Researchers at the University of Colorado Boulder have found that erythritol, a common sugar substitute, may impair critical cellular functions that maintain brain blood vessel health. Their study shows that erythritol increases oxidative stress, disrupts nitric oxide signaling, elevates production of vasoconstrictive peptides, and reduces clot-dissolving ability in human brain microvascular endothelial cells.
Erythritol is widely used in protein bars, low-calorie drinks, and diabetic-friendly foods due to its sweetness—about 60–80% that of sugar—while providing minimal calories and having little impact on blood glucose. It is also naturally produced in the body from glucose and fructose, influenced by both diet and metabolism.
Concerns over erythritol’s safety have grown after studies linked higher blood levels to increased risk of heart attacks and strokes. These associations, observed in large U.S. and European populations, appear independent of other cardiovascular risk factors. However, the underlying mechanism was unclear.
To explore this, the researchers conducted laboratory experiments exposing human brain endothelial cells to erythritol doses comparable to those found after consuming typical beverages. They assessed oxidative stress, antioxidant proteins, nitric oxide availability, endothelin levels, and fibrinolytic activity.
Results showed a 75% rise in reactive oxygen species, indicating heightened oxidative stress. Antioxidant proteins superoxide dismutase-1 and catalase increased by 45% and 25%, respectively. Nitric oxide production dropped nearly 20%, despite unchanged total endothelial nitric oxide synthase (eNOS) levels. Notably, activation-associated phosphorylation of eNOS declined by 33%, while inhibitory phosphorylation rose by 39%. Additionally, release of tissue-type plasminogen activator (t-PA), critical for breaking down blood clots, was reduced.
The study concludes that erythritol disrupts multiple pathways essential for healthy brain blood vessel function. Although limited to short-term cell experiments, these findings support previous links between erythritol and stroke risk. The authors call for further research in long-term and animal studies, as well as clinical trials, to determine whether regular dietary erythritol exposure affects cerebrovascular health.
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