Oral cobalamin supplementation in dogs with chronic enteropathies and low serum cobalamin concentrations : Comparative studies and effects on biochemical markers of intracellular cobalamin deficiency

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http://urn.fi/URN:ISBN:978-951-51-4585-7
Title: Oral cobalamin supplementation in dogs with chronic enteropathies and low serum cobalamin concentrations : Comparative studies and effects on biochemical markers of intracellular cobalamin deficiency
Author: Toresson, Linda
Contributor: University of Helsinki, Faculty of Veterinary Sciences, Department of Equine and small animal medicine
Doctoral Programme in Clinical Veterinary Medicine
Publisher: Helsingin yliopisto
Date: 2018-10-27
URI: http://urn.fi/URN:ISBN:978-951-51-4585-7
http://hdl.handle.net/10138/253101
Thesis level: Doctoral dissertation (article-based)
Abstract: Cobalamin (cbl) deficiency is a common sequela to chronic enteropathies (CE) in dogs. Numerous metabolic and clinical consequences have been reported in association with cbl deficiency, as has a poorer prognosis of the underlying disease. The recommended treatment for dogs is multiple parenteral cbl injections. However, to the best of our knowledge, no studies have been performed on dogs with CE and low cbl concentrations to evaluate the effect of oral cbl supplementation, nor has the currently recommended parenteral cbl protocol been systematically validated. This is in contrast to human medicine, where comparative studies have shown equal efficacy of parenteral and high-dose oral cbl supplementation. Oral supplementation is a cost-effective and very simple treatment in human patients since it can be performed at home, as opposed to parenteral treatment. This thesis aimed to evaluate the effects of oral cbl supplementation on serum cbl concentrations in dogs with CE and low serum cbl concentrations. Further, a comparison of oral and parenteral supplementation was performed and intracellular markers of cbl deficiency, such as homocysteine (HCY) and methylmalonic acid (MMA), were analyzed and compared during the treatment period. First, a retrospective study was performed on dogs with CE and low serum cbl concentrations that had received oral cbl supplementation in clinical practice by the author. A significant difference was found when comparing serum cbl concentrations before and after supplementation. All dogs had serum concentrations within or above the cbl reference interval after supplementation. The increase in serum cbl concentrations was not correlated to Canine Inflammatory Bowel Disease Activity Index at inclusion, degree of cobalamin deficiency or if a change of diet or addition of immunosuppressive treatment was started during supplementation. Second, a prospective block-randomized study was performed, comparing serum cbl concentrations in dogs treated with peroral (PO) versus parenteral (PE) cbl supplementation. All dogs of both groups were within the upper half of the reference interval or above the reference interval limit after 28 days of cbl supplementation. The PO group had significantly lower serum cbl concentrations at this time-point than the the PE group. Ninety days after starting supplementation, the PO group had a significantly higher serum cbl concentration than the PE group. Methylmalonic acid (MMA) decreased significantly in both groups between baseline and 28 days of treatment, with no further reduction after 90 days compared to 28 days in either group. No significant differences in MMA concentrations emerged between the groups at any time-point. Serum HCY concentrations did not differ between baseline and 28 days after initiation of cbl supplementation in any group. Ninety days after cbl supplementation was started, a small increase in serum HCY concentration compared to 28 days was noted in both groups. In parallel with the MMA results, there were no significant differences in HCY concentrations between the groups at any time point. The studies on intracellular markers of cbl deficiency suggest that both treatment protocols are equally effective on a cellular level. In conclusion, this thesis provides evidence-based data that oral cbl supplementation can be used as an alternative treatment to the traditional parenteral protocol. Our results suggest that, similar to humans, an alternative intestinal absorptive pathway of cbl may exist in dogs.Kobalaminbrist (vitamin B12-brist) kan uppstå hos hund som en följd av kronisk tarminflammation. Om kobalaminbrist uppstår leder det till försämrad prognos och ökad risk för avlivning. Den rekommenderade behandlingen vid kobalaminbrist hos hund är upprepade injektioner med kobalamin. Ingen har tidigare undersökt om det fungerar att ge kobalamintabletter i stället. Tablettbehandling skulle vara betydligt billigare och mycket enklare för djurägaren. Flera studier har visat att det går lika bra att ge kobalamin i tablettform som i injektionsform till människor med kobalaminbrist av olika anledningar. De flesta människor föredrar att få kobalamintabletter i stället för injektioner, eftersom det är enklare att ta tabletter, är smärtfritt och behandlingen kan skötas i hemmet. Denna avhandling syftar till att utvärdera om kobalamin kan ges i tablettform till hundar med kronisk tarminflammation och kobalaminbrist. Vi har jämfört kobalaminkoncentrationen i blodet mellan hundar som fått kobalamin i tablettform och hundar som fått det i injektionsform. Vi har också jämfört de intracellulära markörerna metylmalonsyra (MMA) och homocystein (HCY) mellan de två behandlingsgrupperna. Både nivåerna av MMA och HCY kan stiga vid kobalaminbrist. Först utfördes en retrospektiv studie hos hundar med kronisk tarminflammation och kobalaminbrist som tidigare behandlats med kobalamintabletter av huvudförfattaren. Resultaten visade att kobalaminkoncentrationen i blodet steg markant efter tablettbehandling. Alla hundar fick kobalaminvärden som var normala eller högre än det normala av tablettbehandlingen. Det fanns inget samband mellan hur mycket kobalaminkoncentrationen i blodet steg och hur hög sjukdomsaktivitet hundarna hade. Inte heller påverkades förhöjningen av kobalaminnivåerna av hur låga kobalaminvärdena var från början, eller om hundarna fick byta diet eller sattes på annan parallell behandling förutom kobalamin. Därefter utfördes en prospektiv ramdomiserad jämförande studie mellan tablett- och injektionsbehandling hos hundar med kronisk tarminflammation och kobalaminbrist. Hundarna svarade bra på båda behandlingsalternativen. De som hade fått tabletter hade lägre ökning av kobalaminvärdena än de som fått injektioner efter 28 dagar, men efter 90 dagar hade hundarna som fått tabletter högre kobalaminvärden än de som fått injektioner. Metylmalonsyrakoncentrationen sjönk markant i både den grupp som fått kobalamintabletter och de som fått injektioner efter 28 dagars behandling. Det var ingen skillnad mellan de två behandlingsgrupperna. Homocysteinkoncentrationerna var normala hos nästan alla hundarna när studien började, och var oförändrade i båda grupperna efter 28 dagars behandling. Det var ingen skillnad mellan tablett- och injektionsgruppen i detta avseende heller. Våra studier visar att båda behandlingsprotokollen är likvärdiga på cellnivå. Sammanfattningsvis har våra studier visat att vitamin B12 i tablettform fungerar bra till hund med kobalaminbrist, vilket för de flesta djurägare är en både enklare och billigare behandling än kobalamininjektioner.
Subject: Veterinary Medicine
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