Vitamin A deficiency

Vitamin A deficiency usually results from inadequate intakes of vitamin A from animal products (as preformed vitamin A found in fish, liver, dairy products, and eggs) and fruits, vegetables, and other plant-based products (as provitamin A carotenoids that are turned into vitamin A by your body). Vitamin A is important for normal vision, the immune system, male and female reproduction, and growth and development ¹⁾, ²⁾, ³⁾. Vitamin A also helps your heart, lungs, eyes, and other organs to work properly ⁴⁾, ⁵⁾. Vitamin A is also critical for vision as an essential component of rhodopsin, the light-sensitive protein in the retina that responds to light entering the eye, and because it supports the normal differentiation and functioning of the conjunctival membranes and cornea ⁶⁾, ⁷⁾. Vitamin A deficiency is rare in the United States, except in individuals with poor absorption of fats due to cystic fibrosis, ulcerative colitis, Crohn’s disease, weight loss surgery, short bowel syndrome, celiac disease, and, liver disease ⁸⁾, ⁹⁾, ¹⁰⁾. However, vitamin A deficiency is common in many developing countries, often because residents have limited access to foods containing preformed vitamin A from animal-based food sources and they do not commonly consume available foods containing beta-carotene due to poverty or traditional diets ¹¹⁾, ¹²⁾. A pooled analysis of population-based surveys from 138 low-income and middle-income countries found that 29% of children aged 6 months to 5 years had vitamin A deficiency in 2013 ¹³⁾. Vitamin A deficiency rates were highest in sub-Saharan Africa (48%) and South Asia (44%) ¹⁴⁾. In addition, approximately 10% to 20% of pregnant people in low-income countries have vitamin A deficiency ¹⁵⁾. Most vitamin A is stored in the liver, so measuring vitamin A levels in the liver is the best way to assess vitamin A adequacy ¹⁶⁾. In clinical practice, plasma retinol levels alone can be used to document significant vitamin A deficiency ¹⁷⁾. A serum or plasma retinol concentration of 0.70 μmol/L (20 mcg/dL) or less frequently reflects subclinical vitamin A deficiency, and a serum or plasma retinol level of 0.35 μmol/L (10 mcg/dL) or less is considered an indicator of severe vitamin A deficiency, where vitamin A body stores are depleted ¹⁸⁾. Of note, the World Health Organization (WHO) considers vitamin A deficiency a public health problem when the prevalence of low serum retinol (<0.70 μmol/L) reaches 15% or more of a defined population ¹⁹⁾. Long‐term or severe vitamin A deficiency may lead to eye lesions such as xerophthalmia (inability to see in low light) and keratomalacia (an eye disorder that involves drying and clouding of the cornea), eventually resulting in visual impairment, blindness, skin disease and growth retardation in children ²⁰⁾. The most common clinical sign of vitamin A deficiency is xerophthalmia, which develops after plasma retinol has been low and the eye’s vitamin A reserves have become depleted. The first sign is night blindness, or the inability to see in low light or darkness as a result of low rhodopsin levels in the retina ²¹⁾, ²²⁾, ²³⁾. Xerophthalmia also affects the cornea and can eventually lead to permanent blindness; vitamin A deficiency is one of the top causes of preventable blindness in children ²⁴⁾.

In developing countries, vitamin A deficiency and associated disorders predominantly affect children and women of reproductive age. According to the World Health Organization (WHO), 190 million preschool-aged children and 19.1 million pregnant women around the world have a serum retinol concentration below 0.70 micromoles/L ²⁵⁾. In these countries, low vitamin A intake is most strongly associated with health consequences during periods of high nutritional demand, such as during infancy, childhood, pregnancy, and lactation.

Vitamin A deficiency is the leading cause of preventable blindness in children worldwide:

• Impaired dark adaptation (night blindness) due to lack of the photoreceptor pigment rhodopsin.
• Xerophthalmia: dry, thickened conjunctiva and cornea
• Bitot spots: keratinized growths (metaplasia) on the conjunctivae causing hazy vision
• Keratomalacia: corneal erosions and ulceration

Vitamin A deficiency can also be recognized by its keratinizing effect on the skin and mucous membranes:

• Dry, scaly, thickened skin with prominent follicular scale (phrynoderma or follicular hyperkeratosis)
• Dry lips and thickened tongue
• Keratinisation of the urinary, gastrointestinal and respiratory tracts

Other symptoms and signs of vitamin A deficiency are:

• Impaired immunity leading to gastrointestinal and respiratory tract infections
• Growth retardation in children

Chronic vitamin A deficiency has also been associated with abnormal lung development, respiratory diseases (such as pneumonia), and an increased risk of anemia and death ²⁶⁾, ²⁷⁾, ²⁸⁾.

Another effect of chronic vitamin A deficiency is increased severity and mortality risk of infections (particularly measles and infection-associated diarrhea) ²⁹⁾. In 2013, 94,500 children in low-income and middle-income countries died of diarrhea and 11,200 died of measles as a result of vitamin A deficiency ³⁰⁾. More than 95% of deaths attributable to vitamin A deficiency occurred in sub-Saharan Africa and Asia, where vitamin A deficiency was responsible for 2% of all deaths in children younger than 5 years ³¹⁾.

In developing countries, vitamin A deficiency typically begins during infancy, when infants do not receive adequate supplies of colostrum or breast milk ³²⁾. Chronic diarrhea also leads to excessive loss of vitamin A in young children, and vitamin A deficiency increases the risk of diarrhea ³³⁾. The most common symptom of vitamin A deficiency in young children and pregnant women is xerophthalmia. One of the early signs of xerophthalmia is night blindness, or the inability to see in low light or darkness ³⁴⁾. Vitamin A deficiency is one of the top causes of preventable blindness in children ³⁵⁾. People with vitamin A deficiency (and, often, xerophthalmia with its characteristic Bitot’s spots) tend to have low iron status, which can lead to anemia ³⁶⁾. Vitamin A deficiency also increases the severity and mortality risk of infections (particularly diarrhea and measles) even before the onset of xerophthalmia ³⁷⁾.

During pregnancy, vitamin A is essential for fetal organ and skeletal growth and maturation, maintenance of the maternal immune system, development of vision in the fetus, and maintenance of maternal eye health and night vision ³⁸⁾. Although pregnant women are susceptible to vitamin A deficiency throughout gestation, deficiency is most common in the third trimester. It is unclear whether this is due to increased demands during pregnancy from accelerated fetal development and the physiological increase in blood volume during this period ³⁹⁾, or to lowered serum retinol concentration due to an increase in plasma volume. In a pregnant woman with moderate vitamin A deficiency, the fetus can still obtain sufficient vitamin A to develop appropriately but at the expense of the maternal vitamin A stores ⁴⁰⁾.

Figure 1. Eye signs of vitamin A deficiency

Footnote: A 24-year-old, 26 weeks pregnant woman with a 7-week history of progressive loss of vision, most notable at night. The woman had anorexia nervosa and had limited her diet to white onions, white potatoes, and red meat for the past 7 years. Numerous Bitot spots (figure A) and keratitis (figure B) were seen on examination of her eyes; however, her retina was grossly normal (figure C, D). Electroretinography showed a generalized rod-cone dysfunction, and fundus autofluorescence showed faint retinal vasculature in her right eye (figure E) and a black image in the left eye. Autofluorescence from the left eye of an age-match control is shown (figure F). Acquired vitamin A deficiency was confirmed by a serum concentration of <0·002 μmol/L (normal range 0·70–2·8 μmol/L). Her vision and the appearance of her anterior segment returned to normal with vitamin A supplementation.

[Source ⁴¹⁾]

Figure 2. Bitot spots

Footnote: Left eye of an eight-year-old boy, with a large, superficial, triangular, foamy, keratinized patch in the interpalpebral region over the bulbar conjunctiva, adjacent to the temporal limbus (black arrow), suggestive of Bitot’s spots.

[Source ⁴²⁾ ]

Figure 3. Conjunctival xerosis (dryness of the conjunctiva)

Footnote: Conjunctival xerosis (dryness of the conjunctiva) is another sign of long-standing vitamin A deficiency. Note the slight wrinkling of the temporal conjunctiva. Conjunctival xerosis can be quite difficult to detect and is therefore not a very reliable sign.

[Source ⁴³⁾ ]

Figure 4. Corneal xerosis (drying of the cornea)

Footnote: Corneal xerosis (drying of the cornea) is a sign of sudden, acute vitamin A deficiency. The cornea becomes dry because glands in the conjunctiva no longer function normally. This leads to loss of tears and also loss of mucous, which acts as a ‘wetting agent’. The lack of mucus together with lack of tears not only leads to the dry appearance but also increases the risk of eye infection.

[Source ⁴⁴⁾ ]

Figure 5. Corneal ulcer due to vitamin A deficiency

Footnote: If the acute vitamin A deficiency is not reversed as a matter of urgency, the cornea can become ulcerated and melt away. The corneal ulcer may have the appearance of a small, punched-out area in the cornea (top image), or the ulcer may have a more fluffy appearance (lower picture). In the absence of secondary infection, the eye can look surprisingly white, as in both images; however, secondary infection of the corneal ulcer is common, leading to an acutely inflamed eye.

[Source ⁴⁵⁾ ]

Figure 6. Corneal ulcer due to vitamin A deficiency

Footnote: Right eye showing corneal ulcer measuring 2 mm X 10 mm (red arrow) in the setting of chronic alcoholism.

