Multi-Targeted Mechanisms Underlying the Endothelial Protective Effects of the Diabetic-Safe Sweetener Erythritol

Abstract

Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunction onset in diabetic rats. To unravel mechanisms, other than scavenging of radicals, by which erythritol mediates this protective effect, we evaluated effects of erythritol in endothelial cells exposed to normal (7 mM) and high glucose (30 mM) or diabetic stressors (e.g. SIN-1) using targeted and transcriptomic approaches. This study demonstrates that erythritol (i.e. under non-diabetic conditions) has minimal effects on endothelial cells. However, under hyperglycemic conditions erythritol protected endothelial cells against cell death induced by diabetic stressors (i.e. high glucose and peroxynitrite). Also a number of harmful effects caused by high glucose, e.g. increased nitric oxide release, are reversed. Additionally, total transcriptome analysis indicated that biological processes which are differentially regulated due to high glucose are corrected by erythritol. We conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets. Overall, these data indicate a therapeutically important endothelial protective effect of erythritol under hyperglycemic conditions.

Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study

“…In contrast to prior animal studies [2,3], there were no effects of erythritol on markers of oxidative stress and inflammation. These findings might reflect the modest sample size, short duration of treatment, lower relative dose of erythritol, and a lack of correlation between these systemic measures and local effects in the vascular wall.…”

“…In vitro studies suggest that erythritol reduces stress-induced endothelial apoptosis and alters the transcription of genes relevant to mitochondrial function, antioxidant protection, and cell signaling [3]. The present study provides novel information about the relevance of that experimental work to humans.…”

“…Erythritol is a commonly-used polyol sweetener. In experimental models, erythritol reduces oxidative stress and reverses endothelial dysfunction [2,3]. We hypothesized that erythritol would have comparable favorable effects in diabetic patients.…”

Sugar alcohols—their role in the modern world of sweeteners: a review

“…It can also improve mouthfeel and mask certain unwanted aftertastes of intense sweeteners [23]. Erythritol was also reported to protect endothelial cells under hyperglycemic conditions (Table 4) [28]. In vitro studies have also shown that erythritol is an excellent radical scavenger with membrane-protecting properties [19,23].…”

Natural Sweeteners: The Relevance of Food Naturalness for Consumers, Food Security Aspects, Sustainability and Health Impacts

“…Diabetes patients can benefit from the vascular effects of erythritol, as mentioned above. It is assumed that endothelium is not compromised by erythritol in non-diabetic subjects, but in diabetic subjects where endothelium is under diabetic stress, erythritol can transfer a range of damage and dysfunction parameters to a safer side, as in vitro , ex vivo and in vivo studies report [ 148 , 150 , 151 ]. Erythritol can also be regarded as a substance with a beneficial impact on the endothelium under high-glucose conditions by contributing to avoid or delay the onset of diabetic complications [ 152 ].…”