VA Class:VT050

ATC Class:A11CA01

AHFS Class:

• Vitamin A 88:04

Generic Name(s):

• Vitamin A

Vitamin A, a fat-soluble vitamin that is present in foods in a variety of forms, is available for clinical use as retinol (vitamin A alcohol) or esters of retinol formed from edible fatty acids, principally acetic and palmitic acids.

Vitamin A Deficiency

Vitamin A is used to prevent and to treat symptoms of vitamin A deficiency such as xerophthalmia and night blindness. Vitamin A deficiency is common in developing countries, but rare in the US.127,131,132 Among deficient populations, high-dose vitamin A supplements have been used to control xerophthalmia, prevent blindness, and reduce morbidity and mortality associated with certain childhood infections (e.g., measles).115,116,127,129,130,131,132 Guidelines have been established by the World Health Organization (WHO), United Nations Children's Fund (UNICEF), and the International Vitamin A Consultative Group (IVACG, now the Micronutrient Forum) for the use of high-dose vitamin A supplements in the prevention and treatment of severe vitamin A deficiency in certain populations.127,128,129,131 In developing countries where vitamin A deficiency is a public health problem, periodic supplementation with high-dose vitamin A (50,000-200,000 units, depending on age) has been recommended in certain high-risk populations (i.e., postpartum women, children), with reduced doses recommended for pregnant women.127,128,131 Such high doses of vitamin A generally are not used in the US except in individuals with vitamin A deficiency.135,137,138 Patients with active xerophthalmia (e.g., night blindness, conjunctival xerosis with Bitot's spots, corneal xerosis, corneal ulceration, keratomalacia) are considered in imminent danger of corneal destruction and should be treated immediately with high dosages of vitamin A.127,129,131 (See Vitamin A Deficiency under Dosage and Administration: Dosage.) Whenever possible, poor dietary habits should be corrected, and many clinicians recommend administration of multivitamin preparations containing vitamin A in patients with vitamin deficiencies since poor dietary habits often result in concurrent deficiencies. (See Multivitamins 88:28.)

Although an adequate amount of vitamin A usually is obtained from dietary sources in patients with normal GI function, the extent of absorption of vitamin A may be decreased in patients with GI diseases. Patients with chronic malabsorptive states (e.g., celiac disease, Crohn's disease, pancreatic disorders) can develop vitamin A deficiency over time as a result of diarrhea and reduced absorption of vitamin A.132 Parenteral preparations of vitamin A may be useful in treating deficiency in patients with malabsorption with accompanying steatorrhea.137 Malabsorption syndromes should be corrected, if possible.

Increased vitamin A requirements may be associated with pregnancy, lactation, and infections; however, dietary deficiency is rare in these patients. Deficiency of vitamin A may occur as a result of abnormal storage and transport of vitamin A in patients with abetalipoproteinemia, protein deficiency, diabetes mellitus, hyperthyroidism, fever, liver disease, or cystic fibrosis with hepatic involvement.

Because children with severe measles have been found to have low serum concentrations of vitamin A and such a deficiency has been associated with an increased risk of mortality, the American Academy of Pediatrics (AAP) and the WHO currently recommend that vitamin A supplements be given to all children with acute measles, regardless of their country of residence.115,127 Vitamin A supplementation has been shown to reduce morbidity and mortality both during and after an acute measles episode.115,116,127,129,130,131,134 The role of vitamin A supplementation in other infectious diseases is less clear; studies have not shown a consistent effect of vitamin A on the incidence of diarrhea and respiratory tract infections.116,134,135

Dietary Requirements

The National Academy of Sciences (NAS) has issued a comprehensive set of Recommended Dietary Allowances (RDAs) as reference values for dietary nutrient intakes since 1941.112 In 1997, the NAS Food and Nutrition Board (part of the Institute of Medicine [IOM]) announced that they would begin issuing revised nutrient recommendations that would replace RDAs with Dietary Reference Intakes (DRIs).112 DRIs are reference values that can be used for planning and assessing diets for healthy populations and for many other purposes and that encompass the Estimated Average Requirement (EAR), the Recommended Dietary Allowance (RDA), the Adequate Intake (AI), and the Tolerable Upper Intake Level (UL).123