[Source ⁴⁶⁾ ]

Figure 7. Keratomalacia (corneal ulcer covering at least 1/3 of the cornea)

Footnote: The most severe form of vitamin A deficiency xerophthalmia is keratomalacia, in which more than one-third of the cornea is affected. The cornea may become edematous and thickened, and then melt away. This occurs because the structure of the collagen in the cornea is affected by a process known as necrosis. The cornea can be destroyed in just a few days. Children with keratomalacia are often malnourished, but children who previously appeared relatively healthy can also develop keratomalacia following measles infection or episodes of diarrhea; this is usually because they were vitamin A deficient and the measles infection resulted in depletion of their vitamin A stores. If you are not sure whether the child you are seeing has keratomalacia, ask about recent illness, particularly measles.

[Source ⁴⁷⁾ ]

Figure 8. Corneal scarring

Footnote: The end result of corneal ulceration and keratomalacia is corneal scarring, staphylomas (forward bulging of a badly damaged cornea) or phthisis bulbi (an eye that has shrivelled up), depending on the extent of the pathology in the cornea. Most of the eye signs of vitamin A deficiency are symmetrical and bilateral, and so can lead to blindness.

[Source ⁴⁸⁾ ]

Vitamin A deficiency can result from inadequate intake, fat malabsorption, or liver disorders. Vitamin A deficiency impairs immunity and formation of red blood cells (hematopoiesis) and causes skin rashes and typical eye signs and symptoms (e.g., Bitot spots, conjunctival xerosis, corneal xerosis, xerophthalmia, night blindness). Vegetarians, young children, and alcoholics may need extra vitamin A. You might also need more if you have certain conditions, such as liver diseases, cystic fibrosis, Crohn’s disease and ulcerative colitis ⁴⁹⁾.

Vitamin A deficiency 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.

The most specific clinical effect of inadequate vitamin A intake is xerophthalmia ⁵⁰⁾. It is estimated that 3 to 10 million children, mostly in developing countries, become xerophthalmic, and 250,000 to 500,000 go blind annually ⁵¹⁾, ⁵²⁾. The World Health Organization ⁵³⁾ classified various stages of xerophthalmia to include night blindness (impaired dark adaptation due to slowed regeneration of rhodopsin), conjunctival xerosis, Bitot’s spots, corneal xerosis, corneal ulceration, and scarring, all related to vitamin A deficiency. Night blindness is the first ocular symptom to be observed with vitamin A deficiency ⁵⁴⁾, and it responds rapidly to treatment with vitamin A ⁵⁵⁾. High-dose (60 mg) vitamin A supplementation reduced the incidence of night blindness by 63 percent in Nepalese children ⁵⁶⁾. Similarly, night blindness was reduced by 50 percent in women after weekly supplementation with either 7,500 μg RE of vitamin A or β-carotene ⁵⁷⁾.

Because of the role of vitamin A in maintaining the structural integrity of epithelial cells, follicular hyperkeratosis has been observed with inadequate vitamin A intake ⁵⁸⁾, ⁵⁹⁾. Men who were made vitamin A deficient under controlled conditions were then supplemented with either retinol or β-carotene, which caused the hyperkeratosis to gradually clear ⁶⁰⁾.

Vitamin A deficiency has been associated with a reduction in lymphocyte numbers, natural killer cells, and antigen-specific immunoglobulin responses ⁶¹⁾, ⁶²⁾. A decrease in leukocytes and lymphoid organ weights, impaired T cell function, and decreased resistance to immunogenic tumors have been observed with inadequate vitamin A intake ⁶³⁾, ⁶⁴⁾. A generalized dysfunction of humoral and cell-mediated immunity is common in experimental animals and is likely to exist in humans.

In addition to xerophthalmia, vitamin A deficiency has been associated with increased risk of infectious morbidity and mortality in experimental animals and humans, especially in developing countries. A higher risk of respiratory infection and diarrhea has been reported among children with mild to moderate vitamin A deficiency ⁶⁵⁾. Mortality rates were about four times greater among children with mild xerophthalmia than those without it ⁶⁶⁾. The risk of severe morbidity and mortality decreases with vitamin A repletion. In children hospitalized with measles, case fatality ⁶⁷⁾, ⁶⁸⁾ and the severity of complications on admission were reduced when they received high doses (60 to 120 mg) of vitamin A ⁶⁹⁾, ⁷⁰⁾. In some studies, vitamin A supplementation (30 to 60 mg) has been shown to reduce the severity of diarrhea ⁷¹⁾, ⁷²⁾ and Plasmodium falciparum malaria ⁷³⁾ in young children, but vitamin A supplementation has had little effect on the risk or severity of respiratory infections, except when associated with measles ⁷⁴⁾.

In developing countries, vitamin A supplementation has been shown to reduce the risk of mortality among young children ⁷⁵⁾, ⁷⁶⁾, ⁷⁷⁾, ⁷⁸⁾, ⁷⁹⁾, infants ⁸⁰⁾, and pregnant and postpartum women ⁸¹⁾. Meta-analyses of the results from these and other community-based trials are consistent with a 23 to 30 percent reduction in mortality of young children beyond 6 months of age after vitamin A supplementation ⁸²⁾, ⁸³⁾, ⁸⁴⁾. The World Health Organization recommends broad-based prophylaxis in vitamin A-deficient populations. It also recommends treating children who suffer from xerophthalmia, measles, prolonged diarrhea, wasting malnutrition, and other acute infections with vitamin A ⁸⁵⁾. Furthermore, the American Academy of Pediatrics ⁸⁶⁾ recommends vitamin A supplementation for children in the United States who are hospitalized with measles.

Who is at risk of vitamin A deficiency?

The following groups are among those most likely to have inadequate intakes of vitamin A.

Premature infants

Preterm infants have low liver stores of vitamin A at birth, and their plasma concentrations of retinol often remain low throughout the first year of life ⁸⁷⁾, ⁸⁸⁾. Preterm infants with vitamin A deficiency have a higher risk of eye and chronic lung diseases ⁸⁹⁾, ⁹⁰⁾. However, in high-income countries, clinical vitamin A deficiency is rare in infants and occurs only in those with malabsorption disorders ⁹¹⁾.

Infants, children, and pregnant and lactating women in low-income and middle-income countries

Pregnant women need extra vitamin A for fetal growth and tissue maintenance and to support their own metabolism ⁹²⁾, ⁹³⁾, ⁹⁴⁾. The breast milk of lactating women with adequate vitamin A intakes contains sufficient amounts of vitamin A to meet infants’ needs for the first 6 months of life⁹⁵⁾. But in people with vitamin A deficiency, the vitamin A content of breast milk is not sufficient to maintain adequate vitamin A stores in infants who are exclusively breastfed ⁹⁶⁾.

About 190 million preschool-aged children (one third of all children in this age group), mostly in Africa and Southeast Asia, have vitamin A deficiency, according to the World Health Organization ⁹⁷⁾, ⁹⁸⁾. They have a higher risk of visual impairment and of illness and death from childhood infections, such as measles and infections that cause diarrheal diseases ⁹⁹⁾, ¹⁰⁰⁾.

The World Health Organization estimates that 9.8 million pregnant women (15% of all pregnant women) around the world, mostly in low-income and middle-income countries, have xerophthalmia as a result of vitamin A deficiency ¹⁰¹⁾.

People with cystic fibrosis

Up to 90% of people with cystic fibrosis have pancreatic insufficiency, which increases their risk of vitamin A deficiency due to difficulty absorbing fat ¹⁰²⁾, ¹⁰³⁾. Studies in Australia and the Netherlands indicate that 2% to 13% of children and adolescents with cystic fibrosis have vitamin A deficiency ¹⁰⁴⁾, ¹⁰⁵⁾. As a result, standard care for cystic fibrosis includes lifelong treatment with vitamin A (daily amounts of 750 mcg RAE to 3,000 mcg RAE, depending on age, are recommended in the United States and Australia), other fat-soluble vitamins, and pancreatic enzymes ¹⁰⁶⁾, ¹⁰⁷⁾.

Individuals with gastrointestinal disorders

Approximately one quarter of children with Crohn’s disease and ulcerative colitis have vitamin A deficiency; adults with these disorders, especially those who have had the disorder for several years, also have a higher risk of vitamin A deficiency ¹⁰⁸⁾, ¹⁰⁹⁾. Although some evidence supports the use of vitamin A supplements in people with these disorders ¹¹⁰⁾, other research has found that supplementation offers no benefit ¹¹¹⁾. Some children and adults with newly diagnosed celiac disease also have vitamin A deficiency; a gluten-free diet can, but does not always, eliminate vitamin A deficiency ¹¹²⁾, ¹¹³⁾, ¹¹⁴⁾.

What is vitamin A

Vitamin A is the name of a group of fat-soluble retinoids, including retinol, retinal, and retinyl esters ¹¹⁵⁾. Vitamin A is involved in immune function, vision, reproduction, and cellular communication ¹¹⁶⁾. Vitamin A is critical for vision as an essential component of rhodopsin, a protein that absorbs light in the retinal receptors, and because it supports the normal differentiation and functioning of the conjunctival membranes and cornea ¹¹⁷⁾. Vitamin A also supports cell growth and differentiation, playing a critical role in the normal formation and maintenance of the heart, lungs, kidneys, and other organs ¹¹⁸⁾.

