Synonyms: hypovitaminosis A
Vitamin A was the first vitamin identified and hence given the first letter in the alphabet. Vitamin A (retinol) is a fat-soluble vitamin, present in liver, milk and eggs.
Beta carotene and other provitamin carotenoids occur in green leafy and orange/yellow vegetables and fruits. They are converted to retinal by small intestine mucosal cells, reduced to retinol, then esterified and stored in the liver (as retinyl palmitate). Vitamin A is transferred around the body as retinol bound to retinol-binding protein and prealbumin (transthyretin). Retinol is converted to rhodopsin (photoreceptor pigment) in the retina and is also used to regulate gene expression and guide differentiation in a variety of other tissues.
Primary vitamin A deficiency
- This is caused by prolonged dietary deficiency, particularly where rice is the staple food (doesn't contain carotene).
- Vitamin A deficiency occurs with protein-energy malnutrition (marasmus or kwashiorkor) mainly because of dietary deficiency (but vitamin A storage and transport are also impaired).
Secondary vitamin A deficiency
- This occurs where there are problems in converting carotene to vitamin A, or reduced absorption, storage, or transport of vitamin A.
- This occurs in coeliac disease, tropical sprue, giardiasis, cystic fibrosis, other pancreatic disease, cirrhosis, duodenal bypass surgery and bile duct obstruction.
- It is rare in the UK but is extremely common in developing countries, especially in sub-Saharan Africa and South Asia.[1, 2]
- Globally, vitamin A deficiency affects 100-140 million children, of whom 4.4 million have xerophthalmia.
- In pregnant women, vitamin A deficiency occurs especially in the last trimester (demand by fetus and mother is highest).
- Other risk factors for vitamin A deficiency include:
- Fat malabsorption, cholestasis, inflammatory bowel disease, cystic fibrosis, pancreatic insufficiency or following small-bowel bypass surgery.
- Vegan diet.
- Toddlers and preschool children living below the poverty line.
- Recent immigrants or refugees from developing countries.
Mild forms of vitamin A deficiency may cause no symptoms. However, there may still be an increased risk of developing respiratory infections and gastroenteritis, and delayed growth and bone development. There is also a risk of infertility secondary to impaired spermatogenesis, and an increased risk of miscarriage. Fatigue may present as a consequence of vitamin A deficiency anaemia.
Eye and vision
Pathognomonic changes occur in the eye (usually bilateral, although may be of differing degrees):
- Poor adaptation to darkness - night blindness.
- Keratomalacia (thinning and ultimately ulceration of the cornea - colliquative necrosis).
- Conjunctival dryness, corneal dryness, xerophthalmia.
- Bitot's spots (areas of abnormal squamous cell proliferation and keratinisation of the conjunctiva, causing oval, triangular or irregular foamy patches on the white of the eye).
- Corneal perforation.
- Blindness due to structural damage to the retina.
- Reduced vitamin A concentration increases the risk of blindness in children infected with the measles virus.
Skin and hair
- Dry skin, dry hair, pruritus.
- Broken fingernails.
- Follicular hyperkeratosis secondary to blockage of hair follicles, with plugs of keratin.
Other less specific changes
- Keratinisation of mucous membranes.
- Increased susceptibility to infection (due to impairment of the humoral and cell-mediated immunity).
- Skin changes (follicular hyperkeratosis), which are also common.
- Serum retinol study is costly. Serum retinol-binding protein study is easier to perform and less expensive.
- Zinc level (zinc deficiency interferes with production of retinol-binding protein).
- Iron studies (iron deficiency can affect the metabolism of vitamin A).
- FBC: anaemia and infection may occur.
- Renal function tests, electrolytes and LFTs to evaluate for nutritional and hydration status.
- In children, X-rays of the long bones may be useful to evaluate bone growth and for excessive deposition of periosteal bone.
- Dark-adaptation threshold should be tested.
- Treatment for subclinical vitamin A deficiency includes the consumption of vitamin A-rich foods - for example, liver, beef, chicken, eggs, fortified milk, carrots, mangoes, sweet potatoes and leafy green vegetables.
- Good animal sources of vitamin A include liver, egg yolks, whole milk, animal butter and whole small fish (with liver intact).