The NAS and IOM have established an EAR and RDA for vitamin A for adults based on the amount needed to maintain adequate body stores of vitamin A.126 The EAR and RDA for children and adolescents 1-18 years of age were extrapolated from data in adults using metabolic body weight, since specific data in children and adolescents currently are unavailable.126 An AI has been established for infants through 6 months of age based on the observed mean vitamin A intake of infants fed principally human milk.126 An AI for infants 7-12 months of age has been set based on the AI for younger infants and the observed mean vitamin A intake from human milk and from solid food.126 (For a definition of Estimated Average Intake, Recommended Dietary Allowance, Adequate Intake, and other reference values for dietary nutrient intakes, see Uses: Dietary Requirements in Folic Acid 88:08.)

The principal goal of maintaining an adequate intake of vitamin A in the US and Canada is to prevent vitamin A deficiency and the ocular complications (e.g., xerophthalmia) associated with vitamin A deficiency.126 Adequate intake of vitamin A usually can be accomplished through consumption of foodstuffs.126 Preformed vitamin A is obtained from liver, dairy products, and fish; provitamin A carotenoids are obtained from darkly colored fruits and vegetables.126 Although observational epidemiologic evidence suggests that higher blood concentrations of beta carotenes and other carotenoids obtained from foods are associated with a lower risk of several chronic diseases, there is insufficient evidence at this time to support requiring that a specified percentage of dietary vitamin A be provided by provitamin A carotenoids in order for the vitamin A requirement to be met.126

For specific information on currently recommended AI and RDAs of vitamin A for various life-stage and gender groups, see Dosage: Dietary and Replacement Requirements, under Dosage and Administration.

Other Uses

Vitamin A has been used as a screening test for fat malabsorption. Vitamin A may be useful in keratosis follicularis (Darier's disease) and other skin disorders such as ichthyosis and psoriasis; however, other retinoids (e.g., acitretin, etretinate, isotretinoin, tretinoin) have been investigated for use in the treatment of these dermatologic disorders.

Because of the risk of hypervitaminosis A, some clinicians recommend against the use of vitamin A preparations except in vitamin A deficiency and in appropriate preventive situations. Vitamin A has been studied in animals as an anticarcinogen; further study in humans is needed to determine efficacy. Oral administration of vitamin A has not been proven to have any therapeutic value although it has been prescribed for menorrhagia, oligospermia, GI ulcers, pityriasis rubra pilaris, Hurler syndrome (mucopolysaccharidosis), acne, anosmia, wounds and burns, infection prevention, atrophic rhinitis, renal calculi, hyperthyroidism, anemia, deafness, sunburn, atrophic vaginitis, leukoplakia, cancer, and degenerative diseases of the nervous system.

Administration

Vitamin A usually is administered orally. Oral vitamin A capsules containing high strengths (e.g., 50,000 units) no longer are commercially available in the US; however, high-strength oral capsules and solutions may be available from various organizations (e.g., United Nations Children's Fund [UNICEF], the International Dispensary Association [IDA]) for treatment of deficiencies in developing countries.127 When oral administration is not feasible or when malabsorption is present, the drug may be given IM.131,137,138

Dosage

To avoid toxicity, dietary intake of vitamin A should be estimated and considered when determining the dosage of the vitamin. Vitamin A activity is expressed in terms of the equivalent amount of retinol (i.e., as retinol equivalents [RE] or retinol activity equivalents [RAE]) and is expressed also in USP units or International Units (IU, units). USP units and International Units are equivalent.137 One USP vitamin A unit is the specific biologic activity of 0.3 mcg of all- trans -retinol; one retinol equivalent (RE) is the specific biologic activity of 1 mcg of all- trans -retinol; one retinol activity equivalent (RAE) is equal to 1 mcg of all- trans -retinol, 12 mcg of all trans -β-carotene, or 24 mcg of other provitamin A carotenoids.126 The use of RAE is preferred when calculating and reporting the amount of total vitamin A in mixed foods or assessing the amount of dietary and supplemental vitamin A consumed.126