Two forms of vitamin A are available in the human diet ¹¹⁹⁾:

• Preformed vitamin A (retinol and its esterified form, retinyl ester). Preformed vitamin A is found in foods from animal sources, such as fish, organ meats (such as liver), dairy products, and eggs.
• Provitamin A carotenoids. Provitamin A carotenoids are turned into vitamin A by your body. Provitamin A carotenoids are found in fruits, vegetables, and other plant-based products. The most common provitamin A carotenoid in foods and dietary supplements is beta-carotene; other provitamin A carotenoids are alpha-carotene and beta-cryptoxanthin.

Both provitamin A and preformed vitamin A must be metabolized inside the cell to retinal and retinoic acid, the active forms of vitamin A, to support the vitamin’s important biological functions ¹²⁰⁾. Retinol can be converted by the body to retinal, which can be in turn be oxidized to retinoic acid, the form of vitamin A known to regulate gene transcription ¹²¹⁾. Retinol, retinal, retinoic acid, and related compounds are known as retinoids. Beta-carotene and other food carotenoids that can be converted by the body into retinol are referred to as provitamin A carotenoids. Hundreds of different carotenoids are synthesized by plants, but only about 10% of them are capable of being converted to retinol ¹²²⁾. Other carotenoids found in food, such as lycopene, lutein, and zeaxanthin, are not converted into vitamin A.

The various forms of vitamin A are solubilized into micelles in the intestinal lumen and absorbed by duodenal mucosal cells ¹²³⁾. Both retinyl esters and provitamin A carotenoids are converted to retinol, which is oxidized to retinal and then to retinoic acid ¹²⁴⁾. Most of the body’s vitamin A is stored in the liver in the form of retinyl esters.

Retinol and carotenoid levels are typically measured in plasma, and plasma retinol levels are useful for assessing vitamin A inadequacy. However, their value for assessing marginal vitamin A status is limited because they do not decline until vitamin A levels in the liver are almost depleted ¹²⁵⁾. Liver vitamin A reserves can be measured indirectly through the relative dose-response test, in which plasma retinol levels are measured before and after the administration of a small amount of vitamin A ¹²⁶⁾. A plasma retinol level increase of at least 20% indicates an inadequate vitamin A level ¹²⁷⁾. For clinical practice purposes, plasma retinol levels alone are sufficient for documenting significant deficiency.

A plasma retinol concentration lower than 0.70 micromoles/L (or 20 micrograms [mcg]/dL) reflects vitamin A inadequacy in a population, and concentrations of 0.70–1.05 micromoles/L could be marginal in some people ¹²⁸⁾. In some studies, high plasma or serum concentrations of some provitamin A carotenoids have been associated with a lower risk of various health outcomes, but these studies have not definitively demonstrated that this relationship is causal.

Overconsumption of preformed vitamin A (vitamin A in the form retinol and retinyl ester, but not carotenoids) can be highly toxic and is also called hypervitaminosis A, is especially contraindicated prior to and during pregnancy as it can result in severe birth defects ¹²⁹⁾, ¹³⁰⁾, ¹³¹⁾. These birth defects can include malformations of the eye, skull, lungs, and heart ¹³²⁾. Experts advise people who are or might be pregnant and those who are lactating not to take high doses (more than 3,000 mcg RAE [10,000 IU] daily) of vitamin A supplements ¹³³⁾.

Acute vitamin A toxicity is relatively rare and symptoms include nausea, headache, fatigue, loss of appetite, dizziness, dry skin, desquamation, and cerebral edema ¹³⁴⁾. Signs of chronic vitamin A toxicity include dry itchy skin, desquamation, anorexia, weight loss, headache, cerebral edema, enlarged liver, enlarged spleen, anemia, and bone and joint pain ¹³⁵⁾. Also, symptoms of vitamin A toxicity in infants include bulging fontanels ¹³⁶⁾. Severe cases of hypervitaminosis A (overconsumption of preformed vitamin A) may result in liver damage, hemorrhage, and coma. Generally, signs of vitamin A toxicity are associated with long-term consumption of vitamin A in excess of 10 times the RDA (8,000-10,000 mcg RAE/day or 25,000-33,000 IU/day) ¹³⁷⁾. However, more research is necessary to determine if subclinical vitamin A toxicity is a concern in certain populations ¹³⁸⁾. There is evidence that some populations may be more susceptible to vitamin A toxicity at lower doses, including the elderly, chronic alcohol users, and some people with a genetic predisposition to high cholesterol ¹³⁹⁾. In January 2001, the Food and Nutrition Board of the US Institute of Medicine set the tolerable upper intake level (UL) of vitamin A intake for adults at 3,000 mcg RAE (10,000 IU)/day of preformed vitamin A ¹⁴⁰⁾. The tolerable upper intake level (UL) does not apply to vitamin A derived from carotenoids. Retinol activity equivalents (RAE) were developed because provitamin A carotenoids have less vitamin A activity than preformed vitamin A; 1 mcg retinol = 3.33 IU.

Figure 9. Vitamin A chemical structures

Footnote: Structures of vitamin A and retinoids

[Source ¹⁴¹⁾ ]

Recommended vitamin A intakes

The amount of vitamin A you need depends on your age and sex. Average daily recommended amounts of preformed vitamin A and provitamin A carotenoids are listed below in micrograms (mcg) of retinol activity equivalents (RAE).

Intake recommendations for vitamin A and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies (formerly National Academy of Sciences) ¹⁴²⁾. Dietary Reference Intake (DRI) is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and gender, include:

• Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.
• Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA.
• Estimated Average Requirement (EAR): Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals.
• Tolerable Upper Intake Level (UL): Maximum daily intake unlikely to cause adverse health effects.

Recommended Dietary Allowances (RDAs) for vitamin A are given as mcg of retinol activity equivalents (RAE) to account for the different bioactivities of retinol and provitamin A carotenoids (see Table 1). Because the body converts all dietary sources of vitamin A into retinol, 1 mcg of physiologically available retinol is equivalent to the following amounts from dietary sources: 1 mcg of retinol, 12 mcg of beta-carotene, and 24 mcg of alpha-carotene or beta-cryptoxanthin. From dietary supplements, the body converts 2 mcg of beta-carotene to 1 mcg of retinol.

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

Currently, vitamin A is listed on food and supplement labels in international units (IUs) even though nutrition scientists rarely use this measure. Conversion rates between mcg RAE and IU are as follows ¹⁴³⁾:

• 1 IU retinol = 0.3 mcg RAE (retinol activity equivalents)
• 1 IU beta-carotene from dietary supplements = 0.15 mcg RAE
• 1 IU beta-carotene from food = 0.05 mcg RAE
• 1 IU alpha-carotene or beta-cryptoxanthin = 0.025 mcg RAE

However, under FDA’s new labeling regulations for foods and dietary supplements that take effect by January 1, 2020 (for companies with annual sales of $10 million or more) or January 1, 2021 (for smaller companies), vitamin A will be listed only in mcg RAE and not IUs ¹⁴⁴⁾.

An RAE cannot be directly converted into an IU without knowing the source(s) of vitamin A. For example, the RDA of 900 mcg RAE for adolescent and adult men is equivalent to 3,000 IU if the food or supplement source is preformed vitamin A (retinol). However, this RDA is also equivalent to 6,000 IU of beta-carotene from supplements, 18,000 IU of beta-carotene from food, or 36,000 IU of alpha-carotene or beta-cryptoxanthin from food. So a mixed diet containing 900 mcg RAE provides between 3,000 and 36,000 IU of vitamin A, depending on the foods consumed.

Table 1. Recommended Dietary Allowances (RDAs) for Vitamin A

Life Stage	Recommended Amount
Birth to 6 months*	400 mcg RAE
Infants 7–12 months*	500 mcg RAE
Children 1–3 years	300 mcg RAE
Children 4–8 years	400 mcg RAE
Children 9–13 years	600 mcg RAE
Teen males 14–18 years	900 mcg RAE
Teen females 14–18 years	700 mcg RAE
Adult males	900 mcg RAE
Adult females	700 mcg RAE
Pregnant teens	750 mcg RAE
Pregnant adults	770 mcg RAE
Breastfeeding teens	1,200 mcg RAE
Breastfeeding adults	1,300 mcg RAE

Footnote: * Adequate Intake (AI), equivalent to the mean intake of vitamin A in healthy, breastfed infants.

[Source ¹⁴⁵⁾ ]

Sources of Vitamin A

Vitamin A is found naturally in many foods and is added to some foods, such as milk and cereal. You can get recommended amounts of vitamin A by eating a variety of foods, including the following:

• Some types of fish, such as herring and salmon
• Beef liver and other organ meats (which are also high in cholesterol, so limit the amount you eat)
• Green leafy vegetables and other green, orange, and yellow vegetables, such as spinach, sweet potatoes, carrots, broccoli, and winter squash
• Fruits, including cantaloupe, mangos, and apricots
• Dairy products, such as milk and cheese
• Fortified breakfast cereals
• Eggs

Free retinol is not generally found in food. Retinyl esters (including retinyl palmitate) are the storage form of retinol in animals and thus the main precursors of retinol in food from animals. Plants contain carotenoids, some of which are precursors for vitamin A (e.g., α-carotene, β-carotene, and β-cryptoxanthin). Yellow- and orange-colored vegetables contain significant quantities of carotenoids. Green vegetables also contain carotenoids, though yellow-to-red pigments are masked by the green pigment of chlorophyll ¹⁴⁶⁾.

