title: Comparison of the anti-scorbutic activity of L-ascorbic acid and Ester C in the non-ascorbate synthesizing Osteogenic Disorder Shionogi (ODS) rat.
abstract: The Osteogenic Disorder Shionogi (ODS) rat, Clea Inc., Tokyo, Japan lacks the ability to synthesize L-ascorbic acid (AA). As with man, monkey and the guinea pig, this rat lacks L-gulonolactone oxidase necessary for the synthesis of AA from glucose. This study shows this animal to be an alternative to the guinea pig in AA studies. The anti-scorbutic potency of Ester C (EC), a calcium ascorbate and calcium threonate mixture, was compared with an AA dose of equal ascorbate activity equivalents (AAE) for anti-scorbutic activity in the ODS rat. The minimal anti-scorbutic dose of EC was determined to be 0.44 mg/kg/day (AAE), while an AA dose of 0.51 mg/kg/day (AAE) was not anti-scorbutic in a 24 day study. At 24 days EC rats gained 125% of initial body weight (BW) and the AA rats only 45% BW. Scorbutic signs at 24 days were scored on a 0 (min) to 3 (max) scale. The EC/AA ratio scores were: hemorrhage 0/1.4, behavior change 0/2.0, piloerection 0/2.2, mobility 0.4/2.2, dysbasia 0.6/2.8 and ataxia 0.4/1.0. Pearson's correlation coefficient for BW versus AAE was r = .34 for the AA group and r = .90 for the EC group. The morbidity index for EC was 0/5 and for the AA group 2/5. The AAE dose of AA which was 16% higher/day than the EC AAE dose was not anti-scorbutic, while the EC dose was anti-scorbutic. EC rats had 3.5X greater weight gain, a sensitive indicator of scurvy, than the AA rats. EC rats had 3-4 times less, if any, scorbutic signs than AA rats. The results clearly show that, based on ascorbate activity equivalents, EC has more available ascorbate activity/potency than AA. The mechanism of this increased potency is believed to be due to the facilitated transport of AAE into the cell by the threonate (a normal in vivo metabolite of AA) present in the EC product. In addition, previous studies have shown EC (AAE) to be higher in plasma and excreted less rapidly than the AAE derived from AA administered orally.
authors.affiliation: Atherosclerosis Research Laboratories, Department of Pharmacology, University of Mississippi, University 38677.
authors.forename: A J
authors.initials: AJ
authors.lastname: Verlangieri
authors.forename: M J
authors.initials: MJ
authors.lastname: Fay
authors.forename: A W
authors.initials: AW
authors.lastname: Bannon
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000096:biosynthesis / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003683:Dehydroascorbic Acid / Q000494:pharmacology; D004338:Drug Combinations; D011897:Random Allocation; D051381:Rats; D011922:Rats, Mutant Strains; D012614:Scurvy / Q000188:drug therapy* / Q000378:metabolism; D013912:Threonine / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; C069207:calcium ascorbate; D013912:Threonine; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid