Summary: Erythritol, a widely used sugar substitute found in many “sugar-free” and low‑carb products, may negatively affect cells that line brain blood vessels, potentially raising the risk of stroke. New laboratory research reports that exposure of human brain microvascular endothelial cells to erythritol reduced nitric oxide production, increased expression of vessel‑constricting proteins, impaired the cells’ ability to release a natural clot‑dissolving factor, and raised production of damaging free radicals.
Taken together, these cellular changes create an environment more prone to vessel constriction, oxidative stress, and clot formation — all factors that can reduce blood flow to the brain. The investigators stress that the results come from cultured cells and that larger human studies are needed, but the findings add to a growing body of concern about potential cardiovascular and cerebrovascular effects of this non‑nutritive sweetener.
Key facts:
- Erythritol exposure made brain blood vessel cells more constricted in behavior and more prone to facilitate clotting.
- Reactive oxygen species (free radicals) increased while protective, clot‑busting responses were blunted.
- The cellular effects were observed at concentrations similar to those found in a typical single serving of an artificially sweetened beverage.
Source: University of Colorado
From low‑carb ice cream and keto protein bars to many “sugar‑free” sodas, erythritol is a common ingredient.
A team at the University of Colorado Boulder reports that this popular sweetener can adversely affect the function of human cerebral microvascular endothelial cells — the cells that line the smallest blood vessels in the brain. The study, published in the Journal of Applied Physiology, describes multiple cellular alterations that could plausibly raise the risk of ischemic stroke.
“Our study adds to the evidence suggesting that non‑nutritive sweeteners that have generally been considered safe may nevertheless carry negative health consequences,” said Christopher DeSouza, professor of integrative physiology and director of the Integrative Vascular Biology Lab.
Erythritol, a sugar alcohol approved for use by regulatory agencies and widely produced by fermenting corn, delivers almost no calories, is about 80% as sweet as table sugar, and minimally affects insulin. Those properties have made it a popular choice for people managing weight or blood glucose. But emerging research calls for a more cautious view.
The new laboratory study was motivated in part by earlier epidemiological findings in several thousand people that linked higher circulating erythritol levels with greater short‑term risk of heart attack and stroke. To explore potential mechanisms, first author Auburn Berry and colleagues exposed cultured human cerebral microvascular endothelial cells to 6 mM erythritol — an amount comparable to that present in a typical artificially sweetened beverage — for three hours.
Key observations included a significant rise in intracellular reactive oxygen species (ROS), indicating increased oxidative stress, and higher expression of antioxidant response proteins, which signals a cellular attempt to respond to that stress. The treated cells showed reduced activation of endothelial nitric oxide synthase (eNOS) at the activating phosphorylation site and increased inhibitory phosphorylation, which corresponded with lower nitric oxide (NO) production. NO normally relaxes and widens blood vessels; its reduction favors constriction.
At the same time, cells exposed to erythritol expressed more Big endothelin‑1 (Big ET‑1) and released more endothelin‑1 (ET‑1), a potent vasoconstrictor. When researchers stimulated the cells with thrombin, a clot‑forming signal, the expected increase in tissue‑type plasminogen activator (t‑PA)—a natural clot‑dissolving factor—was markedly blunted in erythritol‑treated cells compared with controls.
“If your vessels are more constricted and your ability to dissolve clots is reduced, your stroke risk is likely to rise,” Berry explained. The authors also note that their experiments used a single serving equivalent; frequent or multiple daily servings could plausibly produce larger effects, though that remains to be tested in human studies.
The researchers emphasize that these are in‑vitro findings and cannot by themselves prove that erythritol causes stroke in people. Nevertheless, when combined with prior observational data, the cellular results increase the rationale for further clinical research and for consumers to be mindful of intake.
DeSouza advises reading product labels for erythritol or the term “sugar alcohol” and monitoring consumption of non‑nutritive sweeteners until more is known. “Given the epidemiological signals and now our cellular data, it seems prudent for people to be cautious about habitual consumption,” he said.
About this diet and neurology research news
Author: Lisa Marshall
Source: University of Colorado
Contact: Lisa Marshall – University of Colorado
Image: The image is credited to Neuroscience News
Original Research: Open access. “The non‑nutritive sweetener erythritol adversely affects brain microvascular endothelial cell function” by Auburn Berry et al., Journal of Applied Physiology.
Abstract
The non‑nutritive sweetener erythritol adversely affects brain microvascular endothelial cell function
This in‑vitro study evaluated how erythritol affects oxidative stress, nitric oxide (NO) and endothelin‑1 (ET‑1) production, and tissue‑type plasminogen activator (t‑PA) release in human cerebral microvascular endothelial cells (hCMECs). Cells were treated with 6 mM erythritol (equivalent to a typical amount in a standard artificially sweetened beverage) for three hours.
Erythritol treatment significantly increased intracellular reactive oxygen species (ROS) and upregulated certain antioxidant proteins. Although total eNOS expression did not change appreciably, activating phosphorylation of eNOS was reduced and inhibitory phosphorylation was increased, corresponding with lower NO production. Big ET‑1 expression and ET‑1 release were elevated. In response to thrombin, t‑PA release was markedly blunted in erythritol‑treated cells compared with untreated controls. Overall, erythritol adversely affected oxidative stress markers, NO and ET‑1 balance, and t‑PA release, a combination of changes that may contribute to a higher risk of ischemic stroke associated with erythritol.
NEW & NOTEWORTHY
This study offers novel cellular evidence that erythritol, at concentrations commonly found in commercially available artificially sweetened beverages, can impair brain microvascular endothelial cell function by increasing oxidative stress, altering eNOS activation and NO production, boosting ET‑1 expression, and reducing t‑PA release. These mechanistic insights complement epidemiological observations linking erythritol with higher cardiovascular and cerebrovascular event risk and underscore the need for further human studies and careful consumer consideration.