Concentrations of preformed vitamin A are highest in liver, fish, eggs, and dairy products ¹⁴⁷⁾. Other sources of preformed vitamin A are milk and eggs, which also include some provitamin A ¹⁴⁸⁾. Most dietary provitamin A in the U.S. diet comes from leafy green vegetables, orange and yellow vegetables, tomato products, fruits, and some vegetable oils ¹⁴⁹⁾, ¹⁵⁰⁾, ¹⁵¹⁾. Vitamin A is routinely added to some foods, including milk and margarine ¹⁵²⁾. Some ready-to-eat cereals are also fortified with vitamin A.

Table 2 below lists a number of good food sources of vitamin A. The foods from animal sources in Table 2 contain primarily preformed vitamin A, the plant-based foods have provitamin A, and the foods with a mixture of ingredients from animals and plants contain both preformed vitamin A and provitamin A.

Table 2. Selected Food Sources of Vitamin A

Food	mcg RAE per serving	Percent DV*
Beef liver, pan fried, 3 ounces	6582	731
Sweet potato, baked in skin, 1 whole	1403	156
Spinach, frozen, boiled, ½ cup	573	64
Pumpkin pie, commercially prepared, 1 piece	488	54
Carrots, raw, ½ cup	459	51
Herring, Atlantic, pickled, 3 ounces	219	24
Ice cream, French vanilla, soft serve, ⅔ cup	185	21
Milk, skim, with added vitamin A and vitamin D, 1 cup	149	17
Cantaloupe, raw, ½ cup	135	15
Cheese, ricotta, part skim, ½ cup	133	15
Peppers, sweet, red, raw, ½ cup	117	13
Mangos, raw, 1 whole	112	12
Breakfast cereals, fortified with 10% of the DV for vitamin A, 1 serving	90	10
Egg, hard boiled, 1 large	75	8
Black-eyed peas (cowpeas), boiled, 1 cup	66	7
Apricots, dried, sulfured, 5 apricots	63	7
Broccoli, boiled, ½ cup	60	7
Salmon, sockeye, cooked, 3 ounces	59	7
Tomato juice, canned, ¾ cup	42	5
Yogurt, plain, low fat, 1 cup	32	4
Tuna, light, canned in oil, drained solids, 3 ounces	20	2
Baked beans, canned, plain or vegetarian, 1 cup	13	1
Summer squash, all varieties, boiled, ½ cup	10	1
Chicken, breast meat and skin, roasted, ½ breast	5	1
Pistachio nuts, dry roasted, 1 ounce	4	0

Footnote: *DV = Daily Value. U.S. Food and Drug Administration (FDA) developed Daily Values (DVs) to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The Daily Value (DV) for vitamin A is 900 mcg RAE for adults and children age 4 years and older, where 1 mcg RAE = 1 mcg retinol, 2 mcg beta-carotene from supplements, 12 mcg beta-carotene from foods, 24 mcg alpha-carotene, or 24 mcg beta-cryptoxanthin ¹⁵³⁾. FDA does not require food labels to list vitamin A content unless vitamin A has been added to the food. Foods providing 20% or more of the Daily Value (DV) are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.

The U.S. Department of Agriculture’s (USDA’s) FoodData Central (https://fdc.nal.usda.gov) lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin A in IUs arranged by nutrient content (https://ods.od.nih.gov/pubs/usdandb/VitaminA-Content.pdf) and by food name (https://ods.od.nih.gov/pubs/usdandb/VitaminA-Food.pdf), and foods containing beta-carotene in mcg arranged by nutrient content (https://ods.od.nih.gov/pubs/usdandb/VitA-betaCarotene-Content.pdf) and by food name (https://ods.od.nih.gov/pubs/usdandb/VitA-betaCarotene-Food.pdf).

What kinds of vitamin A dietary supplements are available?

Vitamin A is available in dietary supplements, usually in the form of retinyl acetate or retinyl palmitate (preformed vitamin A), beta-carotene (provitamin A), or a combination of preformed and provitamin A ¹⁵⁴⁾. Most multivitamin-mineral supplements contain vitamin A. Dietary supplements that contain only vitamin A are also available.

The amounts of vitamin A in supplements vary widely, but 3,000 mcg RAE (333% of the DV) is common. This is due to the fact that the Daily Values (DV) used by the US Food and Drug Administration (FDA) for supplement labeling are based on the RDA established in 1968 rather than the most recent RDA, and multivitamin supplements typically provide 100% of the DV for most nutrients.

Multivitamins commonly have somewhat lower vitamin A amounts, often 750 to 1,050 mcg RAE (83% to 117% of the DV). Because retinol intakes of 5,000 IU/day (1,500 mcg RAE) may be associated with an increased risk of osteoporosis in older adults, some companies have reduced the retinol content in their multivitamin supplements to 2,500 IU (750 mcg RAE).

The absorption of preformed vitamin A esters from dietary supplements is 70–90%, and that of beta-carotene ranges from 8.7% to 65% ¹⁵⁵⁾, ¹⁵⁶⁾.

What is the tolerable upper intake level of vitamin A?

Because vitamin A is fat soluble, the body stores excess vitamin A primarily in the liver, and these vitamin A levels can accumulate. Acute vitamin A toxicity also referred to as hypervitaminosis A, occurs within days to weeks after someone ingests one or a few very high doses (typically more than 100 times the Recommended Dietary Allowance [RDA]) of preformed vitamin A (retinol and retinyl ester but not carotenoids) ¹⁵⁷⁾. Resulting signs and symptoms typically include severe headache, blurred vision, nausea, dizziness, aching muscles, and coordination problems. In severe cases, cerebral spinal fluid pressure can increase, leading to drowsiness and, eventually, coma and even death ¹⁵⁸⁾. In January 2001, the Food and Nutrition Board of the US Institute of Medicine set the tolerable upper intake level (UL) of vitamin A intake for adults at 3,000 mcg RAE (10,000 IU)/day of preformed vitamin A ¹⁵⁹⁾. The tolerable upper intake level (UL) does not apply to vitamin A derived from carotenoids (vitamin A in fruits and vegetables) (see Table 3).

• Recommended Dietary Allowance (RDA) is the average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.
• Retinol activity equivalents (RAE) were developed because provitamin A carotenoids have less vitamin A activity than preformed vitamin A; 1 mcg retinol = 3.33 IU.

Chronic hypervitaminosis A (regular consumption of high doses of vitamin A) can cause dry itchy skin, painful muscles and joints, fatigue, depression, weight loss, headache, cerebral edema, enlarged liver, enlarged spleen, anemia and abnormal liver test results ¹⁶⁰⁾, ¹⁶¹⁾. Also, symptoms of vitamin A toxicity in infants include bulging fontanels ¹⁶²⁾. Severe cases of hypervitaminosis A (overconsumption of preformed vitamin A) may result in liver damage, hemorrhage, and coma. Generally, signs of vitamin A toxicity are associated with long-term consumption of vitamin A in excess of 10 times the RDA (8,000-10,000 mcg RAE/day or 25,000-33,000 IU/day) ¹⁶³⁾. However, more research is necessary to determine if subclinical vitamin A toxicity is a concern in certain populations ¹⁶⁴⁾. There is evidence that some populations may be more susceptible to vitamin A toxicity at lower doses, including the elderly, chronic alcohol users, and some people with a genetic predisposition to high cholesterol ¹⁶⁵⁾.

Total intakes of preformed vitamin A that exceed the tolerable upper intake level (UL), as well as some retinoid medications used as topical therapies (such as isotretinoin, used to treat severe acne, and etretinate, a treatment for severe psoriasis) can cause congenital birth defects ¹⁶⁶⁾. These birth defects can include malformations of the eye, skull, lungs, and heart ¹⁶⁷⁾. Experts advise people who are or might be pregnant and those who are lactating not to take high doses (more than 3,000 mcg RAE [10,000 IU] daily) of vitamin A supplements ¹⁶⁸⁾.

Unlike preformed vitamin A, beta-carotene (provitamin A) is not known to be teratogenic or lead to reproductive toxicity ¹⁶⁹⁾. The most common effect of long-term, excess beta-carotene is carotenodermia, a harmless condition in which the skin becomes yellow-orange ¹⁷⁰⁾. Carotenodermia or excess beta-carotene can be reversed by discontinuing beta-carotene ingestion. However, the ATBC trial found that supplementation with a large amount of beta-carotene (20 mg/day), with or without 50 mg/day vitamin E, for 5–8 years increased the risk of lung cancer and mortality (mainly from lung cancer and ischemic heart disease) in male smokers ¹⁷¹⁾. The CARET trial also showed that supplementation with a large amount of beta-carotene (30 mg/day) plus 7,500 mcg RAE (25,000 IU)/day retinyl palmitate for 4–8 years in current and former smokers, as well as some men occupationally exposed to asbestos, increased the risk of lung cancer and death from lung cancer ¹⁷²⁾.

The Food and Nutrition Board of the US Institute of Medicine has not established tolerable upper intake levels (ULs) for beta-carotene and other provitamin A carotenoids ¹⁷³⁾. However, the Food and Nutrition Board advises against the use of beta-carotene supplements for the general population, except as a provitamin A source to prevent vitamin A deficiency.

