THE NON-NUTRITIVE sweetener erythritol, commonly found in sugar-free beverages, may impair brain microvascular endothelial cell function by increasing oxidative stress and disrupting nitric oxide (NO) signaling, according to new in vitro findings. These changes could contribute to a higher risk of cerebrovascular complications such as ischemic stroke.
Researchers cultured human cerebral microvascular endothelial cells (hCMECs) and exposed them to a physiologically relevant concentration of erythritol equivalent to a 30 g dose, an amount typically found in artificially sweetened drinks. Within 3 hours, the cells exhibited a marked increase in intracellular reactive oxygen species, with a 204% elevation compared to controls. This oxidative stress was accompanied by increased expression of antioxidant enzymes, including superoxide dismutase-1 and catalase, indicating cellular efforts to counteract the imbalance.
Although total endothelial nitric oxide synthase (eNOS) levels remained unchanged, its activation profile was significantly altered. Cells treated with erythritol showed a decrease in phosphorylation at Ser1177, a site associated with eNOS activation, and an increase at Thr495, which is linked to eNOS inhibition. These modifications translated to reduced NO production and elevated endothelin-1 (ET-1), a potent vasoconstrictor, suggesting impaired endothelial regulation of vascular tone.
Furthermore, erythritol exposure blunted the release of tissue-type plasminogen activator (t-PA) in response to thrombin. While untreated cells showed a robust increase in t-PA levels, this fibrinolytic response was essentially absent in erythritol-treated cells, raising concerns about compromised thrombolytic potential in cerebral microvasculature.
Taken together, these findings indicate that erythritol may adversely impact brain endothelial cell function by promoting oxidative stress, dysregulating NO and ET-1 production, and inhibiting fibrinolytic activity. While the study was conducted in vitro, the mechanistic insights highlight a potential biological link between erythritol intake and cerebrovascular risk.
Reference:
Berry AR et al. The non-nutritive sweetener erythritol adversely affects brain microvascular endothelial cell function. J Appl Physiol. 2025;138:1571–1577.
