The Non-Nutritive Sweetner Erythritol Adversely Affects Brain Microvascular Endothelial Cell Function
Berry A, Ruzzene S, Ostrander E, Wegerson K, Fersiva N, Stone M, Valenti W,Izaias J, Holzer J, Greiner J, Garcia V, DeSouza C (2025) J Appl Physiol (1985) 2025 Jun 3. doi: 10.1152/japplphysiol.00276.2025
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Abstract:
The experimental aim of this study was to determine, in vitro, the effect of the non-nutritive sweetener erythritol on brain microvascular endothelial cell oxidative stress, nitric oxide (NO) and endothelin (ET)-1 production, as well as tissue-type plasminogen activator (t-PA) release. Human cerebral microvascular endothelial cells (hCMECs) were cultured and treated with 6 mM of erythritol, equivalent to a typical amount of erythritol [30g] in an artificially sweetened beverage, for 3 hr. Intracellular reactive oxygen species (ROS) production was significantly higher in hCMECs treated with erythritol (204±32% vs 105±4%) as well as expression 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). Although endothelial nitric oxide synthase (eNOS) expression was not significantly altered (102.8±21.4 vs 99.0±19.9 AU); expression of p-eNOS (Ser1177) was lower (52.1± 2.1 vs 77.3±9.1 AU; P<0.001) and p-eNOS (Thr495) higher (63.4±8.0 vs 45.6±6.9 AU; P=0.006) in hCMECs treated with erythritol. Cell expression of Big ET-1 was also higher in erythritol-treated cells (56.4±9.8 vs 40.9±6.5 AU; P=0.02). Consequently, endothelial NO production was significantly lower (5.8±0.8 vs 7.3±0.7 μmol/L) and ET-1 production significantly higher (34.6±2.3 vs 26.9±1.5 pg/mL) in response to erythritol. t-PA release in response to thrombin was significantly blunted in erythritol treated (from 87.4±6.3 to 87.6±8.3 pg/mL) versus untreated (90.1±5.5 to 110.2±6.4 pg/mL) hCMECs. In summary, erythritol adversely affects oxidative stress, NO production, ET-1 production and t-PA release in brain microvascular endothelial cells; potentially contributing to the increased risk of ischemic stroke associated with erythritol.FAB RESEARCH COMMENT:
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