Lapis ISSN 2398-2969

Hypervitaminosis D

Synonym(s): Vitamin D toxicity

Contributor(s): Sarah Pellett, Lesa Thompson




  • Incorrectly formulated diets.
  • Overzealous supplementation with oral or injectable preparations.
  • Published requirements for vitamin D3 are 800-1000 IU/kg of diet; excess levels of vitamin D3 (>2000-3000 IU/kg) are associated with disease.

Predisposing factors


  • Access to incorrectly formulated diet.
  • Vitamin D has been added to excess.
  • Incorrect and unnecessary supplementation.
  • Access to rodenticide (vitamin D) preparations.


  • The exact pathophysiology of the soft tissue mineralization in rabbits is unknown. In arterial smooth muscle cells, excess vitamin D upregulates the 1,25-dihydroxyvitamin D3 receptor, resulting in toxicity via increased calcium uptake.
  • High vitamin D levels may also contribute to dental disease as reported in other exotic mammal species.
  • Cholecalciferol is metabolized to 25-hydroxycholecalciferol in the liver. 25-hydroxycholecalciferol is then metabolized to several metabolites within the kidney, one being calcitriol, which in most species is the potent metabolite enhancing calcium absorption from the gastrointestinal tract and calcium resorption from bones.
  • 25-hydroxycholecalciferol is the active metabolite in cholecalciferol toxicity -> results in hypercalcemia and hyperphosphatemia -> metastatic and dystropic mineralization of soft tissues.
  • Cardiovascular insufficiency causes ascites and lung edema. Experimental hypervitaminosis D in rabbits resulting in renal and pulmonary calcifications has been shown be have limited reversibility.


  • Clinical signs of toxicity may take weeks to several years to become apparent in rabbits.


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Further Reading


Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Proença L M & Mayer J (2014) Prescription diets for rabbits. Vet Clin North Am Exotic Anim Pract 17 (3), 485-502 PubMed.
  • Jekl V & Redrobe S (2013) Rabbit dental disease and calcium metabolism–the science behind divided opinions. JSAP 54 (9), 481-490 PubMed.
  • Jekl V, Gumpenberger M, Jeklova E et al (2011) Impact of pelleted diet of different mineral composition on the crown size of mandibular cheek teeth and mandibular relative density in degus (Octodon degus)​. Vet Rec 168 (24), 641 PubMed.
  • Lebas F (2010) Vitamins in rabbit nutrition: Literature review and recommendations. World Rabbit Sci 8 (4), 185-192 ResearchGate.
  • Zanuzzi C N, Barbeito C G, Ortíz M L et al (2010) Glycoconjugate histochemistry in the small and large intestine of normal and Solanum glaucophyllum-intoxicated rabbits. Res Vet Sci 89 (2), 214-222 PubMed.
  • Fisher P G (2006) Exotic mammal renal disease: causes and clinical presentation. Vet Clin North Am Exot Anim Pract 9 (1), 33-67 PubMed.
  • Rajasree S, Umashankar P R, Lal A V et al (2002) 1,25-dihydroxyvitamin D 3 receptor is upregulated in aortic smooth muscle cells during hypervitaminosis D. Life Sci 70 (15), 1777-1788 PubMed.
  • Kampheus J (1991) Calcium metabolism of rabbits as an aetiological factor for urolithiasis. J Nutr 121 (11 Suppl), S95-596 PubMed.
  • Hänichen T & Hermanns W (1990) [The question of reversibility of tissue calcification in enzootic calcinosis of cattle and in experimental hypervitaminosis D]. Deutsche Tierarztliche Wochenschrift 97 (11), 479-482 PubMed.
  • Zimmerman T E, Giddens W E Jr., DiGiacomo R F et al (1990) Soft tissue mineralisation in rabbits fed a diet containing excess vitamin D. Lab Anim Sci 40 (2), 212-215 PubMed.
  • Nyomba B L, Bouillon R & De Moor P (1984) Influence of vitamin D status on insulin secretion and glucose tolerance in the rabbit. Endocrinol 115 (1), 191-197 PubMed.

Other sources of information

  • Orcutt C (2014) Cardiovascular Disease. In: BSAVA Manual of Rabbit Medicine. Eds: Meredith A & Lord B. BSAVA, Gloucester. pp 205-213.
  • Prebble J (2014) Nutrition and Feeding. In: BSAVA Manual of Rabbit MedicineEds: Meredith A & Lord B. BSAVA, Gloucester. pp 205-213.
  • Raymond J L (2013) Pathology of the Rabbit. Presented at the 56th Annual Pathology of Laboratory Animals Course. Website: Last Accessed 18th February 2016.
  • Klaphake E & Paul-Murphy J (2012) Disorders of the Reproductive and Urinary System. In: Ferrets, Rabbits and Rodents: Clinical Medicine and Surgery. 3rd edn. Eds: Quesenberry K E & Carpenter J W. W B Saunders Co, Philadelphia. pp 223-229.
  • Harris I (1994) The Laboratory Rabbit Fact Sheets. ANZCCART News 7 (4).