Table 3. Tolerable Upper Intake Levels (ULs) for Preformed Vitamin A

Age	Male	Female	Pregnancy	Lactation
Birth to 12 months	600 mcg	600 mcg
1–3 years	600 mcg	600 mcg
4–8 years	900 mcg	900 mcg
9–13 years	1,700 mcg	1,700 mcg
14–18 years	2,800 mcg	2,800 mcg	2,800 mcg	2,800 mcg
19+ years	3,000 mcg	3,000 mcg	3,000 mcg	3,000 mcg

Footnotes: These tolerable upper intake levels (ULs) apply only to products from animal sources and supplements whose vitamin A comes entirely from retinol or its ester forms, such as retinyl palmitate. However, many dietary supplements (such as multivitamins) do not provide all of their vitamin A in retinol or its ester forms. For example, the vitamin A in some supplements consists partly or entirely of beta-carotene. In such cases, the percentage of retinol or retinyl ester in the supplement should be used to determine whether an individual’s vitamin A intake exceeds the UL. For example, a supplement whose label indicates that the product contains 3,000 mcg RAE vitamin A and that 60% of this vitamin A comes from beta-carotene (and therefore 40% comes from retinol or retinyl ester) provides 1,200 mcg RAE of preformed vitamin A. That amount is above the UL for children from birth to 8 years but below the UL for older children and adults.

[Source ¹⁷⁴⁾ ]

Benefits of Vitamin A

Vitamin A is an antioxidant. It can come from plant or animal sources. Plant sources include colorful fruits and vegetables. Animal sources include liver and whole milk. Vitamin A is also added to foods like cereals.

Vitamin A plays a role in your:

• Vision
• Bone growth
• Reproduction ¹⁷⁵⁾. The vitamin A metabolite, trans retinoic acid, is essential for reproduction in both the male and female, as well as for many events in the developing embryo.
• Cell functions
• Immune system ¹⁷⁶⁾
  

Scientists are studying vitamin A to understand how it affects health. Here are some examples of what this research has shown.

Cancer

Because of the role vitamin A plays in regulating cell growth and differentiation, several studies have examined the association between vitamin A and various types of cancer. However, the relationship between serum vitamin A levels or vitamin A supplementation and cancer risk or cancer-related death is unclear. However, this does not include studies of all-trans retinoic acid, a vitamin A metabolite that is used as a drug in high doses to treat a form of leukemia ¹⁷⁷⁾, ¹⁷⁸⁾. Furthermore, in addition to tretinoin and alitretinoin, other generation retinoids are already being used clinically as anti-cancer agents ¹⁷⁹⁾, ¹⁸⁰⁾.

Several systematic reviews and meta-analyses of observational studies have shown that higher dietary intakes of retinol, carotenoids, fruits and vegetables, or a combination are associated with a lower risk of lung cancer ¹⁸¹⁾, non-Hodgkin lymphoma ¹⁸²⁾, pancreatic cancer ¹⁸³⁾, oral cavity cancer ¹⁸⁴⁾, laryngeal cancer ¹⁸⁵⁾, esophageal cancer ¹⁸⁶⁾, ovarian cancer ¹⁸⁷⁾, ¹⁸⁸⁾, glioma ¹⁸⁹⁾, and bladder cancer ¹⁹⁰⁾. However, other observational studies have found no association between intakes of different forms of vitamin A and risk of liver cancer ¹⁹¹⁾, non-Hodgkin lymphoma ¹⁹²⁾, colorectal cancer ¹⁹³⁾, prostate cancer ¹⁹⁴⁾ or all cancers ¹⁹⁵⁾.

Some clinical trial evidence suggests that supplemental vitamin A might reduce the risk of certain cancers but increase the risk of other forms of cancer, cardiovascular disease morbidity and mortality, and all-cause mortality. Examples are provided below.

The Carotene and Retinol Efficacy Trial (CARET) included 18,314 male and female current and former smokers (with at least a 20 pack-year history [equivalent to smoking 1 pack per day for 20 years or 2 packs per day for 10 years, for example] of cigarette smoking), as well as some men occupationally exposed to asbestos (who also have a higher risk of lung cancer), all aged 45–74 years. The study randomized participants to take supplements containing 30 mg beta-carotene plus 25,000 IU (7,500 mcg RAE) retinyl palmitate or a placebo daily for about 6 years to evaluate the potential effects on lung cancer risk ¹⁹⁶⁾. The trial was ended prematurely after a mean of 4 years, partly because the supplements were unexpectedly found to have increased lung cancer risk by 28% and death from lung cancer by 46%; the supplements (30 mg beta-carotene plus 25,000 IU (7,500 mcg RAE) retinyl palmitate) also increased the risk of all-cause mortality by 17% ¹⁹⁷⁾.

A subsequent study followed CARET participants for an additional 6 years after they stopped taking the study supplements ¹⁹⁸⁾. During this time, the differences in lung cancer risk between the intervention and placebo groups were no longer statistically significant, with one exception: women in the intervention group had a 33% higher risk of lung cancer. In a separate analysis of CARET study data, men who took the two supplements had a 35% lower risk of nonaggressive prostate cancer during the 4-year active trial, but not during the 6-year postintervention period ¹⁹⁹⁾. In contrast, men who took these two supplements in addition to another self-prescribed supplement (typically a multivitamin) had a 52% higher risk of aggressive prostate cancer during the active trial, but not during the postintervention period ²⁰⁰⁾.

The Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study also found that beta-carotene supplements increased the risk of lung cancer in smokers ²⁰¹⁾. In this study, 29,133 male smokers aged 50–69 years who smoked an average of 20.4 cigarettes a day for an average of 35.9 years took a supplement containing 50 mg/day alpha-tocopherol, 20 mg/day beta-carotene, both alpha-tocopherol and beta-carotene, or a placebo for 5–8 years ²⁰²⁾. The beta-carotene supplements increased the risk of lung cancer by 18%, although they had little to no effect on the incidence of other cancers ²⁰³⁾. The overall rate of death, primarily from lung cancer and ischemic heart disease, was 8% higher in participants who took beta-carotene. A subsequent study followed 25,563 of these participants for an additional 18 years ²⁰⁴⁾. During this period, participants were no longer taking the supplements, but most continued to smoke. Participants who had taken beta-carotene in the original trial did not have a higher risk of lung cancer, but they had a 20% higher risk of death due to prostate cancer ²⁰⁵⁾.

The Age-Related Eye Disease Study 2 (AREDS2) was a 5-year randomized clinical trial with 4,203 participants aged 50–85 years examining the effects on age-related macular degeneration (AMD) of a dietary supplement containing several ingredients with or without beta-carotene (15 mg [7,500 mcg RAE]) ²⁰⁶⁾. No current smokers received the supplements containing beta-carotene. At the end of the trial, more lung cancers were discovered in the beta-carotene group than in the no beta-carotene group (23 vs 11 cases), and 31 of the 34 affected were former smokers. In a follow-up analysis of 3,882 of the participants 5 years after the end of AREDS2 (during which they took the AREDS2 formulation containing lutein and zeaxanthin instead of beta-carotene), the increased lung cancer risk persisted, with an 82% higher risk among participants who took the supplement containing beta-carotene during the 5-year AREDS2 trial ²⁰⁷⁾.

Three other clinical trials have found no relationship between taking vitamin A or beta-carotene supplements and lung cancer incidence or mortality ²⁰⁸⁾. One trial randomized 22,071 male physicians aged 40–84 years to take 50 mg beta carotene on alternate days or a placebo for 12 years ²⁰⁹⁾. Eleven percent of the physicians were current smokers, and 38% were former smokers at the start of the study. The results showed no differences between the groups in number of cases of lung cancer or any malignant neoplasms or number of deaths from cancer. Another trial randomized 7,627 women (mean age 60.4 years) to take 50 mg beta-carotene on alternate days, 600 IU vitamin E on alternate days, 500 mg vitamin C daily, or a placebo for a mean of 9.4 years ²¹⁰⁾. Fifteen percent of the women were current smokers, and 41% were former smokers at the start of the study. None of the supplements had any significant effect on total cancer incidence or cancer mortality, including from lung cancer. A third trial included 29,584 healthy men and women aged 40–69 years who were living in Linxian, China, where micronutrient deficiencies are common ²¹¹⁾. The study randomized participants to take either a placebo or one of four vitamin and mineral combinations (including one providing retinol and zinc and another providing beta carotene, vitamin E, and selenium) for 5.25 years. The investigators followed participants for an additional 10 years after they stopped taking the supplements. The nutrient doses in the supplements were equivalent to or twice as high as U.S. recommended intakes, but the study report did not provide the exact doses. During both the intervention and follow-up periods, lung cancer death rates did not differ among the five groups, even when the investigators further analyzed the results for differences by age, sex, and smoking status ²¹²⁾.

The Carotene and Retinol Efficacy Trial (CARET) and Alpha-Tocopherol, Beta-Carotene (ATBC) study results suggest that large supplemental doses of beta-carotene with or without retinyl palmitate have detrimental effects in current or former smokers and workers exposed to asbestos. However, the other studies described above that used similar vitamin A doses but had smaller proportions of current or former smokers do not raise this concern. Among nonsmokers, beta-carotene and vitamin A supplements do not appear to affect the risk of cancer.

