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Vitamin A Deficiency

(Retinol Deficiency)

By

Larry E. Johnson

, MD, PhD, University of Arkansas for Medical Sciences

Last full review/revision Nov 2020| Content last modified Nov 2020
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Vitamin A deficiency can result from inadequate intake, fat malabsorption, or liver disorders. Deficiency impairs immunity and hematopoiesis and causes rashes and typical ocular effects (eg, xerophthalmia, night blindness). Diagnosis is based on typical ocular findings and low vitamin A levels. Treatment consists of vitamin A given orally or, if symptoms are severe or malabsorption is the cause, parenterally.

Vitamin A is required for the formation of rhodopsin, a photoreceptor pigment in the retina (see table Sources, Functions, and Effects of Vitamins Sources, Functions, and Effects of Vitamins  Vitamins may be Fat soluble (vitamins A, D, E, and K) Water soluble (B vitamins and vitamin C) The B vitamins include biotin, folate, niacin, pantothenic acid, riboflavin (B2), thiamin (B1)... read more ). Vitamin A helps maintain epithelial tissues and is important for lysosome stability and glycoprotein synthesis.

Dietary sources of preformed vitamin A include fish liver oils, liver, egg yolks, butter, and vitamin A–fortified dairy products. Beta-carotene and other provitamin carotenoids, contained in green leafy and yellow vegetables, carrots, and deep- or bright-colored fruits, are converted to vitamin A. Carotenoids are absorbed better from vegetables when they are cooked or homogenized and served with some fat (eg, oils). Normally, the liver stores 80 to 90% of the body’s vitamin A. To use vitamin A, the body releases it into the circulation bound to prealbumin (transthyretin) and retinol-binding protein.

Retinol activity equivalents (RAE) were developed because provitamin A carotenoids have less vitamin A activity than preformed vitamin A; 1 mcg retinol = 3.33 units.

Synthetic vitamin analogs (retinoids) are being used increasingly in dermatology. The possible protective role of beta-carotene, retinol, and retinoids against some epithelial cancers is under study. However, risk of certain cancers may be increased after beta-carotene supplementation.

Etiology of Vitamin A Deficiency

Primary vitamin A deficiency is usually caused by

  • Prolonged dietary deprivation

It is endemic in areas such as southern and eastern Asia, where rice, devoid of beta-carotene, is the staple food. Xerophthalmia due to primary deficiency is a common cause of blindness among young children in developing countries.

Secondary vitamin A deficiency may be due to

  • Decreased bioavailability of provitamin A carotenoids

  • Interference with absorption, storage, or transport of vitamin A

Interference with absorption or storage is likely in celiac disease Celiac Disease Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption... read more Celiac Disease , cystic fibrosis Cystic Fibrosis Cystic fibrosis is an inherited disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems. It leads to chronic lung disease, exocrine pancreatic insufficiency... read more Cystic Fibrosis , pancreatic insufficiency Symptoms and Signs Chronic pancreatitis is persistent inflammation of the pancreas that results in permanent structural damage with fibrosis and ductal strictures, followed by a decline in exocrine and endocrine... read more , duodenal bypass Roux-en-Y gastric bypass (RYGB) surgery Bariatric surgery is the surgical alteration of the stomach, intestine, or both to cause weight loss. In the US, about 250,000 bariatric operations are done in each year. Development of safer... read more , chronic diarrhea Diarrhea Stool is 60 to 90% water. In Western society, stool amount is 100 to 200 g/day in healthy adults and 10 g/kg/day in infants, depending on the amount of unabsorbable dietary material (mainly... read more , bile duct obstruction Choledocholithiasis and Cholangitis Choledocholithiasis is the presence of stones in bile ducts; the stones can form in the gallbladder or in the ducts themselves. These stones cause biliary colic, biliary obstruction, gallstone... read more , giardiasis Giardiasis Giardiasis is infection with the flagellated protozoan Giardia duodenalis (G. lamblia, G. intestinalis). Infection can be asymptomatic or cause symptoms ranging from intermittent flatulence... read more , and cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more . Vitamin A deficiency is common in prolonged protein-energy undernutrition Protein-Energy Undernutrition (PEU) Protein-energy undernutrition (PEU), previously called protein-energy malnutrition, is an energy deficit due to deficiency of all macronutrients. It commonly includes deficiencies of many micronutrients... read more not only because the diet is deficient but also because vitamin A storage and transport is defective.

