- What is Vitamin A
- Vitamin A Supplements
- How much vitamin A do you need ?
- What foods provide vitamin A ?
- Are you getting enough vitamin A ?
- What happens if you don’t get enough vitamin A ?
- Benefits of Vitamin A
- What are some effects of vitamin A on health ?
- Vitamin A Deficiency
- Vitamin A Toxicity: Can Taking Too Much Vitamin A Be Harmful ?
What is Vitamin A
Vitamin A is name of a group of fat-soluble vitamin (retinoids, including retinol, retinal, and retinyl esters) 1), 2), 3), that is naturally present in many foods.
Vitamin A is important for normal vision, gene expression, the immune system, embryonic development, growth, and reproduction. Vitamin A also helps the heart, lungs, kidneys, and other organs work properly 4).
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 5), 6), 7). 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 8).
There are two different types of vitamin A 9).
- The first type, preformed vitamin A (retinol and its esterified form, retinyl ester), is found in meat (especially liver), poultry, fish, and dairy products.
- The second type, provitamin A carotenoids (beta-carotene, alpha-carotene and beta-cryptoxanthin), is found in fruits, vegetables, and other plant-based products (oily fruits and red palm oil). The most common type of provitamin A carotenoids in foods and dietary supplements is beta-carotene (β-carotene). The body converts these plant pigments into vitamin A.
Both provitamin A and preformed vitamin A must be metabolized intracellularly to retinal and retinoic acid, the active forms of vitamin A, to support the vitamin’s important biological functions 10), 11). Other carotenoids found in food, such as lycopene, lutein, and zeaxanthin, are not converted into vitamin A.
Both retinyl esters and provitamin A carotenoids are converted to retinol, which is oxidized to retinal and then to retinoic acid 12). Most of the body’s vitamin A is stored in the liver in the form of retinyl esters.
Normally, the liver stores 80 to 90% of the body’s vitamin A. To use vitamin A, the body releases it into the circulation bound to prealbumin (transthyretin) and retinol-binding protein. Beta-carotene and other provitamin carotenoids, contained in green leafy and yellow vegetables and deep- or bright-colored fruits, are converted to vitamin A. Carotenoids are absorbed better from vegetables when they are cooked or homogenized and served with some fat (eg, oils).
The body can convert beta-carotene into vitamin A to help meet these requirements. Although there is no Recommended Dietary Allowance for beta-carotene, the National Institutes of Health Office of Dietary Supplements recommends eating five or more servings of fruits and vegetables per day, including dark green and leafy vegetables and deep yellow or orange fruits to get appropriate amounts of beta-carotene.
Retinol activity equivalents (RAE) were developed because provitamin A carotenoids have less vitamin A activity than preformed vitamin A; 1 µg retinol = 3.33 IU.
For dietary provitamin A carotenoids (β-carotene, α-carotene, and β-cryptoxanthin), retinol activity equivalents (RAEs) have been set at 12, 24, and 24 μg, respectively. Using μg RAE, the vitamin A activity of provitamin A carotenoids is half the vitamin A activity assumed when using μg retinol equivalents (μg RE) 13). This change in equivalency values is based on data demonstrating that the vitamin A activity of purified β-carotene in oil is half the activity of vitamin A, and based on recent data demonstrating that the vitamin A activity of dietary β-carotene is one-sixth, rather than one-third, the vitamin activity of purified β-carotene in oil. This change in bioconversion means that a larger amount of provitamin A carotenoids, and therefore darkly colored, carotene-rich fruits and vegetables, is needed to meet the vitamin A requirement.
Synthetic vitamin analogs (retinoids) are being used increasingly in dermatology. The possible protective role of beta-carotene, retinol, and retinoids against some epithelial cancers is under study. However, risk of certain cancers may be increased after beta-carotene supplementation 14).
Retinol is the form of vitamin A that causes concern. In addition to getting retinol from their diets, some people may be using synthetic retinoid preparations that are chemically similar to vitamin A to treat acne, psoriasis, and other skin conditions. These preparations have been shown to have the same negative impact on bone health as dietary retinol. Use of these medications in children and teens also has been linked to delays in growth.