Age-Related Macular Degeneration

Age-related macular degeneration (AMD), or the loss of central vision as people age, is one of the most common causes of vision loss in older people ²¹³⁾. Age-related macular degeneration’s causes is usually unknown, but may involve complex interactions among genetic susceptibility, environmental factors (including exposure to oxidative stress), and normal aging ²¹⁴⁾. Because of the role of oxidative stress in age-related macular degeneration (AMD) pathophysiology, supplements containing carotenoids with antioxidant functions, such as beta-carotene, lutein, and zeaxanthin, might be useful for preventing or treating this condition. Lutein and zeaxanthin (which are not precursors of vitamin A), in particular, accumulate in the retina, the tissue in the eye that is damaged by age-related macular degeneration (AMD).

The Age-Related Eye Disease Study (AREDS) trial found that participants with a high risk of developing advanced age-related macular degeneration (AMD) (i.e., those who had intermediate AMD or who had advanced AMD in one eye) had a 25% lower risk of developing advanced AMD after they took a daily supplement containing beta-carotene (15 mg [7,500 mcg RAE]), vitamin E (180 mg [400 IU] dl-alpha-tocopheryl acetate), vitamin C (500 mg), zinc (80 mg), and copper (2 mg) for 5 years than participants taking a placebo ²¹⁵⁾.

The follow-up AREDS2 study confirmed the value of this supplement in reducing the progression of AMD over a median follow-up period of 5 years ²¹⁶⁾. However, this follow-up study showed that adding lutein (10 mg) and zeaxanthin (2 mg) or omega-3 fatty acids to the formulation produced no additional benefits ²¹⁷⁾. Importantly, the follow-up study also revealed that beta-carotene was not a required ingredient; the original AREDS formulation without beta-carotene provided the same protective effect against developing advanced AMD.

In a more detailed analysis, participants with the lowest dietary intakes of lutein and zeaxanthin had a 26% lower risk of advanced AMD when they took a supplement containing these two carotenoids than those who did not take a supplement with these carotenoids ²¹⁸⁾. The risk of advanced AMD was also 18% lower in participants who took the modified AREDS supplement containing lutein and zeaxanthin but not beta-carotene than in participants who took the formulation with beta-carotene but not lutein or zeaxanthin.

A subsequent study monitored dietary intakes of several nutrients in 4,504 AREDS participants and 3,738 AREDS2 participants (mean age 71 years) for a median of 10.2 years ²¹⁹⁾. Participants in the two highest quintiles of intakes for vitamin A, beta-carotene, or lutein and zeaxanthin had a lower risk of progression to late AMD ²²⁰⁾. For example, the risk of late AMD was 18% lower among those in the fifth quintile for vitamin A intake and 20% lower among those in the fourth quintile than among those in the first quintile ²²¹⁾.

At the end of the 5-year AREDS2 trial, participants were all offered the final AREDS2 formulation that included lutein and zeaxanthin in place of beta-carotene. Researchers followed up with 3,882 of these participants for an additional 5 years ²²²⁾. After 10 years, participants who had taken the AREDS2 supplement with lutein and zeaxanthin had an additional 20% reduced risk of progression to late AMD compared with those who took the supplement containing beta-carotene ²²³⁾. This finding confirmed the benefit of replacing beta-carotene with lutein and zeaxanthin.

Individuals who have or are developing age-related macular degeneration (AMD) should talk to their health care provider about their vitamin A intakes and the supplement formulations used in the AREDS studies.

Measles

When children with vitamin A deficiency (which is rare in North America) get measles, the disease tends to be more severe. In these children, taking supplements with high doses of vitamin A can shorten the fever and diarrhea caused by measles. These supplements can also lower the risk of death in children with measles who live in developing countries where vitamin A deficiency is common.

Measles is a major cause of morbidity and mortality in children in developing countries. In 2019, measles was responsible for more than 207,500 deaths around the world, mostly in young children in low-income countries ²²⁴⁾. About half of all measles deaths happen in Africa, but the disease is not limited to low-income countries. Vitamin A deficiency is a known risk factor for severe measles. In 2013, 11,200 deaths from measles were associated with vitamin A deficiency, and more than 95% of these deaths occurred in sub-Saharan Africa and south Asia. In a pooled analysis of randomized controlled trials within this study, vitamin A supplementation was associated with a 26% lower risk of dying from measles.

The World Health Organization recommends high oral doses (200,000 IU) of vitamin A for two days for children over age 1 with measles who live in areas with a high prevalence of vitamin A deficiency ²²⁵⁾, ²²⁶⁾. Recommended doses are 30,000 mcg RAE (100,000 IU) of vitamin A once for infants ages 6–11 months and 60,000 mcg RAE (200,000 IU) every 4–6 months for ages 1–5 years ²²⁷⁾.

However, a Cochrane review that included 6 randomized controlled trials of vitamin A supplementation (15,000 mcg RAE [50,000 IU] to 60,000 mcg RAE [200,000 IU], depending on age) found that the supplementation did not affect risk of death due to measles, although it did help prevent new cases of measles ²²⁸⁾. These randomized controlled trials assessed the value of supplementation to prevent morbidity and mortality due to measles in a total of 19,566 children aged 6 months to 5 years. The vitamin A doses used in these studies are much higher than the UL. The effectiveness of vitamin A supplementation to treat measles in countries, such as the United States, where vitamin A intakes are usually adequate is uncertain.

The body needs vitamin A to maintain the corneas and other epithelial surfaces, so the lower serum concentrations of vitamin A associated with measles, especially in people with protein-calorie malnutrition, can lead to blindness. None of the studies evaluated in a Cochrane review evaluated blindness as a primary outcome ²²⁹⁾. However, a careful clinical investigation of 130 African children with measles revealed that half of all corneal ulcers in these children, and nearly all bilateral blindness, occurred in those with vitamin A deficiency ²³⁰⁾.

Vitamin A deficiency signs and symptoms

Subclinical forms of vitamin A deficiency 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 ²³¹⁾. Patients may have a recent history of increased infections, infertility secondary to impaired spermatogenesis, or recent spontaneous abortion secondary to impaired embryonic development ²³²⁾. The patient may also report increased fatigue, as a manifestation of vitamin A deficiency anemia.

Signs and symptoms of vitamin A deficiency include the following ²³³⁾:

• Bitot spots – Areas of abnormal squamous cell proliferation and keratinization of the conjunctiva can be seen in young children with vitamin A deficiency.
• Blindness – Vitamin A has a major role in phototransduction. The cone cells are responsible for the absorption of light and for color vision in bright light. The rod cells detect motion and are responsible for night vision. In the rod cells of the retina, all-trans-retinol is converted into 11-cis -retinol, which then combines with a membrane-bound protein called opsin to yield rhodopsin. [21] A similar type of reaction occurs in the cone cells of the retina to produce iodopsin. The visual pigments absorb light at different wavelengths, according to the type of cone cell they occupy. Vitamin A deficiency leads to a lack of visual pigments; this reduces the absorption of various wavelengths of light, resulting in blindness.
• Poor adaptation to darkness (nyctalopia)
• Dry skin
• Follicular hyperkeratosis (phrynoderma) secondary to blockage of hair follicles with plugs of keratin.
• Dry hair
• Itchy skin (prutitus)
• Broken fingernails
• Conjunctival xerosis
• Corneal xerosis
• Corneal ulcer
• Keratomalacia
• Corneal perforation
• Corneal scarring
• Blindness
• Other signs of vitamin A deficiency include excessive deposition of periosteal bone secondary to reduced osteoclastic activity, anemia, keratinization of mucous membranes, and impairment of the humoral and cell-mediated immune system.

In the eye, vitamin A is essential for maintenance of conjunctival and corneal epithelia as well as night vision. Vitamin A deficiency causes metaplasia and keratinization of mucus-secreting epithelium, which can cause conjunctival and corneal xerosis, corneal ulcers, keratomalacia, and corneal scarring. Rods are the retinal photoreceptor that is responsible for night vision. Rods have a singular photopigment, rhodopsin. Retinol is a vitamin A-derived cofactor that is required for the formation of rhodopsin; thus, vitamin A deficiency leads to impairment of rod function and causes nyctalopia, or night blindness due to the eye’s inability to adapt from light to dark ²³⁴⁾.

The most common sign of severe vitamin A deficiency is an eye condition called xerophthalmia (dry eye). Xerophthalmia refers to the spectrum of eye disease that affect the conjunctiva, cornea, and retina caused by severe vitamin A deficiency. Xerophthalmia can impair your ability to see in low light (dark adaptation of the eyes), which can lead to night blindness and is an early symptom of severe vitamin A deficiency.

Xerophthalmia (dry eye) is the most common sign of vitamin A deficiency (which is nearly characteristic) results from keratinization of the eyes. It involves drying (xerosis) and thickening of the conjunctivae (conjunctival xerosis) and corneas (corneal xerosis). Superficial foamy patches composed of epithelial debris and secretions on the exposed bulbar conjunctiva (Bitot spots) develop. In advanced vitamin A deficiency, the cornea becomes hazy and can develop erosions (corneal ulcers), which can lead to its destruction (keratomalacia). Xerophthalmia can lead to blindness if it isn’t treated.

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. Infection with the measles virus was found to precipitate conjunctival and corneal damage, leading to blindness in children with poor vitamin A status ²³⁵⁾. Conversely, vitamin A deficiency can be considered a nutritionally acquired immunodeficiency disease ²³⁶⁾. Even children who are only mildly deficient in vitamin A have a higher incidence of respiratory complications and diarrhea, as well as a higher rate of mortality from measles infection compared to children consuming sufficient vitamin A ²³⁷⁾. Because vitamin A supplementation may decrease both the severity and incidence of measles complications in developing countries, WHO recommends that children aged at least one year receive 200,000 IU of vitamin A (60,000 mcg RAE) for two consecutive days in addition to standard treatment when children are infected with measles virus and live in areas of vitamin A deficiency ²³⁸⁾.

