Overview of vitamin A
- Sassan Pazirandeh, MD
Sassan Pazirandeh, MD
- Division of Gastroenterology and Hepatology
- Kaiser Permanente Medical Center
- David L Burns, MD
David L Burns, MD
- Associate Professor of Medicine
- Tufts University School of Medicine
- Section Editors
- Timothy O Lipman, MD
Timothy O Lipman, MD
- Section Editor — Nutrition
- GI-Hepatology-Nutrition Section
- Washington DC Veterans Affairs Medical Center
- Kathleen J Motil, MD, PhD
Kathleen J Motil, MD, PhD
- Section Editor — Pediatric Nutrition
- Professor of Pediatric Nutrition
- Baylor College of Medicine
Vitamins are a number of chemically unrelated families of organic substances that cannot be synthesized by humans and must be ingested in the diet in small quantities to facilitate normal metabolism. They are divided into water-soluble and fat-soluble vitamins (table 1).
Ancient Egyptians recognized that night blindness could be treated by consumption of liver . In the late 1920s, through the efforts of a Swiss scientist named Karrer and his colleagues, the fat-soluble compound in liver was isolated and termed vitamin A .
This topic review will focus on issues related to vitamin A. Overviews of the other fat-soluble vitamins, minerals and water-soluble vitamins are available elsewhere. (See "Overview of vitamin D" and "Overview of vitamin E" and "Overview of vitamin K" and "Overview of dietary trace minerals" and "Overview of water-soluble vitamins" and "Vitamin supplementation in disease prevention".)
Vitamin A is a subclass of a family of lipid-soluble compounds referred to as retinoic acids. These consist of four isoprenoid units joined in a head to tail fashion. There are two main forms of vitamin A: provitamin A carotenoids (beta-carotene and others), and preformed vitamin A.
●Provitamin A carotenoids are found in plants. There are many forms of provitamin A, but beta-carotene is only one that is metabolized by mammals into vitamin A.
- Wolf G. A history of vitamin A and retinoids. FASEB J 1996; 10:1102.
- Ross AC. Vitamin A and Retinoids. In: Modern Nutrition in Health and Disease, Shils M, Olson J, Shike M (Eds), Lippincott, Philadelphia 2000. p.305.
- Harrison EH. Enzymes catalyzing the hydrolysis of retinyl esters. Biochim Biophys Acta 1993; 1170:99.
- Rigtrup KM, Ong DE. A retinyl ester hydrolase activity intrinsic to the brush border membrane of rat small intestine. Biochemistry 1992; 31:2920.
- Green MH, Green JB, Berg T, et al. Changes in hepatic parenchymal and nonparenchymal cell vitamin A content during vitamin A depletion in the rat. J Nutr 1988; 118:1331.
- Saari JC. Retinoids in photosensitive systems. In: The retinoids: Biology, chemistry, and medicine, Sporn MB, Roberts AB, Goodman DS (Eds), Raven Press, New York 1994. p.351.
- Sommer A, West KP Jr. Vitamin A deficiency: Health, survival, and vision, Oxford University press, New York 1996. p.130.
- Morriss-Kay GM, Sokolova N. Embryonic development and pattern formation. FASEB J 1996; 10:961.
- Williams SR. Nutrition and diet therapy, 8th, Mosby, St Louis 1997. p.159.
- Janczewska I, Ericzon BG, Eriksson LS. Influence of orthotopic liver transplantation on serum vitamin A levels in patients with chronic liver disease. Scand J Gastroenterol 1995; 30:68.
- Underwood BA, Arthur P. The contribution of vitamin A to public health. FASEB J 1996; 10:1040.
- Swami HM, Thakur JS, Bhatia SP. Impact of mass supplementation of vitamin A. Indian J Pediatr 2007; 74:443.
- Katz J, West KP Jr, Khatry SK, et al. Impact of vitamin A supplementation on prevalence and incidence of xerophthalmia in Nepal. Invest Ophthalmol Vis Sci 1995; 36:2577.
- Schmitz J, West KP Jr, Khatry SK, et al. Vitamin A supplementation in preschool children and risk of hearing loss as adolescents and young adults in rural Nepal: randomised trial cohort follow-up study. BMJ 2012; 344:d7962.
- Awasthi S, Peto R, Read S, et al. Vitamin A supplementation every 6 months with retinol in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial. Lancet 2013; 381:1469.