Vitamin A Supplements
Vitamin A is available in multivitamins and as a stand-alone supplement, often in the form of retinyl acetate or retinyl palmitate 15). A portion of the vitamin A in some supplements is in the form of beta-carotene and the remainder is preformed vitamin A; others contain only preformed vitamin A or only beta-carotene. Supplement labels usually indicate the percentage of each form of the vitamin. The amounts of vitamin A in stand-alone supplements range widely 16). Multivitamin supplements typically contain 2,500–10,000 IU vitamin A, often in the form of both retinol and beta-carotene.
About 28%–37% of the general population uses supplements containing vitamin A 17). Adults aged 71 years or older and children younger than 9 are more likely than members of other age groups to take supplements containing vitamin A.
How much vitamin A do you need ?
According to an analysis of data from the 2007–2008 National Health and Nutrition Examination Survey (NHANES), the average daily dietary vitamin A intake in Americans aged 2 years and older is 607 mcg Retinol Activity Equivalents (RAE) 18). Adult men have slightly higher intakes (649 mcg RAE) than adult women (580 mcg RAE). Although these intakes are lower than the RDAs for individual men and women, these intake levels are considered to be adequate for population groups.
The adequacy of vitamin A intake decreases with age in children 19). Furthermore, girls and African-American children have a higher risk of consuming less than two-thirds of the vitamin A RDA than other children 20).
There are a variety of foods rich in vitamin A and provitamin A carotenoids that are available to Americans. Thus, current dietary patterns appear to provide sufficient vitamin A to prevent deficiency symptoms such as night blindness 21).
- The Estimated Average Requirement (EAR) is based on the assurance of adequate stores of vitamin A.
- The Recommended Dietary Allowance (RDA) (average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals) for men is 900 μg and women is 700 μg Retinol Activity Equivalents (RAE)/day.
- The Tolerable Upper Intake Level (UL) (maximum daily intake unlikely to cause adverse health effects) for adults is set at 3,000 μg/day of preformed vitamin A.
The Recommended Dietary Allowance (RDA) 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.
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 22):
- 1 IU retinol = 0.3 mcg RAE
- 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
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.
The amount of vitamin A you need depends on your age and reproductive status. Recommended intakes for vitamin A for people aged 14 years and older range between 700 and 900 micrograms (mcg) of retinol activity equivalents (RAE) per day. Recommended intakes for women who are nursing range between 1,200 and 1,300 RAE. Lower values are recommended for infants and children younger than 14.
However, the vitamin A content of foods and dietary supplements is given on product labels in international units (IU), not mcg RAE. Converting between IU and mcg RAE is not easy. A varied diet with 900 mcg RAE of vitamin A, for example, provides between 3,000 and 36,000 IU of vitamin A depending on the foods consumed. See our Health Professional Fact Sheet on Vitamin A for more details.
For adults and children aged 4 years and older, the U.S. Food and Drug Administration has established a vitamin A Daily Value (DV) of 5,000 IU from a varied diet of both plant and animal foods. DVs are not recommended intakes; they don’t vary by age and sex, for example. But trying to reach 100% of the DV each day, on average, is useful to help you get enough vitamin A.
The Institute of Medicine developed the Recommended Dietary Allowance (RDA) for vitamin A (retinol). The recommended intakes are listed in International Units (IU) in the table, below:
|[Source: Institute of Medicine, 2001. 23)]|
|1 to 3||1,000|
|4 to 8||1,320|
|9 to 13||2,000|
|14 to 18||3,000||2,310||2,500||4,000|
What foods provide vitamin A ?
There are a variety of foods rich in vitamin A and provitamin A carotenoids that are available to Americans 24). Vitamin A is found naturally in many foods and is added to some foods, such as milk and cereal.
- The U.S. Department of Agriculture’s (USDA’s) Nutrient Database Web site 25) 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).
Concentrations of preformed vitamin A are highest in liver and fish oils 26). Other sources of preformed vitamin A are milk and eggs, which also include some provitamin A 27). Most dietary provitamin A comes from leafy green vegetables, orange and yellow vegetables, tomato products, fruits, and some vegetable oils 28). The top food sources of vitamin A in the U.S. diet include dairy products, liver, fish, and fortified cereals; the top sources of provitamin A include carrots, broccoli, cantaloupe, and squash 29), 30).
