title: Combined deficiency of vitamins E and C causes paralysis and death in guinea pigs.
abstract: BACKGROUND
  On the basis of in vitro studies, the antioxidant nutrients vitamins E and C are postulated to interact in vivo.
  
  
  OBJECTIVE
  We developed a guinea pig model to evaluate the combined deficiency of vitamins E and C in vivo.
  
  
  METHODS
  Weanling guinea pigs were fed a control diet or a vitamin E-deficient diet for 14 d, after which one-half of each group had vitamin C removed from their diet, thus creating 4 diet groups. Some animals were observed for clinical signs. Others were killed for evaluation.
  
  
  RESULTS
  Of 21 guinea pigs that were observed after being fed the diet deficient in both vitamins, 8 died 9 +/- 2 d (x +/- SD) after starting the diet. Eight additional guinea pigs developed a characteristic syndrome at 11 +/- 3 d. First, they became paralyzed in the hind limbs. Within a few hours, the paralysis progressed to include all 4 limbs and caused difficulty in breathing, which would have caused death had the animals not been euthanized. Histopathologic evaluation did not identify a lesion in the muscles or nervous system that could account for the paralysis. Biochemical measurements confirmed the deficiencies and indicated that the double deficiency caused lipid peroxidation in the central nervous system.
  
  
  CONCLUSIONS
  A distinct clinical syndrome of combined vitamin E and vitamin C deficiency occurs in guinea pigs. This syndrome indicates that these antioxidant vitamins are related in vivo. We speculate that acute oxidative injury in the central nervous system underlies the clinical syndrome.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Hill
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Amy K
authors.initials: AK
authors.lastname: Motley
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: James M
authors.initials: JM
authors.lastname: May
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Burk
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000097:blood; D001206:Ascorbic Acid Deficiency / Q000150:complications*; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D008297:Male; D009994:Osmolar Concentration; D010243:Paralysis / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D012584:Sciatic Nerve / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D014811:Vitamin E Deficiency / Q000150:complications*; D024502:alpha-Tocopherol / Q000097:blood
chemical_list: D024502:alpha-Tocopherol; D001205:Ascorbic Acid