You are in: eMedicine Specialties > Endocrinology > Metabolic Disorders Vitamin A DeficiencyArticle Last Updated: May 12, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Jigna Thakore, MD, Fellow, Department of Gastroenterology, Dayton Veterans Administration Medical Center Jigna Thakore is a member of the following medical societies: American College of Gastroenterology and American Society of Gastrointestinal Endoscopy Coauthor(s): N Gopalswamy, MD, Chairman, Department of Gastroenterology, Professor of Internal Medicine, Wright State University / Veterans Affairs Medical Center Editors: Udaya M Kabadi, MD, Department of Medicine, Professor, University of Iowa School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Romesh Khardori, MD, Chief, Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Professor, Southern Illinois University School of Medicine; Alex J Mechaber, MD, FACP, Division of General Internal Medicine, Associate Professor, Department of Internal Medicine, University of Miami School of Medicine; George T Griffing, MD, Professor of Medicine, Director of General Internal Medicine, St Louis University Author and Editor Disclosure Synonyms and related keywords: VAD, retinoic acid, retinol, beta carotene, beta-carotene, Aquasol A, Palmitate-A, Oleovitamin A, carotenoids, provitamin A, 11-cis-retinol, vision, dark adaptation, nyctalopia, retinol-binding protein, RBP, cellular retinol-binding protein, CRBP, cystic fibrosis, sprue, pancreatic insufficiency, inflammatory bowel disorder, IBD, inflammatory bowel disease, cholestasis, alcoholism, Bitot spots, nyctalopia, dry skin, dry hair, pruritus, broken fingernails, keratomalacia, xerophthalmia, follicular hyperkeratosis, phrynoderma, vitamin deficiency, malnutrition, retinoids, retinoid deficiency, deficiency of vitamin A INTRODUCTIONSection 2 of 11
  BackgroundThe word vitamin was originally derived from Funk's term "vital amine." In 1912, he was referring to Christian Eijkman's discovery of an amine extracted from rice polishings that could prevent beriberi. Funk's recognition of the antiberiberi factor as vital for life was indeed accurate. Researchers have since found that vitamins are essential organic compounds that the human body cannot synthesize. Vitamins A, D, K, and E are classified as fat-soluble vitamins, whereas others are classified as water-soluble vitamins. Vitamin A was the first fat-soluble vitamin to be discovered. Two independent research teams, Osborne and Mendel at Yale University and McCollum and Davis at the University of Wisconsin, simultaneously discovered it in 1913. Vitamin A comprises a family of compounds called the retinoids. The retinoid designation resulted from finding that vitamin A had the biologic activity of retinol, which was originally isolated from the retina. In nature, the active retinoids occur in 3 forms: alcohol (retinol), aldehyde (retinal or retinaldehyde), and acid (retinoic acid). The inactive retinoids, known as provitamins A, are produced as plant pigments and are called carotenoids. Several hundred carotenoids occur in foods, but only approximately 50 can be metabolized into the active retinoid forms; among these 50 compounds, beta-carotene, a retinol dimer, has the most significant provitamin A activity. In the human body, retinol is the predominant form, and 11-cis-retinol is the active form. Retinol-binding protein (RBP) binds vitamin A and regulates its absorption and metabolism. Vitamin A is essential for vision (especially dark adaptation); immune response; epithelial cell growth and repair; bone growth; reproduction; maintenance of the surface linings of the eyes; and epithelial integrity of respiratory, urinary, and intestinal tracts. Vitamin A is also important for embryonic development and regulation of adult genes. It functions as an activator of gene expression by retinoid alpha-receptor transcription factor and ligand-dependent transcription factor. Deficiency of vitamin A is found among malnourished, elderly, and chronically sick populations in the United States, but it is more prevalent in developing countries. Abnormal dark adaptation, dry skin, dry hair, broken fingernails, and decreased resistance to infections are among the first signs of vitamin A deficiency (VAD). PathophysiologyOnce ingested, provitamins A are released from proteins in the stomach. These retinyl esters are then hydrolyzed to retinol in the small intestine because retinol is more efficiently absorbed. Carotenoids are cleaved in the intestinal mucosa into molecules of retinaldehyde, which is subsequently reduced to retinol and then esterified to retinyl esters. The retinyl esters of both retinoid and carotenoid origin are transported via micelles in the lymphatic drainage of the intestine to the blood and then to the liver as components of chylomicrons. Of vitamin A in the body, 50-80% is stored in the liver, where it is bound to the cellular RBP. The remaining vitamin A is deposited into adipose tissue, lungs, and kidneys as retinyl esters, most commonly as retinyl palmitate. Vitamin A can be mobilized from the liver to peripheral tissue by a process of de-esterification of the retinyl esters. In blood, vitamin A is bound to RBP, which transports it as a complex with transthyretin. The hepatic synthesis of RBP is dependent on the presence of zinc and amino acids to maintain its narrow serum range of 40-50 mcg/dL. The retinol is taken up by the peripheral tissues from the RBP-transthyretin complex by a receptor-mediated process. VAD may be secondary to decreased ingestion, defective absorption and altered metabolism, or increased requirements. An adult liver can store up to a year's reserve of vitamin A, whereas a child's liver may have enough stores to last only several weeks. Serum retinol concentration reflects an individual's vitamin A status. Because serum retinol is homeostatically controlled, its levels do not drop until the body's stores are significantly limited. The serum concentration of retinol is affected by several factors, including RBP synthesis in the liver, infection, nutritional status, and an adequate level of other nutrients such as zinc and iron. In zinc deficiency, impaired synthesis of proteins occurs with rapid turnover (eg, RBP). In turn, this