- Animal sources, including vitamin A in breast milk, are more bioavailable than vegetable sources, which include carrots and other orange/yellow fruits and vegetables, and dark green leafy vegetables.
- For clinically evident vitamin A deficiency, treatment includes daily oral vitamin A supplements.
- Massive overdose of vitamin A can cause rough skin, dry hair, an enlarged liver and a raised erythrocyte sedimentation rate and raised serum calcium and serum alkaline phosphatase concentrations.
- In view of evidence suggesting that high levels of vitamin A may cause birth defects, women who are (or may become) pregnant are advised neither to take vitamin A supplements (including tablets and fish-liver oil drops), except on medical advice, nor to eat liver or products such as liver pâté or liver sausage.
Prognosis is good if patients are treated when the deficiency is subclinical. Morbidity increases once blindness has progressed. Irreversible conditions include punctate keratopathy, keratomalacia and corneal perforation.
- For patients with early mild eye problems, prompt treatment can result in full preservation of sight without residual impairment (heals completely within a few weeks).
- In the developing world, because a severe degree of vitamin A deficiency is often accompanied by severe generalised malnutrition, death is the most likely outcome. Mortality in infants with severe vitamin A deficiency is up to 50%.
- Only about 40% of patients with corneal xerophthalmia are alive one year later (25% are totally blind and the remainder partially blind).
- Liver, beef, chicken, eggs, whole milk, fortified milk, carrots, mangoes, orange fruits, sweet potatoes, spinach, kale and other green vegetables are among foods rich in vitamin A.
- Eating at least five servings of fruits and vegetables per day is recommended in order to provide a comprehensive distribution of carotenoids.
- A variety of foods, such as breakfast cereals, pastries, breads, crackers and cereal grain bars, are often fortified with vitamin A.
- In at-risk populations, vitamin A supplements are associated with a reduction of morbidity, mortality and blindness in young children aged 6 months to 5 years.[9, 10]
- There is, however, no convincing evidence that either maternal postpartum or infant vitamin A supplementation results in a reduction in infant mortality or morbidity in low- and middle-income countries.
Further reading and references
Sommer A, Vyas KS; A global clinical view on vitamin A and carotenoids. Am J Clin Nutr. 2012 Nov96(5):1204S-6S. doi: 10.3945/ajcn.112.034868. Epub 2012 Oct 10.
Akhtar S, Ahmed A, Randhawa MA, et al; Prevalence of vitamin A deficiency in South Asia: causes, outcomes, and possible remedies. J Health Popul Nutr. 2013 Dec31(4):413-23.
Iannotti LL, Trehan I, Manary MJ; Review of the safety and efficacy of vitamin A supplementation in the treatment of children with severe acute malnutrition. Nutr J. 2013 Sep 1212:125. doi: 10.1186/1475-2891-12-125.
Vitamin and mineral requirements in human nutrition; World Health Organization, 2004
Sommer A; Vitamin a deficiency and clinical disease: an historical overview. J Nutr. 2008 Oct138(10):1835-9.
Sharma A, Aggarwal S, Sharma V; Bitot's Spots: Look at the Gut. Int J Prev Med. 2014 Aug5(8):1058-9.
Bello S, Meremikwu MM, Ejemot-Nwadiaro RI, et al; Routine vitamin A supplementation for the prevention of blindness due to measles infection in children. Cochrane Database Syst Rev. 2014 Jan 161:CD007719. doi: 10.1002/14651858.CD007719.pub3.
British National Formulary; 69th Edition (Mar 2015) British Medical Association and Royal Pharmaceutical Society of Great Britain, London
Imdad A, Herzer K, Mayo-Wilson E, et al; Vitamin A supplementation for preventing morbidity and mortality in children from Cochrane Database Syst Rev. 2010 Dec 812: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 Aug 25343:d5094. doi: 10.1136/bmj.d5094.
Gogia S, Sachdev HS; Vitamin A supplementation for the prevention of morbidity and mortality in infants six months of age or less. Cochrane Database Syst Rev. 2011 Oct 5(10):CD007480. doi: 10.1002/14651858.CD007480.pub2.
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