You can get recommended amounts of vitamin A by eating a variety of foods, including the following:
- Beef liver and other organ meats (but these foods are also high in cholesterol, so limit the amount you eat).
- Some types of fish, such as salmon.
- Green leafy vegetables and other green, orange, and yellow vegetables, such as broccoli, carrots, and squash.
- Fruits, including cantaloupe, apricots, and mangos.
- Dairy products, which are among the major sources of vitamin A for Americans.
- Fortified breakfast cereals.
Plant sources of beta-carotene are not as well absorbed as the animal sources of vitamin A listed in the chart, but they are still an important source of this vitamin. Dark orange and green vegetables and fruit, including carrots, sweet potatoes, spinach, cantaloupe, and kale are excellent sources of beta-carotene. Because of concerns about the negative effects of too much retinol, some people prefer to eat more foods rich in beta-carotene to satisfy their need for vitamin A.
Although a large body of observational epidemiological evidence suggests that higher blood concentrations of β-carotenes and other carotenoids (provitamin A carotenoids) obtained from foods are associated with a lower risk of several chronic diseases, there is currently not sufficient evidence to support a recommendation that requires a certain percentage of dietary vitamin A to come from provitamin A carotenoids in meeting the vitamin A requirement. However, the existing recommendations for increased consumption of carotenoid-rich fruits and vegetables for their health-promoting benefits are strongly supported (see Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids 31)).
The chart below identifies some common food sources of retinol. Most of the reported cases of vitamin A toxicity have been blamed on the use of supplements. Healthy individuals who eat a balanced diet generally do not need a vitamin A supplement.
Table 2: Common Food Sources of Retinol
|Food Sources of Retinol||Vitamin A (IU)|
|Source: NIH Office of Dietary Supplements|
|Liver, beef, cooked 3 oz.||30,325|
|Liver, chicken, cooked, 3 oz.||13,920|
|Egg substitute, fortified, ¼ cup||1,355|
|Fat-free milk, fortified with vitamin A, 1 cup||500|
|Cheese pizza, ⅛ of a 12-inch pie||380|
|Milk, whole, 3.25% fat, 1 cup||305|
|Cheddar cheese, 1 oz||300|
|Whole egg, 1 medium||280|
Table 3 suggests many dietary sources of vitamin A. The foods from animal sources in Table 3 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 3: Selected Food Sources of Vitamin A
|Food||mcg RAE per|
|Sweet potato, baked in skin, 1 whole||1,403||28,058||561|
|Beef liver, pan fried, 3 ounces||6,582||22,175||444|
|Spinach, frozen, boiled, ½ cup||573||11,458||229|
|Carrots, raw, ½ cup||459||9,189||184|
|Pumpkin pie, commercially prepared, 1 piece||488||3,743||249|
|Cantaloupe, raw, ½ cup||135||2,706||54|
|Peppers, sweet, red, raw, ½ cup||117||2,332||47|
|Mangos, raw, 1 whole||112||2,240||45|
|Black-eyed peas (cowpeas), boiled, 1 cup||66||1,305||26|
|Apricots, dried, sulfured, 10 halves||63||1,261||25|
|Broccoli, boiled, ½ cup||60||1,208||24|
|Ice cream, French vanilla, soft serve, 1 cup||278||1,014||20|
|Cheese, ricotta, part skim, 1 cup||263||945||19|
|Tomato juice, canned, ¾ cup||42||821||16|
|Herring, Atlantic, pickled, 3 ounces||219||731||15|
|Ready-to-eat cereal, fortified with 10% of the DV for vitamin A, ¾–1 cup (more heavily fortified cereals might provide more of the DV)||127–149||500||10|
|Milk, fat-free or skim, with added vitamin A and vitamin D, 1 cup||149||500||10|
|Baked beans, canned, plain or vegetarian, 1 cup||13||274||5|
|Egg, hard boiled, 1 large||75||260||5|
|Summer squash, all varieties, boiled, ½ cup||10||191||4|
|Salmon, sockeye, cooked, 3 ounces||59||176||4|
|Yogurt, plain, low fat, 1 cup||32||116||2|
|Pistachio nuts, dry roasted, 1 ounce||4||73||1|
|Tuna, light, canned in oil, drained solids, 3 ounces||20||65||1|
|Chicken, breast meat and skin, roasted, ½ breast||5||18||0|
*DV = Daily Value. DVs were developed by the FDA to help consumers compare the nutrient contents of products within the context of a total diet. The DV for vitamin A is 5,000 IU for adults and children age 4 and older. Foods providing 20% or more of the DV are considered to be high sources of a nutrient.[Source 32)]
Are you getting enough vitamin A ?
