The health food industry has rushed to incorporate so-called sugar alcohols into everything from protein bars to zero-sugar energy drinks to guilt-free desserts over the past decade—and with some justification. Unlike prior generations of artificial sweeteners, sugar alcohols are naturally occurring, low-calorie substitutes that the human body can metabolize without taking on a variety of potentially deadly and hotly debated health risks.
But researchers at the University of Colorado at Boulder have uncovered compelling evidence that too much of at least one sugar alcohol, erythritol, might raise its own risks: the kind of blood clots in your brain that can lead to a stroke. Crucially, their study documented cellular-level mechanisms induced by erythritol that appear to corroborate an alarming epidemiological study from 2023, which linked higher levels of erythritol in the blood to an elevated risk of a heart attack or stroke within three years.
As a sweetener, erythritol is quite common, appearing in protein bars, sugar-free beverages, keto snacks, and some “natural” sweetener blends, including as an additive you might not expect in organic sweeteners, stevia and monk fruit.
“Given the epidemiological study that inspired our work, and now our cellular findings, we believe it would be prudent for people to monitor their consumption of non-nutrient-sweeteners such as this one,” study coauthor Christopher DeSouza, the director of CU Boulder’s Integrative Vascular Biology Lab, said in a statement.
“Big picture, if your [blood] vessels are more constricted and your ability to break down blood clots is lowered,” coauthor Auburn Berry, a graduate researcher in DeSouza’s lab, added, “your risk of stroke goes up.”
Stressed-out blood vessels
Berry and DeSouza cultured human cerebral microvascular endothelial cells (hCMECs)—cells that form a key part of blood vessels in the brain—for their study. They then exposed these hCMEC cell cultures to a typical amount of the erythritol present in just a single serving of an average zero-sugar beverage, 30 grams, for a period of three hours.
They and their CU Boulder colleagues saw several changes that concerned them. First, the added erythritol resulted in cells producing less nitric oxide, a signaling molecule that helps to relax and widen blood vessels, as well as more endothelin-1, an amino acid that acts as the most potent tightener of blood vessels in the body, often with inflammatory effects. Next, highly reactive free radical oxygen compounds were recorded at roughly 75% higher concentrations in the cell cultures containing the added sugar alcohol compared to the control group hCMEC cultures.
These subtle shifts in biochemistry compounded the risk that the researchers detected with two other compounds that play a key role in how blood vessels create and regulate blood clots. When these cell cultures were exposed to the enzyme thrombin, a coagulant that helps generate blood clots, the added erythritol blunted the cells’ production of tissue-type plasminogen activator (t-PA), a compound that naturally breaks down clots. The cell cultures produced roughly 25% more t-PA without the erythritol present.
DeSouza noted that, although deeper clinical research would be needed, his lab’s findings could be deemed conservative given that only a single serving amount of erythritol was tested in their study, published in the Journal of Applied Physiology. Someone who routinely guzzles zero-sugar energy drinks or pounds multiple low-calorie protein bars in a single day, in other words, could possibly experience a more extreme version of these effects.
Erythritol in food vs. erythritol your body makes
While the CU Boulder study does raise alarm, other medical researchers have argued that it is too early to make broad assumptions about erythritol just yet.
Researchers at Romania’s University of Medicine and Pharmacy of Craiova co-published a letter in the same journal, emphasizing that the human body not only makes erythritol but also tends to do so in response to various kinds of caloric stress, like obesity, insulin resistance, and diabetes. As the name “sugar alcohol” might indicate, erythritol is produced in a fermentation-like process within several organs of the body, including red blood cells (erythrocytes), the liver, and the kidney.
In other words, even though the large, 4,000-person study that inspired CU Boulder’s own work did find a strong correlation between blood levels of erythritol and risks of stroke, there’s no telling yet how much of that erythritol was made due to those patients’ other conditions or personal habits.
“Without addressing this dual origin,” George Dan Mogoşanu, an associate professor at Craiova, and his colleagues noted, “causality between dietary erythritol and vascular risk remains speculative.”