If you have been reaching for beverages sweetened with erythritol, thinking you were making a healthier choice than sugar, a new study published in the Journal of Applied Physiology should give you serious pause. Researchers at the University of Colorado, Boulder, have demonstrated that erythritol, at the exact concentration found in a single can of an artificially sweetened beverage, causes significant damage to the cells lining the tiny blood vessels of the brain.
This is not a theoretical concern or an animal study using impossibly high doses. The researchers used a concentration of erythritol (6 millimolar) that closely matches the amount that enters your bloodstream after drinking one standard-size artificially sweetened drink containing about 30 grams of erythritol. And what they found was alarming on multiple fronts.
What Is Erythritol, and Why Should You Care?
Erythritol is a sugar alcohol (polyol) that has exploded in popularity over the past decade. It contains only 0.2 calories per gram, is about 60-80% as sweet as table sugar, and has virtually no impact on blood glucose or insulin levels. The FDA approved it in 2001, and it has since become a go-to sweetener in “keto-friendly” products, protein bars, flavored waters, and diet beverages. For people managing obesity, metabolic syndrome, or diabetes, it has been widely promoted as a safe way to reduce sugar and calorie intake.
Your body naturally produces small amounts of erythritol. Red blood cells, the liver, and the kidneys all generate it from glucose and fructose via the pentose phosphate pathway. It also occurs in trace amounts in certain fruits, vegetables, and fermented foods. So erythritol is not entirely foreign to human biology. But the amounts consumed in modern artificially sweetened products dwarf what the body produces on its own, and that distinction matters enormously.
What the New Study Found: Four Mechanisms of Harm
The research team, led by Auburn Berry and Christopher DeSouza, cultured human cerebral microvascular endothelial cells (the specialized cells lining the brain’s smallest blood vessels) and exposed them to erythritol for 24 hours. They measured the impact across four critical dimensions of brain vascular health.
1. Oxidative Stress Surged by 75%
Erythritol caused a dramatic 75% increase in reactive oxygen species (ROS) production within the brain endothelial cells. Think of ROS as molecular “sparks” that, in small amounts, serve useful signaling functions, but in excess, act like a blowtorch against delicate cellular structures. The cells attempted to fight back by ramping up production of two key antioxidant defense enzymes: superoxide dismutase-1 (SOD-1, increased ~45%) and catalase (increased ~25%). But this compensatory response was not enough to neutralize the erythritol-driven oxidative surge. The researchers specifically noted that the increase in ROS production was not negated by the rise in antioxidant enzymes. Brain endothelial cells are particularly vulnerable to oxidative damage because they contain an unusually high number of mitochondria, making them highly susceptible to both internal and external triggers of ROS production.
2. Nitric Oxide Production Dropped by 20%
Nitric oxide (NO) is one of the brain’s most important protective molecules. Produced by the enzyme eNOS (endothelial nitric oxide synthase), it keeps blood vessels relaxed and open, prevents blood platelets from clumping into dangerous clots, suppresses inflammation, and maintains healthy cerebral blood flow. Without adequate NO, the brain’s blood supply becomes compromised.
Erythritol did not reduce the total eNOS protein levels in cells. Instead, it attacked the enzyme’s activation switches. Phosphorylation at a site called Ser1177, which turns eNOS “on,” dropped by approximately 35%. Simultaneously, phosphorylation at Thr495, which acts as an “off” switch for eNOS, increased by about 40%. The net result was a 20% reduction in nitric oxide production, a change that significantly shifts the brain’s vascular environment toward constriction, clotting, and inflammation.
3. Endothelin-1 Production Rose by 30%
While nitric oxide relaxes blood vessels, endothelin-1 (ET-1) is the most powerful vasoconstrictor peptide the endothelium produces. Under normal conditions, NO and ET-1 exist in a carefully balanced tug-of-war that maintains proper blood flow. Erythritol disrupted this balance from both directions: it reduced NO while simultaneously increasing ET-1 production by roughly 30%. The precursor protein to ET-1 (called Big ET-1) was also significantly elevated, indicating that erythritol was driving increased synthesis of the vasoconstrictor at the gene expression level, not merely releasing stored ET-1. This double hit, less relaxation combined with more constriction, is precisely the pattern seen in patients who go on to suffer ischemic strokes.