Most people in the United States get enough vitamin A from the foods they eat, and vitamin A deficiency is rare 33). However, certain groups of people are more likely than others to have trouble getting enough vitamin A:
- Premature infants, who often have low levels of vitamin A in their first year.
- Infants, young children, pregnant women, and breastfeeding women in developing countries.
- People with cystic fibrosis.
What happens if you don’t get enough vitamin A ?
Vitamin A deficiency is rare in the United States, although it is common in many developing countries. The most common symptom of vitamin A deficiency in young children and pregnant women is an eye condition called xerophthalmia. Xerophthalmia is the inability to see in low light, and it can lead to blindness if it isn’t treated.
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
- Bone growth
- Reproduction 34). 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 35)
What are some effects of vitamin A on health ?
Scientists are studying vitamin A to understand how it affects health. Here are some examples of what this research has shown.
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 is unclear. People who eat a lot of foods containing beta-carotene might have a lower risk of certain kinds of cancer, such as lung cancer or prostate cancer. But studies to date have not shown that vitamin A or beta-carotene supplements can help prevent cancer or lower the chances of dying from this disease. In fact, studies show that smokers who take high doses of beta-carotene supplements have an increased risk of lung cancer.
Several prospective and retrospective observational studies in current and former smokers, as well as in people who have never smoked, found that higher intakes of carotenoids, fruits and vegetables, or both are associated with a lower risk of lung cancer 36), 37). However, clinical trials have not shown that supplemental beta-carotene and/or vitamin A helps prevent lung cancer. In the Carotene and Retinol Efficacy Trial (CARET), 18,314 current and former smokers (including some males who had been occupationally exposed to asbestos) took daily supplements containing 30 mg beta-carotene and 25,000 IU retinyl palmitate for 4 years, on average 38).
In the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, 29,133 male smokers took 50 mg/day alpha-tocopherol, 20 mg/day beta-carotene, 50 mg/day alpha-tocopherol and 20 mg/day beta-carotene, or placebo for 5–8 years 39). In the beta-carotene component of the Physicians’ Health Study, 22,071 male physicians took 325 mg aspirin plus 50 mg beta-carotene, 50 mg beta-carotene plus aspirin placebo, 325 mg aspirin plus beta-carotene placebo, or both placebos every other day for 12 years 40). In all three of these studies, taking very high doses of beta-carotene, with or without 25,000 IU retinyl palmitate or 325 mg aspirin, did not prevent lung cancer. In fact, both the CARET and ATBC studies showed a significant increase in lung cancer risk among study participants taking beta-carotene supplements or beta-carotene and retinyl palmitate supplements. The Physicians’ Health Study did not find an increased lung cancer risk in participants taking beta-carotene supplements, possibly because only 11% of physicians in the study were current or former smokers.
The evidence on the relationship between beta-carotene and prostate cancer is mixed. CARET study participants who took daily supplements of beta-carotene and retinyl palmitate had a 35% lower risk of nonaggressive prostate cancer than men not taking the supplements 41). However, the ATBC study found that baseline serum beta-carotene and retinol levels and supplemental beta-carotene had no effect on survival 42). Moreover, men in the highest quintile of baseline serum retinol levels were 20% more likely to develop prostate cancer than men in the lowest quintile 43).
The ATBC and CARET 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. The relevance of these results to people who have never smoked or to the effects of beta-carotene or retinol from food or multivitamins (which typically have modest amounts of beta-carotene) is not known. More research is needed to determine the effects of vitamin A on prostate, lung, and other types 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. Age-related macular degeneration’s causes is usually unknown, but the cumulative effect of oxidative stress is postulated to play a role. If so, 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, in particular, accumulate in the retina, the tissue in the eye that is damaged by age-related macular degeneration.