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. Routine vitamin A supplementation with retinol capsule of 200 000 IU retinyl acetate in oil to children in endemic areas leads to a decrease of childhood mortality of 5-15% ²³⁹⁾.

A long-term vitamin A deficiency  can also lead to a higher risk of respiratory diseases (such as pneumonia) and infections (such as measles and diarrhea). It can also cause anemia (a condition in which the red blood cells do not supply enough oxygen to the body). In severe cases, not getting enough vitamin A can increase your chances of dying. A study from Bangladesh showed that almost two-thirds of children with the most severe form of xerophthalmia – known as keratomalacia (a corneal ulcer affecting more than a third of the cornea) – had died within a few months ²⁴⁰⁾.

Table 4. World Health Organization (WHO) classification of vitamin A deficiency and the age groups most affected

Grade of xerophthalmia		Peak age group (years)	Type of deficiency	Risk of death
XN	Night blindness	2–6; adult women	Longstanding. Not blinding	+
X1A	Conjunctival xerosis	3–6	Longstanding. Not blinding	+
X1B	Bitot’s spot	3–6	Longstanding. Not blinding	+
X2	Corneal xerosis	1–4	Acute deficiency. Can be blinding	++
X3A	Corneal ulcer/ <1/3 cornea	1–4	Severe acute deficiency. Blinding	+++
X3B	Corneal ulcer/keratomalacia ≥1/3	1–4	Severe acute deficiency. Blinding	++++
XS	Corneal scarring (from X3)	>2	Consequence of corneal ulceration	+/–
XF	Xerophthalmic fundus	Adults	Longstanding. Not blinding. Rare	–

[Source ²⁴¹⁾ ]

Night blindness

Night blindness or defective vision in dim light is one of the most common manifestations of vitamin A deficiency, especially in children age 2-6 or pregnant or lactating women. Although it is considered one of the earliest manifestations, children with vitamin A deficiency may develop one of the more severe signs, such as corneal ulcers, after infection or diarrhea without any of the classically early signs. Children may not be able to verbalize their symptoms, and parents need to be asked if they have noticed their children behaving differently in the dark, e.g. becoming less active or fearful. Night blindness is considered to be both a sensitive and specific indicator for serum retinol levels.

Conjunctival xerosis

Conjunctival xerosis is characterized by a dull and dry appearance of the conjunctiva with slight wrinkling. It is caused by the loss of goblet cells and insufficient mucin secretion, and it can be subtle and difficult to detect clinically.

Bitot spots

Bitot spots are collections of desquamated, keratinized epithelial cells mixed with the gas-forming bacteria Corynebacterium xerosis. They appear as triangular patches of foamy, whitish, opaque deposits, typically located on the bulbar conjunctiva near the limbus at the 3 and 9 o’clock positions. They are more common temporally.

Corneal xerosis

Corneal xerosis is characterized by a dull and hazy appearance of the cornea that is caused by drying of the cornea secondary to conjunctival gland dysfunction. It may initially present with bilateral punctate corneal epithelial erosions, and it can quickly progress to the stage of corneal ulceration. Up to this stage, high-dose Vitamin A supplementation can result in the full preservation of vision.

Corneal ulceration

Corneal xerosis can lead corneal ulceration and melting if not treated urgently. Keratomalacia, the melting away of the cornea by liquefactive necrosis, is the most severe form of xerophthalmia. It can perforate and destroy the cornea in just a matter of days. A child who appears relatively healthy but develops keratomalacia should be questioned about a recent history of measles or diarrhea, which could rapidly deplete already deficient vitamin A stores.

Corneal scar

Corneal scarring due to vitamin A deficiency is often symmetric and bilateral. Other causes of corneal scarring must be ruled out.

Xerophthalmic fundus

Prolonged vitamin A deficiency can lead to structural changes in the retina. Xerophthalmic fundus changes appear as small, white, deep retinal lesions scattered throughout the posterior pole.

Vitamin A deficiency causes

The major underlying causes of vitamin A deficiency may be summarized as follows ²⁴²⁾, ²⁴³⁾:

• Reduced intake of vitamin A
  
  • Inadequate food supply. Vitamin A deficiency is endemic in areas such as southern and eastern Asia, where rice, devoid of beta-carotene, is the staple food. Xerophthalmia due to primary vitamin A deficiency is a common cause of blindness among young children in developing countries.
  • Alcoholism
  • Mental illness
  • Dysphagia
  • Vitamin A deficiency is common in prolonged protein-energy undernutrition not only because the diet is deficient but also because vitamin A storage and transport is defective.
• Impaired absorption of vitamin A
  
  • Crohn’s disease
  • Ulcerative colitis
  • Celiac disease
  • Pancreatic insufficiency
  • Cystic fibrosis
  • Bile duct obstruction
  • Duodenal bypass
  • Short bowel syndrome
  • Chronic diarrhea
  • Giardiasis
• Disordered transport of vitamin A
  
  • Abetalipoproteinemia
• Reduced storage of vitamin A
  
  • Liver disease and cirrhosis
  • Cystic fibrosis
• Zinc deficiency
  • Zinc deficiency may also be involved with the pathogenesis of secondary vitamin A deficiency. Inadequate zinc can depress the hepatic synthesis of retinol-binding protein (RBP), which is required for mobilization of retinol from the liver. In addition, zinc may play a role in the conversion of beta-carotene to retinol via the enzyme 15-15 dioxygenase ²⁴⁴⁾.

Groups at Risk of Vitamin A Deficiency

The following groups are among those most likely to have inadequate intakes of vitamin A.

Premature infants

Preterm infants have low liver stores of vitamin A at birth, and their plasma concentrations of retinol often remain low throughout the first year of life ²⁴⁵⁾, ²⁴⁶⁾. Preterm infants with vitamin A deficiency have a higher risk of eye and chronic lung diseases ²⁴⁷⁾, ²⁴⁸⁾. However, in high-income countries, clinical vitamin A deficiency is rare in infants and occurs only in those with malabsorption disorders ²⁴⁹⁾.

Infants, children, and pregnant and lactating women in low-income and middle-income countries

Pregnant women need extra vitamin A for fetal growth and tissue maintenance and to support their own metabolism ²⁵⁰⁾, ²⁵¹⁾, ²⁵²⁾. The breast milk of lactating women with adequate vitamin A intakes contains sufficient amounts of vitamin A to meet infants’ needs for the first 6 months of life²⁵³⁾. But in people with vitamin A deficiency, the vitamin A content of breast milk is not sufficient to maintain adequate vitamin A stores in infants who are exclusively breastfed ²⁵⁴⁾.

About 190 million preschool-aged children (one third of all children in this age group), mostly in Africa and Southeast Asia, have vitamin A deficiency, according to the World Health Organization ²⁵⁵⁾, ²⁵⁶⁾. They have a higher risk of visual impairment and of illness and death from childhood infections, such as measles and infections that cause diarrheal diseases ²⁵⁷⁾, ²⁵⁸⁾.

The World Health Organization estimates that 9.8 million pregnant women (15% of all pregnant women) around the world, mostly in low-income and middle-income countries, have xerophthalmia as a result of vitamin A deficiency ²⁵⁹⁾.

People with cystic fibrosis

Up to 90% of people with cystic fibrosis have pancreatic insufficiency, which increases their risk of vitamin A deficiency due to difficulty absorbing fat ²⁶⁰⁾, ²⁶¹⁾. Studies in Australia and the Netherlands indicate that 2% to 13% of children and adolescents with cystic fibrosis have vitamin A deficiency ²⁶²⁾, ²⁶³⁾. As a result, standard care for cystic fibrosis includes lifelong treatment with vitamin A (daily amounts of 750 mcg RAE to 3,000 mcg RAE, depending on age, are recommended in the United States and Australia), other fat-soluble vitamins, and pancreatic enzymes ²⁶⁴⁾, ²⁶⁵⁾.

Individuals with gastrointestinal disorders

Approximately one quarter of children with Crohn’s disease and ulcerative colitis have vitamin A deficiency; adults with these disorders, especially those who have had the disorder for several years, also have a higher risk of vitamin A deficiency ²⁶⁶⁾, ²⁶⁷⁾. Although some evidence supports the use of vitamin A supplements in people with these disorders ²⁶⁸⁾, other research has found that supplementation offers no benefit ²⁶⁹⁾. Some children and adults with newly diagnosed celiac disease also have vitamin A deficiency; a gluten-free diet can, but does not always, eliminate vitamin A deficiency ²⁷⁰⁾, ²⁷¹⁾, ²⁷²⁾.

Vitamin A deficiency prevention

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 IU (60,000 RAE) orally every 6 months are advised for all children between 1 and 5 yr of age; infants < 6 months can be given a one-time dose of 50,000 IU (15,000 RAE), and those aged 6 to 12 months can be given a one-time dose of 100,000 IU (30,000 RAE).