Vitamin A Deficiency

For the treatment of vitamin A deficiency, various vitamin A dosage regimens have been suggested. Some manufacturers have recommended that adults and children older than 8 years of age receive oral dosages of 100,000 units of vitamin A (30,000 RE) daily for 3 days, followed by 50,000 units (15,000 RE) daily for 2 weeks, and then 10,000-20,000 units (3000-6000 RE) daily for 2 months as follow-up therapy.138 If oral administration is not possible or malabsorption is present, vitamin A may be given by IM injection.131,137,138 The recommended IM dosage of vitamin A in adults and children older than 8 years of age is 100,000 units daily for 3 days, followed by 50,000 units daily for 2 weeks.137 The manufacturer states that dosages exceeding the recommended dietary allowance of vitamin A are contraindicated in women who are or may become pregnant.137,138 (See Cautions: Pregnancy and Lactation.) For children 1-8 years of age, an IM dosage of 17,500-35,000 units daily for 10 days is recommended.137 Infants less than 1 year of age should receive 7500-15,000 units once daily for 10 days.137 Follow-up treatment with an oral therapeutic multivitamin preparation is recommended after initial parenteral therapy with vitamin A; adults and children older than 8 years of age should receive an oral preparation containing 10,000-20,000 units of vitamin A, and infants and children younger than 8 years of age should receive an oral preparation containing 5000-10,000 units of vitamin A daily for 2 months.137 The manufacturer states that, although low-birthweight infants may require additional vitamin A, the dosage has not been established for these patients.137

Xerophthalmia

For the treatment of active xerophthalmia (e.g., night blindness, conjunctival xerosis with Bitot's spots, corneal xerosis, corneal ulceration, keratomalacia) in adults and children, a 3-dose regimen of oral vitamin A is recommended by the World Health Organization (WHO); the first dose should be administered immediately upon diagnosis, a second dose given the next day, then a third dose at least 2 weeks later.127 Recommended doses are 50,000 units for infants less than 6 months of age, 100,000 units for children 6-12 months of age, and 200,000 units for adults and children over 12 months of age.127

Because of the potential teratogenic effects of high-dose vitamin A, women of childbearing age generally should receive reduced dosages of vitamin A for the treatment of xerophthalmia.127,129,137 (See Cautions: Pregnancy and Lactation.) The dosage of vitamin A recommended by the WHO for the treatment of night blindness or Bitot's spots in women of childbearing age is 5000-10,000 units orally once daily for at least 4 weeks; alternatively, a weekly dosage not exceeding 25,000 units may be given.127 Severe signs of active xerophthalmia (i.e., acute corneal lesions) are considered a medical emergency since blindness occurs within 24-48 hours in most individuals with such severe symptoms.129 IVACG and WHO state that treatment of women of childbearing age, whether pregnant or not, with high dosages of vitamin A probably is warranted in such severe cases; however, the risk of teratogenicity should be balanced against the benefits of treatment (e.g., prevention of blindness) and the serious consequences (for the woman and her fetus) of vitamin A deficiency.127,129,131 If active corneal lesions are present, WHO recommends that pregnant women be treated with the same doses of vitamin A used in other groups for treatment of xerophthalmia (i.e., 200,000 units of vitamin A immediately upon diagnosis, a second dose given the next day, then a third dose at least 2 weeks later).127

In underdeveloped countries where vitamin A deficiency is common, doses of 50,000-200,000 units of vitamin A have been given orally to children every 4-6 months to prevent keratomalacia and blindness.127,128 Guidelines from appropriate international organizations (e.g., WHO, IVACG) should be consulted for additional information on supplementation programs in regions where vitamin A deficiency occurs.127,128,129,131