The Age-Related Eye Disease Study (AREDS), a large randomized clinical trial, found that participants at high risk of developing advanced age-related macular degeneration (i.e., those with intermediate AMD or those with advanced AMD in one eye) reduced their risk of developing advanced AMD by 25% by taking a daily supplement containing beta-carotene (15 mg), vitamin E (400 IU dl-alpha-tocopheryl acetate), vitamin C (500 mg), zinc (80 mg), and copper (2 mg) for 5 years compared to participants taking a placebo 44).
A follow-up AREDS2 study confirmed the value of this supplement in reducing the progression of age-related macular degeneration over a median follow-up period of 5 years but found that adding lutein (10 mg) and zeaxanthin (2 mg) or omega-3 fatty acids to the formulation did not confer any additional benefits 45). Importantly, the study 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 of results, supplementation with lutein and zeaxanthin reduced the risk of advanced AMD by 26% in participants with the lowest dietary intakes of these two carotenoids who took a supplement containing them compared to those who did not take a supplement with these carotenoids 46). 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.
Individuals who have or are developing AMD should talk to their health care provider about taking one of the supplement formulations used in AREDS.
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. 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. 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 47).
A Cochrane review of eight randomized controlled trials of treatment with vitamin A for children with measles found that 200,000 IU of vitamin A on each of two consecutive days reduced mortality from measles in children younger than 2 and mortality due to pneumonia in children 48). Vitamin A also reduced the incidence of croup but not pneumonia or diarrhea, although the mean duration of fever, pneumonia, and diarrhea was shorter in children who received vitamin A supplements. A meta-analysis of six high-quality randomized controlled trials of measles treatment also found that two doses of 100,000 IU in infants and 200,000 IU in older children significantly reduced measles mortality 49). 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 50). 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 51).
Vitamin A Deficiency
Vitamin A deficiency can result from inadequate intake, fat malabsorption, or liver disorders. Deficiency impairs immunity and hematopoiesis and causes rashes and typical ocular effects (eg, xerophthalmia, night blindness). 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, and Crohn’s disease 52). Diagnosis is based on typical ocular findings and low vitamin A levels. Treatment consists of vitamin A given orally or if symptoms are severe or malabsorption is the cause, parenterally.
Vitamin A deficiency is one of the top causes of preventable blindness in children 53). 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 54), 55).
The most specific clinical effect of inadequate vitamin A intake is xerophthalmia 56). It is estimated that 3 to 10 million children, mostly in developing countries, become xerophthalmic, and 250,000 to 500,000 go blind annually 57), 58). The World Health Organization 59) 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 60), and it responds rapidly to treatment with vitamin A 61). High-dose (60 mg) vitamin A supplementation reduced the incidence of night blindness by 63 percent in Nepalese children 62). 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 63).
In developing countries, vitamin A deficiency typically begins during infancy, when infants do not receive adequate supplies of colostrum or breast milk 64). Chronic diarrhea also leads to excessive loss of vitamin A in young children, and vitamin A deficiency increases the risk of diarrhea 65), 66). 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 67), 68). Vitamin A deficiency also increases the severity and mortality risk of infections (particularly diarrhea and measles) even before the onset of xerophthalmia 69), 70), 71).
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 72), 73). 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 74).
Vitamin A deficiency has been associated with a reduction in lymphocyte numbers, natural killer cells, and antigen-specific immunoglobulin responses 75), 76). 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 77), 78). 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 79). Mortality rates were about four times greater among children with mild xerophthalmia than those without it 80). The risk of severe morbidity and mortality decreases with vitamin A repletion. In children hospitalized with measles, case fatality 81), 82) and the severity of complications on admission were reduced when they received high doses (60 to 120 mg) of vitamin A 83), 84). In some studies, vitamin A supplementation (30 to 60 mg) has been shown to reduce the severity of diarrhea 85), 86) and Plasmodium falciparum malaria 87) in young children, but vitamin A supplementation has had little effect on the risk or severity of respiratory infections, except when associated with measles 88).
