title: Dietary intake of sugar substitutes aggravates cerebral ischemic injury and impairs endothelial progenitor cells in mice.
abstract: OBJECTIVE
  In our current food supply, sugar substitutes are widely used in beverages and other food products. However, there is limited information about the link between dietary consumption of sugar substitutes and stroke to date. This study sought to determine the effect of various sugar substitutes on the cerebral ischemic injury and endothelial progenitor cells, which have been implicated to play an important role in vascular repair and revascularization in ischemic brain tissues, in mice.
  
  
  METHODS
  After treatment with sucrose and various sugar substitutes (the doses are in the range of corresponding acceptable daily intake levels) and vehicle for 6 weeks, mice were subjected to permanent left middle cerebral artery occlusion, and the infarct volumes, angiogenesis, and neurobehavioral outcomes were determined. In addition, the number and function of endothelial progenitor cells were also examined.
  
  
  RESULTS
  After long-term treatment with fructose, erythritol (sugar alcohols), acesulfame K (artificial sweeteners), or rebaudioside A (rare sugars), the cerebral ischemic injury (both infarct volumes and neurobehavioral outcomes) was significantly aggravated, angiogenesis in ischemic brain was reduced, and endothelial progenitor cell function was impaired in mice compared with control. However, the similar impairments were not found in sucrose (with the same dose as fructose's)-treated mice.
  
  
  CONCLUSIONS
  Long-term consumption of sugar substitutes aggravated cerebral ischemic injury in mice, which might be partly attributed to the impairment of endothelial progenitor cells and the reduction of angiogenesis in ischemic brain. This result implies that dietary intake of sugar substitutes warrants further attention in daily life.
authors.affiliation: From the Department of Science for Identifying Chinese Materia Medica, The Second Military Medical University, Shanghai, China (X.-H.D., X.S., A.F.C., H.-H.X.); Department of Cardiology and Center of Clinical Pharmacology, Third Xiangya Hospital and the Institute of Vascular Disease and Translational Medicine, Central South University, Changsha, Hunan, China (A.F.C., H.-H.X.); and Department of Pharmacy, Xiaoshan Hospital, Hangzhou, China (G.-J.J.).
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Dong
authors.affiliation: From the Department of Science for Identifying Chinese Materia Medica, The Second Military Medical University, Shanghai, China (X.-H.D., X.S., A.F.C., H.-H.X.); Department of Cardiology and Center of Clinical Pharmacology, Third Xiangya Hospital and the Institute of Vascular Disease and Translational Medicine, Central South University, Changsha, Hunan, China (A.F.C., H.-H.X.); and Department of Pharmacy, Xiaoshan Hospital, Hangzhou, China (G.-J.J.).
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: From the Department of Science for Identifying Chinese Materia Medica, The Second Military Medical University, Shanghai, China (X.-H.D., X.S., A.F.C., H.-H.X.); Department of Cardiology and Center of Clinical Pharmacology, Third Xiangya Hospital and the Institute of Vascular Disease and Translational Medicine, Central South University, Changsha, Hunan, China (A.F.C., H.-H.X.); and Department of Pharmacy, Xiaoshan Hospital, Hangzhou, China (G.-J.J.).
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Jiang
authors.affiliation: From the Department of Science for Identifying Chinese Materia Medica, The Second Military Medical University, Shanghai, China (X.-H.D., X.S., A.F.C., H.-H.X.); Department of Cardiology and Center of Clinical Pharmacology, Third Xiangya Hospital and the Institute of Vascular Disease and Translational Medicine, Central South University, Changsha, Hunan, China (A.F.C., H.-H.X.); and Department of Pharmacy, Xiaoshan Hospital, Hangzhou, China (G.-J.J.). xhhtom@263.net afychen@yahoo.com.
authors.forename: Alex F
authors.initials: AF
authors.lastname: Chen
authors.affiliation: From the Department of Science for Identifying Chinese Materia Medica, The Second Military Medical University, Shanghai, China (X.-H.D., X.S., A.F.C., H.-H.X.); Department of Cardiology and Center of Clinical Pharmacology, Third Xiangya Hospital and the Institute of Vascular Disease and Translational Medicine, Central South University, Changsha, Hunan, China (A.F.C., H.-H.X.); and Department of Pharmacy, Xiaoshan Hospital, Hangzhou, China (G.-J.J.). xhhtom@263.net afychen@yahoo.com.
authors.forename: He-Hui
authors.initials: HH
authors.lastname: Xie
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D020521:Stroke / Q000378:metabolism* / Q000473:pathology; D013549:Sweetening Agents / Q000009:adverse effects* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D013549:Sweetening Agents
keywords: endothelial progenitor cells; sweetening agents