A sweeping analysis of over 100 studies reveals aspartame is unlikely to alter glucose or hormone levels, challenging claims about its metabolic risks.
Review: The Effects of Aspartame on Glucose, Insulin, and Appetite-Regulating Hormone Responses in Humans: Systematic Review and Meta-Analyses. Image Credit: Monika Wisniewska / Shutterstock
A recent study published in the journal Advances in Nutrition investigated the effects of aspartame on insulin, glucose, and appetite-related hormone responses. High free sugar consumption is associated with elevated energy intake, increasing the risk for obesity, overweight, and chronic conditions. Therefore, the World Health Organization recommends limiting free sugar intake to 10% of total energy intake. One strategy to curb free sugar intake is to reformulate foods and drinks by reducing their sugar content. Many manufacturers achieve this using low-calorie sweeteners (LCSs).
LCSs are considered safe, with studies suggesting benefits for decreasing body weight and energy intake compared to sugar intake. However, the benefits of LCSs are less clear for chronic conditions and over the long term. For instance, LCS intake has been associated with a higher risk of obesity and various metabolic conditions, albeit the evidence remains limited. Aspartame is among the most common LCSs that are completely metabolized by the human digestive system.
Aspartame is recognized as safe for use in foods and beverages. Aspartame is converted into aspartic acid, methanol, and phenylalanine. Given this breakdown of metabolites found in dietary sources, the metabolic effects of aspartame may appear unlikely. However, some studies suggest differing effects for diverse health outcomes from aspartame intake. Controversy over aspartame’s health effects continues, in part because some studies have suggested different outcomes when compared to other LCSs.
About the study
In the present study, researchers investigated the effects of aspartame on insulin, glucose, and appetite-regulating hormone responses. PubMed, CINAHL, Medline, Cochrane Library, and Web of Science databases, as well as four trial registries, were searched for studies examining the effects of aspartame on insulin, appetite-regulating hormones, and glucose responses.
Any controlled intervention study design was eligible for inclusion, regardless of location and setting. Observational, animal, and in vitro studies were excluded from the analysis. Data on methodological aspects and risk of bias (RoB) were extracted from each study. The Cochrane Collaboration RoB-2 tool was used for RoB assessment.
A narrative synthesis of suitable experiments was performed based on the study design type, aspartame exposure, study duration, comparator, and outcomes. Meta-analyses were performed where at least 10 studies of the same design, exposure pattern, and outcome were available. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. The GRADE approach rated certainty as “very low” due to limitations in study design, inconsistency and heterogeneity among studies, indirectness, and possible publication bias.
The review included studies in a range of populations, such as healthy adults, individuals with type 1 or type 2 diabetes, phenylketonuria (PKU), and those with self-reported aspartame sensitivity.
Findings
Database search identified 11,796 records. After de-duplication and title/abstract screening, full texts of 417 articles were screened. Overall, 101 articles were included, which reported on the effects of aspartame alone or in combination with other substances. Furthermore, 73 studies reported on 77 crossover experiments, while 28 studies reported on 23 parallel-group experiments. Thirty-four studies examined the effects of aspartame alone on glucose responses with different comparators.
Aspartame had no effects on blood glucose compared to vehicle or other LCSs. However, blood glucose levels were significantly lower following aspartame intake compared to sweet sugars, non-sweet-tasting carbohydrates, or other nutritive components. Notably, these reductions were most evident in acute, short-term studies. Further, 19 studies provided aspartame with a nutritive component, and no effects of aspartame were noted. For insulin responses, 31 studies examined the effects of aspartame individually.
Aspartame had no effect on blood insulin levels compared to the vehicle; however, blood insulin levels were significantly lower after aspartame intake compared to non-sweet-tasting carbohydrates, sweet sugars, or other nutritive components. Further, blood insulin was significantly elevated with aspartame compared to other LCSs. Again, these significant differences were observed primarily in short-term experimental settings, not in medium- or long-term studies. Few effects were found with appetite-regulating hormones.
When appetite and energy intake were evaluated, the effects mimicked those of blood insulin and glucose. Few adverse events were reported across studies. Four crossover studies, which lasted up to 30 days (medium-term), found that high or low doses of aspartame did not affect blood glucose or insulin levels compared to sucrose or a placebo. Three crossover studies, which lasted more than 30 days (long-term), yielded results similar to those of medium-term studies.
In parallel-group acute studies, aspartame was found to reduce blood glucose levels compared to sucrose or glucose, when provided alone or in combination with nutritive components or LCSs. Four parallel-group, medium-term studies yielded results that mirrored those in short-term studies to some degree, with aspartame reducing blood insulin and glucose levels and improving insulin sensitivity compared to sugars. Ten parallel-group studies were performed over the long term.
No differences were found between aspartame and the comparator(s) in any biochemical measure. Nine studies provided data on energy intake and reported no differences or lower energy intake and density with aspartame compared to sucrose. Likewise, nine studies examined appetite and found no differences between groups. The RoB assessment raised concerns for most studies. The certainty of evidence was “very low” for all primary outcomes. The review also emphasized substantial heterogeneity in methodologies and outcomes across the included studies, further limiting interpretability. The diversity of included populations (such as individuals with diabetes, PKU, or aspartame sensitivity) likely contributed to this heterogeneity.
Conclusions
In sum, most studies investigated blood insulin and glucose levels over the short term, and the meta-analyses revealed no effects of aspartame compared to vehicle or other LCSs. However, lower blood insulin and glucose levels were found with aspartame compared to sugars and other nutritive components, mainly in acute interventions. Long- and medium-term studies had few effects of aspartame intake.
Few studies have assessed appetite-regulating hormones other than insulin, and few effects have been found in these studies. There was high heterogeneity across studies and populations. The inclusion of varied participant groups (e.g., those with metabolic diseases or sensitivities) was an additional factor influencing the overall certainty and generalizability of findings. Together, the findings reveal little to no impact of aspartame intake on glucose metabolism, either in the short term or the long term. Further long-term studies are needed to compare aspartame with other LCSs and assess various appetite-regulating hormones. The certainty of these findings is limited by study quality, heterogeneity, and the risk of bias.