- Imdad A, Herzer K, Mayo-Wilson E, et al. Vitamin A supplementation for preventing morbidity and mortality in children from 6 months to 5 years of age. Cochrane Database Syst Rev 2010; :CD008524.
- Mayo-Wilson E, Imdad A, Herzer K, et al. Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis. BMJ 2011; 343:d5094.
- Lin P, Fintelmann RE, Khalifa YM, et al. Ocular surface disease secondary to vitamin A deficiency in the developed world: it still exists. Arch Ophthalmol 2011; 129:798.
- Feranchak AP, and Sokol RJ. Medical and nutritional management of cholestasis in infants and children. In: Liver Disease in Children, 3rd, Suchy FJ, Sokol RJ, and Balistreri WF (Eds), Cambridge University Press, New York 2007. p.208.
- de Pee S, Dary O. Biochemical indicators of vitamin A deficiency: serum retinol and serum retinol binding protein. J Nutr 2002; 132:2895S.
- Greaves RF, Woollard GA, Hoad KE, et al. Laboratory medicine best practice guideline: vitamins a, e and the carotenoids in blood. Clin Biochem Rev 2014; 35:81.
- Food and Nutrition Board of the Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc (2000). National Academies Press, Washington DC, 2000. p. 162-196. Available at: http://books.nap.edu/openbook.php?isbn=0309072794 (Accessed 4/22/10).
- Morgan SL, Weinsier RL. Fundamentals of clinical nutrition, Mosby, St Louis 1998. p.3.
- World Health Organization Guideline: Vitamin A supplementation for infants and children 6-59 months of age (2011). Available at: http://www.who.int/nutrition/publications/micronutrients/guidelines/vas_6to59_months/en/ (Accessed on April 06, 2015).
- Cantorna MT, Nashold FE, Hayes CE. Vitamin A deficiency results in a priming environment conducive for Th1 cell development. Eur J Immunol 1995; 25:1673.
- Cantorna MT, Nashold FE, Chun TY, Hayes CE. Vitamin A down-regulation of IFN-gamma synthesis in cloned mouse Th1 lymphocytes depends on the CD28 costimulatory pathway. J Immunol 1996; 156:2674.
- Hall JA, Grainger JR, Spencer SP, Belkaid Y. The role of retinoic acid in tolerance and immunity. Immunity 2011; 35:13.
- Spencer SP, Wilhelm C, Yang Q, et al. Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science 2014; 343:432.
- World Health Organization guideline: Vitamin A supplementation in pregnant women (2011). Available at: http://www.who.int/nutrition/publications/micronutrients/guidelines/vas_pregnant/en/ (Accessed on April 07, 2015).
- World Health Organization guideline: Vitamin A supplementation for infants 1–5 months of age (2011) http://www.who.int/nutrition/publications/micronutrients/guidelines/vas_infants_1-5/en/ (Accessed on April 06, 2015).
- World Health Organization guideline: Vitamin A supplementation in postpartum women (2011). Available at: http://www.who.int/nutrition/publications/micronutrients/guidelines/vas_postpartum/en/ (Accessed on April 06, 2015).
- World Health Organization guideline: Neonatal vitamin A supplementation (2011). Available at: http://www.who.int/nutrition/publications/micronutrients/guidelines/vas_neonatal/en/ (Accessed on April 06, 2015).
- Imdad A, Ahmed Z, Bhutta ZA. Vitamin A supplementation for the prevention of morbidity and mortality in infants one to six months of age. Cochrane Database Syst Rev 2016; 9:CD007480.
- Haider BA, Bhutta ZA. Neonatal vitamin A supplementation for the prevention of mortality and morbidity in term neonates in developing countries. Cochrane Database Syst Rev 2011; :CD006980.
- Mazumder S, Taneja S, Bhatia K, et al. Efficacy of early neonatal supplementation with vitamin A to reduce mortality in infancy in Haryana, India (Neovita): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 385:1333.
- Masanja H, Smith ER, Muhihi A, et al. Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania (Neovita): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 385:1324.
- Edmond KM, Newton S, Shannon C, et al. Effect of early neonatal vitamin A supplementation on mortality during infancy in Ghana (Neovita): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 385:1315.
- World Health Organization. Vitamin A supplements: a guide to their use in the treatment and prevention of vitamin A deficiency and xerophthalmia, 2nd Edition (1997). Available at: http://www.who.int/nutrition/publications/micronutrients/vitamin_a_deficiency/9241545062/en/ (Accessed on April 07, 2015).