Measles

Children with acute measles should be treated with 2 doses of vitamin A, administered orally or IM on 2 consecutive days.115,127,130 The American Academy of Pediatrics (AAP) and the WHO recommend that infants less than 6 months of age receive 50,000 units of vitamin A once daily for 2 days, children 6-11 months of age receive 100,000 units once daily for 2 days, and children 12 months of age or older receive 200,000 units once daily for 2 days.115 An additional age-appropriate dose should be given 2-4 weeks later in children with clinical manifestations of vitamin A deficiency.115

Dietary and Replacement Requirements

The Adequate Intake (AI) (see Uses: Dietary Requirements) of vitamin A currently recommended by the Institute of Medicine (IOM) and the National Academy of Sciences (NAS) for healthy infants through 6 months of age is 400 mcg of RAE (1320 units) daily and for those 7-12 months of age is 500 mcg of RAE (1650 units) daily.126,132 The Recommended Dietary Allowance (RDA) of vitamin A currently recommended by IOM and NAS for healthy children 1-3, 4-8, or 9-13 years of age is 300 mcg of RAE (1000 units), 400 mcg of RAE (1320 units), or 600 mcg of RAE (2000 units) daily, respectively.126,132 In establishing the dietary vitamin A requirement in individuals 14 years of age or older, the requirement was considered to be lower in females than males, based on reference weights for females and males.126,132 The RDA of vitamin A for boys 14-18 years of age is 900 mcg of RAE (3000 units) daily, and the RDA for girls 14-18 years of age is 700 mcg of RAE (2310 units) daily.126,132 The RDA for healthy men of all ages (19 years of age and older) is 900 mcg of RAE (3000 units) of vitamin A daily, and the RDA for healthy women of all ages (19 years of age and older) is 700 mcg of RAE (2310 units) daily.126,132

The RDA of vitamin A recommended by IOM and NAS for pregnant women 14-18 or 19-50 years of age is 750 mcg of RAE (2500 units) or 770 mcg of RAE (2565 units) daily, respectively.126,132 An RDA of vitamin A of 1200 mcg of RAE (4000 units) or 1300 mcg of RAE (4300 units) daily is recommended for lactating women 14-18 or 19-50 years of age, respectively.126,132

Adverse Effects

Doses of vitamin A that do not exceed the physiologic requirement are usually nontoxic.

Precautions and Contraindications

Vitamin A is contraindicated in patients with hypervitaminosis A and in those with sensitivity to vitamin A or other ingredients in the commercially available preparations.137 The oral high-dose preparation of vitamin A (no longer commercially available in the US) is contraindicated in patients with malabsorption syndromes.138 The parenteral preparation of vitamin A is contraindicated for IV use.137

The manufacturer states that vitamin A in dosages exceeding the Recommended Daily Allowance (RDA) is contraindicated in women who are or may become pregnant.137,138 (See Cautions: Pregnancy and Lactation.)

Mutagenicity

Vitamin A aldehyde (retinal) was not mutagenic in the Ames microbial mutagen test.100

Pregnancy and Lactation

Pregnancy

Vitamin A is teratogenic in animals; malformations of the CNS, eye, palate, and urogenital tract have been described in several species.100,101,102,103,137 Adequate and well-controlled studies in humans are not available.104 A limited number of reports of human fetal malformations (e.g., cranial neural crest defects) following maternal ingestion of large dosages of vitamin A (10,000 units or more daily) during or both before and during pregnancy suggest potential teratogenicity, at least at high dosages.103,104,105,106,107,108,113 The use of vitamin A in excess of the US RDA generally is contraindicated in women who are or may become pregnant.103,109,110,111,112,114,137 (See Dietary and Replacement Requirements in Dosage and Administration: Dosage.)If vitamin A is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be apprised of the potential fetal hazard.137 It also has been suggested that women of reproductive age should limit their intake of dietary sources (e.g., liver) containing high concentrations of vitamin A;114β-carotene, a precursor of vitamin A, has not been shown to be teratogenic and may be considered as a source of vitamin A supplementation in such women.113,114 Dosages exceeding the RDA may be necessary in women of childbearing age with vitamin A deficiency.127,129 There is some evidence suggesting that dosages up to 10,000 units daily or up to 25,000 units weekly may be used safely in women of childbearing age (13-49 years of age), and such dosages are recommended in those with active xerophthalmia.127,129,136 Even higher dosages may be necessary if active corneal lesions are present.127,129 (See Vitamin A Deficiency under Dosage and Administration: Dosage.)