In developing countries, vitamin A supplementation has been shown to reduce the risk of mortality among young children 89), 90), 91), 92), 93), infants 94), and pregnant and postpartum women 95). 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 96), 97), 98). 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 99). Furthermore, the American Academy of Pediatrics 100) recommends vitamin A supplementation for children in the United States who are hospitalized with measles.
- Causes of Vitamin A Deficiency
Primary vitamin Adeficiency is usually caused by:
- Prolonged dietary deprivation
It is endemic in areas such as southern and eastern Asia, where rice, devoid of beta-carotene, is the staple food. Xerophthalmia due to primary deficiency is a common cause of blindness among young children in developing countries.
Secondary vitamin A deficiencymay be due to:
- Decreased bioavailability of provitamin A carotenoids
- Interference with absorption, storage, or transport of vitamin A
Interference with absorption or storage is likely in celiac disease, cystic fibrosis, pancreatic insufficiency, duodenal bypass, chronic diarrhea, bile duct obstruction, giardiasis, and cirrhosis. 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.
Groups at Risk of Vitamin A Deficiency
The following groups are among those most likely to have inadequate intakes of vitamin A.
- Premature Infants
In developed countries, clinical vitamin A deficiency is rare in infants and occurs only in those with malabsorption disorders 101). However, preterm infants do not have adequate liver stores of vitamin A at birth and their plasma concentrations of retinol often remain low throughout the first year of life 102), 103). Preterm infants with vitamin A deficiency have an increased risk of eye, chronic lung, and gastrointestinal diseases 104).
- Infants and Young Children in Developing Countries
In developed countries, the amounts of vitamin A in breast milk are sufficient to meet infants’ needs for the first 6 months of life. But in women with vitamin A deficiency, breast milk volume and vitamin A content are suboptimal and not sufficient to maintain adequate vitamin A stores in infants who are exclusively breastfed 105). The prevalence of vitamin A deficiency in developing countries begins to increase in young children just after they stop breastfeeding 106). The most common and readily recognized symptom of vitamin A deficiency in infants and children is xerophthalmia.
- Pregnant and Lactating Women in Developing Countries
Pregnant women need extra vitamin A for fetal growth and tissue maintenance and for supporting their own metabolism 107). The World Health Organization estimates that 9.8 million pregnant women around the world have xerophthalmia as a result of vitamin A deficiency 108). Other effects of vitamin A deficiency in pregnant and lactating women include increased maternal and infant morbidity and mortality, increased anemia risk, and slower infant growth and development.
- People with Cystic Fibrosis
Most people with cystic fibrosis have pancreatic insufficiency, increasing their risk of vitamin A deficiency due to difficulty absorbing fat 109), 110). Several cross-sectional studies found that 15%–40% of patients with cystic fibrosis have vitamin A deficiency 111). However, improved pancreatic replacement treatments, better nutrition, and caloric supplements have helped most patients with cystic fibrosis become vitamin A sufficient 112). Several studies have shown that oral supplementation can correct low serum beta-carotene levels in people with cystic fibrosis, but no controlled studies have examined the effects of vitamin A supplementation on clinical outcomes in patients with cystic fibrosis 113), 114), 115).
- Symptoms and Signs of Vitamin A Deficiency
Impaired dark adaptation of the eyes, which can lead to night blindness, is an early symptom of vitamin A deficiency. Xerophthalmia (which is nearly characteristic) results from keratinization of the eyes. It involves drying (xerosis) and thickening of the conjunctivae and corneas. Superficial foamy patches composed of epithelial debris and secretions on the exposed bulbar conjunctiva (Bitot spots) develop. In advanced deficiency, the cornea becomes hazy and can develop erosions, which can lead to its destruction (keratomalacia).
Keratinization of the skin and of the mucous membranes in the respiratory, GI, and urinary tracts can occur. Drying, scaling, and follicular thickening of the skin and respiratory infections can result.
Immunity is generally impaired.
The younger the patient, the more severe are the effects of vitamin A deficiency. Growth retardation and infections are common among children. Mortality rate can exceed 50% in children with severe vitamin A deficiency.
- Diagnosis of Vitamin A Deficiency
Serum retinol levels, clinical evaluation, and response to vitamin A 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 is 28 to 86 mcg/dL (1 to 3 mcmol/L). However, levels decrease only after the deficiency is advanced because the liver contains large stores of vitamin A. Also, decreased levels may result from acute infection, which causes retinol-binding protein and transthyretin (also called prealbumin) levels to decrease transiently.
