicated in increased risk for several chronic health conditions, yet underlying mechanisms remain unclear. OBJECTIVE: To systematically identify and summarize all controlled intervention studies investigating effects of aspartame consumption on glucose, insulin and appetite-related hormone responses. METHODOLOGY: Five academic databases, four trial registries, and additional resources were searched until June 2024. Search hits were screened, in duplicate, for intervention studies of aspartame versus comparator, which assessed glucose, insulin and/or any other appetite-regulating hormone. Results were tabulated, and meta-analyses run where ≥10 studies with similar methodology were found. Risk of bias was assessed using RoB-2. Certainty of the evidence was assessed using GRADE. RESULTS: 101 articles were identified, detailing 100 experiments: 79 acute (<1 day), 8 medium-term (2-30 days), 13 long-term (>30 days). Experiments involved healthy adults, individuals with aspartame sensitivity and individuals with compromised glucose metabolism, varied widely in aspartame provision and comparator/s, and while almost all assessed glucose and/or insulin responses, few experiments investigated other appetite-regulating hormones. Meta-analyses (acute cross-over studies) revealed few effects of aspartame on blood glucose/insulin compared with vehicle or low-calorie-sweeteners (LCS), and lower blood glucose/insulin levels compared with sugars, other carbohydrates or nutritive elements. Over the medium- and long-term, few effects of aspartame were found, and high heterogeneity between studies remained. Similar effects were found in other populations, and other outcomes, with few adverse events. Risk of bias assessments suggested 'some concerns' for the majority of studies. The certainty of the evidence for all outcomes in all populations was judged to be 'very low'. CONCLUSIONS: Our findings suggest little to no effects of aspartame consumption on glucose metabolism over the short- or longer-term. Further studies over the longer-term, assessing a range of appetite-regulating hormones, and comparing aspartame with other LCS would be of value. PROTOCOL REGISTRATION: PROSPERO:CRD42024540781, 29.04.24. STATEMENT OF SIGNIFICANCE: While the health impacts of aspartame consumption remain controversial, this work identified 100 experiments investigating the effects of aspartame consumption on glucose, insulin and other appetite-regulating hormone responses. Little to no effects of aspartame were found over the short- or long-term, with no contra-indications for health.