Lactation

Vitamin A is distributed into milk.103 Unless the maternal diet is inadequate, infants can usually obtain sufficient vitamin A from nursing, at least for the first 6 months of life.103,109,127 The effect of large maternal dosages of vitamin A on nursing infants is not known.103

For information on the currently recommended RDAs of vitamin A for pregnant and lactating women, see Dietary and Replacement Requirements, under Dosage and Administration: Dosage.

Drugs Affecting GI Absorption of Vitamin A

Administration of cholestyramine may result in decreased absorption of vitamin A, presumably by decreasing bile acids and preventing the micellar phase in the GI lumen. Daily supplements of water-miscible preparations of vitamin A have been recommended during long-term cholestyramine administration. Oral administration of neomycin may also result in decreased absorption of vitamin A. Since mineral oil may impair absorption of vitamin A, it has been recommended that these drugs not be administered concurrently.

Orlistat may result in decreased GI absorption of fat-soluble vitamins such as vitamin A.117 At least 2 hours should elapse between (before or after) any orlistat dose and vitamin A administration; administering fat-soluble vitamins at bedtime may be a convenient time.117,119,123,125 Although the manufacturer of orlistat recommends that a vitamin supplement containing fat-soluble vitamins (A, D, E and K) be used during orlistat therapy,117,123 such vitamin concentrations remained within the normal range in clinical studies with the drug for most patients despite decreases, and vitamin supplementation was only occasionally needed.118,119,120,121,122,124

Oral Contraceptives

Increased plasma vitamin A concentrations have been reported in women receiving oral contraceptives.137,138

Retinoids

Because of the potential for additive adverse effects, patients receiving a retinoid (e.g., etretinate, isotretinoin) should be warned to avoid concomitant use of preparations containing vitamin A or its derivatives.

Warfarin

Large doses of vitamin A may increase the hypoprothrombinemic effect of warfarin.

Laboratory Test Interferences

Vitamin A has also been reported to falsely elevate bilirubin determinations using Ehrlich's reagent.

Acute Toxicity

Toxicity from a large dose of vitamin A is more common in young children than in adults. A few hours after administration of vitamin A in a dose of about 25,000 units/kg, irritability, drowsiness, vertigo, delirium, coma, vomiting, and diarrhea may occur. Increased intracranial pressure with bulging fontanelles in infants, headache, papilledema, exophthalmos, and visual disturbances have been reported. Erythema and generalized peeling of the skin occur a few days later and may persist for several weeks. However, symptoms usually disappear within a few days after the drug is discontinued.

Chronic Toxicity

Pathogenesis

The amount of vitamin A required to produce hypervitaminosis varies considerably among individuals. Chronic administration of vitamin A 4000 units/kg daily for 6-15 months in adults or of water-miscible vitamin A 18,500 units/kg daily for 1-3 months in infants has resulted in hypervitaminosis A. Equally large cumulative doses over shorter or longer periods of time may result in hypervitaminosis A. One survey indicated that a small percentage of individuals taking daily vitamin and mineral supplements inappropriately take 5 times or more vitamin A than the recommended daily dietary allowance. Patients receiving more than 25,000 units of vitamin A daily should be closely supervised.

