ERYTHRITOL, a widely-used non-nutritive sweetener, has been found to significantly impair brain microvascular endothelial cell function, increase oxidative stress, alter nitric oxide and endothelin-1 signalling, and reduce the release of tissue-type plasminogen activator in vitro.
Non-nutritive sweeteners such as erythritol have become popular alternatives to sugar in a variety of foods and drinks, particularly those marketed for weight management or diabetes. However, growing evidence has raised concerns about their effects on cardiovascular and cerebrovascular health, with some studies suggesting an association with increased risk of adverse vascular events. Understanding the impact of erythritol at the cellular level is therefore important, especially considering the widespread consumption of artificially sweetened beverages containing levels of erythritol equivalent to those studied.
This experimental study investigated the direct effects of erythritol on human cerebral microvascular endothelial cells (hCMECs) in vitro. Cells were treated with 6 mM erythritol, replicating the concentration found in a typical serving of an artificially sweetened drink, for three hours. The treatment resulted in a substantial rise in intracellular reactive oxygen species (ROS) production (204 ± 32% vs 105 ± 4%, erythritol vs control), and upregulation of antioxidant proteins superoxide dismutase-1 (332.1 ± 16.2 vs 214.9 ± 4.7 AU; P = 0.002) and catalase (30.9 ± 0.3 vs 24.4 ± 0.9 AU; P = 0.002). Despite no significant change in total endothelial nitric oxide synthase (eNOS) expression, phosphorylated eNOS at Ser1177 was reduced (52.1 ± 2.1 vs 77.3 ± 9.1 AU; P < 0.001), and at Thr495 was increased (63.4 ± 8.0 vs 45.6 ± 6.9 AU; P = 0.006) in erythritol-treated cells, resulting in lower nitric oxide production (5.8 ± 0.8 vs 7.3 ± 0.7 µmol/L). Expression and secretion of endothelin-1 were also higher (34.6 ± 2.3 vs 26.9 ± 1.5 pg/mL), and the release of t-PA in response to thrombin was notably blunted, indicating impaired vascular protective capacity.
The findings suggest that erythritol, at doses comparable to regular dietary exposure, can adversely affect the function of brain microvascular endothelial cells, potentially heightening oxidative stress and disturbing critical vascular signalling pathways. From a clinical perspective, these results urge caution when recommending products containing erythritol, particularly for individuals at elevated risk of cardiovascular or cerebrovascular disease. Future research should focus on in vivo studies, confirmation in larger populations, and elucidation of long-term consequences, in order to better inform dietary guidelines and public health recommendations.
Reference
Berry AR et al. The non-nutritive sweetener erythritol adversely affects brain microvascular endothelial cell function. Journal of Applied Physiology. 2025;138(6):1571-7.