impairment affects retinol transport by RBP from the liver to the circulation and other tissues. The mechanism by which iron affects vitamin A metabolism has not been identified, but randomized, double-blind studies have shown that vitamin A supplementation alone is not sufficient to improve VAD in the presence of coexisting iron deficiency. The bioavailability of the carotenoids varies and depends on absorption and their yield of retinol. Only 40-60% of ingested beta-carotene from plant sources is absorbed by the human body, whereas 80-90% of retinyl esters from animal proteins are absorbed. Carotenoid absorption is affected by dietary factors such as zinc deficiency, abetalipoproteinemia, and protein deficiency. Because vitamin A is a fat-soluble vitamin, any GI diseases affecting the absorption of fats also affect vitamin A absorption. Patients with cystic fibrosis, sprue, pancreatic insufficiency, inflammatory bowel disorder (IBD), cholestasis, and small-bowel bypass surgery are at increased risk for VAD. These patients should be advised to consume vitamin A. One factor affecting the metabolism of vitamin A is alcoholism. Alcohol dehydrogenase catalyzes the conversion of retinol to retinaldehyde, which is then oxidized to retinoic acid. The affinity of alcohol dehydrogenase to ethanol impedes the conversion of retinol to retinoic acid. Increased requirements of vitamin A most commonly occur among sick children. In the United States, the American Academy of Pediatrics recommends vitamin A supplementation for infants aged 6-24 months who are hospitalized with measles and for all hospitalized children older than 6 months. In the 1960s, the World Health Organization (WHO) undertook the first global survey of VAD with associated xerophthalmia and complicated measles. In 1973, an international vitamin A board was set up to alleviate global malnutrition. The WHO and United Nations International Children's Emergency Fund (UNICEF) have issued joint statements recommending vitamin A administration for all children, especially those younger than 2 years, who are diagnosed with measles. Coexistent VAD in young children increases the risk of death. The Cochrane Database Systemic Review concluded that daily treatment with 200,000 IU of vitamin A for at least 2 days reduces mortality rates (D'Souza, 2002). Pregnant women do not require increased vitamin A supplementation. In fact, the Teratology Society advocates that women should be informed of the possible risk of cranial neural crest defects and other malformations resulting from excessive use of vitamin A shortly before or during pregnancy. The recommended daily allowance (RDA) of 800 mcg for all adult females is also appropriate for pregnant women because their stores of vitamin A meet the fetal accretion rate. The requirements for lactating women have been debated, but the current RDA is 1300 mcg in the first 6 months and 1200 mcg in the second 6 months. The RDAs of vitamin A for various age groups are as follows:
FrequencyUnited StatesStatistics from the US Centers for Disease Control and Prevention from the 1988-1991 survey show that age-specific intakes of carotenes were higher among males than females and were higher among adults than children. Significant differences in intake existed among different ethnic groups. InternationalClinical and subclinical VAD are problems in at least 75 countries. In 1994, the WHO classified countries as having clinical or subclinical, severe, moderate, or mild VAD. Most countries with clinical VAD (children demonstrate eye signs and symptoms, including blindness) are in Southeast Asia and sub-Saharan Africa. Severe VAD is also found in persons in refugee settlements and in displaced populations. Mortality/Morbidity
CLINICALSection 3 of 11
HistorySubclinical forms of VAD may not cause any symptoms, but the risk of developing respiratory and diarrheal infections is increased, the growth rate is decreased, and bone development is slowed. Patients may have a recent history of increased infections, infertility secondary to impaired spermatogenesis, or recent spontaneous abortion secondary to impaired embryonic development. The patient may also report increased fatigue as a manifestation of VAD anemia. PhysicalSigns and symptoms include Bitot spots, poor dark adaptation (nyctalopia), dry skin, dry hair, pruritus, broken fingernails, keratomalacia, xerophthalmia, and follicular hyperkeratosis (phrynoderma) secondary to blockage of hair follicles with plugs of keratin. Other signs include excessive deposition of periosteal bone secondary to reduced osteoclastic activity, anemia, and keratination of mucous membranes. CausesThe risk of VAD is increased in patients with fat malabsorption, cystic fibrosis, sprue, pancreatic insufficiency, IBD, cholestasis, and/or small-bowel bypass surgery. It is also increased in vegans, refugees, recent immigrants, persons with alcoholism, and toddlers and preschool children living below the poverty line. These patients should be advised to consume vitamin A. DIFFERENTIALSSection 4 of 11
Hypothyroidism
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| Drug Name | Vitamin A (Del-Vi-A, Del-Vi-A) |
|---|---|
| Description | Cofactor in many biochemical processes. |
| Adult Dose | 3000 mcg (10,000 IU) PO qd Severe disease: 60,000 mcg (200,000 IU) PO for at least 2 d |
| Pediatric Dose | <3 years: 600 mcg (2000 IU) PO qd 4-8 years: 900 mcg (3000 IU) PO qd 9-13 years: 1700 mcg (5665 IU) PO qd 14-18 years: 2800 mcg (9335 IU) PO qd Severe disease: 60,000 mcg (200,000 IU) PO for at least 2 d |
| Contraindications | Documented hypersensitivity; hypervitaminosis A; pregnancy (if dose >800 mcg/d) |
| Interactions | Cholestyramine, neomycin, and mineral oil may decrease absorption |
| Pregnancy | A - Safe in pregnancy |
| Precautions | Risk of teratogenicity increases in pregnant women at doses >800 mcg/d (not recommended); parenteral vitamin A in infants of low birth weight may be associated with thrombocytopenia, renal dysfunction, hepatomegaly, cholestasis, ascites, hypotension, and metabolic acidosis (E-Ferol syndrome) |
| Media file 1: Clinical signs of Vitamin A deficiency and toxicity. | |
 | View Full Size Image | Media type: Graph |
Article Last Updated: May 12, 2006