A therapeutic trial of vitamin A may help confirm the diagnosis.
- Prevention of Vitamin A Deficiency
The diet should include dark green leafy vegetables, deep- or bright-colored fruits (eg, papayas, oranges), carrots, and yellow vegetables (eg, squash, pumpkin). Vitamin A–fortified milk and cereals, liver, egg yolks, and fish liver oils are helpful. Carotenoids are absorbed better when consumed with some dietary fat. If milk allergy is suspected in infants, they should be given adequate vitamin A in formula feedings.
In developing countries, prophylactic supplements of vitamin A palmitate in oil 200,000 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).
- Treatment of Vitamin A Deficiency
Vitamin A Palmitate
Dietary deficiency of vitamin A is traditionally treated with vitamin A palmitate in oil 60,000 IU po once/day for 2 days, followed by 4500 IU po once/day. If vomiting or malabsorption is present or xerophthalmia is probable, a dose of 50,000 IU for infants < 6 mo, 100,000 IU for infants 6 to 12 mo, or 200,000 IU for children > 12 mo and adults should be given for 2 days, with a third dose at least 2 wk later. The same doses are recommended for infants and children with complicated measles.
Vitamin A deficiency is a risk factor for severe measles; treatment with vitamin A can shorten the duration of the disorder and may reduce the severity of symptoms and risk of death. The WHO recommends that all children with measles in developing countries should receive 2 doses of vitamin A, (100,000 IU for children < 12 mo and 200,000 IU for those >12 mo) given 24 h apart.
Infants born of HIV-positive mothers should receive 50,000 IU (15,000 RAE) within 48 h of birth. Prolonged daily administration of large doses, especially to infants, must be avoided because toxicity may result.
For pregnant or breastfeeding women, prophylactic or therapeutic doses should not exceed 10,000 IU (3000 RAE)/day to avoid possible damage to the fetus or infant.
Vitamin A Toxicity: Can Taking Too Much Vitamin A Be Harmful ?
Yes, high intakes of some forms, usually from supplements or certain medicines, of vitamin A can be harmful. Hypervitaminosis A is having too much vitamin A in the body 116). Getting too much preformed vitamin A can cause dizziness, nausea, headaches, coma, and even death.
Although carotene is converted to vitamin A in the body, excessive ingestion of carotene causes carotenemia, not vitamin A toxicity. Carotenemia is usually asymptomatic but may lead to carotenosis, in which the skin becomes yellow.
When taken as a supplement, beta-carotene has been associated with increased cancer risk; risk does not seem to increase when carotenoids are consumed in fruits and vegetables.
Although symptoms of vitamin Atoxicity may vary, headache and rash usually develop during acute or chronic toxicity.
- Acute toxicity causes increased intracranial pressure. Drowsiness, irritability, abdominal pain, nausea, and vomiting are common. Sometimes the skin subsequently peels.
- Early symptoms of chronic toxicity are sparsely distributed, coarse hair; alopecia of the eyebrows; dry, rough skin; dry eyes; and cracked lips. Later, severe headache, pseudotumor cerebri, and generalized weakness develop. Cortical hyperostosis of bone and arthralgia may occur, especially in children. Fractures may occur easily, especially in the elderly. In children, toxicity can cause pruritus, anorexia, and failure to thrive. Hepatomegaly and splenomegaly may occur.
Vitamin A Toxicity
- Too much vitamin A can make you sick.
- Large doses of vitamin A during pregnancy can cause birth defects in the babies. Women who might be pregnant should not take high doses of vitamin A supplements.
- Acute vitamin A poisoning occurs quickly, most often when an adult takes several hundred thousand international units (IUs) of vitamin A.
- Chronic vitamin A poisoning may occur over time in adults who regularly take more than 25,000 IU a day.
- Babies and children are more sensitive to vitamin A. They can become sick after taking smaller doses of vitamin A or if they swallow products that contain vitamin A, such as skin cream with retinol in it.