Vitamin A deficiency diagnosis

Patients presenting with clinical signs of xerophthalmia (or, in the case of a children, their parents) must be questioned on dietary, medical, and social history, including alcohol intake. Be sure to ask about any malabsorptive process, as described above, or risk factors such as living in a resource-poor country or current pregnancy or lactation. Because xerophthalmia is a manifestation of moderate-to-severe vitamin A deficiency, it is important to ask about the systemic signs of milder vitamin A deficiency, including frequent gastrointestinal and respiratory tract infections, anemia, iron deficiency, and development of xeroderma and phrynoderma (follicular hyperkeratosis often found on extensor surfaces, shoulders, and buttocks) ²⁷³⁾.

Serum retinol levels, clinical evaluation, and response to vitamin A help diagnose vitamin A deficiency in people with symptoms, such as night blindness, or in people with diseases that impair intestinal absorption of nutrients and who are at risk of vitamin A deficiency.

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 of vitamin A/retinol is 28 to 86 mcg/dL (1 to 3 mcmol/L). Vitamin A deficiency is defined as serum retinol levels of below 28 μg/dL. 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.

Physical exam

Aside from the ocular exam, the physical exam should include assessments for weight/body habitus, jaundice, and abdominal exam for hepatomegaly.

Blood tests

The following laboratory studies may be considered in the workup ²⁷⁴⁾, ²⁷⁵⁾:

• Serum vitamin A or retinol (reference range: 20-60 mcg/dL). These levels can be normal due to maintenance of circulating retinol levels by hepatic stores. A serum retinol concentration of 0.70 μmol/L (20 mcg/dL) or less frequently reflects subclinical vitamin A deficiency. A value of less than 0.70 μmol/L (20 mcg/dL) in children younger than 12 years is considered low ²⁷⁶⁾. Vitamin A deficiency-related ocular symptoms have been shown to develop at serum retinol concentration less than 0.35 μmol/L (10 mcg/dL), and is considered an indicator of severe vitamin A deficiency, where vitamin A body stores are depleted ²⁷⁷⁾
• Serum retinol-binding protein (RBP) (reference range: 30-75 ug/ml). A serum retinol-binding protein (RBP) study is easier to perform and less expensive than a serum retinol study, because retinol-binding protein (RBP) is a protein and can be detected by an immunologic assay. Retinol-binding protein (RBP) is also a more stable compound than retinol with respect to light and temperature. However, retinol-binding protein (RBP) levels are less accurate, because they are affected by serum protein concentrations and because types of retinol-binding protein (RBP) cannot be differentiated ²⁷⁸⁾, ²⁷⁹⁾, ²⁸⁰⁾. The serum retinol level may be low during infection because of a transient decrease in the retinol-binding protein (RBP).
• Serum zinc (reference range: 75-120 mcg/dL). A zinc level is useful because zinc deficiency interferes with retinol-binding protein (RBP) production.
• An iron panel is useful because iron deficiency can affect the metabolism of vitamin A.
• Albumin levels are indirect measures of vitamin A levels.
• Obtain a complete blood count (CBC) with differential if anemia, infection, or sepsis is a possibility.
• An electrolyte evaluation and liver function studies should be performed to evaluate for nutritional and volume status.

Other testing

• Dark adatopmetry and night vision threshold tests ²⁸¹⁾
• Electroretinogram (ERG): Retinopathy from vitamin A deficiency is associated with decreased amplitude
• Impression cytology: conjunctival specimens can be viewed for the presence of goblet cells. A decrease in normal amount is considered an effective measurement of vitamin A deficiency ²⁸²⁾.
• In children, radiographic films of the long bones may be useful when an evaluation is being made for bone growth and for excessive deposition of periosteal bone.
• Liver biopsy: considered the gold standard for evaluating total body vitamin A, although it is not routinely used outside of the research setting due to procedural risks.

Vitamin A deficiency treatment

The recommended vitamin A deficiency treatment regimens are described in table 5 below. Dietary deficiency of vitamin A is traditionally treated with vitamin A palmitate in oil 60,000 IU oral once/day for 2 days, followed by 4500 IU oral once/day. If vomiting or malabsorption is present or xerophthalmia is probable, a dose of 50,000 IU for infants less than 6 months of age, 100,000 IU for infants 6 to 12 months of age, or 200,000 IU for children greater than 12 months of age and adults should be given for 2 days, with a third dose at least 2 weeks later. Vitamin A deficiency is a risk factor for severe measles; treatment with vitamin A can shorten the duration of the measles and may reduce the severity of symptoms and risk of death. The World Health Organization (WHO) recommends that all children with measles in developing countries should receive 2 doses of vitamin A, (100,000 IU for children < 12 months and 200,000 IU for those >12 months) given 24 hour apart ²⁸³⁾.

Vitamin A deficiency associated with malabsorptive or other processes is treated based on the severity of vitamin A deficiency and at the doctor’s discretion, usually involving daily treatment.

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

Patients with concomitant zinc deficiency should also undergo zinc supplementation ²⁸⁴⁾. If the patient’s vitamin A deficiency is from malabsorption, doctors should consider intramuscular vitamin A supplementation formulations.

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

In regions with a high prevalence of vitamin A deficiency, the World Health Organization (WHO) recommends universal vitamin A supplementation of select populations ²⁸⁵⁾. The World Health Organization (WHO) recommends a one-time dose of 100,000 IU in children 6 to 11 months of age followed by doses of 200,000 IU every 4 to 6 months up to 5 years of age ²⁸⁶⁾. At-risk pregnant women should receive vitamin A supplementation at lower doses due to concern for fetotoxicity; the recommended dosing is 10,000 IU daily or 25,000 IU weekly for 12 weeks ²⁸⁷⁾. The WHO no longer recommends universal supplementation for children less than 6 months of age or postpartum women ²⁸⁸⁾, ²⁸⁹⁾, ²⁹⁰⁾.

International guidelines do not clearly outline dosing of vitamin A supplementation for asymptomatic vitamin A deficiency in resource-rich regions ²⁹¹⁾. Treatment for subclinical vitamin A deficiency includes the consumption of vitamin A rich foods, such as liver, beef, chicken, eggs, fortified milk, carrots, mangoes, sweet potatoes, and leafy green vegetables ²⁹²⁾.

In resource-rich countries, post-weight loss surgery patients and neonates have particular dosing recommendations. Post-weight loss surgery patients are recommended to take 10,000 IU vitamin A supplementation daily and adjust as needed based on regular serum retinol level monitoring. Some weight loss surgery patients have been known to need up to 100,000 IU vitamin A supplementation daily ²⁹³⁾. For premature infants, guidelines do not exist yet for vitamin A supplementation. Still, recent studies have shown that vitamin A supplementation of 10,000 IU every other day in very low birth weight neonates for 4 weeks has significant results, decreasing all-cause mortality by 56% and decreasing rates of oxygen requirement, sepsis, patent ductus arteriosus, and length of hospital stay ²⁹⁴⁾. Vitamin A supplementation of 1,500 IU daily in extremely premature infants had a significant decrease in retinopathy of prematurity (1.6% vs. 6.9%) and a nearly 50% decrease in bronchopulmonary dysplasia ²⁹⁵⁾. Vitamin A deficiency associated with other malabsorptive processes is treated on a case-by-case basis.

Treatment can be adjusted as needed based on regular serum retinol level monitoring.

Localized ocular treatment includes intense lubrication, topical retinoid acid, and management of perforation.

Table 5. Vitamin A deficiency treatment regimens

	Vitamin A dosage (IU)
Young infants 0-5 months 1	50,000 IU
Older infants 6-11 months 1	100,000 IU
Children (males: 12 mo or more; females 12 mo to 12 y and 50 y or more) 1	200,000 IU
Women (13-49 years of age) with night blindness and/or Bitot’s spots	10,000 every day or 25,000 every week for at least 3 months
Women (13-49 years of age) with active corneal lesions	200,000 on days 1, 2, and 14

Footnote: ¹ Schedule: severe malnutrition, day 1; measles, days 1 and 2; xerophthalmia, days 1, 2, and 14.

[Source ²⁹⁶⁾ ]

Vitamin A deficiency prognosis

The prognosis of vitamin A deficiency depends on the severity of the disease at treatment initiation ²⁹⁷⁾. If treated promptly, patients with subclinical vitamin A deficiency have a very good prognosis without long term consequences. Treatment at any stage of severity can show improvement within a week ²⁹⁸⁾.

The early ophthalmologic signs, such as night blindness, conjunctival xerosis, and Bitot spots, will resolve completely within about 2 months of vitamin A supplementation, while corneal xerosis and ulceration results in scarring that may lead to permanent vision loss despite treatment ²⁹⁹⁾, ³⁰⁰⁾. Irreversible conditions include punctate keratopathy, keratomalacia, and corneal perforation. At the onset of vitamin A deficiency eye signs and symptoms, patients develop an increased susceptibility to infection. In preschool children with vitamin A deficiency, the presence of ophthalmologic signs indicates increased overall mortality from gastrointestinal, pulmonary, and other vitamin A deficiency-related mucosal infections ³⁰¹⁾.

Xerophthalmia signifies a severity of vitamin A deficiency that can cause mortality from malnutrition and increased susceptibility to mucosal infections. The death rate (mortality) in children with night blindness is triple the mortality found in children with subclinical vitamin A deficiency ³⁰²⁾. Children with both Bitot’s spots and night blindness have death rate nine times that of children with subclinical vitamin A deficiency. Nearly two-thirds of children with keratomalacia die within months ³⁰³⁾.