Manifestations

Early manifestations of hypervitaminosis A include fatigue, malaise, lethargy, irritability, psychiatric changes mimicking severe depression or schizophrenic disorder, anorexia, abdominal discomfort, nausea and vomiting, mild fever, and excessive sweating. Children may fail to gain weight normally, and adults may lose weight. Slow growth, premature epiphyseal closure, painful hyperostosis of the long bones, arthralgia, myalgia, hypercalcemia, and hypercalciuria have been reported. CNS signs and symptoms also include increased intracranial pressure, bulging fontanelles in infants, headache, papilledema, exophthalmos, vertigo, and visual disturbances. Dryness and cracking of the skin and lips, scaling, pruritus, brittle nails, alopecia, erythema, hyperpigmentation, and massive desquamation may also occur. Hypomenorrhea, hepatosplenomegaly, cirrhosis, jaundice, elevated serum AST (SGOT) and ALT (SGPT) concentrations, urinary complaints, anemia, leukopenia, leukocytosis, and thrombocytopenia have also been reported. Increased plasma concentrations of vitamin A usually occur but do not necessarily correlate with the severity of toxicity.

Treatment

Treatment of hypervitaminosis A consists of discontinuance of vitamin A and supportive therapy as indicated. Symptoms begin to improve within a few days, but complete recovery may not occur for several weeks to months. Vitamin E may increase the absorption, utilization, and storage of vitamin A and may protect against hypervitaminosis A; however, these effects are controversial.

Pharmacology

In humans, an exogenous source of vitamin A is required for growth and bone development, vision, reproduction, and the integrity of mucosal and epithelial surfaces. In the retina, retinol is converted to the aldehyde, cis -retinal, which combines with opsin to form rhodopsin, the visual pigment. Vitamin A has been reported to act as a cofactor in various biochemical reactions including mucopolysaccharide synthesis, cholesterol synthesis, and hydroxysteroid metabolism.

Vitamin A deficiency leads to xerophthalmia, Bitot's spots, keratomalacia, night blindness (nyctalopia), hyperkeratosis of the skin, epithelial metaplasia of mucous membranes, and decreased resistance to infections. Administration of vitamin A completely reverses signs of vitamin deficiency unless keratomalacia has resulted in irreversible ocular damage.

Pharmacokinetics

Absorption

In oral doses that do not greatly exceed the physiologic requirement, vitamin A is readily and completely absorbed if fat absorption is normal. Absorption is incomplete following administration of larger doses and in patients with fat malabsorption, low protein intake, or hepatic or pancreatic disease. Water-miscible preparations of retinol or its esters are absorbed more rapidly from the GI tract than are oil solutions. Retinol esters are hydrolyzed in the GI lumen by pancreatic enzymes. Retinol is absorbed and then reesterified, mainly to retinyl palmitate. Fatty acid esters of retinol enter the circulation by transport in chylomicrons of lymph. Peak plasma concentrations of retinol esters occur about 4-5 hours after oral administration of retinol in an oil solution and 3-4 hours after administration of water-miscible retinol; higher plasma concentrations are obtained after administration of a water-miscible preparation of vitamin A than after an oil solution. Normal serum concentrations of retinol range from 300-700 ng/mL in adults and from 200-500 ng/mL in infants.

Distribution

Retinyl palmitate and small amounts of retinol and retinal are stored in the liver. Lesser amounts of retinyl palmitate are stored in kidneys, lungs, adrenals, retinas, and intraperitoneal fat. Normal body stores of vitamin A are sufficient to meet the body's requirements for several months. Vitamin A is distributed into milk. The vitamin does not readily cross the placenta. (See Cautions: Pregnancy and Lactation.)

Retinol is released from the liver bound to a specific α₁-globulin, retinol-binding protein (RBP). Release of retinol from the liver depends on several factors including protein and zinc. RBP circulates as a complex with a prealbumin protein, and concentrations of RBP may be decreased in patients with protein malnutrition. Serum concentrations of retinol are not necessarily a good indicator of vitamin A nutritional status, since serum concentrations depend on the concentration of RBP and do not reflect liver stores until storage is severely diminished. After ingestion of a diet deficient in vitamin A, normal serum concentrations are maintained until liver stores are depleted. In patients with vitamin A deficiency, administration of vitamin A results in correction of concentrations in the retinas followed by accumulation of the vitamin in the liver; serum concentrations remain normal until the liver stores are saturated. Patients with glomerulonephritis or lipoid nephrosis may have increased serum concentrations of vitamin A because of RBP or storage abnormalities. If large doses of vitamin A are administered after saturation of storage sites, the binding capacity of RBP may be exceeded and unbound retinol carried by lipoproteins may enter the circulation. This unbound retinol may be responsible for many of the toxic effects on cellular membranes that result from hypervitaminosis A.