Vitamin A Toxicity in Infants and Children
There are numerous case reports of infants, toddlers, and children who have demonstrated toxic effects due to excess vitamin A intakes for months to years. Of particular concern are intracranial (bulging fontanel) and skeletal abnormalities that can result in infants given vitamin A doses of 5,500 to 6,750 μg/day 117). The clinical presentation of vitamin A toxicity in infants and young children varies widely. The more commonly recognized signs and symptoms include skeletal abnormalities, bone tenderness and pain, increased intracranial pressure, desquamation, brittle nails, mouth fissures, alopecia, fever, headache, lethargy, irritability, weight loss, vomiting, and hepatomegaly 118). Furthermore, tolerance to excess vitamin A intake also appears to vary 119). Carpenter and coworkers 120) described two boys who developed hypervitaminosis A by age 2 years for one and by age 6 years for the other. Both were given chicken liver that supplied about 690 μg/day of vitamin A and various supplements that supplied another 135 to 750 μg/day. An older sister who had been treated similarly remained completely healthy.
How Does Vitamin A Affect Your Bones ?
Vitamin A is a family of fat-soluble compounds that play an important role in vision, bone growth, reproduction, cell division, and cell differentiation. Vitamin A is important for healthy bones. However, too much vitamin A has been linked to bone loss and an increase in the risk of hip fracture. Scientists believe that excessive amounts of vitamin A trigger an increase in osteoclasts, the cells that break down bone. They also believe that too much vitamin A may interfere with vitamin D, which plays an important role in preserving bone 121).
Beta-carotene, on the other hand, is largely considered to be safe and has not been linked to adverse effects in bone or elsewhere in the body.
Causes of Vitamin A Toxicity
Vitamin A is a fat-soluble vitamin that is stored in the liver. Many foods contain vitamin A, including:
- Meat, fish, and poultry
- Dairy products
- Some fruits and vegetables
Some dietary supplements also contain Vitamin A.
Symptoms of Vitamin A Toxicity
Symptoms may include:
- Abnormal softening of the skull bone (in infants and children)
- Blurred vision
- Bone pain or swelling
- Bulging of the soft spot in an infant’s skull (fontanelle)
- Changes in alertness or consciousness
- Decreased appetite
- Double vision (in young children)
- Hair changes, such as hair loss and oily hair
- Liver damage
- Poor weight gain (in infants and children)
- Skin changes, such as cracking at corners of the mouth, higher sensitivity to sunlight, oily skin, peeling, itching, and yellow color to the skin
- Vision changes
Diagnosis of Vitamin A Toxicity
These tests may be done if a high vitamin A level is suspected:
- Bone x-rays
- Blood calcium test
- Cholesterol test
- Liver function test
- Blood test to check vitamin A level
Diagnosis of vitamin A toxicity is clinical. Blood vitamin levels correlate poorly with toxicity. However, if clinical diagnosis is equivocal, laboratory testing may help. In vitamin A toxicity, fasting serum retinol levels may increase from normal (28 to 86 mcg/dL [1 to 3 mcmol/L]) to > 100 mcg/dL (> 3.49 mcmol/L), sometimes to > 2000 mcg/dL (> 69.8 mcmol/L). Hypercalcemia is common.
Differentiating vitamin A toxicity from other disorders may be difficult. Carotenosis may also occur in severe hypothyroidism and anorexia nervosa, possibly because carotene is converted to vitamin A more slowly.
Treatment of Vitamin A Toxicity
Treatment involves simply stopping supplements (or rarely, foods) that contain vitamin A.
Symptoms and signs of chronic toxicity usually disappear within 1 to 4 wk.
However, birth defects in the fetus of a mother who has taken megadoses of vitamin A are not reversible.
Most people fully recover.
Possible Complications of Vitamin A Toxicity
Complications can include:
- Excessively high calcium level
- Failure to thrive (in infants)
- Kidney damage due to high calcium
- Liver damage
Taking too much vitamin A during pregnancy may cause abnormal development in the growing baby. Talk to your health care provider about eating a proper diet while you are pregnant.
Consuming high amounts of beta-carotene or other forms of provitamin A can turn the skin yellow-orange, but this condition is harmless. High intakes of beta-carotene do not cause birth defects or the other more serious effects caused by getting too much preformed vitamin A.
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