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Artificial Sweeteners and Cardiovascular Disease: Systematic Review and Meta-analysis
Sofía Gimeno-Ruiz1,2, Carolina Torrijo-Belanche1, Ainara Muñoz-Cabrejas3
1Department of Preventive Medicine and Public Health, Universidad de Zaragoza, Zaragoza, 50009, Spain.
Context:
The recommendation of a low-sugar diet to prevent cardiovascular disease (CVD) has led to the popularity of artificial sweeteners (AS). Although their consumption is considered mostly safe, their potential associations with cardiovascular health remain controversial.
Objectives:
The aim of this study was to review the existing published evidence on the association between AS and CVD, specifically excluding artificially sweetened beverages, which have been studied more recently.
Data Sources:
Articles were retrieved from the PubMed, Web of Science, and Scopus databases from inception to February 2025.
Data Extraction:
Study characteristics related to AS and CVD meeting the inclusion criteria were extracted by 2 independent reviewers. Relevant information was extracted and presented according to PRISMA guidelines. A random-effects model was used to estimate the pooled hazard ratio with its 95% CI, and I2 was used to assess heterogeneity. Funnel plots and Egger's tests were used to evaluate publication bias.
Data Analysis:
A total of 11 articles were identified (6 for serum/plasma measurements of AS and 5 for dietary consumption). The meta-analysis showed a positive association for serum/plasma polyols, with a 26% higher risk of cardiovascular events when comparing extreme categories. However, there was high heterogeneity and suspicion of publication bias. Second, the systematic review of AS consumption found mixed results for CVD mortality, although most estimates for cardiovascular events were positive. However, the number of included articles was relatively small and based on specific foods, making it difficult to draw conclusions.
Conclusion:
Elevated serum/plasma polyols are positively associated with a higher presence of cardiovascular events. However, total AS consumption was not clearly associated with CVD mortality or cardiovascular events. Future research is needed to better establish the association between AS and CVD.
Systematic Review Registration:
PROSPERO registration no. CRD42025644601.
Insights
Artificial sweeteners (AS) are popular for low-sugar diets, but their cardiovascular disease (CVD) link is debated. Elevated serum polyols show a higher CVD risk, but total AS consumption lacks clear association.
Area of Science:
- Nutrition Science
- Cardiovascular Research
- Public Health
Background:
- Artificial sweeteners (AS) are widely used as sugar substitutes, particularly in low-sugar diets recommended for cardiovascular disease (CVD) prevention.
- Despite widespread consumption and perceived safety, the association between AS and cardiovascular health remains a subject of ongoing scientific debate.
- This study addresses the controversial link between AS and CVD, focusing on direct measurements and dietary intake, excluding artificially sweetened beverages.
Purpose of the Study:
- To systematically review and synthesize existing evidence on the association between artificial sweeteners (AS) and cardiovascular disease (CVD).
- To specifically investigate the relationship between serum/plasma levels of AS and CVD outcomes.
- To examine the association between dietary consumption of AS and CVD mortality and events, excluding studies on artificially sweetened beverages.
Main Methods:
- A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus databases up to February 2025.
- Data extraction followed PRISMA guidelines, with study characteristics and AS/CVD associations extracted by two independent reviewers.
- Meta-analysis employed a random-effects model to estimate pooled hazard ratios, with heterogeneity assessed using I2 and publication bias evaluated via funnel plots and Egger's tests.
Main Results:
- Meta-analysis of 6 studies on serum/plasma AS revealed a positive association for polyols, indicating a 26% higher risk of cardiovascular events when comparing extreme intake categories.
- High heterogeneity and suspected publication bias were noted in the serum/plasma polyol analysis.
- Systematic review of 5 studies on AS consumption showed mixed results for CVD mortality but generally positive associations for cardiovascular events, though limited by small sample sizes and focus on specific food products.
Conclusions:
- Elevated serum/plasma polyol levels are significantly associated with an increased risk of cardiovascular events.
- Current evidence does not establish a clear association between overall artificial sweetener consumption and cardiovascular disease mortality or events.
- Further rigorous research is essential to elucidate the complex relationship between artificial sweetener intake and cardiovascular health.
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