title: Fructose levels are markedly elevated in cerebrospinal fluid compared to plasma in pregnant women.
abstract: BACKGROUND
  Fructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000 th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS) fructose production from glucose via the polyol pathway (glucose → sorbitol → fructose) contributes to brain exposure to fructose.
  
  
  METHODS
  In this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF), maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM) undergoing spinal anesthesia and elective cesarean section.
  
  
  RESULTS
  As expected, CSF glucose was ~ 60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001), and CSF sorbitol was ~ 9-times higher than plasma levels (p < 0.001). Moreover, CSF fructose correlated positively with CSF glucose (ρ 0.45, p = 0.02) and sorbitol levels (ρ 0.75, p < 0.001). Cord blood sorbitol was also ~ 7-fold higher than maternal plasma sorbitol levels (p = 0.001). There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups.
  
  
  CONCLUSIONS
  These data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption.
authors.affiliation: Yale University School of Medicine, Division of Endocrinology, New Haven, Connecticut, United States of America.
authors.forename: Janice J
authors.initials: JJ
authors.lastname: Hwang
authors.affiliation: Yale University School of Medicine, Department of Obstetrics and Gynecology, New Haven, Connecticut, United States of America.
authors.forename: Andrea
authors.initials: A
authors.lastname: Johnson
authors.affiliation: Yale University School of Medicine, Division of Endocrinology, New Haven, Connecticut, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Cline
authors.affiliation: Yale University School of Medicine, Division of Endocrinology, New Haven, Connecticut, United States of America.
authors.forename: Renata
authors.initials: R
authors.lastname: Belfort-DeAguiar
authors.affiliation: Yale University School of Medicine, Department of Anesthesia, New Haven, Connecticut, United States of America.
authors.forename: Denis
authors.initials: D
authors.lastname: Snegovskikh
authors.affiliation: Yale University School of Medicine, Department of Neurology, New Haven, Connecticut, United States of America.
authors.forename: Babar
authors.initials: B
authors.lastname: Khokhar
authors.affiliation: Yale University School of Medicine, Department of Obstetrics and Gynecology, New Haven, Connecticut, United States of America.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Han
authors.affiliation: Yale University School of Medicine, Division of Endocrinology, New Haven, Connecticut, United States of America.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood* / Q000134:cerebrospinal fluid*; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology; D016640:Diabetes, Gestational / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology; D005260:Female; D005632:Fructose / Q000097:blood* / Q000134:cerebrospinal fluid*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D009765:Obesity / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology; D050177:Overweight / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology; D010949:Plasma / Q000737:chemistry*; D011247:Pregnancy; D013012:Sorbitol / Q000032:analysis*; D013851:Thinness / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D005632:Fructose; D013012:Sorbitol