- World Health Organization guideline: Treating measles in children (2004). Available at: http://www.who.int/immunization/programmes_systems/interventions/TreatingMeaslesENG300.pdf?ua=1&ua=1 (Accessed on April 06, 2015).
- Biesalski HK. Comparative assessment of the toxicology of vitamin A and retinoids in man. Toxicology 1989; 57:117.
- Myhre AM, Carlsen MH, Bøhn SK, et al. Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations. Am J Clin Nutr 2003; 78:1152.
- Geubel AP, De Galocsy C, Alves N, et al. Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases. Gastroenterology 1991; 100:1701.
- Guarascio P, Portmann B, Visco G, Williams R. Liver damage with reversible portal hypertension from vitamin A intoxication: demonstration of Ito cells. J Clin Pathol 1983; 36:769.
- Weber FL Jr, Mitchell GE Jr, Powell DE, et al. Reversible hepatotoxicity associated with hepatic vitamin A accumulation in a protein-deficient patient. Gastroenterology 1982; 82:118.
- Olson JA. Upper limits of vitamin A in infant formulas, with some comments on vitamin K. J Nutr 1989; 119:1820.
- Soprano DR, Soprano KJ. Retinoids as teratogens. Annu Rev Nutr 1995; 15:111.
- Mahoney CP, Margolis MT, Knauss TA, Labbe RF. Chronic vitamin A intoxication in infants fed chicken liver. Pediatrics 1980; 65:893.
- Lam HS, Chow CM, Poon WT, et al. Risk of vitamin A toxicity from candy-like chewable vitamin supplements for children. Pediatrics 2006; 118:820.
- Cheruvattath R, Orrego M, Gautam M, et al. Vitamin A toxicity: when one a day doesn't keep the doctor away. Liver Transpl 2006; 12:1888.
- Penniston KL, Tanumihardjo SA. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr 2006; 83:191.
- Smith FR, Goodman DS. Vitamin A transport in human vitamin A toxicity. N Engl J Med 1976; 294:805.
- Krasinski SD, Russell RM, Otradovec CL, et al. Relationship of vitamin A and vitamin E intake to fasting plasma retinol, retinol-binding protein, retinyl esters, carotene, alpha-tocopherol, and cholesterol among elderly people and young adults: increased plasma retinyl esters among vitamin A-supplement users. Am J Clin Nutr 1989; 49:112.
- Graham-Maar RC, Schall JI, Stettler N, et al. Elevated vitamin A intake and serum retinol in preadolescent children with cystic fibrosis. Am J Clin Nutr 2006; 84:174.
- Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA 2002; 287:47.
- Michaëlsson K, Lithell H, Vessby B, Melhus H. Serum retinol levels and the risk of fracture. N Engl J Med 2003; 348:287.
- Crandall C. Vitamin A intake and osteoporosis: a clinical review. J Womens Health (Larchmt) 2004; 13:939.
- Rothman KJ, Moore LL, Singer MR, et al. Teratogenicity of high vitamin A intake. N Engl J Med 1995; 333:1369.
- Huiming Y, Chaomin W, Meng M. Vitamin A for treating measles in children. Cochrane Database Syst Rev 2005; :CD001479.
- Bello S, Meremikwu MM, Ejemot-Nwadiaro RI, Oduwole O. Routine vitamin A supplementation for the prevention of blindness due to measles infection in children. Cochrane Database Syst Rev 2014; :CD007719.
- Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC. Current use and future potential role of retinoids in dermatology. Drugs 1997; 53:358.
- Chomienne C, Fenaux P, Degos L. Retinoid differentiation therapy in promyelocytic leukemia. FASEB J 1996; 10:1025.
- Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr 1999; 69:1071.
- Feranchak AP, Gralla J, King R, et al. Comparison of indices of vitamin A status in children with chronic liver disease. Hepatology 2005; 42:782.
- American Academy of Pediatrics. Liver disease. In: Pediatric Nutrition, 7th ed, Kleinman RE, Greer FR. (Eds), American Academy of Pediatrics, Elk Grove Village 2011. p.1063.
- Cellular differentiation
- Clinical manifestations
- - Universal periodic distribution
- - Targeted supplementation for disease
- High-risk measles
- Acute toxicity
- Chronic toxicity
- Adverse effects on bone
- Teratogenic effects
- THERAPEUTIC USES
- Acute promyelocytic leukemia
- General population
- Special populations
- SUMMARY AND RECOMMENDATIONS