The sweetener erythritol is recommended for people with obesity and diabetes. University of Colorado Boulder research shows the popular sugar substitute impacts brain cells in  ways that boost risk of stroke.

WHAT EXACTLY WAS DONE

hCMECs exposed to 6 mM erythritol for 24 h — a level seen briefly after drinking a diet beverage sweetened with 30 g erythritol — showed 75–95 % more ROS,  20 % less NO,  30 % more ET‑1, and lost the normal 22 % thrombin‑triggered rise in t‑PA (basal t‑PA unchanged). Antioxidant enzymes (SOD‑1, catalase) also rose, suggesting a compensatory but insufficient response.

EXPLANATION

6 mM erythritol for 24 h

That concentration is designed to mimic the peak level that can circulate in a person’s blood for a short period after drinking a single can of a diet beverage sweetened with about 30 grams of erythritol.

The cells were bathed in that erythritol‑containing medium for roughly one full day. In cell‑culture work, 24 hours counts as an “acute” exposure: long enough for many biochemical systems to react, but short enough that most cells are still alive and dividing normally.

double ROS

Reactive oxygen species (ROS) are chemically reactive molecules that damage proteins and DNA when they build up. In the experiment, the erythritol exposure caused the cells to generate about twice as much ROS as untreated cells, indicating a marked spike in oxidative stress.

Cells constantly produce small amounts of reactive oxygen species (ROS) as by‑products of normal metabolism, and they normally keep these molecules in check with dedicated antioxidant enzymes. When an external factor—such as a brief spike in blood levels of the sweetener erythritol — pushes ROS production beyond the cell’s neutralising capacity, the excess ROS quickly react with nearby proteins, membrane lipids and DNA. These reactions alter the structure of proteins, make membranes less stable and introduce errors into genetic material, impairing essential cell functions.

Endothelial cells, which line all blood vessels, rely on finely tuned chemistry to regulate vessel diameter and prevent unwanted clotting. Elevated ROS disrupt this balance in two important ways. 

First, they lower production of nitric oxide, a signal that normally tells the vessel wall to relax, and simultaneously raise production of endothelin‑1, a signal that tightens vessels. 

Second, they blunt release of tissue‑type plasminogen activator, a protein that dissolves forming clots. Together, these changes make vessels narrower, more prone to clot formation and less able to clear clots once they start. 

Repeated or sustained episodes of oxidative stress can therefore contribute to conditions such as high blood pressure, heart attack and stroke by progressively undermining the protective functions of the vascular lining.

NO bioavailability cut by 20 %

Nitric oxide (NO) is a gas that endothelial cells release to make blood vessels relax. A 20 percent drop means the cells produced substantially less NO than normal, so their ability to signal vessel dilation was noticeably weakened.

Nitric oxide is a tiny gas molecule that the cells lining our blood vessels continually make. Its job is to tell the muscle layer around each vessel to loosen up so blood can flow easily. 

In the laboratory study, those cells made about one‑fifth less nitric oxide after a day of exposure to a blood‑level dose of erythritol. 

That reduction matters because a weaker “relax” signal leaves the vessel slightly tighter than it should be. 

If such drops happen often, vessels spend more time in a narrowed state, which increases resistance to blood flow, raises local pressure, and may limit oxygen delivery—especially in the brain, where steady flow is crucial. 

Over time, chronically lower nitric‑oxide signalling can contribute to high blood pressure and make stroke‑causing clots more likely.

Raise ET‑1 by 30 %

Endothelin‑1 (ET‑1) is a peptide that does the opposite of NO: it makes vessels constrict. A 30 percent increase means the balance tips toward vasoconstriction, which can reduce blood flow and elevate blood‑pressure stress on the vessel wall.

Endothelin‑1 is a small signalling protein made by the cells that line blood‑vessel walls. Its job is to tell the neighbouring muscle layer to contract. When the muscle contracts, the vessel becomes narrower and blood flow drops. 

In the cell study, one day of exposure to a realistic blood level of erythritol raised the amount of endothelin‑1 released by about 30 %. At the same time, nitric‑oxide production— the signal that normally tells the muscle to relax—fell.

Because the constricting signal increased and the relaxing signal decreased, the overall chemical balance shifted toward keeping vessels tighter than usual. 

If the same pattern occurred repeatedly in the body, vessels would spend more time in a constricted state. Narrower vessels resist blood flow, which forces the heart to push harder and raises internal pressure. Higher pressure and sustained narrowing put extra mechanical strain on vessel walls and can limit oxygen delivery to tissues, especially in small brain vessels. 

Over months or years, that added strain can promote high blood pressure and make clot‑related problems such as strokes more likely.

Abolish thrombin‑evoked t‑PA release

Under healthy conditions, adding thrombin (a clotting enzyme) makes endothelial cells release tissue‑type plasminogen activator (t‑PA), which dissolves clots. After erythritol exposure, that protective burst of t‑PA simply did not happen. In practical terms, the cells lost a key anti‑clotting response.

When blood‑vessel lining cells (endothelial cells) sense a sudden clotting signal, they normally protect the vessel by releasing an enzyme called tissue‑type plasminogen activator (t‑PA). t‑PA starts a chemical chain that dissolves fibrin, the main structural component of a clot, so small blockages are cleared before they become harmful.

In laboratory tests, scientists mimic that clotting signal by adding a small amount of thrombin— the same enzyme that begins clot formation in blood. Healthy endothelial cells respond with a noticeable burst of t‑PA: about a 25 % rise in the enzyme’s level within a day.

After the cells were exposed to erythritol for 24 hours, this safety mechanism failed. When thrombin was added, the usual rise in t‑PA did not occur; the enzyme’s level stayed flat. The cells still contained the machinery to make t‑PA, but the trigger no longer worked.

If a similar loss of response happened inside the body, an early clot in a small brain vessel might not be dissolved quickly. That could allow the clot to grow or persist, increasing the chance it will block blood flow and cause an ischemic stroke. 

hCMECs

All of this was observed in human cerebral microvascular endothelial cells, a lab‑grown model of the cells that line the tiny blood vessels in the brain. Although the study was done in a dish, these cells faithfully reproduce many features of brain capillary behavior, so the findings raise concerns about how erythritol spikes might affect real cerebral vessels.