Vitamin A (Retinol) - Nutrition

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What is Vitamin A (Retinol)?

Vitamin A is a general term for the group of essential fat-soluble retinoids. Retinol is the alcohol form of Vitamin A found in circulation, while retinal, retinyl esters, and β-carotene are more commonly found in foods. Dietary retinal and retinyl esters are found in animal tissues and are hydrolysed by pancreatic and intestinal enzymes in the intestinal lumen, incorporated into mixed micelles with dietary fat, and absorbed by diffusion across the mucosal surface of the small intestine. β-carotene is synthesized by plants and is considered a pro-Vitamin A molecule comprised of 2 retinol subunits. β-carotene is absorbed across the small intestine intact and in dogs is cleaved into two retinal molecules by β-carotene 15,15 dioxygenase. Cats lack this enzyme and require preformed Vitamin A in the diet[1]. After absorption, retinol is released into the lymphatics with chylomicrons and transported to the liver where it is bound to retinol-binding protein (RBP). Liver is the primary storage site of Vitamin A. Retinol bound to RBP is released into portal circulation and is transported to target tissues. Retinoic acid is the primary active retinol metabolite within the cell.

Why is it Important?

Vitamin A is important for normal vision, cellular differentiation, morphogenesis, immune function, and transmembrane protein transfer.

Roles in the Body

  1. Vision: Vitamin A in the form of 11-cis-retinal is attached to a lysine residue in rhodopsin within the retina[2]. When light hits rhodopsin it undergoes a conformational change resulting in the generation of a nerve impulse and normal phototransduction.
  2. Growth and Cellular Differentiation: Retinoic acid receptors (RAR) are found in DNA gene sequences affecting normal foetal development[3][4]. Retinoic acid receptors also control transcription of genes that synthesise extracellular matrix proteins[5], differentiation of mucous-secreting epithelial cells[6][7], and cellular RBP may help stabilize RNA during gene transcription[8].
  3. Immune Function: Retinoic acid promotes T-cell differentiation and antibody production[9].

Consequences of Vitamin A Deficiency

Vitamin A deficiencies can occur due to low dietary intake of retinol, with concurrent diseases affecting absorption of dietary fat (e.g. protein-losing enteropathy) or with abnormal storage and transport of retinol (i.e.liver disease).

Dogs:

Puppies fed Vitamin A deficient diets have poor growth rates and develop defective remodelling of bone during active growth[7], especially the bones of the cranium, which can result in deafness[10]. Adult dogs fed Vitamin A deficient diets experience anorexia, weight loss, squamous metaplasia of mucus secreting cells that can result in xerophthalmia (dry eye) and increased susceptibility to pneumonia[11]. Cutaneous hyperkeratosis and skin lesions are also associated with Vitamin A deficiency in adult dogs[12]. Adult females fed inadequate levels of Vitamin A during gestation have an increased risk of foetal abnormalities[7].

Cats:

Feeding Vitamin A deficient diets to pregnant queens can result in increased risk of spontaneous abortions, foetal resorptions, and cleft palate in kittens[7]. Adult cats fed Vitamin A deficient diets will also experience weight loss and squamous metaplasia of mucous secreting cells[7], with xerosis and associated corneal keratinization and vascularization.

Toxicity

Carotenoids, such as β-carotene, have low toxicity in dogs and cats, but high intake of pre-formed retinoid either acute or chronic exposure can cause harmful effects in both species. Retinol toxicity can occur when dogs or cats are fed diets comprised largely of liver or through excess supplementation of the diet, or formulation errors in commercial pet foods.

Dogs:

Puppies fed high levels of Vitamin A can develop disorder of bone remodelling resulting in stunted growth and hyperashthesia[13][14]. Adult dogs showed no adverse effect when fed high levels of vitamin A up to to 1 year[15], but longer term studies are lacking.

Cats:

Kittens fed high levels of Vitamin A can also develop abnormal remodelling and metaplasia of bone, especially affecting the first three vertebrae. This change results in restricted movement of the neck in affected kittens and has been seen in adult cats fed diets with chronically high Vitamin A levels[16].

Dietary Sources

Pre-formed Vitamin A is found animal tissue, primarily liver, and whole eggs. Plant carotenoids are found in dark leafy vegetables, such as spinach and broccoli, and yellow-orange vegetables, such as carrot and sweet potato. Commercial dog and cat foods intended to be complete and balanced are fortified with retinyl esters, either retinyl palmatate or retinyl acetate, to ensure adequate Vitamin A intake.

Diagnosing Vitamin A Deficiency

Diagnosis of Vitamin A deficiency is based on measurement of serum retinol and retinyl ester concentrations, though not routinely tested through veterinary reference laboratories. As Vitamin A is stored in the liver, increased concentration of Vitamin A can also be seen on liver biopsy. Diagnosis is also made on clinical signs consistent with deficiency and evaluation of diet (either direct measurement or computer evaluation for Vitamin A and other retinoids).

References

  1. Morris JG. Idiosyncratic nutrient requirements of cats appear to be diet-induced evolutionary adaptation. Nutr Res Rev 2002;15:153-168.
  2. Conway HH, et al. Vitamin A Metabolism, Action, and Role in Skeletal Homeostasis. Endocr Rev 2013 Dec;34(6):766-797.
  3. Rhinn M and Dolle P. Retinoic acid signaling during development. Development 2012;139:843–858.
  4. Mark M, et al. Function of retinoic acid receptors during embryonic development. Nucl Recept Signal 2009;7:e002.
  5. Barber T, et al. Vitamin A Deficiency and Alterations in the Extracellular Matrix. Nutrients 2014;6:4984-5017
  6. Koo JS, et al. Restoration of the mucous phenotype by retinoic acid in retinoid-deficient human bronchial cell cultures: changes in mucin gene expression. Am J Respir Cell Mol Biol 1999;20:43-52.
  7. 7.0 7.1 7.2 7.3 7.4 National Research Council (NRC). Vitamins. In Nutrient Requirements for Dogs and Cats. 2006 Washington, DC: National Academies Press p.194-200.
  8. Veerland AC, et al. Transcript stabilization by the RNA-binding protein HuR is regulated by cellular retinoic acid-binding protein 2. Mol Cell Biol 2014;34:2135-2146.
  9. Ross AC. Vitamin A and retinoic acid in T cell-related immunity. Am J Clin Nutr 2012;96:1166S–1172S.
  10. Mallenby E. The experimental production if deafness in young animals by diet. J Physiol 1938;94:380-398.
  11. Russell WC and Morris ML. Vitamin A deficiency in the dog. Experimental production of vitamin A deficient condition. JAVMA 1939;95:316-320.
  12. Ihrke PJ and Goldschmidt MH. Vitamin A-responsive dermatosis in the dog. JAVMA 1983;182:687-690.
  13. Maddock CL, et al. Hypervitaminosis A in the dog. J Nutr 1949;39:117-137.
  14. Cho Y, et al. Hypervitaminosis A in the dog. AJVR 1975;36:1597-1603.
  15. Cline JL, et al. Effect of increasing dietary vitamin A on bone density in adult dogs. J Amin Sci 1997;75:2980-2985.
  16. Freytag TL, et al. Teratogenic effects of chronic ingestion of high levels of vitamin A in cats. JAPAN (Berl) 2003;87:42-51.



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