4. Clot-Dissolving Capacity Was Abolished
Perhaps the most striking finding involved tissue-type plasminogen activator (t-PA), a protein that brain endothelial cells release to dissolve blood clots before they can block cerebral blood flow. When normal, healthy brain endothelial cells were stimulated with thrombin (a clotting factor), they responded by increasing t-PA release by about 25%, exactly the protective response the body depends on when a clot begins to form. But when erythritol-treated cells received the same stimulus, their t-PA release did not increase. The clot-dissolving response was completely blunted. In a real-world scenario, this means that erythritol exposure could leave the brain’s blood vessels unable to mount an adequate defense against forming clots, a direct pathway to ischemic stroke.
The Bigger Picture: Connecting the Dots to Stroke Risk
This study does not exist in isolation. In 2023, a landmark study by Witkowski and colleagues published in Nature Medicine found that elevated circulating erythritol levels were positively associated with a significantly higher 3-year risk of heart attack and stroke, independent of other cardiometabolic risk factors, and this association held true across populations in both the United States and Europe. A follow-up intervention study demonstrated that consuming just 30 grams of erythritol (one drink’s worth) significantly increased platelet reactivity and clotting potential in healthy volunteers. A 2024 Mendelian randomization study added further weight to the causal argument, and separate research linked serum erythritol levels to increased risk of both heart disease and overall mortality.
What the Berry et al. study adds is the mechanistic “how.” Those earlier studies told us that erythritol is associated with more strokes and heart attacks. This new research shows us exactly what erythritol does to the cells that are supposed to protect the brain from those events. It is also worth noting that erythritol crosses the blood-brain barrier, meaning these are not just theoretical laboratory effects. The sweetener physically reaches the very cells it was shown to damage.
What We Still Do Not Know
The researchers are transparent about the limitations of their work. This was an in vitro study, meaning the cells were studied in a laboratory dish rather than inside a living human brain. We cannot draw definitive clinical conclusions from cell culture experiments alone. The exposure was also acute (a single 24-hour treatment), so the long-term effects of repeated daily erythritol consumption remain unknown.
However, the authors make a compelling point: many people consume erythritol-sweetened beverages multiple times per day, potentially exposing the brain’s blood vessels to repeated, chronic exposure. Whether antioxidant defense systems (SOD-1 and catalase) will eventually become overwhelmed under chronic conditions remains an open and troubling question. Additional clinical studies are clearly warranted.
Practical Takeaways
The accumulating evidence should prompt a serious conversation between you and your healthcare provider if erythritol is a regular part of your diet, particularly if you are over 50 or have existing cardiovascular risk factors. The very populations who have been encouraged to use erythritol (those with obesity, metabolic syndrome, and diabetes) are the same populations already at elevated risk for stroke and heart disease.
This does not mean you must go back to consuming large amounts of sugar. But it does mean that swapping sugar for erythritol may not be the free pass it was once believed to be. For those seeking healthier alternatives, consider using small amounts of whole-food sweeteners like raw honey or date paste, moderating overall sweetness in your diet, flavoring water with fresh fruit or herbs instead of reaching for artificially sweetened beverages, and discussing your individual risk profile with a physician who understands the nuances of metabolic and vascular health.
Sometimes the healthiest choice is the simplest one: learning to appreciate foods and beverages that are less sweet, allowing your palate to recalibrate away from the hyper-sweetened standard that modern food manufacturing has normalized.
Your brain’s blood vessels are quietly doing the most important work in your body, delivering oxygen and nutrients to the organ that makes you who you are. They deserve better than a sweetener that undermines their ability to protect you.