Elimination

Retinol is conjugated with glucuronic acid; the β-glucuronide undergoes enterohepatic circulation and oxidation to retinal and retinoic acid. Retinoic acid undergoes decarboxylation and conjugation with glucuronic acid, and is excreted in feces via biliary elimination. Retinal, retinoic acid, and other water-soluble metabolites are excreted in urine and feces. Normally, no unchanged retinol is excreted in urine; however, in patients with pneumonia or chronic nephritis, unchanged vitamin may be excreted.

Chemistry and Stability

Chemistry

Vitamin A is a fat-soluble vitamin that is present in foods in a variety of forms. The term vitamin A includes provitamin A carotenoids that are dietary precursors of retinol.126 Retinol (vitamin A₁), which occurs as various stereoisomers, is present in esterified form in eggs, whole milk, butter, fortified margarine, meat, and oily salt-water fish. Cod liver oil contains about 780 units of vitamin A and 2 mcg of cholecalciferol (vitamin D) per mL. 3-Dehydroretinol (vitamin A₂) is present in fresh-water fish (usually mixed with retinol) and has only 30-40% of the biologic activity of retinol. Provitamin A carotenoid pigments (including α-, β-, and γ-carotene and cryptoxanthin), the most active of which is beta carotene, are present in green and yellow vegetables and fruits and are converted to retinol in humans. Vitamin A activity is expressed in terms of the equivalent amount of retinol (i.e., as retinol equivalents [RE] or retinol activity equivalents [RAE]) and also is expressed in USP units or International Units (IU, units). USP units and International Units are equivalent and 1 unit of vitamin A equals the biologic activity of 0.3 mcg of all- trans -retinol. One retinol equivalent equals the activity of 1 mcg of all- trans -retinol, 6 mcg of all trans -β-carotene, or 12 mcg of other provitamin A carotenoids. Retinol activity equivalents for provitamin A carotenoids were set in 2001 by the Institute of Medicine.126 One retinol activity equivalent (RAE) is equal to 1 µg of all- trans -retinol, 12 µg of all trans -β-carotene, or 24 mcg of other provitamin A carotenoids.126 Therefore, the amount of vitamin A activity of provitamin A retinoids using RAE is one-half the amount when using RE; RAE equivalency values are based on results of recent absorption and bioconversion studies of provitamin A carotenoids that indicated lower vitamin A activity of carotenoids from dietary sources (i.e., dark green leafy vegetables) than previously studies indicated.126 The use of RAE is preferred when calculating and reporting the amount of total vitamin A in mixed foods or assessing the amount of dietary and supplemental vitamin A consumed.126

For clinical use, vitamin A is available as retinol (vitamin A alcohol) or esters of retinol formed from edible fatty acids, principally acetic and palmitic acids. Vitamin A may be diluted with edible oils or it may be incorporated in solid edible carriers or excipients. Preparations of the vitamin may contain suitable antimicrobial agents, dispersants, and antioxidants. In liquid form, vitamin A is insoluble in water and soluble in absolute alcohol and in vegetable oils. In solid form, the vitamin may be dispersible in water. Water-miscible preparations of vitamin A (prepared with suitable solubilizing agents) are also commercially available. Commercially available vitamin A palmitate injection is a light yellow to amber oil that has been solubilized in water for IM administration.137

Stability

Vitamin A is unstable in, and should be protected from, air and light.127,137,139 Vitamin A palmitate injection should be stored at 2-8°C and should not be frozen.137 Oral vitamin A preparations should be stored in tight, light-resistant containers.127,139

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