title: Role of vitamin A metabolism in IIH: Results from the idiopathic intracranial hypertension treatment trial.
abstract: BACKGROUND
  Vitamin A and its metabolites (called retinoids) have been thought to play a role in the development of idiopathic intracranial hypertension (IIH). The IIH Treatment Trial (IIHTT) showed the efficacy of acetazolamide (ACZ) in improving visual field function, papilledema grade, quality of life and cerebrospinal fluid (CSF) pressure. We postulated that IIH patients would demonstrate elevated measures of vitamin A metabolites in the serum and CSF.
  
  
  METHODS
  Comprehensive measures of serum vitamin A and its metabolites were obtained from 96 IIHTT subjects, randomly assigned to treatment with ACZ or placebo, and 25 controls with similar gender, age and body mass index (BMI). These included retinol, retinol binding protein, all-trans retinoic acid (ATRA), alpha- and beta-carotenes, and beta-cryptoxanthin. The IIHTT subjects also had CSF and serum vitamin A and metabolite measurements obtained at study entry and at six months.
  
  
  RESULTS
  At study entry, of the vitamin A metabolites only serum ATRA was significantly different in IIHTT subjects (median 4.33nM) and controls (median 5.04nM, p=0.02). The BMI of IIHTT subjects showed mild significant negative correlations with serum ATRA, alpha- and beta-carotene, and beta-cryptoxanthin. In contrast, the control subject BMI correlated only with serum ATRA. At six months, the serum retinol, alpha-carotene, beta-carotene, and CSF retinol were increased from baseline in the ACZ treated group, but only increases in alpha-carotene (p=0.02) and CSF ATRA (p=0.04) were significantly greater in the ACZ group compared with the placebo group. No other vitamin A measures were significantly altered over the six months in either treatment group. Weight loss correlated with only with the change in serum beta-carotene (r=-0.44, p=0.006) and the change in CSF retinol (r=-0.61, p=0.02).
  
  
  CONCLUSIONS
  Vitamin A toxicity is unlikely a contributory factor in the causation of IIH. Our findings differ from those of prior reports in part because of our use of more accurate quantitative methods and measuring vitamin A metabolites in both serum and CSF. ACZ may alter retinoid metabolism in IIH patients.
authors.affiliation: Pathology, State University of New York, Downstate School of Medicine, Brooklyn, NY, United States.
authors.forename: J
authors.initials: J
authors.lastname: Libien
authors.affiliation: Neurology and Ophthalmology, Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: mkuper@chpnet.org.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kupersmith
authors.affiliation: Medicine, College of Physicians and Surgeons, Columbia University School of Medicine, New York, NY, United States.
authors.forename: W
authors.initials: W
authors.lastname: Blaner
authors.affiliation: Biostatistics, University of Rochester, Rochester, NY, United States.
authors.forename: M P
authors.initials: MP
authors.lastname: McDermott
authors.affiliation: Biostatistics, University of Rochester, Rochester, NY, United States.
authors.forename: S
authors.initials: S
authors.lastname: Gao
authors.affiliation: Pathology, State University of New York, Downstate School of Medicine, Brooklyn, NY, United States.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Neurology, University of Mississippi School of Medicine, Jackson, MS, United States.
authors.forename: J
authors.initials: J
authors.lastname: Corbett
authors.affiliation: Neurology, University of Iowa School of Medicine, Iowa City, IA, United States.
authors.forename: M
authors.initials: M
authors.lastname: Wall
mesh_terms: D000086:Acetazolamide / Q000627:therapeutic use; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D002338:Carotenoids / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D009765:Obesity / Q000378:metabolism; D011559:Pseudotumor Cerebri / Q000097:blood* / Q000134:cerebrospinal fluid / Q000150:complications / Q000188:drug therapy; D012177:Retinol-Binding Proteins / Q000378:metabolism; D014212:Tretinoin / Q000097:blood; D014794:Visual Fields / Q000187:drug effects; D014801:Vitamin A / Q000097:blood* / Q000134:cerebrospinal fluid; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D012177:Retinol-Binding Proteins; D014801:Vitamin A; D002338:Carotenoids; D014212:Tretinoin; D000086:Acetazolamide
keywords: Idiopathic intracranial hypertension; Obesity; Retinoids; Vitamin A