Symptoms and Signs of Vitamin A Deficiency

Impaired dark adaptation of the eyes, which can lead to night blindness, is an early symptom of vitamin A deficiency. Xerophthalmia (which is nearly pathognomonic) results from keratinization of the eyes. It involves drying (xerosis) and thickening of the conjunctivae and corneas. Superficial foamy patches composed of epithelial debris and secretions on the exposed bulbar conjunctiva (Bitot spots) develop. In advanced deficiency, the cornea becomes hazy and can develop erosions, which can lead to its destruction (keratomalacia).

Keratinization of the skin and of the mucous membranes in the respiratory, gastrointestinal, and urinary tracts can occur. Drying, scaling, and follicular thickening of the skin and respiratory infections can result.

Immunity is generally impaired.

The younger the patient, the more severe are the effects of vitamin A deficiency. Growth retardation and infections are common among children. Mortality rate can exceed 50% in children with severe vitamin A deficiency.

Diagnosis of Vitamin A Deficiency

  • Serum retinol levels, clinical evaluation, and response to vitamin A

Ocular findings suggest vitamin A deficiency. Dark adaptation can be impaired in other disorders (eg, zinc deficiency, retinitis pigmentosa, severe refractive errors, cataracts, diabetic retinopathy). If dark adaptation is impaired, rod scotometry and electroretinography are done to determine whether vitamin A deficiency is the cause.

Serum levels of retinol are measured. Normal range is 28 to 86 mcg/dL (1 to 3 mcmol/L). However, levels decrease only after the deficiency is advanced because the liver contains large stores of vitamin A. Also, decreased levels may result from acute infection, which causes retinol-binding protein and transthyretin (also called prealbumin) levels to decrease transiently.

A therapeutic trial of vitamin A may help confirm the diagnosis.

Prevention of Vitamin A Deficiency

The diet should include dark green leafy vegetables, deep- or bright-colored fruits (eg, papayas, oranges), carrots, and yellow vegetables (eg, squash, pumpkin). Vitamin A–fortified milk and cereals, liver, egg yolks, and fish liver oils are helpful. Carotenoids are absorbed better when consumed with some dietary fat. If milk allergy is suspected in infants, they should be given adequate vitamin A in formula feedings.

In developing countries, prophylactic supplements of vitamin A palmitate in oil 200,000 units (60,000 retinol activity equivalent [RAE]) orally every 6 months are advised for all children between 1 and 5 years of age; infants < 6 months can be given a one-time dose of 50,000 units (15,000 RAE), and those aged 6 to 12 months can be given a one-time dose of 100,000 units (30,000 RAE).

Treatment of Vitamin A Deficiency

  • Vitamin A palmitate

Dietary deficiency of vitamin A is traditionally treated with vitamin A palmitate in oil 60,000 units orally once a day for 2 days, followed by 4500 units orally once a day. If vomiting or malabsorption is present or xerophthalmia is probable, a dose of 50,000 units for infants < 6 months, 100,000 units for infants 6 to 12 months, or 200,000 units for children > 12 months and adults should be given for 2 days, with a third dose at least 2 weeks later. The same doses are recommended for infants and children with complicated measles.

Vitamin A deficiency is a risk factor for severe measles Measles Measles is a highly contagious viral infection that is most common among children. It is characterized by fever, cough, coryza, conjunctivitis, an enanthem (Koplik spots) on the oral mucosa... read more Measles ; treatment with vitamin A can shorten the duration of the disorder and may reduce the severity of symptoms and risk of death. It is recommended that all children with measles receive 2 doses of vitamin A (100,000 units for children < 12 months and 200,000 units for those > 12 months) given 24 hours apart (see also WHO: Measles Fact Sheet).

Infants born of HIV-positive mothers should receive 50,000 units (15,000 RAE) within 48 hours of birth. Prolonged daily administration of large doses, especially to infants, must be avoided because toxicity may result.

For pregnant or breastfeeding women, prophylactic or therapeutic doses should not exceed 10,000 units (3000 RAE)/day to avoid possible damage to the fetus or infant.

Key Points

  • Vitamin A deficiency usually results from dietary deficiency, as occurs in areas where rice, devoid of beta-carotene, is the staple food, but it may result from disorders that interfere with the absorption, storage, or transport of vitamin A.

  • Ocular findings include impaired night vision (early), conjunctival deposits, and keratomalacia.

  • In children with severe deficiency, growth is slowed and risk of infection is increased.

  • Diagnose based on ocular findings and serum retinol levels.

  • Treat with vitamin A palmitate.

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